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•COVID-19 is a state of hypercoagulability and often complicates thrombosis.,•Cerebral venous thrombosis (CVT) is a serious complication in COVID-19.,•Intravenous unfractionated heparin followed by edoxaban improved CVT.,•Regular monitoring of coagulopathy should be performed in hospitalized patients with COVID-19.,COVID-19 is a state of hypercoagulability and often complicates thrombosis.,Cerebral venous thrombosis (CVT) is a serious complication in COVID-19.,Intravenous unfractionated heparin followed by edoxaban improved CVT.,Regular monitoring of coagulopathy should be performed in hospitalized patients with COVID-19.,COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first reported in Wuhan, China in December 2019, and is ongoing pandemic.,While a majority of patients with SARS-CoV-2 infection shows asymptomatic or mild disease, hospitalized patients can develop critical condition, such as pneumonia, sepsis, and respiratory failure.,Some cases deteriorate into sever systemic disease and multiorgan failure.,Many patients of severe COVID-19 show hypercoagulable state and complicate with venous thromboembolism and atrial thrombosis.,We herein reported a case of COVID-19 who developed cerebral venous thrombosis (CVT) co-incidence with pulmonary thromboembolism (PTE).,A 56-year-old Japanese man was presented with fever and malaise and diagnosed with COVID-19.,He was treated with ciclesonide and azithromycin, but his respiratory condition deteriorated.,Thus, systemic corticosteroids and favipiravir were initiated and these treatments resulted in afebrile state, improving malaise and respiratory failure.,However, he suddenly developed severe headache and vomiting with increased concentration of D-dimer.,Brain CT and MRI showed typical images of CVT in the left transvers sinus and CT pulmonary angiography showed PE.,Administration of unfractionated heparin followed by edoxaban treatment reduced the levels of D-dimer and improved his clinical presentation and thrombosis.,Monitoring coagulopathy is important in COVID-19 patients and in case of venous thromboembolism, including cerebral venous system, appropriate anticoagulant therapy should be initiated.

The COVID‐19 pandemic has become an urgent issue in every country.,Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)‐like massive intravascular clot formation is frequently seen in this cohort.,Therefore, coagulation tests may be considered useful to discriminate severe cases of COVID‐19.,The clinical presentation of COVID‐19‐associated coagulopathy is organ dysfunction primarily, whereas hemorrhagic events are less frequent.,Changes in hemostatic biomarkers represented by increase in D‐dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation.,In comparison with bacterial‐sepsis‐associated coagulopathy/DIC, prolongation of prothrombin time, and activated partial thromboplastin time, and decrease in antithrombin activity is less frequent and thrombocytopenia is relatively uncommon in COVID‐19.,The mechanisms of the coagulopathy are not fully elucidated, however.,It is speculated that the dysregulated immune responses orchestrated by inflammatory cytokines, lymphocyte cell death, hypoxia, and endothelial damage are involved.,Bleeding tendency is uncommon, but the incidence of thrombosis in COVID‐19 and the adequacy of current recommendations regarding standard venous thromboembolic dosing are uncertain.

Hyperglycemia-induced oxidative stress and fibrosis play a crucial role in the development of diabetic cardiomyopathy (DCM).,Tetrahydrocurcumin (THC), a major bioactive metabolite of natural antioxidant curcumin, is reported to exert even more effective antioxidative and superior antifibrotic properties as well as anti-inflammatory and antidiabetic abilities.,This study was designed to investigate the potential protective effects of THC on experimental DCM and its underlying mechanisms, pointing to the role of high glucose-induced oxidative stress and interrelated fibrosis.,In STZ-induced diabetic mice, oral administration of THC (120 mg/kg/d) for 12 weeks significantly improved the cardiac function and ameliorated myocardial fibrosis and cardiac hypertrophy, accompanied by reduced reactive oxygen species (ROS) generation.,Mechanically, THC administration remarkably increased the expression of the SIRT1 signaling pathway both in vitro and in vivo, further evidenced by decreased downstream molecule Ac-SOD2 and enhanced deacetylated production SOD2, which finally strengthened antioxidative stress capacity proven by repaired activities of SOD and GSH-Px and reduced MDA production.,Additionally, THC treatment accomplished its antifibrotic effect by depressing the ROS-induced TGFβ1/Smad3 signaling pathway followed by reduced expression of cardiac fibrotic markers α-SMA, collagen I, and collagen III.,Collectively, these finds demonstrated the therapeutic potential of THC treatment to alleviate DCM mainly by attenuating hyperglycemia-induced oxidative stress and fibrosis via activating the SIRT1 pathway.

Reducing oxidative stress is a crucial therapeutic strategy for ameliorating diabetic myocardial ischemia/reperfusion (MI/R) injury.,Honokiol (HKL) acts as an effective cardioprotective agent for its strong antioxidative activity.,However, its roles and underlying mechanisms against MI/R injury in type 1 diabetes (T1D) remain unknown.,Since SIRT1 and Nrf2 are pivotal regulators in diabetes mellitus patients suffering from MI/R injury, we hypothesized that HKL ameliorates diabetic MI/R injury via the SIRT1-Nrf2 signaling pathway.,Streptozotocin-induced T1D rats and high-glucose-treated H9c2 cells were exposed to HKL, with or without administration of the SIRT1 inhibitor EX527, SIRT1 siRNA, or Nrf2 siRNA, and then subjected to I/R operation.,We found that HKL markedly improved the postischemic cardiac function, decreased the infarct size, reduced the myocardial apoptosis, and diminished the reactive oxygen species generation.,Intriguingly, HKL remarkably activated SIRT1 signaling, enhanced Nrf2 nuclear translocation, increased antioxidative signaling, and decreased apoptotic signaling.,However, these effects were largely abolished by EX527 or SIRT1 siRNA.,Additionally, our cellular experiments showed that Nrf2 siRNA blunted the cytoprotective effects of HKL, without affecting SIRT1 expression and activity.,Collectively, these novel findings indicate that HKL abates MI/R injury in T1D by ameliorating myocardial oxidative damage and apoptosis via the SIRT1-Nrf2 signaling pathway.

Coronavirus disease 2019 (COVID-19) causes a hypercoagulable state.,Several autopsy studies have found microthrombi in pulmonary circulation.,In this randomized, open-label, phase II study, we randomized COVID-19 patients requiring mechanical ventilation to receive either therapeutic enoxaparin or the standard anticoagulant thromboprophylaxis.,We evaluated the gas exchange over time through the ratio of partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) at baseline, 7, and 14 days after randomization, the time until successful liberation from mechanical ventilation, and the ventilator-free days.,Ten patients were assigned to the therapeutic enoxaparin and ten patients to prophylactic anticoagulation.,There was a statistically significant increase in the PaO2/FiO2 ratio over time in the therapeutic group (163 [95% confidence interval - CI 133-193] at baseline, 209 [95% CI 171-247] after 7 days, and 261 [95% CI 230-293] after 14 days), p = 0.0004.,In contrast, we did not observe this improvement over time in the prophylactic group (184 [95% CI 146-222] at baseline, 168 [95% CI 142-195] after 7 days, and 195 [95% CI 128-262] after 14 days), p = 0.487.,Patients of the therapeutic group had a higher ratio of successful liberation from mechanical ventilation (hazard ratio: 4.0 [95% CI 1.035-15.053]), p = 0.031 and more ventilator-free days (15 days [interquartile range IQR 6-16] versus 0 days [IQR 0-11]), p = 0.028 when compared to the prophylactic group.,Therapeutic enoxaparin improves gas exchange and decreases the need for mechanical ventilation in severe COVID-19.,REBEC RBR-949z6v.,•COVID-19 is associated with microthrombi in pulmonary circulation.,•We randomized severe COVID-19 patients to receive either therapeutic enoxaparin or the standard thromboprophylaxis.,•Therapeutic enoxaparin resulted in improved gas exchange over time.,•Larger clinical trial is urgently needed to evaluate the anticoagulant therapy in severe COVID-19.,COVID-19 is associated with microthrombi in pulmonary circulation.,We randomized severe COVID-19 patients to receive either therapeutic enoxaparin or the standard thromboprophylaxis.,Therapeutic enoxaparin resulted in improved gas exchange over time.,Larger clinical trial is urgently needed to evaluate the anticoagulant therapy in severe COVID-19.

A remarkably high incidence of venous thromboembolism (VTE) has been reported among critically ill patients with COVID‐19 assisted in the intensive care unit (ICU).,However, VTE burden among non‐ICU patients hospitalized for COVID‐19 that receive guideline‐recommended thromboprophylaxis is unknown.,To determine the incidence of VTE among non‐ICU patients hospitalized for COVID‐19 that receive pharmacological thromboprophylaxis.,We performed a systematic screening for the diagnosis of deep vein thrombosis (DVT) by lower limb vein compression ultrasonography (CUS) in consecutive non‐ICU patients hospitalized for COVID‐19, independent of the presence of signs or symptoms of DVT.,All patients were receiving pharmacological thromboprophylaxis with either enoxaparin or fondaparinux.,The population that we screened consisted of 84 consecutive patients, with a mean age of 67.6 ± 13.5 years and a mean Padua Prediction Score of 5.1 ± 1.6.,Seventy‐two patients (85.7%) had respiratory insufficiency, required oxygen supplementation, and had reduced mobility or were bedridden.,In this cohort, we found 10 cases of DVT, with an incidence of 11.9% (95% confidence interval [CI] 4.98‐18.82).,Of these, 2 were proximal DVT (incidence rate 2.4%, 95% CI −0.87‐5.67) and 8 were distal DVT (incidence rate 9.5%, 95% CI 3.23‐5.77).,Significant differences between subjects with and without DVT were D‐dimer > 3000 µg/L (P < .05), current or previous cancer (P < .05), and need of high flow nasal oxygen therapy and/or non‐invasive ventilation (P < .01).,DVT may occur among non‐ICU patients hospitalized for COVID‐19, despite guideline‐recommended thromboprophylaxis.

Inconsistent findings have been found among studies evaluating the risk of cardiovascular disease for women who have had pregnancies complicated by gestational hypertension (the new onset of high blood pressure without proteinuria during pregnancy).,We provide a comprehensive review of studies to quantify the association between gestational hypertension and cardiovascular events in women.,We conducted a systematic search of PubMed, Embase, and Web of Science in March 2019 for studies examining the association between gestational hypertension and any cardiovascular event.,Two reviewers independently assessed the abstracts and full‐text articles.,Study characteristics and the relative risk (RR) of cardiovascular events associated with gestational hypertension were extracted from the eligible studies.,Where appropriate, the estimates were pooled with inverse variance weighted random‐effects meta‐analysis.,A total of 21 studies involving 3 60 1192 women (127 913 with gestational hypertension) were identified.,Gestational hypertension in the first pregnancy was associated with a greater risk of overall cardiovascular disease (RR, 1.45; 95% CI, 1.17-1.80) and coronary heart disease (RR, 1.46; 95% CI, 1.23-1.73), but not stroke (RR, 1.26; 95% CI, 0.96-1.65) or thromboembolic events (RR, 0.88; 95% CI, 0.73-1.07).,Women with 1 or more pregnancies affected by gestational hypertension were at greater risk of cardiovascular disease (RR, 1.81; 95% CI, 1.42-2.31), coronary heart disease (RR, 1.83; 95% CI, 1.33-2.51), and heart failure (RR, 1.77; 95% CI, 1.47-2.13), but not stroke (RR, 1.50; 95% CI, 0.75-2.99).,Gestational hypertension is associated with a greater risk of overall cardiovascular disease, coronary heart disease, and heart failure.,More research is needed to assess the presence of a dose-response relationship between gestational hypertension and subsequent cardiovascular disease.,URL: https://www.crd.york.ac.uk/prosp​ero/; Unique identifier: CRD42018119031.

Preeclampsia and gestational hypertension (GH) are the most common hypertensive pregnancy disorders.,Preeclampsia has been linked to increased risk of cardiovascular disease (CVD), but a similar association for GH has not been established.,We aimed to determine the association between GH and subsequent CVD, and explore the additional role of small‐for‐gestational‐age infants, preterm delivery, and parity.,Data from the Medical Birth Registry of Norway were linked to the Cardiovascular Disease in Norway project and the Norwegian Cause of Death Registry.,Hazard ratios and 95% confidence intervals were computed using Cox proportional hazard regression, comparing women with and without GH during their first and/or second pregnancy.,We included all women with a first delivery from 1980 through 2009 (n=617 589) and followed them for a median of 14.3 (quartile 1-quartile 3: 6.9-21.5) years.,Women with GH in the first pregnancy had 1.8‐fold (95% confidence interval, 1.7-2.0) higher risk of subsequent CVD compared with women without any hypertensive pregnancy disorder.,When GH occurred in combination with small‐for‐gestational‐age infants and/or preterm delivery, the hazard ratio was 2.6 (95% confidence interval, 2.3-3.0).,When women with GH were compared with women with preeclampsia, the risk of CVD was comparable when the pregnancy complications occurred in either the first or second pregnancy but was significantly higher for preeclampsia without complications when the disorder occurred in both pregnancies.,GH was associated with increased risk of subsequent CVD, and the highest risk was observed when GH was combined with small‐for‐gestational‐age infants and/or preterm delivery.

The aim of this study was to evaluate the association between vitamin D deficiency and risk of heart failure in elderly patients of cardiology outpatient clinics.,A cross‐sectional study with an analytical approach was employed.,Clinical data were collected from the elderly from August 2015 to February 2016.,The dependent variable was the risk of heart failure; the independent variable was vitamin D deficiency; and intervening factors were age, gender, education, ethnicity, hypertension, diabetes mellitus, hypothyroidism, renal failure, dementia, stroke, dyslipidaemia, depression, smoking, alcoholism, obesity, andropause, and cardiac arrhythmia.,To analyse the association between vitamin D deficiency and risk of heart failure, we used the bivariate logistic analysis, followed by analysis through the multivariate logistic regression model.,Of the 137 elderly, the study found the following: women (75.9%); overweight (48.2%); obese (30.6%); increase in the index waist/hip (88.3%); dyslipidaemia (94.2%) and hypertension (91.2%); coronary artery disease (35.0%); and 27.7% with cardiac arrhythmia or left ventricular hypertrophy.,Sixty‐five per cent of the elderly were deficient in vitamin D.,The risk of heart failure was significantly associated with vitamin D deficiency [odds ratio (OR): 12.19; 95% confidence interval (CI) = 4.23-35.16; P = 0.000], male gender (OR: 15.32; 95% CI = 3.39-69.20, P = 0.000), obesity (OR: 4.17; 95% CI = 1.36-12.81; P = 0.012), and cardiac arrhythmia (OR: 3.69; 95% CI = 1.23-11.11; P = 0.020).,There was a high prevalence of vitamin D deficiency in the elderly, and the evidence shows a strong association between vitamin D deficiency and increased risk of heart failure in this population.

Cardiac cachexia frequently accompanies the progression of heart failure despite the use of effective therapies for left ventricular dysfunction.,Activation of the sympathetic nervous system has been implicated in the pathogenesis of weight loss, but the effects of sympathetic antagonism on cachexia are not well defined.,We prospectively evaluated changes in body weight in 2289 patients with heart failure who had dyspnoea at rest or on minimal exertion and a left ventricular ejection fraction <25%.,Patients were randomly assigned (double‐blind) to receive either placebo (n = 1133) or carvedilol (n = 1156) and were followed for the occurrence of major clinical events for up to 29 months (COPERNICUS trial).,Patients were not enrolled if they had signs of clinically significant fluid retention due to heart failure.,Patients in the carvedilol group were 33% less likely than patients in the placebo group to experience a further significant loss of weight (>6%) (95% confidence interval: 14-48%, P = 0.002) and were 37% more likely to experience a significant gain in weight (≥5%) (95% confidence interval: 12-66%, P = 0.002).,Carvedilol's ability to prevent weight loss was most marked in patients with increased body mass index at baseline, whereas its ability to promote weight gain was most marked in patients with decreased body mass index at baseline.,Increases in weight were not accompanied by evidence of fluid retention.,Baseline values for body mass index and change in body weight were significant predictors of survival regardless of treatment.,Carvedilol attenuated the development and promoted a partial reversal of cachexia in patients with severe chronic heart failure, supporting a role for prolonged sympathetic activation in the genesis of weight loss.

Compare gender disparities in ST-elevation myocardial infarction (STEMI) regarding first medical contact (FMC) and prehospital delay times and explore factors associated with prehospital delay in men and women separately.,Cross-sectional study based on medical records and a validated questionnaire.,Eligible patients were enrolled within 24 hours after admittance to hospital.,Patients were included from November 2012 to January 2014 from five Swedish hospitals with catheterisation facilities 24/7.,340 men and 109 women aged between 31 and 95 years completed the survey.,FMC were divided into five possible contacts: primary healthcare centre by phone or directly, national advisory nurse by phone, emergency medical services (EMS) and emergency room directly.,Two parts of prehospital delay times were studied: time from symptom onset to FMC and time from symptom onset to diagnostic ECG.,Women more often called an advisory nurse as FMC (28% vs 18%, p=0.02).,They had a longer delay until FMC, 90 (IQR 39-221) vs 66 (28-161) min, p=0.04 and until ECG, 146 (68-316) vs 103 (61-221) min, p=0.03.,Men went to hospital because of believing they were stricken by an MI to a higher extent than women did (25% vs 15%, p=0.04) and were more often recommended to call EMS by bystanders (38% vs 22%, p<0.01).,Hesitating about going to hospital and experiencing pain in the stomach/back/shoulders were factors associated with longer delays in women.,Believing the symptoms would disappear or interpreting them as nothing serious were corresponding factors in men.,In both genders bystanders acting by contacting EMS explained shorter prehospital delays.,In STEMI, women differed from men in FMC and they had longer delays.,This was partly due to atypical symptoms and a longer decision time.,Bystanders acted more promptly when men than when women fell ill.,Public knowledge of MI symptoms, and how to act properly, still seems insufficient.

Women with ST‐segment-elevation myocardial infarction (STEMI) have higher mortality rates than men.,We investigated whether sex‐related differences in timely access to care among STEMI patients may be a factor associated with excess risk of early mortality in women.,We identified 6022 STEMI patients who had information on time of symptom onset to time of hospital presentation at 41 hospitals participating in the ISACS‐TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry (NCT01218776) from October 2010 through April 2016.,Patients were stratified into time‐delay cohorts.,We estimated the 30‐day risk of all‐cause mortality in each cohort.,Despite similar delays in seeking care, the overall time from symptom onset to hospital presentation was longer for women than men (median: 270 minutes [range: 130-776] versus 240 minutes [range: 120-600]).,After adjustment for baseline variables, female sex was independently associated with greater risk of 30‐day mortality (odds ratio: 1.58; 95% confidence interval, 1.27-1.97).,Sex differences in mortality following STEMI were no longer observed for patients having delays from symptom onset to hospital presentation of ≤1 hour (odds ratio: 0.77; 95% confidence interval, 0.29-2.02).,Sex difference in mortality following STEMI persists and appears to be driven by prehospital delays in hospital presentation.,Women appear to be more vulnerable to prolonged untreated ischemia.,URL: https://www.clinicaltrials.gov/.,Unique identifier: NCT01218776.

The novel coronavirus disease of 2019 (COVID-19) is associated with significant morbidity and mortality.,The impact of thrombotic complications has been increasingly recognized as an important component of this disease.,This narrative review summarizes the thrombotic complications associated with COVID-19 with an emphasis on information for Emergency Medicine clinicians.,Thrombotic complications from COVID-19 are believed to be due to a hyperinflammatory response caused by the virus.,Several complications have been described in the literature.,These include acute limb ischemia, abdominal and thoracic aortic thrombosis, mesenteric ischemia, myocardial infarction, venous thromboembolism, acute cerebrovascular accident, and disseminated intravascular coagulation.,It is important for Emergency Medicine clinicians to be aware of the thrombotic complications of COVID-19.,Knowledge of these components are essential to rapidly recognize and treat to reduce morbidity and mortality in these patients.

Critically ill patients diagnosed with COVID-19 may develop a pro-thrombotic state that places them at a dramatically increased lethal risk.,Although platelet activation is critical for thrombosis and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear.,Using platelets from healthy volunteers, non-COVID-19 and COVID-19 patients, as well as wild-type and hACE2 transgenic mice, we evaluated the changes in platelet and coagulation parameters in COVID-19 patients.,We investigated ACE2 expression and direct effect of SARS-CoV-2 virus on platelets by RT-PCR, flow cytometry, Western blot, immunofluorescence, and platelet functional studies in vitro, FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo.,We demonstrated that COVID-19 patients present with increased mean platelet volume (MPV) and platelet hyperactivity, which correlated with a decrease in overall platelet count.,Detectable SARS-CoV-2 RNA in the blood stream was associated with platelet hyperactivity in critically ill patients.,Platelets expressed ACE2, a host cell receptor for SARS-CoV-2, and TMPRSS2, a serine protease for Spike protein priming.,SARS-CoV-2 and its Spike protein directly enhanced platelet activation such as platelet aggregation, PAC-1 binding, CD62P expression, α granule secretion, dense granule release, platelet spreading, and clot retraction in vitro, and thereby Spike protein enhanced thrombosis formation in wild-type mice transfused with hACE2 transgenic platelets, but this was not observed in animals transfused with wild-type platelets in vivo.,Further, we provided evidence suggesting that the MAPK pathway, downstream of ACE2, mediates the potentiating role of SARS-CoV-2 on platelet activation, and that platelet ACE2 expression decreases following SARS-COV-2 stimulation.,SARS-CoV-2 and its Spike protein directly stimulated platelets to facilitate the release of coagulation factors, the secretion of inflammatory factors, and the formation of leukocyte-platelet aggregates.,Recombinant human ACE2 protein and anti-Spike monoclonal antibody could inhibit SARS-CoV-2 Spike protein-induced platelet activation.,Our findings uncovered a novel function of SARS-CoV-2 on platelet activation via binding of Spike to ACE2.,SARS-CoV-2-induced platelet activation may participate in thrombus formation and inflammatory responses in COVID-19 patients.

The impact of atrial arrhythmias on coronavirus disease 2019 (COVID‐19)‐associated outcomes are unclear.,We sought to identify prevalence, risk factors and outcomes associated with atrial arrhythmias among patients hospitalized with COVID‐19.,An observational cohort study of 1053 patients with severe acute respiratory syndrome coronavirus 2 infection admitted to a quaternary care hospital and a community hospital was conducted.,Data from electrocardiographic and telemetry were collected to identify atrial fibrillation (AF) or atrial flutter/tachycardia (AFL).,The association between atrial arrhythmias and 30‐day mortality was assessed with multivariable analysis.,Mean age of patients was 62 ± 17 years and 62% were men.,Atrial arrhythmias were identified in 166 (15.8%) patients, with AF in 154 (14.6%) patients and AFL in 40 (3.8%) patients.,Newly detected atrial arrhythmias occurred in 101 (9.6%) patients.,Age, male sex, prior AF, renal disease, and hypoxia on presentation were independently associated with AF/AFL occurrence.,Compared with patients without AF/AFL, patients with AF/AFL had significantly higher levels of troponin, B‐type natriuretic peptide, C‐reactive protein, ferritin and d‐dimer.,Mortality was significantly higher among patients with AF/AFL (39.2%) compared to patients without (13.4%; p < .001).,After adjustment for age and co‐morbidities, AF/AFL (adjusted odds ratio [OR]: 1.93; p = .007) and newly detected AF/AFL (adjusted OR: 2.87; p < .001) were independently associated with 30‐day mortality.,Atrial arrhythmias are common among patients hospitalized with COVID‐19.,The presence of AF/AFL tracked with markers of inflammation and cardiac injury.,Atrial arrhythmias were independently associated with increased mortality.

Supplemental Digital Content is available in the text.,Patients with coronavirus disease 2019 (COVID-19) who develop cardiac injury are reported to experience higher rates of malignant cardiac arrhythmias.,However, little is known about these arrhythmias-their frequency, the underlying mechanisms, and their impact on mortality.,We extracted data from a registry (NCT04358029) regarding consecutive inpatients with confirmed COVID-19 who were receiving continuous telemetric ECG monitoring and had a definitive disposition of hospital discharge or death.,Between patients who died versus discharged, we compared a primary composite end point of cardiac arrest from ventricular tachycardia/fibrillation or bradyarrhythmias such as atrioventricular block.,Among 800 patients with COVID-19 at Mount Sinai Hospital with definitive dispositions, 140 patients had telemetric monitoring, and either died (52) or were discharged (88).,The median (interquartile range) age was 61 years (48-74); 73% men; and ethnicity was White in 34%.,Comorbidities included hypertension in 61%, coronary artery disease in 25%, ventricular arrhythmia history in 1.4%, and no significant comorbidities in 16%.,Compared with discharged patients, those who died had elevated peak troponin I levels (0.27 versus 0.02 ng/mL) and more primary end point events (17% versus 4%, P=0.01)-a difference driven by tachyarrhythmias.,Fatal tachyarrhythmias invariably occurred in the presence of severe metabolic imbalance, while atrioventricular block was largely an independent primary event.,Hospitalized patients with COVID-19 who die experience malignant cardiac arrhythmias more often than those surviving to discharge.,However, these events represent a minority of cardiovascular deaths, and ventricular tachyarrhythmias are mainly associated with severe metabolic derangement.,URL: https://www.clinicaltrials.gov; Unique identifier: NCT04358029.

Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features of myocardial involvement including elevated serum troponin levels and acute heart failure with reduced ejection fraction.,The cardiac pathological changes in these patients with COVID-19 have yet to be well described.,In an international multicentre study, cardiac tissue from the autopsies of 21 consecutive COVID-19 patients was assessed by cardiovascular pathologists.,The presence of myocarditis, as defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analysed by immunohistochemistry.,Other forms of acute myocyte injury and inflammation were also described, as well as coronary artery, endocardium, and pericardium involvement.,Lymphocytic myocarditis was present in 3 (14%) of the cases.,In two of these cases, the T lymphocytes were CD4 predominant and in one case the T lymphocytes were CD8 predominant.,Increased interstitial macrophage infiltration was present in 18 (86%) of the cases.,A mild pericarditis was present in four cases.,Acute myocyte injury in the right ventricle, most probably due to strain/overload, was present in four cases.,There was a non-significant trend toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis.,Disrupted coronary artery plaques, coronary artery aneurysms, and large pulmonary emboli were not identified.,In SARS-CoV-2 there are increased interstitial macrophages in a majority of the cases and multifocal lymphocytic myocarditis in a small fraction of the cases.,Other forms of myocardial injury are also present in these patients.,The macrophage infiltration may reflect underlying diseases rather than COVID-19.

Data on the impact of COVID‐19 in chronic heart failure (CHF) patients and its potential to trigger acute heart failure (AHF) are lacking.,The aim of this work was to study characteristics, cardiovascular outcomes and mortality in patients with confirmed COVID‐19 infection and a prior diagnosis of heart failure (HF).,Further aims included the identification of predictors and prognostic implications for AHF decompensation during hospital admission and the determination of a potential correlation between the withdrawal of HF guideline‐directed medical therapy (GDMT) and worse outcomes during hospitalization.,Data for a total of 3080 consecutive patients with confirmed COVID‐19 infection and follow‐up of at least 30 days were analysed.,Patients with a previous history of CHF (n = 152, 4.9%) were more prone to the development of AHF (11.2% vs.,2.1%; P < 0.001) and had higher levels of N‐terminal pro brain natriuretic peptide.,In addition, patients with previous CHF had higher mortality rates (48.7% vs.,19.0%; P < 0.001).,In contrast, 77 patients (2.5%) were diagnosed with AHF, which in the vast majority of cases (77.9%) developed in patients without a history of HF.,Arrhythmias during hospital admission and CHF were the main predictors of AHF.,Patients developing AHF had significantly higher mortality (46.8% vs.,19.7%; P < 0.001).,Finally, the withdrawal of beta‐blockers, mineralocorticoid receptor antagonists and angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant increase in in‐hospital mortality.,Patients with COVID‐19 have a significant incidence of AHF, which is associated with very high mortality rates.,Moreover, patients with a history of CHF are prone to developing acute decompensation after a COVID‐19 diagnosis.,The withdrawal of GDMT was associated with higher mortality.,Heart failure in COVID‐19 patients: prevalence, incidence and prognostic implications.

Historically, the vaccination strategies developed in the second half of the 20th century have facilitated the eradication of infectious diseases.,From the onset of COVID-19 pandemic to the end of April 2021, more than 150 million cases and 3 million deaths were documented worldwide with disruption of the economic and social activity, and with devastating material, physical, and psychological consequences.,Reports of unusual and severe thrombotic events, including cerebral and splanchnic venous thrombosis and other autoimmune adverse reactions, such as immune thrombocytopenia or thrombotic microangiopathies in connection with some of the SARS-CoV-2 vaccines, have caused a great deal of concern within the population and the medical community.,This report is intended to provide practical answers following an overview of our knowledge on these thrombotic events that are extremely rare but have serious consequences.,Vaccine hesitancy threatens to reverse the progress made in controlling vaccine-preventable diseases.,These adverse events must be put into perspective with an objective analysis of the facts and the issues of the vaccination strategy during this SARS-CoV-2 pandemic.,Health care professionals remain the most pertinent advisors and influencers regarding vaccination decisions; they have to be supported to provide reliable and credible information on vaccines.,We need to inform, reassure, and support our patients when the prescription is made.,Facing these challenges and observations, a panel of experts express their insights and propose a tracking algorithm for vaccinated patients based on a 10-point guideline for decision-making on what to do and not to do.

Reports of ChAdOx1 vaccine-associated thrombocytopenia and vascular adverse events have led to some countries restricting its use.,Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis.,An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0-27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41-13.83), with an estimated incidence of 1.13 (0.62-1.63) cases per 100,000 doses.,An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29-3.02)).,There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12-1.34) 0-27 d after vaccination, with an SCCS RR of 0.97 (0.93-1.02).,For hemorrhagic events 0-27 d after vaccination, the aRR was 1.48 (1.12-1.96), with an SCCS RR of 0.95 (0.82-1.11).,A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events.,The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication.,Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1.,No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.,New data from the EAVE II cohort in Scotland suggests that a first dose of the ChAdOx1 nCoV-19 vaccine might be associated with a small increase in the risk of idiopathic thrombocytopenic purpura between 0 and 27 d after vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe and disproportionately affected New York City between March and May 2020.,Here, we report on the first 100 COVID-19-positive autopsies performed at the Mount Sinai Hospital in New York City.,Autopsies revealed large pulmonary emboli in six cases.,Diffuse alveolar damage was present in over 90% of cases.,We also report microthrombi in multiple organ systems including the brain, as well as hemophagocytosis.,We additionally provide electron microscopic evidence of the presence of the virus in our samples.,Laboratory results of our COVID-19 cohort disclose elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8, and TNFα.,Our autopsy series of COVID-19-positive patients reveals that this disease, often conceptualized as a primarily respiratory viral illness, has widespread effects in the body including hypercoagulability, a hyperinflammatory state, and endothelial dysfunction.,Targeting of these multisystemic pathways could lead to new treatment avenues as well as combination therapies against SARS-CoV-2 infection.

Emerging data indicate an increased risk of cerebrovascular events with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and highlight the potential impact of coronavirus disease (COVID‐19) on the management and outcomes of acute stroke.,We conducted a systematic review and meta‐analysis to evaluate the aforementioned considerations.,We performed a meta‐analysis of observational cohort studies reporting on the occurrence and/or outcomes of patients with cerebrovascular events in association with their SARS‐CoV‐2 infection status.,We used a random‐effects model.,Summary estimates were reported as odds ratios (ORs) and corresponding 95% confidence intervals (CIs).,We identified 18 cohort studies including 67,845 patients.,Among patients with SARS‐CoV‐2, 1.3% (95% CI = 0.9-1.6%, I 2 = 87%) were hospitalized for cerebrovascular events, 1.1% (95% CI = 0.8-1.3%, I 2 = 85%) for ischemic stroke, and 0.2% (95% CI = 0.1-0.3%, I 2 = 64%) for hemorrhagic stroke.,Compared to noninfected contemporary or historical controls, patients with SARS‐CoV‐2 infection had increased odds of ischemic stroke (OR = 3.58, 95% CI = 1.43-8.92, I 2 = 43%) and cryptogenic stroke (OR = 3.98, 95% CI = 1.62-9.77, I 2 = 0%).,Diabetes mellitus was found to be more prevalent among SARS‐CoV‐2 stroke patients compared to noninfected historical controls (OR = 1.39, 95% CI = 1.00-1.94, I 2 = 0%).,SARS‐CoV‐2 infection status was not associated with the likelihood of receiving intravenous thrombolysis (OR = 1.42, 95% CI = 0.65-3.10, I 2 = 0%) or endovascular thrombectomy (OR = 0.78, 95% CI = 0.35-1.74, I 2 = 0%) among hospitalized ischemic stroke patients during the COVID‐19 pandemic.,Odds of in‐hospital mortality were higher among SARS‐CoV‐2 stroke patients compared to noninfected contemporary or historical stroke patients (OR = 5.60, 95% CI = 3.19-9.80, I 2 = 45%).,SARS‐CoV‐2 appears to be associated with an increased risk of ischemic stroke, and potentially cryptogenic stroke in particular.,It may also be related to an increased mortality risk.,ANN NEUROL 2021;89:380-388

Supplemental Digital Content is available in the text.,Reports indicate an increased risk of ischemic stroke during coronavirus disease 2019 (COVID-19) infection.,We aimed to identify patients with COVID-19 and ischemic stroke and explore markers of inflammation, hypercoagulability, and endotheliopathy, a structural and functional disturbance of the vascular endothelium due to a stressor.,This was a retrospective, observational cohort study comparing acute ischemic stroke patients with and without COVID-19 across 3 hospitals.,Timing of stroke onset during COVID-19 course and markers of inflammation, hypercoagulability, and endothelial activation were evaluated by COVID-19 status and stroke cause.,Twenty-one patients with ischemic stroke were diagnosed with COVID-19 during the study period.,Patients with COVID-19 had a similar age and burden of vascular risk factors compared with the control cohort (n=168).,We identified a temporal correlation between stroke onset and the peak of acute phase reactants, including CRP (C-reactive protein), ferritin, and d-dimer.,In subsets of patients with labs available, embolic stroke of undetermined source was associated with elevated IL (interleukin)-6 (median, 171 [interquartile range, 13-375] versus 8 [4-11], P<0.01) and sIL (soluble IL)-2 receptor (1972 [1525-4720] versus 767 [563-1408.5], P=0.05) levels.,Stroke patients with COVID-19 demonstrated elevated levels of endothelial activation markers compared with non-COVID-19 stroke controls (median von Willebrand activity 285.0% [interquartile range, 234%-382%] versus 150% [128%-183%], P=0.034; von Willebrand antigen 330.0% [265%-650%] versus 152% [130%-277%], P=0.007, and factor VIII 301% [289%-402%] versus 49% [26%-94%], P<0.001).,Ischemic stroke in patients with COVID-19 is associated with endotheliopathy and a systemic inflammatory response in patients with vascular risk factors.,Further research evaluating endothelial and inflammatory markers in the setting of ischemic stroke and COVID-19 in larger, prospective cohorts is needed to validate the findings.

Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users.

We describe the first case of acute cardiac injury directly linked to myocardial localization of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in a 69‐year‐old patient with flu‐like symptoms rapidly degenerating into respiratory distress, hypotension, and cardiogenic shock.,The patient was successfully treated with venous‐arterial extracorporeal membrane oxygenation (ECMO) and mechanical ventilation.,Cardiac function fully recovered in 5 days and ECMO was removed.,Endomyocardial biopsy demonstrated low‐grade myocardial inflammation and viral particles in the myocardium suggesting either a viraemic phase or, alternatively, infected macrophage migration from the lung.

Coronavirus disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia.,Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis.,A 63-year-old male was admitted with pneumonia and cardiac symptoms.,He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission.,He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography.,The highest level of interleukin-6 was 272.40 pg/ml.,Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia.,Laboratory test results for viruses that cause myocarditis were all negative.,The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis.,After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/mL.,Moreover, the LVEF of the patient gradually recovered to 68%.,The patient died of aggravation of secondary infection on the 33rd day of hospitalization.,COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure.,This is the first report of COVID-19 complicated with fulminant myocarditis.,The mechanism of cardiac pathology caused by COVID-19 needs further study.

Coronavirus disease 2019 (COVID-19) predisposes to arterial and venous thromboembolic complications.,We describe the clinical presentation, management, and outcomes of acute arterial ischemia and concomitant infection at the epicenter of cases in the United States.,Patients with confirmed COVID-19 infection between March 1, 2020 and May 15, 2020 with an acute arterial thromboembolic event were reviewed.,Data collected included demographics, anatomical location of the thromboembolism, treatments, and outcomes.,Over the 11-week period, the Northwell Health System cared for 12,630 hospitalized patients with COVID-19.,A total of 49 patients with arterial thromboembolism and confirmed COVID-19 were identified.,The median age was 67 years (58-75) and 37 (76%) were men.,The most common preexisting conditions were hypertension (53%) and diabetes (35%).,The median D-dimer level was 2,673 ng/mL (723-7,139).,The distribution of thromboembolic events included upper 7 (14%) and lower 35 (71%) extremity ischemia, bowel ischemia 2 (4%), and cerebral ischemia 5 (10%).,Six patients (12%) had thrombus in multiple locations.,Concomitant deep vein thrombosis was found in 8 patients (16%).,Twenty-two (45%) patients presented with signs of acute arterial ischemia and were subsequently diagnosed with COVID-19.,The remaining 27 (55%) developed ischemia during hospitalization.,Revascularization was performed in 13 (27%) patients, primary amputation in 5 (10%), administration of systemic tissue‐ plasminogen activator in 3 (6%), and 28 (57%) were treated with systemic anticoagulation only.,The rate of limb loss was 18%.,Twenty-one patients (46%) died in the hospital.,Twenty-five (51%) were successfully discharged, and 3 patients are still in the hospital.,While the mechanism of thromboembolic events in patients with COVID-19 remains unclear, the occurrence of such complication is associated with acute arterial ischemia which results in a high limb loss and mortality.

The COVID‐19 pandemic has become an urgent issue in every country.,Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)‐like massive intravascular clot formation is frequently seen in this cohort.,Therefore, coagulation tests may be considered useful to discriminate severe cases of COVID‐19.,The clinical presentation of COVID‐19‐associated coagulopathy is organ dysfunction primarily, whereas hemorrhagic events are less frequent.,Changes in hemostatic biomarkers represented by increase in D‐dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation.,In comparison with bacterial‐sepsis‐associated coagulopathy/DIC, prolongation of prothrombin time, and activated partial thromboplastin time, and decrease in antithrombin activity is less frequent and thrombocytopenia is relatively uncommon in COVID‐19.,The mechanisms of the coagulopathy are not fully elucidated, however.,It is speculated that the dysregulated immune responses orchestrated by inflammatory cytokines, lymphocyte cell death, hypoxia, and endothelial damage are involved.,Bleeding tendency is uncommon, but the incidence of thrombosis in COVID‐19 and the adequacy of current recommendations regarding standard venous thromboembolic dosing are uncertain.

Prior studies demonstrated that elevated troponin in patients with COVID-19 was associated with increased in-hospital mortality.,However, the association of cardiac injury and electrocardiogram (ECG) changes remains unclear.,The aim of this study was to investigate the association of cardiac injury with ECG abnormality and with in-hospital mortality.,We conducted a retrospective cohort study of patients who were hospitalised with COVID-19 between 13 March and 31 March 2020.,Those patients with troponin I measurement were included in the study and divided into those who had elevated troponin I (cardiac injury group) and those who did not (no cardiac injury group).,Statistical analyses were performed to compare differences between the groups, and a multivariate logistic regression model was constructed to assess the effect of cardiac injury on in-hospital mortality.,One hundred and eight-one (181) patients were included, 54 of whom were in the cardiac injury group and 127 in the no cardiac injury group.,The mean age was 64.0±16.6 years and 55.8% were male.,The cardiac injury group was more likely to be older, have a history of coronary artery disease, atrial fibrillation and congestive heart failure compared to the no cardiac injury group (all p<0.05); there was no difference in presence of chest pain (cardiac injury group versus no cardiac injury group: 17.0% versus 22.5%, p=0.92); the cardiac injury group had a significantly higher value of brain natriuretic peptide, procalcitonin, interleukin-6 and D-dimer (all p<0.05); they had numerically more frequent ECG abnormalities such as T wave inversion (13.2% versus 7.5%, p=0.23) and ST depression (1.9% versus 0.0%, p=0.13) although statistically not significant; they had significantly higher in-hospital mortality (42.3% versus 12.6%, p<0.001).,With a multivariate logistic regression model, age (odds ratio [95% confidence interval]: 1.033 [1.002-1.065], p=0.034) and cardiac injury (3.25 [1.40-7.54], p=0.006) were independent predictors of in-hospital mortality.,Patients with COVID-19 with elevated troponin I had a relatively low proportion of chest pain and ECG abnormality.,Cardiac injury was independently associated with in-hospital mortality.

The degree of myocardial injury, as reflected by troponin elevation, and associated outcomes among U.S. hospitalized patients with coronavirus disease-2019 (COVID-19) are unknown.,The purpose of this study was to describe the degree of myocardial injury and associated outcomes in a large hospitalized cohort with laboratory-confirmed COVID-19.,Patients with COVID-19 admitted to 1 of 5 Mount Sinai Health System hospitals in New York City between February 27, 2020, and April 12, 2020, with troponin-I (normal value <0.03 ng/ml) measured within 24 h of admission were included (n = 2,736).,Demographics, medical histories, admission laboratory results, and outcomes were captured from the hospitals’ electronic health records.,The median age was 66.4 years, with 59.6% men.,Cardiovascular disease (CVD), including coronary artery disease, atrial fibrillation, and heart failure, was more prevalent in patients with higher troponin concentrations, as were hypertension and diabetes.,A total of 506 (18.5%) patients died during hospitalization.,In all, 985 (36%) patients had elevated troponin concentrations.,After adjusting for disease severity and relevant clinical factors, even small amounts of myocardial injury (e.g., troponin I >0.03 to 0.09 ng/ml; n = 455; 16.6%) were significantly associated with death (adjusted hazard ratio: 1.75; 95% CI: 1.37 to 2.24; p < 0.001) while greater amounts (e.g., troponin I >0.09 ng/dl; n = 530; 19.4%) were significantly associated with higher risk (adjusted HR: 3.03; 95% CI: 2.42 to 3.80; p < 0.001).,Myocardial injury is prevalent among patients hospitalized with COVID-19; however, troponin concentrations were generally present at low levels.,Patients with CVD are more likely to have myocardial injury than patients without CVD.,Troponin elevation among patients hospitalized with COVID-19 is associated with higher risk of mortality.

Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services.,This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care; inpatient intensive or stroke units; posthospitalization rehabilitation; follow-up including at-risk family and community; and multispecialty departmental developments in the allied professions.,The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19.,Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction.,International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase.,For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods.,For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs.,Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high.,COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs.,As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction.,This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered.,Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions.,As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers.,Postdischarge outpatient care currently includes continued secondary prevention measures.,Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts.,Many online resources are available to patients and physicians.,Like prior challenges, stroke care teams will also overcome this one.,Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.

Coronavirus disease 2019 (COVID-19) has become a global pandemic, affecting millions of people.,However, the relationship between COVID-19 and acute cerebrovascular diseases is unclear.,We aimed to characterize the incidence, risk factors, clinical-radiological manifestations, and outcome of COVID-19-associated stroke.,Three medical databases were systematically reviewed for published articles on acute cerebrovascular diseases in COVID-19 (December 2019-September 2020).,The review protocol was previously registered (PROSPERO ID = CRD42020185476).,Data were extracted from articles reporting ≥5 stroke cases in COVID-19.,We complied with the PRISMA guidelines and used the Newcastle-Ottawa Scale to assess data quality.,Data were pooled using a random-effect model.,Of 2277 initially identified articles, 61 (2.7%) were entered in the meta-analysis.,Out of 108,571 patients with COVID-19, acute CVD occurred in 1.4% (95%CI: 1.0-1.9).,The most common manifestation was acute ischemic stroke (87.4%); intracerebral hemorrhage was less common (11.6%).,Patients with COVID-19 developing acute cerebrovascular diseases, compared to those who did not, were older (pooled median difference = 4.8 years; 95%CI: 1.7-22.4), more likely to have hypertension (OR = 7.35; 95%CI: 1.94-27.87), diabetes mellitus (OR = 5.56; 95%CI: 3.34-9.24), coronary artery disease (OR = 3.12; 95%CI: 1.61-6.02), and severe infection (OR = 5.10; 95%CI: 2.72-9.54).,Compared to individuals who experienced a stroke without the infection, patients with COVID-19 and stroke were younger (pooled median difference = −6.0 years; 95%CI: −12.3 to −1.4), had higher NIHSS (pooled median difference = 5; 95%CI: 3-9), higher frequency of large vessel occlusion (OR = 2.73; 95%CI: 1.63-4.57), and higher in-hospital mortality rate (OR = 5.21; 95%CI: 3.43-7.90).,Acute cerebrovascular diseases are not uncommon in patients with COVID-19, especially in those whom are severely infected and have pre-existing vascular risk factors.,The pattern of large vessel occlusion and multi-territory infarcts suggests that cerebral thrombosis and/or thromboembolism could be possible causative pathways for the disease.

Trillions of microbes inhabit the human gut, not only providing nutrients and energy to the host from the ingested food, but also producing metabolic bioactive signaling molecules to maintain health and elicit disease, such as cardiovascular disease (CVD).,CVD is the leading cause of mortality worldwide.,In this review, we presented gut microbiota derived metabolites involved in cardiovascular health and disease, including trimethylamine-N-oxide (TMAO), uremic toxins, short chain fatty acids (SCFAs), phytoestrogens, anthocyanins, bile acids and lipopolysaccharide.,These gut microbiota derived metabolites play critical roles in maintaining a healthy cardiovascular function, and if dysregulated, potentially causally linked to CVD.,A better understanding of the function and dynamics of gut microbiota derived metabolites holds great promise toward mechanistic predicative CVD biomarker discoveries and precise interventions.,The online version of this article (10.1007/s13238-018-0549-0) contains supplementary material, which is available to authorized users.

Trimethylamine‐N‐oxide (TMAO) has recently been identified as a novel and independent risk factor for promoting atherosclerosis through inducing vascular inflammation.,However, the exact mechanism is currently unclear.,Studies have established a central role of nucleotide‐binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in the pathogenesis of vascular inflammation.,Here, we examined the potential role of the NLRP3 inflammasome in TMAO‐induced vascular inflammation in vitro and in vivo and the underlying mechanisms.,Experiments using liquid chromatography‐tandem mass spectrometry, Western blot, and fluorescent probes showed that TMAO‐induced inflammation in human umbilical vein endothelial cells (HUVECs) and aortas from ApoE−/− mice.,Moreover, TMAO promoted NLRP3 and activated caspase‐1 p20 expression and caspase‐1 activity in vitro and in vivo.,Notably, a caspase‐1 inhibitor (YVAD), an NLRP3 inhibitor (MCC950), as well as NLRP3 short interfering RNA attenuated TMAO‐induced activation of the NLRP3 inflammasome, subsequently leading to suppression of inflammation in HUVECs.,TMAO additionally stimulated reactive oxygen species (ROS) generation, in particular, mitochondrial ROS, while inhibiting manganese superoxide dismutase 2 (SOD2) activation and sirtuin 3 (SIRT3) expression in HUVECs and aortas from ApoE−/− mice.,TMAO‐induced endothelial NLRP3 inflammasome activation was ameliorated by the mitochondrial ROS scavenger Mito‐TEMPO, or SIRT3 overexpression in HUVECs.,Conversely, TMAO failed to further inhibit magnesium SOD2 and activate the NLRP3 inflammasome or induce inflammation in SIRT3 short interfering RNA-treated HUVECs and aortas from SIRT3−/− mice.,TMAO promoted vascular inflammation by activating the NLRP3 inflammasome, and the NLRP3 inflammasome activation in part was mediated through inhibition of the SIRT3‐SOD2-mitochondrial ROS signaling pathway.

One of the defining features of the novel coronavirus disease 2019 infection has been high rates of venous thromboses.,The present study aimed to describe the prevalence of venous thromboembolism in critically ill patients receiving different regimens of prophylactic anticoagulation.,Single-center retrospective review using data from patients with confirmed severe acute respiratory syndrome coronavirus 2 requiring intubation.,Tertiary-care center in Indianapolis, IN, United States.,Patients hospitalized at international units Health Methodist Hospital with severe acute respiratory syndrome coronavirus 2 requiring intubation between March 23, 2020, and April 8, 2020, who underwent ultrasound evaluation for venous thrombosis.,None.,A total of 45 patients were included.,Nineteen of 45 patients (42.2%) were found to have deep venous thrombosis.,Patients found to have deep venous thrombosis had no difference in time to intubation (p = 0.97) but underwent ultrasound earlier in their hospital course (p = 0.02).,Sequential Organ Failure Assessment scores were similar between the groups on day of intubation and day of ultrasound (p = 0.44 and p = 0.07, respectively). d-dimers were markedly higher in patients with deep venous thrombosis, both for maximum value and value on day of ultrasound (p < 0.01 for both).,Choice of prophylactic regimen was not related to presence of deep venous thrombosis (p = 0.35).,Ultrasound evaluation is recommended if d-dimer is greater than 2,000 ng/mL (sensitivity 95%, specificity 46%) and empiric anticoagulation considered if d-dimer is greater than 5,500 ng/mL (sensitivity 53%, specificity 88%).,Deep venous thrombosis is very common in critically ill patients with coronavirus disease 2019.,There was no difference in incidence of deep venous thrombosis among different pharmacologic prophylaxis regimens, although our analysis is limited by small sample size. d-dimer values are elevated in the majority of these patients, but there may be thresholds at which screening ultrasound or even empiric systemic anticoagulation is indicated.

COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital.,Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes.,We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020.,The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h.,Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation.,All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet-fibrin thrombi (in 33 cases).,The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases).,Electron microscopy revealed that viral particles were predominantly located in the pneumocytes.,The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses.,Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent.,Importantly, the presence of platelet-fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy.,None.

Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca).,More data were needed on the pathogenesis of this unusual clotting disorder.,We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19.,We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)-heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions.,Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4-heparin immunoassay.,Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49).,Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage.,Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died.,Five patients had disseminated intravascular coagulation.,None of the patients had received heparin before symptom onset.,All 28 patients who tested positive for antibodies against PF4-heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin.,Platelet activation was inhibited by high levels of heparin, Fc receptor-blocking monoclonal antibody, and immune globulin (10 mg per milliliter).,Additional studies with PF4 or PF4-heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation.,Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia.,(Funded by the German Research Foundation.)

To investigate whether severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-induced myocarditis constitutes an important mechanism of cardiac injury, a review was conducted of the published data and the authors’ experience was added from autopsy examination of 16 patients dying of SARS-CoV-2 infection.,Myocarditis is an uncommon pathologic diagnosis occurring in 4.5% of highly selected cases undergoing autopsy or endomyocardial biopsy.,Although polymerase chain reaction-detectable virus could be found in the lungs of most coronavirus disease-2019 (COVID-19)-infected subjects in our own autopsy registry, in only 2 cases was the virus detected in the heart.,It should be appreciated that myocardial inflammation alone by macrophages and T cells can be seen in noninfectious deaths and COVID-19 cases, but the extent of each is different, and in neither case do such findings represent clinically relevant myocarditis.,Given its extremely low frequency and unclear therapeutic implications, the authors do not advocate use of endomyocardial biopsy to diagnose myocarditis in the setting of COVID-19.

Stroke is a leading cause of death and disability in humans.,The excessive production of reactive oxygen species (ROS) is an important contributor to oxidative stress and secondary brain damage after stroke.,Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, an enzyme complex consisting of membrane subunits and cytoplasmic subunits, regulates neuronal maturation and cerebrovascular homeostasis.,However, NADPH oxidase overproduction contributes to neurotoxicity and cerebrovascular disease.,NADPH oxidase has been implicated as the principal source of ROS in the brain, and numerous studies have shown that the knockout of NADPH exerts a protective effect in the model of ischemic stroke.,In this review, we summarize the mechanism of activation of the NADPH oxidase family members, the pathophysiological effects of NADPH oxidase isoforms in ischemic stroke, and the studies of NADPH oxidase inhibitors to explore potential clinical applications.

Good nutrition could maintain health and life.,Polyphenols are common nutrient mainly derived from fruits, vegetables, tea, coffee, cocoa, mushrooms, beverages, and traditional medicinal herbs.,They are potential substances against oxidative-related diseases, for example, cardiovascular disease, specifically, atherosclerosis-related ischemic heart disease and stroke, which are health and economic problems recognized worldwide.,In this study, we reviewed the risk factors for atherosclerosis, including hypertension, diabetes mellitus, hyperlipidemia, obesity, and cigarette smoking as well as the antioxidative activity of polyphenols, which could prevent the pathology of atherosclerosis, including endothelial dysfunction, low-density lipoprotein oxidation, vascular smooth muscle cell proliferation, inflammatory process by monocytes, macrophages or T lymphocytes, and platelet aggregation.,The strong radical-scavenging properties of polyphenols would exhibit antioxidative and anti-inflammation effects.,Polyphenols reduce ROS production by inhibiting oxidases, reducing the production of superoxide, inhibiting OxLDL formation, suppressing VSMC proliferation and migration, reducing platelet aggregation, and improving mitochondrial oxidative stress.,Polyphenol consumption also inhibits the development of hypertension, diabetes mellitus, hyperlipidemia, and obesity.,Despite the numerous in vivo and in vitro studies, more advanced clinical trials are necessary to confirm the efficacy of polyphenols in the treatment of atherosclerosis-related vascular diseases.

With the establishment of the heart-gut axis concept, accumulating studies suggest that the gut microbiome plays an important role in the pathogenesis of cardiovascular diseases.,Yet, little evidence has been reported in characterizing the gut microbiota shift in atrial fibrillation.,We include the result of the global alterations that occur in the intestinal microbiota in a cohort of 50 patients with atrial fibrillation and 50 matched controls based on a strategy of metagenomic and metabolomic analyses.,The alterations include a dramatic elevation in microbial diversity and a specific perturbation of gut microbiota composition.,Overgrowth of Ruminococcus, Streptococcus, and Enterococcus, as well as reduction of Faecalibacterium, Alistipes, Oscillibacter, and Bilophila were detected in patients with atrial fibrillation.,A gut microbial function imbalance and correlated metabolic pattern changes were observed with atrial fibrillation in both fecal and serum samples.,The differential gut microbiome signatures could be used to identify patients with atrial fibrillation.,Our findings characterize the disordered gut microbiota and microbial metabolite profiles in atrial fibrillation.,Further research could determine whether intervention strategies targeting intestinal microbiome composition might be useful to counteract the progression of atrial fibrillation.

Introduction: Human gut microbiota is believed to be directly or indirectly involved in cardiovascular diseases and hypertension.,However, the identification and functional status of the hypertension-related gut microbe(s) have not yet been surveyed in a comprehensive manner.,Methods: Here we characterized the gut microbiome in hypertension status by comparing fecal samples of 60 patients with primary hypertension and 60 gender-, age-, and body weight-matched healthy controls based on whole-metagenome shotgun sequencing.,Results: Hypertension implicated a remarkable gut dysbiosis with significant reduction in within-sample diversity and shift in microbial composition.,Metagenome-wide association study (MGWAS) revealed 53,953 microbial genes that differ in distribution between the patients and healthy controls (false discovery rate, 0.05) and can be grouped into 68 clusters representing bacterial species.,Opportunistic pathogenic taxa, such as, Klebsiella spp., Streptococcus spp., and Parabacteroides merdae were frequently distributed in hypertensive gut microbiome, whereas the short-chain fatty acid producer, such as, Roseburia spp. and Faecalibacterium prausnitzii, were higher in controls.,The number of hypertension-associated species also showed stronger correlation to the severity of disease.,Functionally, the hypertensive gut microbiome exhibited higher membrane transport, lipopolysaccharide biosynthesis and steroid degradation, while in controls the metabolism of amino acid, cofactors and vitamins was found to be higher.,We further provided the microbial markers for disease discrimination and achieved an area under the receiver operator characteristic curve (AUC) of 0.78, demonstrating the potential of gut microbiota in prediction of hypertension.,Conclusion: These findings represent specific alterations in microbial diversity, genes, species and functions of the hypertensive gut microbiome.,Further studies on the causality relationship between hypertension and gut microbiota will offer new prospects for treating and preventing the hypertension and its associated diseases.

Supplemental Digital Content is available in the text.,Pulmonary thrombosis is observed in severe acute respiratory syndrome coronavirus 2 pneumonia.,Aim was to investigate whether subpopulations of platelets were programmed to procoagulant and inflammatory activities in coronavirus disease 2019 (COVID-19) patients with pneumonia, without comorbidities predisposing to thromboembolism.,Overall, 37 patients and 28 healthy subjects were studied.,Platelet-leukocyte aggregates, platelet-derived microvesicles, the expression of P-selectin, and active fibrinogen receptor on platelets were quantified by flow cytometry.,The profile of 45 cytokines, chemokines, and growth factors released by platelets was defined by immunoassay.,The contribution of platelets to coagulation factor activity was selectively measured.,Numerous platelet-monocyte (mean±SE, 67.9±4.9%, n=17 versus 19.4±3.0%, n=22; P<0.0001) and platelet-granulocyte conjugates (34.2±4.04% versus 8.6±0.7%; P<0.0001) were detected in patients.,Resting patient platelets had similar levels of P-selectin (10.9±2.6%, n=12) to collagen-activated control platelets (8.7±1.5%), which was not further increased by collagen activation on patient platelets (12.4±2.5%, P=nonsignificant).,The agonist-stimulated expression of the active fibrinogen receptor was reduced by 60% in patients (P<0.0001 versus controls).,Cytokines (IL [interleukin]-1α, IL-1β, IL-1RA, IL-4, IL-10, IL-13, IL, 17, IL-27, IFN [interferon]-α, and IFN-γ), chemokines (MCP-1/CCL2 [monocyte chemoattractant protein 1]), and growth factors (VEGF [vascular endothelial growth factor]-A/D) were released in significantly larger amounts upon stimulation of COVID-19 platelets.,Platelets contributed to increased fibrinogen, VWF (von Willebrand factor), and factor XII in COVID-19 patients.,Patients (28.5±0.7 s, n=32), unlike controls (31.6±0.5 s, n=28; P<0.001), showed accelerated factor XII-dependent coagulation.,Platelets in COVID-19 pneumonia are primed to spread proinflammatory and procoagulant activities in systemic circulation.

COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital.,Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes.,We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020.,The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h.,Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation.,All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet-fibrin thrombi (in 33 cases).,The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases).,Electron microscopy revealed that viral particles were predominantly located in the pneumocytes.,The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses.,Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent.,Importantly, the presence of platelet-fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy.,None.

Coronavirus disease 2019 (COVID-19) is a global pandemic impacting 213 countries/territories and more than 5,934,936 patients worldwide.,Cardiac injury has been reported to occur in severe and death cases.,This meta-analysis was done to summarize available findings on the association between cardiac injury and severity of COVID-19 infection.,Online databases including Scopus, PubMed, Web of Science, Cochrane Library and Google Scholar were searched to detect relevant publications up to 20 May 2020, using relevant keywords.,To pool data, a fixed- or random-effects model was used depending on the heterogeneity between studies.,In total, 22 studies with 3684 COVID-19 infected patients (severe cases=1095 and death cases=365) were included in this study.,Higher serum levels of lactate dehydrogenase (weighted mean difference (WMD) =108.86 U/L, 95% confidence interval (CI)=75.93-141.79, p<0.001) and creatine kinase-MB (WMD=2.60 U/L, 95% CI=1.32-3.88, p<0.001) were associated with a significant increase in the severity of COVID-19 infection.,Furthermore, higher serum levels of lactate dehydrogenase (WMD=213.44 U/L, 95% CI=129.97-296.92, p<0.001), cardiac troponin I (WMD=26.35 pg/mL, 95% CI=14.54-38.15, p<0.001), creatine kinase (WMD=48.10 U/L, 95% CI=0.27-95.94, p = 0.049) and myoglobin (WMD=159.77 ng/mL, 95% CI=99.54-220.01, p<0.001) were associated with a significant increase in the mortality of COVID-19 infection.,Cardiac injury, as assessed by serum analysis (lactate dehydrogenase, cardiac troponin I, creatine kinase (-MB) and myoglobin), was associated with severe outcome and death from COVID-19 infection.

Hydroxychloroquine and azithromycin combination therapy is often prescribed for coronavirus disease 2019 (COVID-19).,Electrocardiographic (ECG) monitoring is warranted because both medications cause corrected QT-interval (QTc) prolongation.,Whether QTc duration significantly varies during the day, potentially requiring multiple ECGs, remains to be established.,We performed 12-lead ECGs and 12-lead 24-h Holter ECG monitoring in all patients aged <80 years admitted to our medical unit for COVID-19, in oral therapy with hydroxychloroquine (200 mg, twice daily) and azithromycin (500 mg, once daily) for at least 3 days.,A group of healthy individuals matched for age and sex served as control.,Out of 126 patients, 22 (median age 64, 82% men) met the inclusion criteria.,ECG after therapy showed longer QTc-interval than before therapy (450 vs 426 ms, p = .02).,Four patients had a QTc ≥ 480 ms: they showed higher values of aspartate aminotransferase (52 vs 30 U/L, p = .03) and alanine aminotransferase (108 vs 33 U/L, p < .01) compared with those with QTc < 480 ms.,At 24-h Holter ECG monitoring, 1 COVID-19 patient and no control had ≥1 run of non-sustained ventricular tachycardia (p = .4).,No patients showed “R on T" premature ventricular beats.,Analysis of 24-h QTc dynamics revealed that COVID-19 patients had higher QTc values than controls, with no significant hourly variability.,Therapy with hydroxychloroquine and azithromycin prolongs QTc interval in patients with COVID-19, particularly in those with high levels of transaminases.,Because QTc duration remains stable during the 24 h, multiple daily ECG are not recommendable.

•Fever and cough are the most common symptoms in patients with COVID-19.,•The most prevalent comorbidities are hypertension and diabetes which are associated with the severity of COVID-19.,•ARDS and ACI may be the main obstacles to treatment recovery for patients.,•The case severe rate and mortality is lower than that of SARS and MERS.,Fever and cough are the most common symptoms in patients with COVID-19.,The most prevalent comorbidities are hypertension and diabetes which are associated with the severity of COVID-19.,ARDS and ACI may be the main obstacles to treatment recovery for patients.,The case severe rate and mortality is lower than that of SARS and MERS.,Since being first reported in Wuhan, China, in December 8, 2019, the outbreak of the novel coronavirus, now known as COVID-19, has spread globally.,Some case studies regarding the characteristics and outcome of patients with COVID-19 have been published recently.,We conducted a meta-analysis to evaluate the risk factors of COVID-19.,Medline, SinoMed, EMBASE, and Cochrane Library were searched for clinical and epidemiological studies on confirmed cases of COVID-19.,The incidence of fever, cough, fatigue, and dyspnea symptoms were 85.6 % (95CI 81.3-89.9 %), 65.7 % (95CI 60.1-71.4 %), 42.4 % (95CI 32.2-52.6 %) and 21.4 % (95CI 15.3-27.5 %).,The prevalence of diabetes was 7.7 % (95CI 6.1-9.3 %), hypertension was 15.6 % (95CI 12.6-18.6 %), cardiovascular disease was 4.7 % (95CI 3.1-6.2 %), and malignancy was 1.2 % (95CI 0.5-1.8 %).,The complications, including ARDS risk, ranged from 5.6-13.2 %, with the pooled estimate of ARDS risk at 9.4 %, ACI at 5.8 % (95CI 0.7-10.8 %), AKI at 2.1 % (95CI 0.6-3.7 %), and shock at 4.7 % (95CI 0.9-8.6 %).,The risks of severity and mortality ranged from 12.6 to 23.5% and from 2.0 to 4.4 %, with pooled estimates at 18.0 and 3.2 %, respectively.,The percentage of critical cases in diabetes and hypertension was 44.5 % (95CI 27.0-61.9 %) and 41.7 % (95CI 26.4-56.9 %), respectively.,Fever is the most common symptom in patients with COVID-19.,The most prevalent comorbidities are hypertension and diabetes which are associated with the severity of COVID-19.,ARDS and ACI may be the main obstacles for patients to treatment recovery.,The case severe rate and mortality is lower than that of SARS and MERS.

COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality.,To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes.,Prospective autopsy study.,Single pathology department.,11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy).,Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values.,Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women).,Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients.,Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts.,Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients.,Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients.,Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis.,Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes.,Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile.,The sample was small.,COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency.,Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation.,Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory, and imaging studies and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism.,None.,The clinicopathological basis for morbidity and mortality with SARS-CoV-2 infection is not well understood.,This study reports the clinical and autopsy findings of patients who died of COVID-19.

Coronavirus disease 2019 (COVID-19) is a viral infection that can, in severe cases, result in cytokine storm, systemic inflammatory response and coagulopathy that is prognostic of poor outcomes.,While some, but not all, laboratory findings appear similar to sepsis-associated disseminated intravascular coagulopathy (DIC), COVID-19- induced coagulopathy (CIC) appears to be more prothrombotic than hemorrhagic.,It has been postulated that CIC may be an uncontrolled immunothrombotic response to COVID-19, and there is growing evidence of venous and arterial thromboembolic events in these critically ill patients.,Clinicians around the globe are challenged with rapidly identifying reasonable diagnostic, monitoring and anticoagulant strategies to safely and effectively manage these patients.,Thoughtful use of proven, evidence-based approaches must be carefully balanced with integration of rapidly emerging evidence and growing experience.,The goal of this document is to provide guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of anticoagulant therapies in patients with COVID-19.,We discuss in-hospital and post-discharge venous thromboembolism (VTE) prevention, treatment of suspected but unconfirmed VTE, laboratory monitoring of COVID-19, associated anticoagulant therapies, and essential elements for optimized transitions of care specific to patients with COVID-19.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Coronavirus disease 2019 (COVID-19) is a viral infection that can, in severe cases, result in cytokine storm, systemic inflammatory response and coagulopathy that is prognostic of poor outcomes.,While some, but not all, laboratory findings appear similar to sepsis-associated disseminated intravascular coagulopathy (DIC), COVID-19- induced coagulopathy (CIC) appears to be more prothrombotic than hemorrhagic.,It has been postulated that CIC may be an uncontrolled immunothrombotic response to COVID-19, and there is growing evidence of venous and arterial thromboembolic events in these critically ill patients.,Clinicians around the globe are challenged with rapidly identifying reasonable diagnostic, monitoring and anticoagulant strategies to safely and effectively manage these patients.,Thoughtful use of proven, evidence-based approaches must be carefully balanced with integration of rapidly emerging evidence and growing experience.,The goal of this document is to provide guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of anticoagulant therapies in patients with COVID-19.,We discuss in-hospital and post-discharge venous thromboembolism (VTE) prevention, treatment of suspected but unconfirmed VTE, laboratory monitoring of COVID-19, associated anticoagulant therapies, and essential elements for optimized transitions of care specific to patients with COVID-19.

Heightened inflammation, dysregulated immunity, and thrombotic events are characteristic of hospitalized COVID‐19 patients.,Given that platelets are key regulators of thrombosis, inflammation, and immunity they represent prime candidates as mediators of COVID‐19‐associated pathogenesis.,The objective of this study was to understand the contribution of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) to the platelet phenotype via phenotypic (activation, aggregation) and transcriptomic characterization.,In a cohort of 3915 hospitalized COVID‐19 patients, we analyzed blood platelet indices collected at hospital admission.,Following adjustment for demographics, clinical risk factors, medication, and biomarkers of inflammation and thrombosis, we find platelet count, size, and immaturity are associated with increased critical illness and all‐cause mortality.,Bone marrow, lung tissue, and blood from COVID‐19 patients revealed the presence of SARS‐CoV‐2 virions in megakaryocytes and platelets.,Characterization of COVID‐19 platelets found them to be hyperreactive (increased aggregation, and expression of P‐selectin and CD40) and to have a distinct transcriptomic profile characteristic of prothrombotic large and immature platelets.,In vitro mechanistic studies highlight that the interaction of SARS‐CoV‐2 with megakaryocytes alters the platelet transcriptome, and its effects are distinct from the coronavirus responsible for the common cold (CoV‐OC43).,Platelet count, size, and maturity associate with increased critical illness and all‐cause mortality among hospitalized COVID‐19 patients.,Profiling tissues and blood from COVID‐19 patients revealed that SARS‐CoV‐2 virions enter megakaryocytes and platelets and associate with alterations to the platelet transcriptome and activation profile.

Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.

Hospitals play a critical role in providing communities with essential medical care during all types of disaster.,Depending on their scope and nature, disasters can lead to a rapidly increasing service demand that can overwhelm the functional capacity and safety of hospitals and the healthcare system at large.,Planning during the community outbreak of coronavirus disease 2019 (Covid-19) is critical for maintaining healthcare services during our response.,This paper describes, besides general measures in times of a pandemic, also the necessary changes in the invasive diagnosis and treatment of patients presenting with different entities of acute coronary syndromes including structural adaptations (networks, spokes and hub centres) and therapeutic adjustments.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury.

Doxorubicin is a chemotherapeutic drug used for the treatment of various malignancies; however, patients can experience cardiotoxic effects and this has limited the use of this potent drug.,The mechanisms by which doxorubicin kills cardiomyocytes has been elusive and despite extensive research the exact mechanisms remain unknown.,This review focuses on recent advances in our understanding of doxorubicin induced regulated cardiomyocyte death pathways including autophagy, ferroptosis, necroptosis, pyroptosis and apoptosis.,Understanding the mechanisms by which doxorubicin leads to cardiomyocyte death may help identify novel therapeutic agents and lead to more targeted approaches to cardiotoxicity testing.

Doxorubicin (DOX) is the mainstay chemotherapeutic agent against a variety of human neoplasmas.,However, its clinical utility is limited by its marked cardiotoxicity.,Chrysin, is a natural flavone which possesses antioxidant, anti-inflammatory and anti-cancer properties.,The current study aimed to investigate the potential protective effect of chrysin against DOX-induced chronic cardiotoxicity and the underlying molecular mechanisms.,Male Sprague-Dawley rats were treated with either DOX (5 mg/kg, once a week) and/or chrysin (50 mg/kg, four times a week) for four weeks.,Chrysin prevented DOX-induced cardiomyopathy which was evident by conduction abnormalities, elevated serum CKMB and LDH and histopathological changes.,Chrysin also ameliorated DOX-induced oxidative stress by decreasing lipid peroxidation and upregulating the antioxidant enzymes.,Moreover, chrysin attenuated DOX-induced apoptosis via decreasing expression of p53, Bax, Puma, Noxa, cytochrome c and caspase-3 while increasing expression of Bcl-2.,DOX induced activation of MAPK; p38 and JNK and increased expression of NF-κB.,Meanwhile, DOX suppressed AKT pathway via decreasing expression of its upstream activator VEGF and increasing expression of PTEN.,Conversely, chrysin effectively neutralised all these effects.,Collectively, these findings indicate that chrysin effectively protected against DOX-induced cardiomyopathy via suppressing oxidative stress, p53-dependent apoptotic pathway, MAPK and NF-κB pathways while augmenting the VEGF/AKT pathway.

Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE.

Coagulopathy in COVID-19 is a burning issue and strategies to prevent thromboembolic events are debated and highly heterogeneous.,The objective was to determine incidence and risk factors of venous thromboembolism (VTE) in COVID-19 inpatients receiving thromboprophylaxis.,In this retrospective French cohort study, patients hospitalized in medical wards non-ICU with confirmed COVID-19 and adequate thromboprophylaxis were included.,A systematic low limb venous duplex ultrasonography was performed at hospital discharge or earlier if deep venous thrombosis (DVT) was clinically suspected.,Chest angio-CT scan was performed when pulmonary embolism (PE) was suspected.,Of 71 patients, 16 developed VTE (22.5%) and 7 PE (10%) despite adequate thromboprophylaxis.,D-dimers at baseline were significantly higher in patients with DVT (p < 0.001).,Demographics, comorbidities, disease manifestations, severity score, and other biological parameters, including inflammatory markers, were similar in patients with and without VTE.,The negative predictive value of a baseline D-dimer level < 1.0 µg/ml was 90% for VTE and 98% for PE.,The positive predictive value for VTE was 44% and 67% for D-dimer level ≥ 1.0 µg/ml and ≥ 3 µg/ml, respectively.,The association between D-dimer level and VTE risk increased by taking into account the latest available D-dimer level prior to venous duplex ultrasonography for the patients with monitoring of D-dimer.,Despite thromboprophylaxis, the risk of VTE is high in COVID-19 non-ICU inpatients.,Increased D-dimer concentrations of more than 1.0 μg/ml predict the risk of venous thromboembolism.,D-dimer level-guided aggressive thromboprophylaxis regimens using higher doses of heparin should be evaluated in prospective studies.

The cardiovascular system is affected broadly by severe acute respiratory syndrome coronavirus 2 infection.,Both direct viral infection and indirect injury resulting from inflammation, endothelial activation, and microvascular thrombosis occur in the context of coronavirus disease 2019.,What determines the extent of cardiovascular injury is the amount of viral inoculum, the magnitude of the host immune response, and the presence of co-morbidities.,Myocardial injury occurs in approximately one-quarter of hospitalized patients and is associated with a greater need for mechanical ventilator support and higher hospital mortality.,The central pathophysiology underlying cardiovascular injury is the interplay between virus binding to the angiotensin-converting enzyme 2 receptor and the impact this action has on the renin-angiotensin system, the body’s innate immune response, and the vascular response to cytokine production.,The purpose of this review was to describe the mechanisms underlying cardiovascular injury, including that of thromboembolic disease and arrhythmia, and to discuss their clinical sequelae.,•The cardiovascular system is affected in diverse ways by severe acute respiratory syndrome coronavirus 2 infection (COVID-19).,•Myocardial injury can be detected in ∼25% of hospitalized patients with COVID-19 and is associated with an increased risk of mortality.,•Described mechanisms of myocardial injury in patients with COVID-19 include oxygen supply-demand imbalance, direct viral myocardial invasion, inflammation, coronary plaque rupture with acute myocardial infarction, microvascular thrombosis, and adrenergic stress.,The cardiovascular system is affected in diverse ways by severe acute respiratory syndrome coronavirus 2 infection (COVID-19).,Myocardial injury can be detected in ∼25% of hospitalized patients with COVID-19 and is associated with an increased risk of mortality.,Described mechanisms of myocardial injury in patients with COVID-19 include oxygen supply-demand imbalance, direct viral myocardial invasion, inflammation, coronary plaque rupture with acute myocardial infarction, microvascular thrombosis, and adrenergic stress.

Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias.,Severe acute respiratory syndrome coronavirus 2 infection may cause injury to cardiac myocytes and increase arrhythmia risk.,The purpose of this study was to evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19.,We also evaluated correlations between the presence of these arrhythmias and mortality.,We reviewed the characteristics of all patients with COVID-19 admitted to our center over a 9-week period.,Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias, and inpatient mortality.,We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, chronic kidney disease, and intensive care unit (ICU) status as potential risk factors for each arrhythmia.,Among 700 patients (mean age 50 ± 18 years; 45% men; 71% African American; 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs.,All cardiac arrests occurred in patients admitted to the ICU.,In addition, admission to the ICU was associated with incident AF (odds ratio [OR] 4.68; 95% confidence interval [CI] 1.66-13.18) and NSVT (OR 8.92; 95% CI 1.73-46.06) after multivariable adjustment.,Also, age and incident AF (OR 1.05; 95% CI 1.02-1.09) and prevalent heart failure and bradyarrhythmias (OR 9.75; 95% CI 1.95-48.65) were independently associated.,Only cardiac arrests were associated with acute in-hospital mortality.,Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality.,To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes.,Prospective autopsy study.,Single pathology department.,11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy).,Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values.,Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women).,Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients.,Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts.,Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients.,Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients.,Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis.,Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes.,Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile.,The sample was small.,COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency.,Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation.,Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory, and imaging studies and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism.,None.,The clinicopathological basis for morbidity and mortality with SARS-CoV-2 infection is not well understood.,This study reports the clinical and autopsy findings of patients who died of COVID-19.

Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.

Cerebral small vessel disease (SVD) is the primary cause of vascular cognitive impairment and is associated with decline in executive function (EF) and information processing speed (IPS).,Imaging biomarkers are needed that can monitor and identify individuals at risk of severe cognitive decline.,Recently there has been interest in combining several magnetic resonance imaging (MRI) markers of SVD into a unitary score to describe disease severity.,Here we apply a diffusion tensor image (DTI) segmentation technique (DSEG) to describe SVD related changes in a single unitary score across the whole cerebrum, to investigate its relationship with cognitive change over a three-year period.,98 patients (aged 43-89) with SVD underwent annual MRI scanning and cognitive testing for up to three years.,DSEG provides a vector of 16 discrete segments describing brain microstructure of healthy and/or damaged tissue.,By calculating the scalar product of each DSEG vector in reference to that of a healthy ageing control we generate an angular measure (DSEG θ) describing the patients' brain tissue microstructural similarity to a disease free model of a healthy ageing brain.,Conventional MRI markers of SVD brain change were also assessed including white matter hyperintensities, cerebral atrophy, incident lacunes, cerebral-microbleeds, and white matter microstructural damage measured by DTI histogram parameters.,The impact of brain change on cognition was explored using linear mixed-effects models.,Post-hoc sample size analysis was used to assess the viability of DSEG θ as a tool for clinical trials.,Changes in brain structure described by DSEG θ were related to change in EF and IPS (p < 0.001) and remained significant in multivariate models including other MRI markers of SVD as well as age, gender and premorbid IQ.,Of the conventional markers, presence of new lacunes was the only marker to remain a significant predictor of change in EF and IPS in the multivariate models (p = 0.002).,Change in DSEG θ was also related to change in all other MRI markers (p < 0.017), suggesting it may be used as a surrogate marker of SVD damage across the cerebrum.,Sample size estimates indicated that fewer patients would be required to detect treatment effects using DSEG θ compared to conventional MRI and DTI markers of SVD severity.,DSEG θ is a powerful tool for characterising subtle brain change in SVD that has a negative impact on cognition and remains a significant predictor of cognitive change when other MRI markers of brain change are accounted for.,DSEG provides an automatic segmentation of the whole cerebrum that is sensitive to a range of SVD related structural changes and successfully predicts cognitive change.,Power analysis shows DSEG θ has potential as a monitoring tool in clinical trials.,As such it may provide a marker of SVD severity from a single imaging modality (i.e.,DTIs).,•A diffusion tensor image segmentation pipeline (DSEG) is proposed.,•The DSEG summary metric describes small vessel disease burden in a single score.,•DSEG is highly related to conventional markers of SVD (WMH, lacunes, CMB, atrophy).,•Change in DSEG over 3-years is highly related to change in executive function and processing speed.,•DSEG and lacunes are powerful markers for predicting SVD-related cognitive change.,A diffusion tensor image segmentation pipeline (DSEG) is proposed.,The DSEG summary metric describes small vessel disease burden in a single score.,DSEG is highly related to conventional markers of SVD (WMH, lacunes, CMB, atrophy).,Change in DSEG over 3-years is highly related to change in executive function and processing speed.,DSEG and lacunes are powerful markers for predicting SVD-related cognitive change.

To describe and compare diffusion tensor imaging (DTI) parameters between patients with subcortical ischemic vascular disease (SIVD) and Alzheimer’s disease (AD) diagnosed using structuralized neuropsychiatric assessments, and investigate potential neuronal substrates related to cognitive performance.,Thirty-five patients with SIVD, 40 patients with AD, and 33 cognitively normal control (NC) subjects matched by age and education level were consecutively recruited and underwent cognitive function assessments and DTI examinations.,Comparisons among these three subgroups with regards to cognitive performance and DTI parameters including fractional anisotropy (FA) and mean diffusivity (MD) values were performed.,Partial correlation analysis after controlling for age and education was used to evaluate associations between cognitive performance and DTI parameters.,With regards to cognitive performance, the patients with SIVD had lower total scores in frontal assessment battery (FAB) compared to those with AD (p < 0.05) in the context of comparable Mini-Mental Status Examination and Cognitive Abilities Screening Instrument scores.,With regards to DTI parameters, there were more regions of significant differences in FA among these three subgroups compared with MD.,Compared with NC group, the patients with SIVD had significant global reductions in FA (p < 0.001 ~ 0.05), while significant reductions in FA among the patients with AD were regionally confined within the left superior longitudinal fasciculus, genu and splenium of the corpus callosum, and bilateral forceps major, and the anterior thalamic radiation, uncinate fasciculus, and cingulum of the left side (p < 0.01 ~ 0.05).,Analysis of FA values within the left forceps major, left anterior thalamic radiation, and genu of the corpus callosum revealed a 71.8% overall correct classification (p < 0.001) with sensitivity of 69.4%, specificity of 73.8%, positive predictive value of 69.4%, and negative predictive value of 73.8% in discriminating patients with SIVD from those with AD.,In combined analysis of the patients with SIVD and AD (n = 75), the total FAB score was positively correlated with FA within the bilateral forceps minor, genu of the corpus callosum, left forceps major, left uncinate fasciculus, and right inferior longitudinal fasciculus (p = 0.001 ~ 0.038), and inversely correlated with MD within the right superior longitudinal fasciculus, genu and body of the corpus callosum, bilateral forceps minor, right uncinate fasciculus, and right inferior longitudinal fasciculus (p = 0.003 ~ 0.040),Our findings suggest the effectiveness of DTI measurements in distinguishing patients with early-stage AD from those with SIVD, with discernible changes in spatial distribution and magnitude of significance of the DTI parameters.,Strategic FA assessments provided the most robust discriminative power to differentiate SIVD from AD, and FAB may serve as an additional cognitive marker.,We also identified the neuronal substrates responsible for FAB performance.

A remarkably high incidence of venous thromboembolism (VTE) has been reported among critically ill patients with COVID‐19 assisted in the intensive care unit (ICU).,However, VTE burden among non‐ICU patients hospitalized for COVID‐19 that receive guideline‐recommended thromboprophylaxis is unknown.,To determine the incidence of VTE among non‐ICU patients hospitalized for COVID‐19 that receive pharmacological thromboprophylaxis.,We performed a systematic screening for the diagnosis of deep vein thrombosis (DVT) by lower limb vein compression ultrasonography (CUS) in consecutive non‐ICU patients hospitalized for COVID‐19, independent of the presence of signs or symptoms of DVT.,All patients were receiving pharmacological thromboprophylaxis with either enoxaparin or fondaparinux.,The population that we screened consisted of 84 consecutive patients, with a mean age of 67.6 ± 13.5 years and a mean Padua Prediction Score of 5.1 ± 1.6.,Seventy‐two patients (85.7%) had respiratory insufficiency, required oxygen supplementation, and had reduced mobility or were bedridden.,In this cohort, we found 10 cases of DVT, with an incidence of 11.9% (95% confidence interval [CI] 4.98‐18.82).,Of these, 2 were proximal DVT (incidence rate 2.4%, 95% CI −0.87‐5.67) and 8 were distal DVT (incidence rate 9.5%, 95% CI 3.23‐5.77).,Significant differences between subjects with and without DVT were D‐dimer > 3000 µg/L (P < .05), current or previous cancer (P < .05), and need of high flow nasal oxygen therapy and/or non‐invasive ventilation (P < .01).,DVT may occur among non‐ICU patients hospitalized for COVID‐19, despite guideline‐recommended thromboprophylaxis.

Corona virus outbreak started in December 2019, and the disease has been defined by the World Health Organization as a public health emergency.,Coronavirus is a source of deep venous thrombosis (DVT) due to complications such as over-coagulation, blood stasis, and endothelial damage.,In this study, we report a 26-year-old pregnant woman with coronavirus who was hospitalized with a right ovarian vein thrombosis at Besat Hospital in Sanandaj.,Risk classification for deep vein thrombosis (DVT) disease is of crucial importance for the forecast of coronavirus.

At our institution, 2 of the initial 7 pregnant patients with confirmed coronavirus disease 2019 severe infection (28.6%; 95% CI, 8.2%-64.1%) developed cardiac dysfunction with moderately reduced left ventricular ejection fractions of 40%-45% and hypokinesis.,Viral myocarditis and cardiomyopathy have also been reported in nonpregnant coronavirus disease 2019 patients.,A case series of nonpregnant patients with coronavirus disease 2019 found that 33% of those in intensive care developed cardiomyopathy.,More data are needed to ascertain the incidence of cardiomyopathy from coronavirus disease 2019 in pregnancy, in all pregnant women with coronavirus disease 2019, and those with severe disease (eg, pneumonia).,We suggest an echocardiogram in pregnant women with coronavirus disease 2019 pneumonia, in particular those necessitating oxygen, or those who are critically ill, and we recommend the use of handheld, point-of-care devices where possible to minimize contamination of staff and traditional large echocardiogram machines.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system.,Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19.

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many countries have introduced strict hygiene measures of social distancing to prevent further spreading of the disease.,This may have led to a decreased presentation to hospital of patients with acute medical conditions and time-dependent management, such as stroke.,We conducted a nationwide cohort study using administrative database of all hospitalized patients with main diagnosis of acute ischemic stroke (AIS), transient ischemic attack, or intracerebral hemorrhage.,Data from a total of 1463 hospitals in Germany were included.,We compared case numbers and treatment characteristics of pandemic (March 16 to May 15, 2020) and prepandemic (January 16 to March 15, 2020) cases and also with corresponding time period in 2019.,We identified a strong decline for hospitalization of AIS (−17.4%), transient ischemic attack (−22.9%), and intracerebral hemorrhage (−15.8%) patients during the pandemic compared with prepandemic period.,IVT rate in patients with AIS was comparable (prepandemic versus pandemic: 16.4% versus 16.6%, P=0.448), whereas mechanical thrombectomy rate was significantly higher during the pandemic (8.1% versus 7.7%, P=0.044).,In-hospital mortality was significantly increased in patients with AIS during the pandemic period (8.1% versus 7.6%, P=0.006).,Besides a massive decrease in absolute case numbers, our data suggest that patients with AIS who did seek acute care during the pandemic, continued to receive acute recanalization treatment in Germany.

There are concerns that the coronavirus disease 2019 (COVID-19) outbreak negatively affects the quality of care for acute cardiovascular conditions.,We assessed the impact of the COVID-19 outbreak on trends in hospital admissions and workflow parameters of acute stroke care in Amsterdam, The Netherlands.,We used data from the three hospitals that provide acute stroke care for the Amsterdam region.,We compared two 7-week periods: one during the peak of the COVID-19 outbreak (March 16th-May 3th 2020) and one prior to the outbreak (October 21st-December 8th 2019).,We included consecutive patients who presented to the emergency departments with a suspected stroke and assessed the change in number of patients as an incidence-rate ratio (IRR) using a Poisson regression analysis.,Other outcomes were the IRR for stroke subtypes, change in use of reperfusion therapy, treatment times, and in-hospital complications.,During the COVID-19 period, 309 patients presented with a suspected stroke compared to 407 patients in the pre-COVID-19 period (IRR 0.76 95%CI 0.65-0.88).,The proportion of men was higher during the COVID-19 period (59% vs. 47%, p < 0.001).,There was no change in the proportion of stroke patients treated with intravenous thrombolysis (28% vs. 30%, p = 0.58) or endovascular thrombectomy (11% vs 12%, p = 0.82) or associated treatment times.,Seven patients (all ischemic strokes) were diagnosed with COVID-19.,We observed a 24% decrease in suspected stroke presentations during the COVID-19 outbreak, but no evidence for a decrease in quality of acute stroke care.

During the coronavirus disease 2019 (COVID-19) pandemic, the World Health Organization recommended measures to mitigate the outbreak such as social distancing and confinement.,Since these measures have been put in place, anecdotal reports describe a decrease in the number of endovascular therapy (EVT) treatments for acute ischemic stroke due to large vessel occlusion.,The purpose of our study was to determine the effect on EVT for patients with acute ischemic stroke during the COVID-19 confinement.,In this retrospective, observational study, data were collected from November 1, 2019, to April 15, 2020, at 17 stroke centers in countries where confinement measures have been in place since March 2020 for the COVID-19 pandemic (Switzerland, Italy, France, Spain, Portugal, Germany, Canada, and United States).,This study included 1600 patients treated by EVT for acute ischemic stroke.,Date of EVT and symptom onset-to-groin puncture time were collected.,Mean number of EVTs performed per hospital per 2-week interval and mean stroke onset-to-groin puncture time were calculated before confinement measures and after confinement measures.,Distributions (non-normal) between the 2 groups (before COVID-19 confinement versus after COVID-19 confinement) were compared using 2-sample Wilcoxon rank-sum test.,The results show a significant decrease in mean number of EVTs performed per hospital per 2-week interval between before COVID-19 confinement (9.0 [95% CI, 7.8-10.1]) and after COVID-19 confinement (6.1 [95% CI, 4.5-7.7]), (P<0.001).,In addition, there is a significant increase in mean stroke onset-to-groin puncture time (P<0.001), between before COVID-19 confinement (300.3 minutes [95% CI, 285.3-315.4]) and after COVID-19 confinement (354.5 minutes [95% CI, 316.2-392.7]).,Our preliminary analysis indicates a 32% reduction in EVT procedures and an estimated 54-minute increase in symptom onset-to-groin puncture time after confinement measures for COVID-19 pandemic were put into place.

Supplemental Digital Content is available in the text.,We aimed to investigate the acute stroke presentations during the coronavirus disease 2019 (COVID-19) pandemic.,The data were obtained from a health system with 19 emergency departments in northeast Ohio in the United States.,Baseline period from January 1 to March 8, 2020, was compared with the COVID period from March 9, to April 2, 2020.,The variables included were total daily stroke alerts across the hospital emergency departments, thrombolysis, time to presentation, stroke severity, time from door-to-imaging, time from door-to-needle in thrombolysis, and time from door-to-puncture in thrombectomy.,The 2 time periods were compared using nonparametric statistics and Poisson regression.,Nine hundred two stroke alerts during the period across the emergency departments were analyzed.,Total daily stroke alerts decreased from median, 10 (interquartile range, 8-13) during baseline period to median, 8 (interquartile range, 4-10, P=0.001) during COVID period.,Time to presentation, stroke severity, and time to treatment were unchanged.,COVID period was associated with decrease in stroke alerts with rate ratio of 0.70 (95% CI, 0.60-0.28).,Thrombolysis also decreased with rate ratio, 0.52 (95% CI, 0.28-0.97) but thrombectomy remained unchanged rate ratio, 0.93 (95% CI, 0.52-1.62),We observed a significant decrease in acute stroke presentations by ≈30% across emergency departments at the time of surge of COVID-19 cases.,This observation could be attributed to true decline in stroke incidence or patients not seeking medical attention for emergencies during the pandemic.

Supplemental Digital Content is available in the text.,Coronavirus disease 2019 (COVID-19) has led to over 1 million deaths worldwide and has been associated with cardiac complications including cardiac arrhythmias.,The incidence and pathophysiology of these manifestations remain elusive.,In this worldwide survey of patients hospitalized with COVID-19 who developed cardiac arrhythmias, we describe clinical characteristics associated with various arrhythmias, as well as global differences in modulations of routine electrophysiology practice during the pandemic.,We conducted a retrospective analysis of patients hospitalized with COVID-19 infection worldwide with and without incident cardiac arrhythmias.,Patients with documented atrial fibrillation, atrial flutter, supraventricular tachycardia, nonsustained or sustained ventricular tachycardia, ventricular fibrillation, atrioventricular block, or marked sinus bradycardia (heart rate<40 bpm) were classified as having arrhythmia.,Deidentified data was provided by each institution and analyzed.,Data were collected for 4526 patients across 4 continents and 12 countries, 827 of whom had an arrhythmia.,Cardiac comorbidities were common in patients with arrhythmia: 69% had hypertension, 42% diabetes, 30% had heart failure, and 24% had coronary artery disease.,Most had no prior history of arrhythmia.,Of those who did develop an arrhythmia, the majority (81.8%) developed atrial arrhythmias, 20.7% developed ventricular arrhythmias, and 22.6% had bradyarrhythmia.,Regional differences suggested a lower incidence of atrial fibrillation in Asia compared with other continents (34% versus 63%).,Most patients in North America and Europe received hydroxychloroquine, although the frequency of hydroxychloroquine therapy was constant across arrhythmia types.,Forty-three percent of patients who developed arrhythmia were mechanically ventilated and 51% survived to hospital discharge.,Many institutions reported drastic decreases in electrophysiology procedures performed.,Cardiac arrhythmias are common and associated with high morbidity and mortality among patients hospitalized with COVID-19 infection.,There were significant regional variations in the types of arrhythmias and treatment approaches.

Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined.,We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients.,One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days.,Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%).,Late gadolinium enhancement and/or ischaemia was found in 54% (80/148).,This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148).,Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis.,Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia).,Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease.,There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms).,During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence.,In a proportion of patients, there is evidence of possible ongoing localized inflammation.,A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history.,Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined.,Diffuse oedema or fibrosis was not detected.

Can a pretest probability score make it possible to rule out pulmonary embolism solely on clinical criteria and optimized D-dimer measurement to safely decrease imaging testing?,In this study, the 4-Level Pulmonary Embolism Clinical Probability Score (4PEPS) was derived and validated using databases from 3 merged management studies.,The safety and the efficacy of the 4PEPS strategy was confirmed in 2 external validation cohorts (false-negative rates: 0.71% and 0.89%; absolute reductions in imaging testing: −19% and −22%, respectively).,The 4PEPS strategy may lead to a substantial and safe reduction in imaging testing for patients with suspected pulmonary embolism.,This study derives and validates a 4-level pretest probability rule that makes it possible to rule out pulmonary embolism solely on clinical criteria and optimized D-dimer measurement to safely decrease imaging testing for suspected pulmonary embolism.,In patients with suspected pulmonary embolism (PE), overuse of diagnostic imaging is an important point of concern.,To derive and validate a 4-level pretest probability rule (4-Level Pulmonary Embolism Clinical Probability Score [4PEPS]) that makes it possible to rule out PE solely on clinical criteria and optimized D-dimer measurement to safely decrease imaging testing for suspected PE.,This study included consecutive outpatients suspected of having PE from US and European emergency departments.,Individual data from 3 merged management studies (n = 11 114; overall prevalence of PE, 11%) were used for the derivation cohort and internal validation cohort.,The external validation cohorts were taken from 2 independent studies, the first with a high PE prevalence (n = 1548; prevalence, 21.5%) and the second with a moderate PE prevalence (n = 1669; prevalence, 11.7%).,A prior definition of pretest probability target values to achieve a posttest probability less than 2% was used on the basis of the negative likelihood ratios of D-dimer.,Data were collected from January 2003 to April 2016, and data were analyzed from June 2018 to August 2019.,The rate of PE diagnosed during the initial workup or during follow-up and the rate of imaging testing.,Of the 5588 patients in the derivation cohort, 3441 (61.8%) were female, and the mean (SD) age was 52 (18.5) years.,The 4PEPS comprises 13 clinical variables scored from −2 to 5.,It results in the following strategy: (1) very low probability of PE if 4PEPS is less than 0: PE ruled out without testing; (2) low probability of PE if 4PEPS is 0 to 5: PE ruled out if D-dimer level is less than 1.0 μg/mL; (3) moderate probability of PE if 4PEPS is 6 to 12: PE ruled out if D-dimer level is less than the age-adjusted cutoff value; (4) high probability of PE if 4PEPS is greater than 12: PE ruled out by imaging without preceding D-dimer test.,In the first and the second external validation cohorts, the area under the receiver operator characteristic curves were 0.79 (95% CI, 0.76 to 0.82) and 0.78 (95% CI, 0.74 to 0.81), respectively.,The false-negative testing rates if the 4PEPS strategy had been applied were 0.71% (95% CI, 0.37 to 1.23) and 0.89% (95% CI, 0.53 to 1.49), respectively.,The absolute reductions in imaging testing were −22% (95% CI, −26 to −19) and −19% (95% CI, −22 to −16) in the first and second external validation cohorts, respectively.,The 4PEPS strategy compared favorably with all recent strategies in terms of imaging testing.,The 4PEPS strategy may lead to a substantial and safe reduction in imaging testing for patients with suspected PE.,It should now be tested in a formal outcome study.

Individual studies have reported widely variable rates for VTE and bleeding among hospitalized patients with coronavirus disease 2019 (COVID-19).,What is the incidence of VTE and bleeding among hospitalized patients with COVID-19?,In this systematic review and meta-analysis, 15 standard sources and COVID-19-specific sources were searched between January 1, 2020, and July 31, 2020, with no restriction according to language.,Incidence estimates were pooled by using random effects meta-analyses.,Heterogeneity was evaluated by using the I2 statistic, and publication bias was assessed by using the Begg and Egger tests.,The pooled incidence was 17.0% (95% CI, 13.4-20.9) for VTE, 12.1% (95% CI, 8.4-16.4) for DVT, 7.1% (95% CI, 5.3-9.1) for pulmonary embolism (PE), 7.8% (95% CI, 2.6-15.3) for bleeding, and 3.9% (95% CI, 1.2-7.9) for major bleeding.,In subgroup meta-analyses, the incidence of VTE was higher when assessed according to screening (33.1% vs 9.8% by clinical diagnosis), among patients in the ICU (27.9% vs 7.1% in the ward), in prospective studies (25.5% vs 12.4% in retrospective studies), and with the inclusion of catheter-associated thrombosis/isolated distal DVTs and isolated subsegmental PEs.,The highest pooled incidence estimate of bleeding was reported for patients receiving intermediate- or full-dose anticoagulation (21.4%) and the lowest in the only prospective study that assessed bleeding events (2.7%).,Among hospitalized patients with COVID-19, the overall estimated pooled incidence of VTE was 17.0%, with higher rates with routine screening, inclusion of distal DVT, and subsegmental PE, in critically ill patients and in prospective studies.,Bleeding events were observed in 7.8% of patients and were sensitive to use of escalated doses of anticoagulants and nature of data collection.,Additional studies are required to ascertain the significance of various thrombotic events and to identify strategies to improve patient outcomes.,PROSPERO; No.: CRD42020198864; URL: https://www.crd.york.ac.uk/prospero/.

COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital.,Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes.,We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020.,The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h.,Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation.,All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet-fibrin thrombi (in 33 cases).,The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases).,Electron microscopy revealed that viral particles were predominantly located in the pneumocytes.,The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses.,Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent.,Importantly, the presence of platelet-fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy.,None.

Coagulopathy is a common abnormality in patients with COVID‐19.,However, the exact incidence of venous thromboembolic event is unknown in anticoagulated, severe COVID‐19 patients.,Systematic assessment of venous thromboembolism (VTE) using complete duplex ultrasound (CDU) in anticoagulated COVID‐19 patients.,We performed a retrospective study in 2 French intensive care units (ICU) where CDU is performed as a standard of care.,A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID‐19.,Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis.,Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation.,Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration.,From March 19 to April 11, 2020, 26 consecutive patients with severe COVID‐19 were screened for VTE.,Eight patients (31%) were treated with prophylactic anticoagulation, whereas 18 patients (69%) were treated with therapeutic anticoagulation.,The overall rate of VTE in patients was 69%.,The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with the other group (100% vs 56%, respectively, P = .03).,Surprisingly, we found a high rate of thromboembolic events in COVID‐19 patients treated with therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms.,Our results suggest considering both systematic screening of VTE and early therapeutic anticoagulation in severe ICU COVID‐19 patients.

This cohort study assesses the prevalence of myocarditis in athletes with COVID-19 and compares screening strategies for safe return to play.,What is the prevalence of myocarditis in competitive athletes after COVID-19 infection, and how would different approaches to screening affect detection?,In this cohort study of 1597 US competitive collegiate athletes undergoing comprehensive cardiovascular testing, the prevalence of clinical myocarditis based on a symptom-based screening strategy was only 0.31%.,Screening with cardiovascular magnetic resonance imaging increased the prevalence of clinical and subclinical myocarditis by a factor of 7.4 to 2.3%.,These cardiac magnetic resonance imaging findings provide important data on the prevalence of clinical and subclinical myocarditis in college athletes recovering from symptomatic and asymptomatic COVID-19 infections.,Myocarditis is a leading cause of sudden death in competitive athletes.,Myocardial inflammation is known to occur with SARS-CoV-2.,Different screening approaches for detection of myocarditis have been reported.,The Big Ten Conference requires comprehensive cardiac testing including cardiac magnetic resonance (CMR) imaging for all athletes with COVID-19, allowing comparison of screening approaches.,To determine the prevalence of myocarditis in athletes with COVID-19 and compare screening strategies for safe return to play.,Big Ten COVID-19 Cardiac Registry principal investigators were surveyed for aggregate observational data from March 1, 2020, through December 15, 2020, on athletes with COVID-19.,For athletes with myocarditis, presence of cardiac symptoms and details of cardiac testing were recorded.,Myocarditis was categorized as clinical or subclinical based on the presence of cardiac symptoms and CMR findings.,Subclinical myocarditis classified as probable or possible myocarditis based on other testing abnormalities.,Myocarditis prevalence across universities was determined.,The utility of different screening strategies was evaluated.,SARS-CoV-2 by polymerase chain reaction testing.,Myocarditis via cardiovascular diagnostic testing.,Representing 13 universities, cardiovascular testing was performed in 1597 athletes (964 men [60.4%]).,Thirty-seven (including 27 men) were diagnosed with COVID-19 myocarditis (overall 2.3%; range per program, 0%-7.6%); 9 had clinical myocarditis and 28 had subclinical myocarditis.,If cardiac testing was based on cardiac symptoms alone, only 5 athletes would have been detected (detected prevalence, 0.31%).,Cardiac magnetic resonance imaging for all athletes yielded a 7.4-fold increase in detection of myocarditis (clinical and subclinical).,Follow-up CMR imaging performed in 27 (73.0%) demonstrated resolution of T2 elevation in all (100%) and late gadolinium enhancement in 11 (40.7%).,In this cohort study of 1597 US competitive athletes with CMR screening after COVID-19 infection, 37 athletes (2.3%) were diagnosed with clinical and subclinical myocarditis.,Variability was observed in prevalence across universities, and testing protocols were closely tied to the detection of myocarditis.,Variable ascertainment and unknown implications of CMR findings underscore the need for standardized timing and interpretation of cardiac testing.,These unique CMR imaging data provide a more complete understanding of the prevalence of clinical and subclinical myocarditis in college athletes after COVID-19 infection.,The role of CMR in routine screening for athletes safe return to play should be explored further.

Coronavirus disease 2019 (COVID-19) induces myocardial injury, either direct myocarditis or indirect injury due to systemic inflammatory response.,Myocardial involvement has been proved to be one of the primary manifestations of COVID-19 infection, according to laboratory test, autopsy, and cardiovascular magnetic resonance (CMR).,However, the middle-term outcome of cardiac involvement after the patients were discharged from the hospital is yet unknown.,The present study aimed to evaluate mid-term cardiac sequelae in recovered COVID-19 patients by CMR,A total of 47 recovered COVID-19 patients were prospectively recruited and underwent CMR examination.,The CMR protocol consisted of black blood fat-suppressed T2 weighted imaging, T2 star mapping, left ventricle (LV) cine imaging, pre- and post-contrast T1 mapping, and late gadolinium enhancement (LGE).,LGE were assessed in mixed both recovered COVID-19 patients and healthy controls.,The LV and right ventricle (RV) function and LV mass were assessed and compared with healthy controls.,A total of 44 recovered COVID-19 patients and 31 healthy controls were studied.,LGE was found in 13 (30%) of COVID-19 patients.,All LGE lesions were located in the mid myocardium and/or sub-epicardium with a scattered distribution.,Further analysis showed that LGE-positive patients had significantly decreased LV peak global circumferential strain (GCS), RV peak GCS, RV peak global longitudinal strain (GLS) as compared to non-LGE patients (p < 0.05), while no difference was found between the non-LGE patients and healthy controls.,Myocardium injury existed in 30% of COVID-19 patients.,These patients have depressed LV GCS and peak RV strains at the 3-month follow-up.,CMR can monitor the COVID-19-induced myocarditis progression, and CMR strain analysis is a sensitive tool to evaluate the recovery of LV and RV dysfunction.

•Myocarditis in COVID-19 was relatively rare but can be severe and lead to mortality.,•Cardiac MRI showing cardiac oedema and injury was valuable in diagnosing myocarditis.,•Left ventricular dysfunction and hypokinesis was common and should be managed.,•Steroids were often used but implications on viral clearance should be considered.,Myocarditis in COVID-19 was relatively rare but can be severe and lead to mortality.,Cardiac MRI showing cardiac oedema and injury was valuable in diagnosing myocarditis.,Left ventricular dysfunction and hypokinesis was common and should be managed.,Steroids were often used but implications on viral clearance should be considered.,Myocarditis caused by SARS-CoV-2 infection was proposed to account for a proportion of cardiac injury in patients with COVID-19.,However, reports of coronavirus-induced myocarditis were scarce.,The aim of this review was to summarise the published cases of myocarditis and describe their presentations, diagnostic processes, clinical characteristics and outcomes.,A literature search of MEDLINE, EMBASE, Scopus, Web of Science, CENTRAL and OpenGrey on was performed on 3 June 2020.,Studies of myocarditis in patients with COVID-19 were included, and those only reporting cardiac injury or heart failure were excluded.,Cases were “confirmed” myocarditis if diagnosed on cardiac magnetic resonance imaging (CMR) or histopathology.,Those without were grouped as “possible” myocarditis.,A total of 31 studies on 51 patients were included; 12 cases were confirmed myocarditis while 39 had possible myocarditis.,The median age was 55 and 69% were male.,The most common presenting symptoms were fever, shortness of breath, cough and chest pain.,Electrocardiogram changes included non-specific ST-segment and T-wave changes and ventricular tachycardia.,Most patients had elevated cardiac and inflammatory biomarkers.,Left ventricular dysfunction and hypokinesis was common.,CMR established the diagnosis in 10 patients, with features of cardiac oedema and cardiac injury.,Five patients had histopathological examination.,Some cases required mechanical ventilation and extracoporeal membrane oxygenation, and 30% of patients recovered but 27% died.,COVID-19 myocarditis was associated with ECG, cardiac biomarker and echocardiographic changes, and the manifestation could be severe leading to mortality.,Endomyocardial biopsy was not available in most cases but CMR was valuable.

This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury.

Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications.,To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19.,Single‐center cohort study of 198 hospitalized patients with COVID‐19.,Seventy‐five patients (38%) were admitted to the intensive care unit (ICU).,At time of data collection, 16 (8%) were still hospitalized and 19% had died.,During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis.,The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively.,For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36).,VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5).,The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days).,The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE.,Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

One of the defining features of the novel coronavirus disease 2019 infection has been high rates of venous thromboses.,The present study aimed to describe the prevalence of venous thromboembolism in critically ill patients receiving different regimens of prophylactic anticoagulation.,Single-center retrospective review using data from patients with confirmed severe acute respiratory syndrome coronavirus 2 requiring intubation.,Tertiary-care center in Indianapolis, IN, United States.,Patients hospitalized at international units Health Methodist Hospital with severe acute respiratory syndrome coronavirus 2 requiring intubation between March 23, 2020, and April 8, 2020, who underwent ultrasound evaluation for venous thrombosis.,None.,A total of 45 patients were included.,Nineteen of 45 patients (42.2%) were found to have deep venous thrombosis.,Patients found to have deep venous thrombosis had no difference in time to intubation (p = 0.97) but underwent ultrasound earlier in their hospital course (p = 0.02).,Sequential Organ Failure Assessment scores were similar between the groups on day of intubation and day of ultrasound (p = 0.44 and p = 0.07, respectively). d-dimers were markedly higher in patients with deep venous thrombosis, both for maximum value and value on day of ultrasound (p < 0.01 for both).,Choice of prophylactic regimen was not related to presence of deep venous thrombosis (p = 0.35).,Ultrasound evaluation is recommended if d-dimer is greater than 2,000 ng/mL (sensitivity 95%, specificity 46%) and empiric anticoagulation considered if d-dimer is greater than 5,500 ng/mL (sensitivity 53%, specificity 88%).,Deep venous thrombosis is very common in critically ill patients with coronavirus disease 2019.,There was no difference in incidence of deep venous thrombosis among different pharmacologic prophylaxis regimens, although our analysis is limited by small sample size. d-dimer values are elevated in the majority of these patients, but there may be thresholds at which screening ultrasound or even empiric systemic anticoagulation is indicated.

Sodium glucose co-transporter 2 inhibitor (SGLT2i), a new class of anti-diabetic drugs acting on inhibiting glucose resorption by kidneys, is shown beneficial in reduction of heart failure hospitalization and cardiovascular mortality.,The mechanisms remain unclear.,We hypothesized that SGLT2i, empagliflozin can improve cardiac hemodynamics in non-diabetic hypertensive heart failure.,The hypertensive heart failure model had been created by feeding spontaneous hypertensive rats (SHR) with high fat diet for 32 weeks (total n = 13).,Half SHRs were randomized to be administered with SGLT2i, empagliflozin at 20 mg/kg/day for 12 weeks.,After evaluation of electrocardiography and echocardiography, invasive hemodynamic study was performed and followed by blood sample collection and tissue analyses.,Empagliflozin exhibited cardiac (improved atrial and ventricular remodeling) and renal protection, while plasma glucose level was not affected.,Empagliflozin normalized both end-systolic and end-diastolic volume in SHR, in parallel with parameters in echocardiographic evaluation.,Empagliflozin also normalized systolic dysfunction, in terms of the reduced maximal velocity of pressure incline and the slope of end-systolic pressure volume relationship in SHR.,In histological analysis, empagliflozin significantly attenuated cardiac fibrosis in both atrial and ventricular tissues.,The upregulation of atrial and ventricular expression of PPARα, ACADM, natriuretic peptides (NPPA and NPPB), and TNF-α in SHR, was all restored by treatment of empagliflozin.,Empagliflozin improves hemodynamics in our hypertensive heart failure rat model, associated with renal protection, attenuated cardiac fibrosis, and normalization of HF genes.,Our results contribute some understanding of the pleiotropic effects of empagliflozin on improving heart function.

Type 2 diabetes mellitus (T2DM) greatly increases the risks of cardiovascular disease and heart failure.,In particular, left ventricular diastolic dysfunction that develops from the early stages of T2DM is an important factor in the onset and exacerbation of heart failure.,The effect of sodium-glucose cotransporter 2 inhibitors on left ventricular diastolic function has not been elucidated.,We have performed the first prospective study on the effects of canagliflozin on left ventricular diastolic function in T2DM.,This study was performed to evaluate the effects of additional treatment with canagliflozin for 3 months on left ventricular diastolic function in patients with T2DM.,A total of 38 patients with T2DM were consecutively recruited for this study.,Left ventricular diastolic function was assessed by echocardiography.,The primary study outcome was a change in the septal E/e′ as a parameter of left ventricular diastolic function.,A total of 37 patients (25 males and 12 females) were included in the analysis.,Mean age of participants was 64.2 ± 8.1 years (mean ± SD), mean duration of diabetes was 13.5 ± 8.1 years, and mean HbA1c was 7.9 ± 0.7%.,Of the participants, 86.5% had hypertension, 100% had dyslipidemia, and 32.4% had cardiovascular disease.,Canagliflozin significantly improved left ventricular diastolic function (septal E/e′ ratio 13.7 ± 3.5-12.1 ± 2.8, p = 0.001).,Furthermore, among the various parameters that changed through the administration of canagliflozin, only changes in hemoglobin significantly correlated with changes in the septal E/e′ ratio (p = 0.002).,In multiple regression analysis, changes in hemoglobin were also revealed to be an independent predictive factor for changes in the septal E/e′ ratio.,This study showed for the first time that canagliflozin could improve left ventricular diastolic function within 3 months in patients with T2DM.,The benefit was especially apparent in patients with substantially improved hemoglobin values.,Trial registration UMIN Clinical Trials Registry UMIN000028141,The online version of this article (10.1186/s12933-018-0717-9) contains supplementary material, which is available to authorized users.

Activated microglia-mediated neuroinflammation has been regarded as an underlying key player in the pathogenesis of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI).,The therapeutic potential of bone marrow mesenchymal stem cells (BMSCs) transplantation has been demonstrated in several brain injury models and is thought to involve modulation of the inflammatory response.,The present study investigated the salutary effects of BMSCs on EBI after SAH and the potential mechanism mediated by Notch1 signaling pathway inhibition.,The Sprague-Dawley rats SAH model was induced by endovascular perforation method.,BMSCs (3 × 106 cells) were transplanted intravenously into rats, and N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester (DAPT), a Notch1 activation inhibitor, and Notch1 small interfering RNA (siRNA) were injected intracerebroventricularly.,The effects of BMSCs on EBI were assayed by neurological score, brain water content (BWC), blood-brain barrier (BBB) permeability, magnetic resonance imaging, hematoxylin and eosin staining, and Fluoro-Jade C staining.,Immunofluorescence and immunohistochemistry staining, Western blotting, and quantitative real-time polymerase chain reaction were used to analyze various proteins and transcript levels.,Pro-inflammatory cytokines were measured by enzyme-linked immunosorbent assay.,BMSCs treatment mitigated the neurobehavioral dysfunction, BWC and BBB disruption associated with EBI after SAH, reduced ionized calcium binding adapter molecule 1 and cluster of differentiation 68 staining and interleukin (IL)-1 beta, IL-6 and tumor necrosis factor alpha expression in the left hemisphere but concurrently increased IL-10 expression.,DAPT or Notch1 siRNA administration reduced Notch1 signaling pathway activation following SAH, ameliorated neurobehavioral impairments, and BBB disruption; increased BWC and neuronal degeneration; and inhibited activation of microglia and production of pro-inflammatory factors.,The augmentation of Notch1 signal pathway agents and phosphorylation of nuclear factor-κB after SAH were suppressed by BMSCs but the levels of Botch were upregulated in the ipsilateral hemisphere.,Botch knockdown in BMSCs abrogated the protective effects of BMSCs treatment on EBI and the suppressive effects of BMSCs on Notch1 expression.,BMSCs treatment alleviated neurobehavioral impairments and the inflammatory response in EBI after SAH; these effects may be attributed to Botch upregulation in brain tissue, which subsequently inhibited the Notch1 signaling pathway.,The online version of this article (10.1186/s12974-019-1396-5) contains supplementary material, which is available to authorized users.

Aneurysmal subarachnoid hemorrhage (aSAH) represents only a small portion of all strokes, but accounts for almost half of the deaths caused by stroke worldwide.,Neurosurgical clipping and endovascular coiling can successfully obliterate the bleeding aneurysms, but ensuing complications such as cerebral vasospasm, acute and chronic hydrocephalus, seizures, cortical spreading depression, delayed ischemic neurological deficits, and delayed cerebral ischemia lead to poor clinical outcomes.,The mechanisms leading to these complications are complex and poorly understood.,Early brain injury resulting from transient global ischemia can release molecules that may be critical to initiate and sustain inflammatory response.,Hence, the events during early brain injury can influence the occurrence of delayed brain injury.,Since the damage associated molecular pattern molecules (DAMPs) might be the initiators of inflammation in the pathophysiology of aSAH, so the aim of this review is to highlight their role in the context of aSAH from diagnostic, prognostic, therapeutic, and drug therapy monitoring perspectives.,DAMPs represent a diverse and a heterogenous group of molecules derived from different compartments of cells upon injury.,Here, we have reviewed the most important DAMPs molecules including high mobility group box-1 (HMGB1), S100B, hemoglobin and its derivatives, extracellular matrix components, IL-1α, IL-33, and mitochondrial DNA in the context of aSAH and their role in post-aSAH complications and clinical outcome after aSAH.

To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.,Retrospective case series.,Tongji Hospital in Wuhan, China.,Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed.,Data were collected until 28 February 2020.,Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.,The median age of deceased patients (68 years) was significantly older than recovered patients (51 years).,Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%).,Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)).,Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)).,The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days.,Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively.,Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients.,Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%).,Patients with cardiovascular comorbidity were more likely to develop cardiac complications.,Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.,Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk.,Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

To report the methods and findings of two complete autopsies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive individuals who died in Oklahoma (United States) in March 2020.,Complete postmortem examinations were performed according to standard procedures in a negative-pressure autopsy suite/isolation room using personal protective equipment, including N95 masks, eye protection, and gowns.,The diagnosis of coronavirus disease 2019 (COVID-19) was confirmed by real-time reverse transcriptase polymerase chain reaction testing on postmortem swabs.,A 77-year-old obese man with a history of hypertension, splenectomy, and 6 days of fever and chills died while being transported for medical care.,He tested positive for SARS-CoV-2 on postmortem nasopharyngeal and lung parenchymal swabs.,Autopsy revealed diffuse alveolar damage and chronic inflammation and edema in the bronchial mucosa.,A 42-year-old obese man with a history of myotonic dystrophy developed abdominal pain followed by fever, shortness of breath, and cough.,Postmortem nasopharyngeal swab was positive for SARS-CoV-2; lung parenchymal swabs were negative.,Autopsy showed acute bronchopneumonia with evidence of aspiration.,Neither autopsy revealed viral inclusions, mucus plugging in airways, eosinophils, or myocarditis.,SARS-CoV-2 testing can be performed at autopsy.,Autopsy findings such as diffuse alveolar damage and airway inflammation reflect true virus-related pathology; other findings represent superimposed or unrelated processes.

The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide.,However, little is known about the causes of death and the virus's pathologic features.,To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests.,Prospective cohort study.,Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19.,The first 12 consecutive COVID-19-positive deaths.,Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed.,Clinical data and medical course were evaluated.,Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2).,Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively).,Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients.,Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients.,In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart.,Limited sample size.,The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy.,Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it.,University Medical Center Hamburg-Eppendorf.,Little is known of the pathologic changes that lead to death in patients with COVID-19.,This study reports the autopsy findings of consecutive patients who died with a diagnosis of COVID-19.

Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.

Supplemental Digital Content is available in the text.,Coronavirus disease 2019 (COVID-19) evolved quickly into a global pandemic with myriad systemic complications, including stroke.,We report the largest case series to date of cerebrovascular complications of COVID-19 and compare with stroke patients without infection.,Retrospective case series of COVID-19 patients with imaging-confirmed stroke, treated at 11 hospitals in New York, between March 14 and April 26, 2020.,Demographic, clinical, laboratory, imaging, and outcome data were collected, and cases were compared with date-matched controls without COVID-19 from 1 year prior.,Eighty-six COVID-19-positive stroke cases were identified (mean age, 67.4 years; 44.2% women).,Ischemic stroke (83.7%) and nonfocal neurological presentations (67.4%) predominated, commonly involving multivascular distributions (45.8%) with associated hemorrhage (20.8%).,Compared with controls (n=499), COVID-19 was associated with in-hospital stroke onset (47.7% versus 5.0%; P<0.001), mortality (29.1% versus 9.0%; P<0.001), and Black/multiracial race (58.1% versus 36.9%; P=0.001).,COVID-19 was the strongest independent risk factor for in-hospital stroke (odds ratio, 20.9 [95% CI, 10.4-42.2]; P<0.001), whereas COVID-19, older age, and intracranial hemorrhage independently predicted mortality.,COVID-19 is an independent risk factor for stroke in hospitalized patients and mortality, and stroke presentations are frequently atypical.

Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.

Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications.,To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19.,Single‐center cohort study of 198 hospitalized patients with COVID‐19.,Seventy‐five patients (38%) were admitted to the intensive care unit (ICU).,At time of data collection, 16 (8%) were still hospitalized and 19% had died.,During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis.,The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively.,For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36).,VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5).,The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days).,The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE.,Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

Coronavirus disease 2019 (COVID-19) is an infectious disease that primarily affects the respiratory system, but it may cause cardiovascular complications such as thromboembolism.,Rarely, pulmonary embolism may be encountered in patients with severe COVID-19 infection, especially in intensive care units.,An asymptomatic young case of COVID-19 presenting with sudden death due to acute massive pulmonary embolism has not been previously described.,We report a 41-year-old woman presented to emergency department with sudden death during physical activity.,She had only history of diabetes mellitus and she was asymptomatic until sudden death.,CT pulmonary angiography and chest CT scans revealed acute massive embolism and typical imaging findings of COVID-19 pneumonia, respectively.,Interestingly, the patient had no symptoms or signs of infection and also had no risk factors for thromboembolism.,COVID-19 infection appears to induce venous thromboembolism, especially pulmonary embolism.,The case is remarkable in terms of showing how insidious and life-threatening COVID-19 infection can be.

In patients with aortic stenosis (AS), risk stratification for aortic valve replacement (AVR) relies mainly on valve-related factors, symptoms and co-morbidities.,We sought to evaluate the prognostic impact of a newly-defined staging classification characterizing the extent of extravalvular (extra-aortic valve) cardiac damage among patients with severe AS undergoing AVR.,Patients with severe AS from the PARTNER 2 trials were pooled and classified according to the presence or absence of cardiac damage as detected by echocardiography prior to AVR: no extravalvular cardiac damage (Stage 0), left ventricular damage (Stage 1), left atrial or mitral valve damage (Stage 2), pulmonary vasculature or tricuspid valve damage (Stage 3), or right ventricular damage (Stage 4).,One-year outcomes were compared using Kaplan-Meier techniques and multivariable Cox proportional hazards models were used to identify 1-year predictors of mortality.,In 1661 patients with sufficient echocardiographic data to allow staging, 47 (2.8%) patients were classified as Stage 0, 212 (12.8%) as Stage 1, 844 (50.8%) as Stage 2, 413 (24.9%) as Stage 3, and 145 (8.7%) as Stage 4.,One-year mortality was 4.4% in Stage 0, 9.2% in Stage 1, 14.4% in Stage 2, 21.3% in Stage 3, and 24.5% in Stage 4 (Ptrend < 0.0001).,The extent of cardiac damage was independently associated with increased mortality after AVR (HR 1.46 per each increment in stage, 95% confidence interval 1.27-1.67, P < 0.0001).,This newly described staging classification objectively characterizes the extent of cardiac damage associated with AS and has important prognostic implications for clinical outcomes after AVR.

Cardiac magnetic resonance (CMR) was used to investigate the extracellular compartment and myocardial fibrosis in patients with aortic stenosis, as well as their association with other measures of left ventricular decompensation and mortality.,Progressive myocardial fibrosis drives the transition from hypertrophy to heart failure in aortic stenosis.,Diffuse fibrosis is associated with extracellular volume expansion that is detectable by T1 mapping, whereas late gadolinium enhancement (LGE) detects replacement fibrosis.,In a prospective observational cohort study, 203 subjects (166 with aortic stenosis [69 years; 69% male]; 37 healthy volunteers [68 years; 65% male]) underwent comprehensive phenotypic characterization with clinical imaging and biomarker evaluation.,On CMR, we quantified the total extracellular volume of the myocardium indexed to body surface area (iECV).,The iECV upper limit of normal from the control group (22.5 ml/m2) was used to define extracellular compartment expansion.,Areas of replacement mid-wall LGE were also identified.,All-cause mortality was determined during 2.9 ± 0.8 years of follow up.,iECV demonstrated a good correlation with diffuse histological fibrosis on myocardial biopsies (r = 0.87; p < 0.001; n = 11) and was increased in patients with aortic stenosis (23.6 ± 7.2 ml/m2 vs.,16.1 ± 3.2 ml/m2 in control subjects; p < 0.001). iECV was used together with LGE to categorize patients with normal myocardium (iECV <22.5 ml/m2; 51% of patients), extracellular expansion (iECV ≥22.5 ml/m2; 22%), and replacement fibrosis (presence of mid-wall LGE, 27%).,There was evidence of increasing hypertrophy, myocardial injury, diastolic dysfunction, and longitudinal systolic dysfunction consistent with progressive left ventricular decompensation (all p < 0.05) across these groups.,Moreover, this categorization was of prognostic value with stepwise increases in unadjusted all-cause mortality (8 deaths/1,000 patient-years vs. 36 deaths/1,000 patient-years vs. 71 deaths/1,000 patient-years, respectively; p = 0.009).,CMR detects ventricular decompensation in aortic stenosis through the identification of myocardial extracellular expansion and replacement fibrosis.,This holds major promise in tracking myocardial health in valve disease and for optimizing the timing of valve replacement.,(The Role of Myocardial Fibrosis in Patients With Aortic Stenosis; NCT01755936)

There has been a huge impact of the COVID-19 pandemic on global healthcare systems.,Advisories across the world have appealed to people to stay at home and observe social distancing to slow down the pandemic.,However it is important to realize as to how this is affecting acute cardiovascular care.,Recent studies from Europe and USA have reported > 50% reduction in hospital admissions for ACS and declining rates of coronary interventions.,The possible reasons for this noticeable reduction in patients with ACS/STEMI during the COVID-19 pandemic are multi-factorial.,On one hand, it is due to change in thresholds for referring patients of ACS/STEMI for cardiac catheterization, with fibrinolysis being acceptable for many stable STEMI patients and conservative management being preferred for NSTEMI patients.,Theories abound on how “staying at home” strategy may have led to an reduction in acute coronary events due to healthier lifestyle, better compliance and reduced stress.,Realistically however, a more disquieting reason would be a “pseudo-reduction” ie. the incidence of ACS/STEMI is actually the same, but these patients are staying away from hospitals due to fear of contracting the infection.,Lockdown restrictions have also limited transport options for patients seeking to reach hospitals in time.,Healthcare systems need to be prepared for an anticipated downstream deluge of such untreated patients who may present with sequelae like heart failure, reinfarction, arrhythmias, mechanical complications etc.,Scientific societies should have proactive campaigns to alleviate patient concerns, and encourage them to seek timely medical attention despite the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients.,First, those with COVID-19 and pre-existing cardiovascular disease have an increased risk of severe disease and death.,Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism.,Third, therapies under investigation for COVID-19 may have cardiovascular side effects.,Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions.,Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become hosts or vectors of virus transmission.,We hereby review the peer-reviewed and pre-print reports pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.,•Patients with pre-existing CVD appear to have worse outcomes with COVID-19.,•CV complications include biomarker elevations, myocarditis, heart failure, and venous thromboembolism, which may be exacerbated by delays in care.,•Therapies under investigation for COVID-19 may have significant drug-drug interactions with CV medications.,•Health care workers and health systems should take measures to ensure safety while providing high-quality care for COVID-19 patients.,Patients with pre-existing CVD appear to have worse outcomes with COVID-19.,CV complications include biomarker elevations, myocarditis, heart failure, and venous thromboembolism, which may be exacerbated by delays in care.,Therapies under investigation for COVID-19 may have significant drug-drug interactions with CV medications.,Health care workers and health systems should take measures to ensure safety while providing high-quality care for COVID-19 patients.

Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome.,We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States.,The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month.,Clinicians abstracted the data onto standardized forms.,We report on 186 patients with MIS-C in 26 states.,The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020.,Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%).,The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died.,Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki’s disease-like features were documented in 74 (40%).,Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation.,The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%).,Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents.,(Funded by the Centers for Disease Control and Prevention.)

Current data suggest that COVID-19 is less frequent in children, with a milder course.,However, over the past weeks, an increase in the number of children presenting to hospitals in the greater Paris region with a phenotype resembling Kawasaki disease (KD) has led to an alert by the French national health authorities.,Multicentre compilation of patients with KD in Paris region since April 2020, associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (‘Kawa-COVID-19’).,A historical cohort of ‘classical’ KD served as a comparator.,Sixteen patients were included (sex ratio=1, median age 10 years IQR (4·7 to 12.5)).,SARS-CoV-2 was detected in 12 cases (69%), while a further three cases had documented recent contact with a quantitative PCR-positive individual (19%).,Cardiac involvement included myocarditis in 44% (n=7).,Factors prognostic for the development of severe disease (ie, requiring intensive care, n=7) were age over 5 years and ferritinaemia >1400 µg/L.,Only five patients (31%) were successfully treated with a single intravenous immunoglobulin (IVIg) infusion, while 10 patients (62%) required a second line of treatment.,The Kawa-COVID-19 cohort differed from a comparator group of ‘classical’ KD by older age at onset 10 vs 2 years (p<0.0001), lower platelet count (188 vs 383 G/L (p<0.0001)), a higher rate of myocarditis 7/16 vs 3/220 (p=0.0001) and resistance to first IVIg treatment 10/16 vs 45/220 (p=0.004).,Kawa-COVID-19 likely represents a new systemic inflammatory syndrome temporally associated with SARS-CoV-2 infection in children.,Further prospective international studies are necessary to confirm these findings and better understand the pathophysiology of Kawa-COVID-19.,Trial registration number,NCT02377245

The focus on wild‐type transthyretin amyloid cardiomyopathy (ATTRwt‐CM) is increasing because of novel treatment options.,There is currently no report on a large number of Japanese patients with ATTRwt‐CM.,The study aimed to examine the characteristics and prognosis of ATTRwt‐CM in Japan.,Consecutive patients (78.5 ± 6.4 years old at diagnosis) with ATTRwt‐CM diagnosed at Kumamoto University Hospital between December 2002 and December 2019 were retrospectively reviewed.,Data, including demographic characteristics, co‐morbidities, clinical manifestations at diagnosis, laboratory results, electrocardiographic and echocardiographic data, imaging and pathological findings, and treatment were obtained.,Of 129 patients included in this study, 110 patients (85%) were male.,The median period from initial symptom onset to diagnosis was 15.5 (2-75) months.,Heart failure was the most common clinical manifestation leading to diagnosis (61%) and initial manifestations (49%).,Of 106 patients, carpal tunnel syndrome was observed in 57 patients (54%), and the median period from initial symptom onset to diagnosis was 96 (48-120) months.,Histopathological confirmation of transthyretin amyloid was achieved in 94 patients (73%), including 66 (51%) and 28 cases (22%) with endomyocardial and extracardiac biopsies.,During the observation period (median 15.0 [inter‐quartile range, 5.4-33.2] months after diagnosis), 34 patients (26%) died.,Of these, 27 patients (79%) had cardiovascular deaths (heart failure, 25; sudden death, two).,The median survival duration was 58.9 months and the 5 years' survival rate was 48%.,According to a multivariate Cox hazard analysis, age [hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.05-1.23, P = 0.002] and low serum sodium levels (HR, 0.89; 95% CI, 0.79-0.996; P = 0.04) contributed to all‐cause mortality, and low serum sodium levels contributed to hospitalization for heart failure (HR, 0.86; 95% CI, 0.77-0.96; P = 0.005).,Clinical characteristics and prognosis of ATTRwt‐CM patients in Japan were examined.,Carpal tunnel syndrome can be considered an indication for diagnosis of ATTRwt‐CM.,Age and low serum sodium level were significant predictive factors of all survival outcomes.,The clinical features of ATTRwt‐CM should be recognized to provide appropriate treatment.

Congo red staining of an endomyocardial biopsy is the diagnostic gold-standard in suspected cardiac amyloidosis (CA), but the procedure is associated with the risk, albeit small, of serious complications, and delay in diagnosis due to the requirement for technical expertise.,In contrast, abdominal fat pad fine needle aspiration (FPFNA) is a simple, safe and well-established procedure in systemic amyloidosis, but its diagnostic sensitivity in patients with suspected CA remains unclear.,We assessed the diagnostic sensitivity of FPFNA in 600 consecutive patients diagnosed with CA [216 AL amyloidosis, 113 hereditary transthyretin (ATTRm), and 271 wild-type transthyretin (ATTRwt) amyloidosis] at our Centre.,Amyloid was detected on Congo red staining of FPFNAs in 181/216 (84%) patients with cardiac AL amyloidosis, including 100, 97, and 78% of those with a large, moderate, and small whole-body amyloid burden, respectively, as assessed by serum amyloid P (SAP) component scintigraphy (P < 0.001); the deposits were successfully typed as AL by immunohistochemistry in 102/216 (47%) cases.,Amyloid was detected in FPFNAs of 51/113 (45%) patients with ATTRm CA, and only 42/271 (15%) cases with ATTRwt CA.,FPFNA has reasonable diagnostic sensitivity in cardiac AL amyloidosis, particularly in patients with a large whole-body amyloid burden.,Although the diagnostic sensitivity of FPFNA is substantially lower in transthyretin CA, particularly ATTRwt, it may nevertheless sometimes obviate the need for endomyocardial biopsy.

At our institution, 2 of the initial 7 pregnant patients with confirmed coronavirus disease 2019 severe infection (28.6%; 95% CI, 8.2%-64.1%) developed cardiac dysfunction with moderately reduced left ventricular ejection fractions of 40%-45% and hypokinesis.,Viral myocarditis and cardiomyopathy have also been reported in nonpregnant coronavirus disease 2019 patients.,A case series of nonpregnant patients with coronavirus disease 2019 found that 33% of those in intensive care developed cardiomyopathy.,More data are needed to ascertain the incidence of cardiomyopathy from coronavirus disease 2019 in pregnancy, in all pregnant women with coronavirus disease 2019, and those with severe disease (eg, pneumonia).,We suggest an echocardiogram in pregnant women with coronavirus disease 2019 pneumonia, in particular those necessitating oxygen, or those who are critically ill, and we recommend the use of handheld, point-of-care devices where possible to minimize contamination of staff and traditional large echocardiogram machines.

Studies have reminded that cardiovascular metabolic comorbidities made patients more susceptible to suffer 2019 novel corona virus (2019-nCoV) disease (COVID-19), and exacerbated the infection.,The aim of this analysis is to determine the association of cardiovascular metabolic diseases with the development of COVID-19.,A meta-analysis of eligible studies that summarized the prevalence of cardiovascular metabolic diseases in COVID-19 and compared the incidences of the comorbidities in ICU/severe and non-ICU/severe patients was performed.,Embase and PubMed were searched for relevant studies.,A total of six studies with 1527 patients were included in this analysis.,The proportions of hypertension, cardia-cerebrovascular disease and diabetes in patients with COVID-19 were 17.1%, 16.4% and 9.7%, respectively.,The incidences of hypertension, cardia-cerebrovascular diseases and diabetes were about twofolds, threefolds and twofolds, respectively, higher in ICU/severe cases than in their non-ICU/severe counterparts.,At least 8.0% patients with COVID-19 suffered the acute cardiac injury.,The incidence of acute cardiac injury was about 13 folds higher in ICU/severe patients compared with the non-ICU/severe patients.,Patients with previous cardiovascular metabolic diseases may face a greater risk of developing into the severe condition and the comorbidities can also greatly affect the prognosis of the COVID-19.,On the other hand, COVID-19 can, in turn, aggravate the damage to the heart.

The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing global pandemic has presented a health emergency of unprecedented magnitude.,Recent clinical data has highlighted that coronavirus disease 2019 (COVID-19) is associated with a significant risk of thrombotic complications ranging from microvascular thrombosis, venous thromboembolic disease, and stroke.,Importantly, thrombotic complications are markers of severe COVID-19 and are associated with multiorgan failure and increased mortality.,The evidence to date supports the concept that the thrombotic manifestations of severe COVID-19 are due to the ability of SARS-CoV-2 to invade endothelial cells via ACE-2 (angiotensin-converting enzyme 2), which is expressed on the endothelial cell surface.,However, in patients with COVID-19 the subsequent endothelial inflammation, complement activation, thrombin generation, platelet, and leukocyte recruitment, and the initiation of innate and adaptive immune responses culminate in immunothrombosis, ultimately causing (micro)thrombotic complications, such as deep vein thrombosis, pulmonary embolism, and stroke.,Accordingly, the activation of coagulation (eg, as measured with plasma D-dimer) and thrombocytopenia have emerged as prognostic markers in COVID-19.,Given thrombotic complications are central determinants of the high mortality rate in COVID-19, strategies to prevent thrombosis are of critical importance.,Several antithrombotic drugs have been proposed as potential therapies to prevent COVID-19-associated thrombosis, including heparin, FXII inhibitors, fibrinolytic drugs, nafamostat, and dipyridamole, many of which also possess pleiotropic anti-inflammatory or antiviral effects.,The growing awareness and mechanistic understanding of the prothrombotic state of COVID-19 patients are driving efforts to more stringent diagnostic screening for thrombotic complications and to the early institution of antithrombotic drugs, for both the prevention and therapy of thrombotic complications.,The shifting paradigm of diagnostic and treatment strategies holds significant promise to reduce the burden of thrombotic complications and ultimately improve the prognosis for patients with COVID-19.

Coronavirus disease 2019 (COVID-19) represents a public health crisis of pandemic proportions.,Caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the symptoms most commonly reported include cough, fever and shortness of breath, but extra-pulmonary symptoms may also be present, such as neurological and gastroenterological manifestations.,Endothelial cell dysfunction and impaired microcirculatory function contribute markedly to life-threatening complications of COVID-19, such as venous thromboembolic disease and multiple organ involvementhttps://bit.ly/3cZMjKV

NMDA (N-methyl-d-aspartate) receptors (NMDARs) play a central role in excitotoxic neuronal death caused by ischemic stroke, but NMDAR channel blockers have failed to be translated into clinical stroke treatments.,However, recent research on NMDAR-associated signaling complexes has identified important death-signaling pathways linked to NMDARs.,This led to the generation of inhibitors that inhibit these pathways downstream from the receptor without necessarily blocking NMDARs.,This therapeutic approach may have fewer side effects and/or provide a wider therapeutic window for stroke as compared to the receptor antagonists.,In this review, we highlight the key findings in the signaling cascades downstream of NMDARs and the novel promising therapeutics for ischemic stroke.

Aberrant NMDA receptor (NMDAR) activity contributes to several neurological disorders, but direct antagonism is poorly tolerated therapeutically.,The GluN2B cytoplasmic C-terminal domain (CTD) represents an alternative therapeutic target since it potentiates excitotoxic signaling.,The key GluN2B CTD-centred event in excitotoxicity is proposed to involve its phosphorylation at Ser-1303 by Dapk1, that is blocked by a neuroprotective cell-permeable peptide mimetic of the region.,Contrary to this model, we find that excitotoxicity can proceed without increased Ser-1303 phosphorylation, and is unaffected by Dapk1 deficiency in vitro or following ischemia in vivo.,Pharmacological analysis of the aforementioned neuroprotective peptide revealed that it acts in a sequence-independent manner as an open-channel NMDAR antagonist at or near the Mg2+ site, due to its high net positive charge.,Thus, GluN2B-driven excitotoxic signaling can proceed independently of Dapk1 or altered Ser-1303 phosphorylation.,DOI:http://dx.doi.org/10.7554/eLife.17161.001

There is emerging evidence for enhanced blood coagulation in coronavirus 2019 (COVID-19) patients, with thromboembolic complications contributing to morbidity and mortality.,The mechanisms underlying this prothrombotic state remain enigmatic.,Further data to guide anticoagulation strategies are urgently required.,We used viscoelastic rotational thromboelastometry (ROTEM) in a single-center cohort of 40 critically ill COVID-19 patients.,Clear signs of a hypercoagulable state due to severe hypofibrinolysis were found.,Maximum lysis, especially following stimulation of the extrinsic coagulation system, was inversely associated with an enhanced risk of thromboembolic complications.,Combining values for maximum lysis with D-dimer concentrations revealed high sensitivity and specificity of thromboembolic risk prediction.,The study identifies a reduction in fibrinolysis as an important mechanism in COVID-19-associated coagulopathy.,The combination of ROTEM and D-dimer concentrations may prove valuable in identifying patients requiring higher intensity anticoagulation.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus.,Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity.,However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown.,We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10-31 March 2020.,The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission.,Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint.,ORs are reported for a 1 SD increase after standardisation.,The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th-75th percentile: 25.0-32.7) kg/m2; with a predominance of type 2 diabetes (88.5%).,Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively.,The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7.,In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA1c, diabetic complications or glucose-lowering therapies.,In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]).,On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome.,Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7.,In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days.,clinicaltrials.gov NCT04324736.,The online version of this article (10.1007/s00125-020-05180-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Current understanding of the impact of coronavirus disease-2019 (COVID-19) on arrhythmias continues to evolve as new data emerge.,Cardiac arrhythmias are more common in critically ill COVID-19 patients.,The potential mechanisms that could result in arrhythmogenesis among COVID-19 patients include hypoxia caused by direct viral tissue involvement of lungs, myocarditis, abnormal host immune response, myocardial ischemia, myocardial strain, electrolyte derangements, intravascular volume imbalances, and drug sides effects.,To manage these arrhythmias, it is imperative to increase the awareness of potential drug-drug interactions, to monitor QTc prolongation while receiving COVID therapy and provide special considerations for patients with inherited arrhythmia syndromes.,It is also crucial to minimize exposure to COVID-19 infection by stratifying the need for intervention and using telemedicine.,As COVID-19 infection continues to prevail with a potential for future surges, more data are required to better understand pathophysiology and to validate management strategies.,•Cardiac arrhythmias are more common in critically ill COVID-19 patients.,•Arrhythmias occur not only as a result of direct viral effect, but also due to systemic illness and drug interactions.,•Management strategies to minimize the impact on arrhythmias and exposure to COVID-19 infection are imperative.,•More data are required to better understand the pathophysiology and to validate management strategies.,Cardiac arrhythmias are more common in critically ill COVID-19 patients.,Arrhythmias occur not only as a result of direct viral effect, but also due to systemic illness and drug interactions.,Management strategies to minimize the impact on arrhythmias and exposure to COVID-19 infection are imperative.,More data are required to better understand the pathophysiology and to validate management strategies.

This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury.

Complement activation has been implicated in the pathogenesis of severe SARS-CoV-2 infection.,However, it remains to be determined whether increased complement activation is a broad indicator of critical illness (and thus, no different in COVID-19).,It is also unclear which pathways are contributing to complement activation in COVID-19, and if complement activation is associated with certain features of severe SARS-CoV-2 infection, such as endothelial injury and hypercoagulability.,To address these questions, we investigated complement activation in the plasma from patients with COVID-19 prospectively enrolled at two tertiary care centers: Washington University School of Medicine (n=134) and Yale School of Medicine (n=49).,We compared our patients to two non-COVID cohorts: (a) patients hospitalized with influenza (n=54), and (b) patients admitted to the intensive care unit (ICU) with acute respiratory failure requiring invasive mechanical ventilation (IMV, n=22).,We demonstrate that circulating markers of complement activation are elevated in patients with COVID-19 compared to those with influenza and to patients with non-COVID-19 respiratory failure.,Further, the results facilitate distinguishing those who are at higher risk of worse outcomes such as requiring ICU admission, or IMV.,Moreover, the results indicate enhanced activation of the alternative complement pathway is most prevalent in patients with severe COVID-19 and is associated with markers of endothelial injury (i.e., angiopoietin-2) as well as hypercoagulability (i.e., thrombomodulin and von Willebrand factor).,Our findings identify complement activation to be a distinctive feature of COVID-19, and provide specific targets that may be utilized for risk prognostication, drug discovery and personalized clinical trials.,Increased complement activation is observed in COVID-19 compared to non-COVID respiratory illness, and is a key marker of organ failure.

The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing global pandemic has presented a health emergency of unprecedented magnitude.,Recent clinical data has highlighted that coronavirus disease 2019 (COVID-19) is associated with a significant risk of thrombotic complications ranging from microvascular thrombosis, venous thromboembolic disease, and stroke.,Importantly, thrombotic complications are markers of severe COVID-19 and are associated with multiorgan failure and increased mortality.,The evidence to date supports the concept that the thrombotic manifestations of severe COVID-19 are due to the ability of SARS-CoV-2 to invade endothelial cells via ACE-2 (angiotensin-converting enzyme 2), which is expressed on the endothelial cell surface.,However, in patients with COVID-19 the subsequent endothelial inflammation, complement activation, thrombin generation, platelet, and leukocyte recruitment, and the initiation of innate and adaptive immune responses culminate in immunothrombosis, ultimately causing (micro)thrombotic complications, such as deep vein thrombosis, pulmonary embolism, and stroke.,Accordingly, the activation of coagulation (eg, as measured with plasma D-dimer) and thrombocytopenia have emerged as prognostic markers in COVID-19.,Given thrombotic complications are central determinants of the high mortality rate in COVID-19, strategies to prevent thrombosis are of critical importance.,Several antithrombotic drugs have been proposed as potential therapies to prevent COVID-19-associated thrombosis, including heparin, FXII inhibitors, fibrinolytic drugs, nafamostat, and dipyridamole, many of which also possess pleiotropic anti-inflammatory or antiviral effects.,The growing awareness and mechanistic understanding of the prothrombotic state of COVID-19 patients are driving efforts to more stringent diagnostic screening for thrombotic complications and to the early institution of antithrombotic drugs, for both the prevention and therapy of thrombotic complications.,The shifting paradigm of diagnostic and treatment strategies holds significant promise to reduce the burden of thrombotic complications and ultimately improve the prognosis for patients with COVID-19.

The novel coronavirus 2019 (COVID-19) is clinically characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for a high number of patients needing mechanical ventilation or intensive care units treatment and for the elevated mortality risk.,A link between COVID-19 and multiorgan failure may be dependent on the fact that most COVID-19 patients are complicated by pneumonia, which is known to be associated with early changes of clotting and platelet activation and artery dysfunction; these changes may implicate in thrombotic-related events such as myocardial infarction and ischemic stroke.,Recent data showed that myocardial injury compatible with coronary ischemia may be detectable in SARS-CoV-2 patients and laboratory data exploring clotting system suggest the presence of a hypercoagulation state.,Thus, we performed a systematic review of COVID-19 literature reporting measures of clotting activation to assess if changes are detectable in this setting and their relationship with clinical severity.,Furthermore, we discussed the biologic plausibility of the thrombotic risk in SARS-CoV-2 and the potential use of an antithrombotic treatment.

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality.,To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes.,Prospective autopsy study.,Single pathology department.,11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy).,Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values.,Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women).,Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients.,Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts.,Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients.,Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients.,Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis.,Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes.,Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile.,The sample was small.,COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency.,Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation.,Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory, and imaging studies and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism.,None.,The clinicopathological basis for morbidity and mortality with SARS-CoV-2 infection is not well understood.,This study reports the clinical and autopsy findings of patients who died of COVID-19.

We report on the presentation and course of 33 children with multisystem inflammatory syndrome in children and confirmed severe acute respiratory syndrome coronavirus 2 infection.,Hemodynamic instability and cardiac dysfunction were prominent findings, with most patients exhibiting rapid resolution following anti-inflammatory therapy.

As an acute febrile and inflammatory disease, Kawasaki disease (KD) could develop Kawasaki disease shock syndrome (KDSS) sometimes.,However its pathogenesis was still not well known.,This study was to learn more about the clinical features and evaluate the role of cytokines in the pathogenesis of KDSS.,We collected clinical and laboratory data retrospectively for all patients with KDSS(KDSS, n = 27)who were hospitalized at our hospital from Jan 2014 to Oct 2017.,For patient with KDSS, we randomly identified 43 patients with KD as control subjects (KD, n = 43).,Clinical features, laboratory evaluations were collected.,Cytokines IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in serum were assayed using flow cytometric bead array.,The patients with KDSS were older age (43.41 ± 31.42 vs 28.81 ± 21.51 months, P < 0.05), longer duration of fever (10.63 ± 5.12 vs 6.98 ± 2.45 days, P < 0.05), higher WBC count, neutrophils, CRP, ESR, PCT and D-dimer, and lower hemoglobin and albumin, more severe hyponatremia and hypokalemia, more refractory to IVIG therapy, more coronary artery abnormalities (CAAs), aseptic meningitis, and longer duration of hospitalization than patients with KD (all P < 0.05).,The levels of serum IL-6 [184.1 (27.7-2577.3) vs 54.1 (4-425) pg/ml], IL-10 [42.6 (5-236.7) vs 9.4 (3-94) pg/ml], TNF-α [2.6 (1.0-23.4) vs 2.1 (1-6) pg/ml] and IFN-γ [18.3 (4.5-94.4) vs 6.7 (2-56) pg/ml] in KDSS patients were significant higher than KD patients (all P < 0.05).,ROC curves showed that 66.7 pg/ml of IL-6, 20.85 pg/ml of IL-10 and 8.35 pg/ml of IFN-γ had sensitivity and specificity for identifying KDSS as 85.2 and 62.8%; 66.7 and 83.7%; 74.1 and 74.4% respectively.,No fatality was recorded in this series.,KDSS were characteristic as more cytokine production and prone to developing IVIG non-responsiveness and CAAs.,KD patients with IL-6 above 66.7 pg/ml, IL-10 above 20.85 pg/ml, and IFN-γ above 8.35 pg/ml suggested higher risk for KDSS.

Supplemental Digital Content is available in the text.,Severe acute respiratory syndrome corona virus 2 infection causes severe pneumonia (coronavirus disease 2019 [COVID-19]), but the mechanisms of subsequent respiratory failure and complicating renal and myocardial involvement are poorly understood.,In addition, a systemic prothrombotic phenotype has been reported in patients with COVID-19.,A total of 62 subjects were included in our study (n=38 patients with reverse transcriptase polymerase chain reaction-confirmed COVID-19 and n=24 non-COVID-19 controls).,We performed histopathologic assessment of autopsy cases, surface marker-based phenotyping of neutrophils and platelets, and functional assays for platelet, neutrophil functions, and coagulation tests, as well.,We provide evidence that organ involvement and prothrombotic features in COVID-19 are linked by immunothrombosis.,We show that, in COVID-19, inflammatory microvascular thrombi are present in the lung, kidney, and heart, containing neutrophil extracellular traps associated with platelets and fibrin.,Patients with COVID-19 also present with neutrophil-platelet aggregates and a distinct neutrophil and platelet activation pattern in blood, which changes with disease severity.,Whereas cases of intermediate severity show an exhausted platelet and hyporeactive neutrophil phenotype, patients severely affected with COVID-19 are characterized by excessive platelet and neutrophil activation in comparison with healthy controls and non-COVID-19 pneumonia.,Dysregulated immunothrombosis in severe acute respiratory syndrome corona virus 2 pneumonia is linked to both acute respiratory distress syndrome and systemic hypercoagulability.,Taken together, our data point to immunothrombotic dysregulation as a key marker of disease severity in COVID-19.,Further work is necessary to determine the role of immunothrombosis in COVID-19.

Studies have reminded that cardiovascular metabolic comorbidities made patients more susceptible to suffer 2019 novel corona virus (2019-nCoV) disease (COVID-19), and exacerbated the infection.,The aim of this analysis is to determine the association of cardiovascular metabolic diseases with the development of COVID-19.,A meta-analysis of eligible studies that summarized the prevalence of cardiovascular metabolic diseases in COVID-19 and compared the incidences of the comorbidities in ICU/severe and non-ICU/severe patients was performed.,Embase and PubMed were searched for relevant studies.,A total of six studies with 1527 patients were included in this analysis.,The proportions of hypertension, cardia-cerebrovascular disease and diabetes in patients with COVID-19 were 17.1%, 16.4% and 9.7%, respectively.,The incidences of hypertension, cardia-cerebrovascular diseases and diabetes were about twofolds, threefolds and twofolds, respectively, higher in ICU/severe cases than in their non-ICU/severe counterparts.,At least 8.0% patients with COVID-19 suffered the acute cardiac injury.,The incidence of acute cardiac injury was about 13 folds higher in ICU/severe patients compared with the non-ICU/severe patients.,Patients with previous cardiovascular metabolic diseases may face a greater risk of developing into the severe condition and the comorbidities can also greatly affect the prognosis of the COVID-19.,On the other hand, COVID-19 can, in turn, aggravate the damage to the heart.

Infection by the 2019 novel coronavirus (COVID-19) has been reportedly associated with a high risk of thrombotic complications.,So far information is scarce and rapidly emerging.,We conducted a scoping review using a single engine search for studies assessing thrombosis and coagulopathy in COVID-19 patients.,Additional studies were identified by secondary review and alert services.,Studies reported the occurrence of venous thromboembolism and stroke in approximately 20% and 3% of patients, respectively.,A higher frequency seems to be present in severely ill patients, in particular those admitted to intensive care units.,The thrombotic risk is elevated despite the use of anticoagulant prophylaxis but optimal doses of anticoagulation are not yet defined.,Although an increase of biomarkers such as D-dimer has been consistently reported in severely ill COVID-19, the optimal cut-off level and prognostic value are not known.,A number of pressing issues were identified by this review, including defining the true incidence of VTE in COVID patients, developing algorithms to identify those susceptible to develop thrombotic complications and severe disease, determining the role of biomarkers and/or scoring systems to stratify patients' risk, designing adequate and feasible diagnostic protocols for PE, establishing the optimal thromboprophylaxis strategy, and developing uniform diagnostic and reporting criteria.,•Thrombotic events, venous and arterial are frequent in COVID-19, more so in critically ill patients.,•Valid biomarkers to define risk and prognosis are still lacking.,•Anticoagulant prophylaxis is needed in all patients.,•The role of higher doses of anticoagulants in all patients is unclear.,•There is a need to develop standard clinical definitions, common data elements, and standard reporting criteria.,Thrombotic events, venous and arterial are frequent in COVID-19, more so in critically ill patients.,Valid biomarkers to define risk and prognosis are still lacking.,Anticoagulant prophylaxis is needed in all patients.,The role of higher doses of anticoagulants in all patients is unclear.,There is a need to develop standard clinical definitions, common data elements, and standard reporting criteria.

The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide.,However, little is known about the causes of death and the virus's pathologic features.,To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests.,Prospective cohort study.,Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19.,The first 12 consecutive COVID-19-positive deaths.,Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed.,Clinical data and medical course were evaluated.,Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2).,Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively).,Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients.,Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients.,In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart.,Limited sample size.,The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy.,Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it.,University Medical Center Hamburg-Eppendorf.,Little is known of the pathologic changes that lead to death in patients with COVID-19.,This study reports the autopsy findings of consecutive patients who died with a diagnosis of COVID-19.

Stroke, especially ischemic stroke (IS), has been a severe public health problem around the world.,However, the association between air pollution and ischemic stroke remains ambiguous.,A total of 63, 997 IS cases aged 18 years or above in Shenzhen were collected from 2008 to 2014.,We used the time-stratified case-crossover design combining with distributed lag nonlinear model (DLNM) to estimate the association between air pollution and IS onset.,Furthermore, this study explored the variability across gender and age groups.,The cumulative exposure-response curves were J-shaped for SO2, NO2 and PM10, and V-shaped for O3, and crossed over the relative risk (RR) of one.,The 99th, 50th (median) and 1st percentiles of concentration (μg/m3) respectively were 37.86, 10.06, 3.71 for SO2, 116.26, 41.29, 18.51 for NO2, 145.94, 48.29, 16.14 for PM10, and 111.57, 49.82, 16.00 for O3.,Extreme high-SO2, high-NO2, high-PM10, high-O3, and low-O3 concentration increased the risk of IS, with the maximum RR values and 95% CIs: 1.50(1.22, 1.84) (99th vs median) at 0-12 lag days, 1.37(1.13, 1.67) (99th vs median) at 0-10 lag days, 1.26(1.04, 1.53) (99th vs median) at 0-12 lag days, 1.25(1.04, 1.49) (99th vs median) at 0-14 lag days, and 1.29(1.03, 1.61) (1st vs median) at 0-14 lag days, respectively.,The statistically significant minimal RR value and 95% CI was 0.79(0.66,0.94) at 0-10 lag days for extreme low-PM10.,The elderly aged over 65 years were susceptible to extreme pollution conditions.,Difference from the vulnerability of males to extreme high-SO2, high-NO2 and low-O3, females were vulnerable to extreme high-PM10 and high-O3.,Comparing with the elderly, adults aged 18-64 year were immune to extreme low-NO2 and low-PM10.,However, no association between CO and IS onset was found.,SO2, NO2, PM10 and O3 exerted non-linear and delayed influence on IS, and such influence varied with gender and age.,These findings may have significant public health implications for the prevention of IS.

Evidence of the short-term effects of ambient air pollution on the risk of ischemic stroke in low- and middle-income countries is limited and inconsistent.,We aimed to examine the associations between air pollution and daily hospital admissions for ischemic stroke in China.,We identified hospital admissions for ischemic stroke in 2014-2016 from the national database covering up to 0.28 billion people who received Urban Employee Basic Medical Insurance (UEBMI) in China.,We examined the associations between air pollution and daily ischemic stroke admission using a two-stage method.,Poisson time-series regression models were firstly fitted to estimate the effects of air pollution in each city.,Random-effects meta-analyses were then conducted to combine the estimates.,Meta-regression models were applied to explore potential effect modifiers.,More than 2 million hospital admissions for ischemic stroke were identified in 172 cities in China.,In single-pollutant models, increases of 10 μg/m3 in particulate matter with aerodynamic diameter <2.5 μm (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) and 1 mg/m3 in carbon monoxide (CO) concentrations were associated with 0.34% (95% confidence interval [CI], 0.20%-0.48%), 1.37% (1.05%-1.70%), 1.82% (1.45%-2.19%), 0.01% (−0.14%-0.16%), and 3.24% (2.05%-4.43%) increases in hospital admissions for ischemic stroke on the same day, respectively.,SO2 and NO2 associations remained significant in two-pollutant models, but not PM2.5 and CO associations.,The effect estimates were greater in cities with lower air pollutant levels and higher air temperatures, as well as in elderly subgroups.,The main limitation of the present study was the unavailability of data on individual exposure to ambient air pollution.,As the first national study in China to systematically examine the associations between short-term exposure to ambient air pollution and ischemic stroke, our findings indicate that transient increase in air pollution levels may increase the risk of ischemic stroke, which may have significant public health implications for the reduction of ischemic stroke burden in China.,Yonghua Hu and colleagues, in a large-scale analysis of 172 cities in China, reveal associations between short-term air pollution exposure and increased incidences of stroke.

Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications.,To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19.,Single‐center cohort study of 198 hospitalized patients with COVID‐19.,Seventy‐five patients (38%) were admitted to the intensive care unit (ICU).,At time of data collection, 16 (8%) were still hospitalized and 19% had died.,During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis.,The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively.,For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36).,VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5).,The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days).,The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE.,Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

An important feature of severe acute respiratory syndrome coronavirus 2 pathogenesis is COVID-19-associated coagulopathy, characterised by increased thrombotic and microvascular complications.,Previous studies have suggested a role for endothelial cell injury in COVID-19-associated coagulopathy.,To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19.,In this single-centre cross-sectional study, hospitalised adult (≥18 years) patients with laboratory-confirmed COVID-19 were identified in the medical intensive care unit (ICU) or a specialised non-ICU COVID-19 floor in our hospital.,Asymptomatic, non-hospitalised controls were recruited as a comparator group for biomarkers that did not have a reference range.,We assessed markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes.,We compared the level of each marker in ICU patients, non-ICU patients, and controls, where applicable.,We assessed correlations between these laboratory results with clinical outcomes, including hospital discharge and mortality.,Kaplan-Meier analysis was used to further explore the association between biochemical markers and survival.,68 patients with COVID-19 were included in the study from April 13 to April 24, 2020, including 48 ICU and 20 non-ICU patients, as well as 13 non-hospitalised, asymptomatic controls.,Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen (mean 565% [SD 199] in ICU patients vs 278% [133] in non-ICU patients; p<0·0001) and soluble P-selectin (15·9 ng/mL [4·8] vs 11·2 ng/mL [3·1]; p=0·0014).,VWF antigen concentrations were also elevated above the normal range in 16 (80%) of 20 non-ICU patients.,We found mortality to be significantly correlated with VWF antigen (r = 0·38; p=0·0022) and soluble thrombomodulin (r = 0·38; p=0·0078) among all patients.,In all patients, soluble thrombomodulin concentrations greater than 3·26 ng/mL were associated with lower rates of hospital discharge (22 [88%] of 25 patients with low concentrations vs 13 [52%] of 25 patients with high concentrations; p=0·0050) and lower likelihood of survival on Kaplan-Meier analysis (hazard ratio 5·9, 95% CI 1·9-18·4; p=0·0087).,Our findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death.,Early identification of endotheliopathy and strategies to mitigate its progression might improve outcomes in COVID-19.,This work was supported by a gift donation from Jack Levin to the Benign Hematology programme at Yale, and the National Institutes of Health.

Kawasaki disease (KD) is an acute, self-limiting systemic vasculitis that predominately affects children.,Neurological involvement is a known complication of KD, however, its association with KD severity remains elusive.,We aimed to systematically describe the general manifestations of neurological involvement in KD, determine whether neurological involvement is a marker of disease severity in patients with KD, and assess the relationship of such involvement with intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs).,We retrospectively reviewed data from 1582 patients with KD between January 2013 and December 2017.,Profiles of patients with neurological symptoms (group A, n = 80) were compared to those of gender- and admission date-matched patients without neurological involvement (group B, n = 512).,Multivariate logistic regression analyses were performed to determine whether neurological involvement was significantly associated with IVIG resistance.,Neurological involvement was observed in 5.1% (80/1582) of patients with KD.,The neurological manifestations were diffuse, presenting as headache (13/80, 16.3%), convulsions (14/80, 17.5%), somnolence (40/80, 50.1%), extreme irritability (21/80, 26.3%), signs of meningeal irritation (15/80, 18.8%), bulging fontanelles (7/80, 8.8%), and facial palsy (1/80, 1.3%).,Neurological symptoms represented the initial and/or predominant manifestation in 47.5% (38/80) of patients with KD.,The incidence of IVIG resistance and levels of inflammatory markers were higher in group A than in group B.,However, neurological involvement was not an independent risk factor for IVIG resistance or CALs.,Rates of neurological involvement were relatively low in patients with KD.,Neurological involvement was associated with an increased risk of IVIG resistance and severe inflammatory burden.,Our results highlight the need for pediatricians to recognize KD with neurological involvement and the importance of standard IVIG therapy.,Retrospectively registered.

The Bergamo province, which is extensively affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic, is a natural observatory of virus manifestations in the general population.,In the past month we recorded an outbreak of Kawasaki disease; we aimed to evaluate incidence and features of patients with Kawasaki-like disease diagnosed during the SARS-CoV-2 epidemic.,All patients diagnosed with a Kawasaki-like disease at our centre in the past 5 years were divided according to symptomatic presentation before (group 1) or after (group 2) the beginning of the SARS-CoV-2 epidemic.,Kawasaki- like presentations were managed as Kawasaki disease according to the American Heart Association indications.,Kawasaki disease shock syndrome (KDSS) was defined by presence of circulatory dysfunction, and macrophage activation syndrome (MAS) by the Paediatric Rheumatology International Trials Organisation criteria.,Current or previous infection was sought by reverse-transcriptase quantitative PCR in nasopharyngeal and oropharyngeal swabs, and by serological qualitative test detecting SARS-CoV-2 IgM and IgG, respectively.,Group 1 comprised 19 patients (seven boys, 12 girls; aged 3·0 years [SD 2·5]) diagnosed between Jan 1, 2015, and Feb 17, 2020.,Group 2 included ten patients (seven boys, three girls; aged 7·5 years [SD 3·5]) diagnosed between Feb 18 and April 20, 2020; eight of ten were positive for IgG or IgM, or both.,The two groups differed in disease incidence (group 1 vs group 2, 0·3 vs ten per month), mean age (3·0 vs 7·5 years), cardiac involvement (two of 19 vs six of ten), KDSS (zero of 19 vs five of ten), MAS (zero of 19 vs five of ten), and need for adjunctive steroid treatment (three of 19 vs eight of ten; all p<0·01).,In the past month we found a 30-fold increased incidence of Kawasaki-like disease.,Children diagnosed after the SARS-CoV-2 epidemic began showed evidence of immune response to the virus, were older, had a higher rate of cardiac involvement, and features of MAS.,The SARS-CoV-2 epidemic was associated with high incidence of a severe form of Kawasaki disease.,A similar outbreak of Kawasaki-like disease is expected in countries involved in the SARS-CoV-2 epidemic.,None.

Supplemental Digital Content is available in the text.,Coronavirus disease 2019 (COVID-19) evolved quickly into a global pandemic with myriad systemic complications, including stroke.,We report the largest case series to date of cerebrovascular complications of COVID-19 and compare with stroke patients without infection.,Retrospective case series of COVID-19 patients with imaging-confirmed stroke, treated at 11 hospitals in New York, between March 14 and April 26, 2020.,Demographic, clinical, laboratory, imaging, and outcome data were collected, and cases were compared with date-matched controls without COVID-19 from 1 year prior.,Eighty-six COVID-19-positive stroke cases were identified (mean age, 67.4 years; 44.2% women).,Ischemic stroke (83.7%) and nonfocal neurological presentations (67.4%) predominated, commonly involving multivascular distributions (45.8%) with associated hemorrhage (20.8%).,Compared with controls (n=499), COVID-19 was associated with in-hospital stroke onset (47.7% versus 5.0%; P<0.001), mortality (29.1% versus 9.0%; P<0.001), and Black/multiracial race (58.1% versus 36.9%; P=0.001).,COVID-19 was the strongest independent risk factor for in-hospital stroke (odds ratio, 20.9 [95% CI, 10.4-42.2]; P<0.001), whereas COVID-19, older age, and intracranial hemorrhage independently predicted mortality.,COVID-19 is an independent risk factor for stroke in hospitalized patients and mortality, and stroke presentations are frequently atypical.

This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury.

Gut microbiota and its metabolites such as short chain fatty acids (SCFA), lipopolysaccharides (LPS), and trimethylamine-N-oxide (TMAO) impact cardiovascular health.,In this review, we discuss how gut microbiota and gut metabolites can affect hypertension and atherosclerosis.,Hypertensive patients were shown to have lower alpha diversity, lower abundance of SCFA-producing microbiota, and higher abundance of gram-negative bacteria, which are a source of LPS.,Animal studies point towards a direct role for SCFAs in blood pressure regulation and show that LPS has pro-inflammatory effects.,Translocation of LPS into the systemic circulation is a consequence of increased gut permeability.,Atherosclerosis, a multifactorial disease, is influenced by the gut microbiota through multiple pathways.,Many studies have focused on the pro-atherogenic role of TMAO, however, it is not clear if this is a causal factor.,In addition, gut microbiota play a key role in bile acid metabolism and some interventions targeting bile acid receptors tend to decrease atherosclerosis.,Concluding, gut microbiota affect hypertension and atherosclerosis through many pathways, providing a wide range of potential therapeutic targets.,Challenges ahead include translation of findings and mechanisms to humans and development of therapeutic interventions that target cardiovascular risk by modulation of gut microbes and metabolites.

Cardiovascular disease is a leading cause of death and reduced quality of life, proven by the latest data of the Global Burden of Disease Study, and is only gaining in prevalence worldwide.,Clinical trials have identified chronic inflammatory disorders as cardiovascular risks, and recent research has revealed a contribution by various inflammatory cells to vascular oxidative stress.,Atherosclerosis and cardiovascular disease are closely associated with inflammation, probably due to the close interaction of inflammation with oxidative stress.,Classical therapies for inflammatory disorders have demonstrated protective effects in various models of cardiovascular disease; especially established drugs with pleiotropic immunomodulatory properties have proven beneficial cardiovascular effects; normalization of oxidative stress seems to be a common feature of these therapies.,The close link between inflammation and redox balance was also supported by reports on aggravated inflammatory phenotype in the absence of antioxidant defense proteins (e.g., superoxide dismutases, heme oxygenase-1, and glutathione peroxidases) or overexpression of reactive oxygen species producing enzymes (e.g., NADPH oxidases).,The value of immunomodulation for the treatment of cardiovascular disease was recently supported by large-scale clinical trials demonstrating reduced cardiovascular mortality in patients with established atherosclerotic disease when treated by highly specific anti-inflammatory therapies (e.g., using monoclonal antibodies against cytokines).,Modern antidiabetic cardiovascular drugs (e.g., SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 analogs) seem to share these immunomodulatory properties and display potent antioxidant effects, all of which may explain their successful lowering of cardiovascular risk.

Coronavirus induced disease 2019 (COVID-19) can be complicated by severe organ damage leading to dysfunction of the lungs and other organs.,The processes that trigger organ damage in COVID-19 are incompletely understood.,Samples were donated from hospitalized patients.,Sera, plasma, and autopsy-derived tissue sections were examined employing flow cytometry, enzyme-linked immunosorbent assays, and immunohistochemistry.,Here, we show that severe COVID-19 is characterized by a highly pronounced formation of neutrophil extracellular traps (NETs) inside the micro-vessels.,Intravascular aggregation of NETs leads to rapid occlusion of the affected vessels, disturbed microcirculation, and organ damage.,In severe COVID-19, neutrophil granulocytes are strongly activated and adopt a so-called low-density phenotype, prone to spontaneously form NETs.,In accordance, markers indicating NET turnover are consistently increased in COVID-19 and linked to disease severity.,Histopathology of the lungs and other organs from COVID-19 patients showed congestions of numerous micro-vessels by aggregated NETs associated with endothelial damage.,These data suggest that organ dysfunction in severe COVID-19 is associated with excessive NET formation and vascular damage.,Deutsche Forschungsgemeinschaft (DFG), EU, Volkswagen-Stiftung

SARS-CoV-2 is characterized by a spike protein allowing viral binding to the angiotensin-converting enzyme (ACE)-2, which acts as a viral receptor and is expressed on the surface of several pulmonary and extra-pulmonary cell types, including cardiac, renal, intestinal and endothelial cells.,There is evidence that also endothelial cells are infected by SARS-COV-2, with subsequent occurrence of systemic vasculitis, thromboembolism and disseminated intravascular coagulation.,Those effects, together with the “cytokine storm” are involved in a worse prognosis.,In clinical practice, angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) are extensively used for the treatment of hypertension and other cardiovascular diseases.,In in vivo studies, ACE-Is and ARBs seem to paradoxically increase ACE-2 expression, which could favour SARS-CoV-2 infection of host’s cells and tissues.,By contrast, in patients treated with ACE-Is and ARBs, ACE-2 shows a downregulation at the mRNA and protein levels in kidney and cardiac tissues.,Yet, it has been claimed that both ARBs and ACE-Is could result potentially useful in the clinical course of SARS-CoV-2-infected patients.,As detected in China and as the Italian epidemiological situation confirms, the most prevalent comorbidities in deceased patients with COVID-19 are hypertension, diabetes and cardiovascular diseases.,Older COVID-19-affected patients with cardiovascular comorbidities exhibit a more severe clinical course and a worse prognosis, with many of them being also treated with ARBs or ACE-Is.,Another confounding factor is cigarette smoking, which has been reported to increase ACE-2 expression in both experimental models and humans.,Sex also plays a role, with chromosome X harbouring the gene coding for ACE-2, which is one of the possible explanations of why mortality in female patients is lower.,Viral entry also depends on TMPRSS2 protease activity, an androgen dependent enzyme.,Despite the relevance of experimental animal studies, to comprehensively address the question of the potential hazards or benefits of ACE-Is and ARBs on the clinical course of COVID-19-affected patients treated by these anti-hypertensive drugs, we will need randomized human studies.,We claim the need of adequately powered, prospective studies aimed at answering the following questions of paramount importance for cardiovascular, internal and emergency medicine: Do ACE-Is and ARBs exert similar or different effects on infection or disease course?,Are such effects dangerous, neutral or even useful in older, COVID-19-affected patients?,Do they act on multiple cell types?,Since ACE-Is and ARBs have different molecular targets, the clinical course of SARS-CoV-2 infection could be also different in patients treated by one or the other of these two drug classes.,At present, insufficient detailed data from trials have been made available.

To assess the association between covid-19 vaccines and risk of thrombocytopenia and thromboembolic events in England among adults.,Self-controlled case series study using national data on covid-19 vaccination and hospital admissions.,Patient level data were obtained for approximately 30 million people vaccinated in England between 1 December 2020 and 24 April 2021.,Electronic health records were linked with death data from the Office for National Statistics, SARS-CoV-2 positive test data, and hospital admission data from the United Kingdom’s health service (NHS).,29 121 633 people were vaccinated with first doses (19 608 008 with Oxford-AstraZeneca (ChAdOx1 nCoV-19) and 9 513 625 with Pfizer-BioNTech (BNT162b2 mRNA)) and 1 758 095 people had a positive SARS-CoV-2 test.,People aged ≥16 years who had first doses of the ChAdOx1 nCoV-19 or BNT162b2 mRNA vaccines and any outcome of interest were included in the study.,The primary outcomes were hospital admission or death associated with thrombocytopenia, venous thromboembolism, and arterial thromboembolism within 28 days of three exposures: first dose of the ChAdOx1 nCoV-19 vaccine; first dose of the BNT162b2 mRNA vaccine; and a SARS-CoV-2 positive test.,Secondary outcomes were subsets of the primary outcomes: cerebral venous sinus thrombosis (CVST), ischaemic stroke, myocardial infarction, and other rare arterial thrombotic events.,The study found increased risk of thrombocytopenia after ChAdOx1 nCoV-19 vaccination (incidence rate ratio 1.33, 95% confidence interval 1.19 to 1.47 at 8-14 days) and after a positive SARS-CoV-2 test (5.27, 4.34 to 6.40 at 8-14 days); increased risk of venous thromboembolism after ChAdOx1 nCoV-19 vaccination (1.10, 1.02 to 1.18 at 8-14 days) and after SARS-CoV-2 infection (13.86, 12.76 to 15.05 at 8-14 days); and increased risk of arterial thromboembolism after BNT162b2 mRNA vaccination (1.06, 1.01 to 1.10 at 15-21 days) and after SARS-CoV-2 infection (2.02, 1.82 to 2.24 at 15-21 days).,Secondary analyses found increased risk of CVST after ChAdOx1 nCoV-19 vaccination (4.01, 2.08 to 7.71 at 8-14 days), after BNT162b2 mRNA vaccination (3.58, 1.39 to 9.27 at 15-21 days), and after a positive SARS-CoV-2 test; increased risk of ischaemic stroke after BNT162b2 mRNA vaccination (1.12, 1.04 to 1.20 at 15-21 days) and after a positive SARS-CoV-2 test; and increased risk of other rare arterial thrombotic events after ChAdOx1 nCoV-19 vaccination (1.21, 1.02 to 1.43 at 8-14 days) and after a positive SARS-CoV-2 test.,Increased risks of haematological and vascular events that led to hospital admission or death were observed for short time intervals after first doses of the ChAdOx1 nCoV-19 and BNT162b2 mRNA vaccines.,The risks of most of these events were substantially higher and more prolonged after SARS-CoV-2 infection than after vaccination in the same population.

Reports of ChAdOx1 vaccine-associated thrombocytopenia and vascular adverse events have led to some countries restricting its use.,Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis.,An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0-27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41-13.83), with an estimated incidence of 1.13 (0.62-1.63) cases per 100,000 doses.,An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29-3.02)).,There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12-1.34) 0-27 d after vaccination, with an SCCS RR of 0.97 (0.93-1.02).,For hemorrhagic events 0-27 d after vaccination, the aRR was 1.48 (1.12-1.96), with an SCCS RR of 0.95 (0.82-1.11).,A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events.,The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication.,Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1.,No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.,New data from the EAVE II cohort in Scotland suggests that a first dose of the ChAdOx1 nCoV-19 vaccine might be associated with a small increase in the risk of idiopathic thrombocytopenic purpura between 0 and 27 d after vaccination.

Severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019 (COVID-19)-induced infection can be associated with a coagulopathy, findings consistent with infection-induced inflammatory changes as observed in patients with disseminated intravascular coagulopathy (DIC).,The lack of prior immunity to COVID-19 has resulted in large numbers of infected patients across the globe and uncertainty regarding management of the complications that arise in the course of this viral illness.,The lungs are the target organ for COVID-19; patients develop acute lung injury that can progress to respiratory failure, although multiorgan failure can also occur.,The initial coagulopathy of COVID-19 presents with prominent elevation of D-dimer and fibrin/fibrinogen-degradation products, whereas abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon in initial presentations.,Coagulation test screening, including the measurement of D-dimer and fibrinogen levels, is suggested.,COVID-19-associated coagulopathy should be managed as it would be for any critically ill patient, following the established practice of using thromboembolic prophylaxis for critically ill hospitalized patients, and standard supportive care measures for those with sepsis-induced coagulopathy or DIC.,Although D-dimer, sepsis physiology, and consumptive coagulopathy are indicators of mortality, current data do not suggest the use of full-intensity anticoagulation doses unless otherwise clinically indicated.,Even though there is an associated coagulopathy with COVID-19, bleeding manifestations, even in those with DIC, have not been reported.,If bleeding does occur, standard guidelines for the management of DIC and bleeding should be followed.

The aim of our study was to determine the incidence, characteristics, and clinical outcomes of patients with the novel coronavirus (COVID-19) infection who had presented with and been treated for acute limb ischemia (ALI) during the 2020 coronavirus pandemic.,We performed a single-center, observational cohort study.,The data from all patients who had tested positive for COVID-19 and had presented with ALI requiring urgent operative treatment were collected in a prospectively maintained database.,For the present series, successful revascularization of the treated arterial segment was defined as the absence of early (<30 days) re-occlusion or major amputation or death within 24 hours.,The primary outcomes were successful revascularization, early (≤30 days) and late (≥30 days) survival, postoperative (≤30 days) complications, and limb salvage.,We evaluated the data from 20 patients with ALI who were positive for COVID-19.,For the period from January to March, the incidence rate of patients presenting with ALI in 2020 was significantly greater than that for the same months in 2019 (23 of 141 [16.3%] vs 3 of 163 [1.8%]; P < .001)].,Of the 20 included patients, 18 were men (90%) and two were women (10%).,Their mean age was 75 ± 9 years (range, 62-95 years).,All 20 patients already had a diagnosis of COVID-19 pneumonia.,Operative treatment was performed in 17 patients (85%).,Revascularization was successful in 12 of the 17 (70.6%).,Although successful revascularization was not significantly associated with the postoperative use of intravenous heparin (64.7% vs 83.3%; P = .622), no patient who had received intravenous heparin required reintervention.,Of the 20 patients, eight (40%) had died in the hospital.,The patients who had died were significantly older (81 ± 10 years vs 71 ± 5 years; P = .008).,The use of continuous postoperative systemic heparin infusion was significantly associated with survival (0% vs 57.1%; P = .042).,In our preliminary experience, the incidence of ALI has significantly increased during the COVID-19 pandemic in the Italian Lombardy region.,Successful revascularization was lower than expected, which we believed was due to a virus-related hypercoagulable state.,The use of prolonged systemic heparin might improve surgical treatment efficacy, limb salvage, and overall survival.

In this hypothesis paper, we suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce intravascular pulmonary thrombosis, which may result in the rapid worsening of clinical conditions and, eventually, exitus.,Previously published papers have demonstrated that increased levels of D-dimer at hospital admission correlate with a more severe disease (0.5 mg/L) or occurrence of death (1 mg/L).,The potential prothrombotic action of the SARS-CoV-2 is supported by the topographical involvement of the lung regions with a predilection for the lower lobe with peripheral involvement.,If this hypothesis is demonstrated, this could suggest the benefit of using antithrombotic/coagulation regimens for SARS-CoV-2 and, at the same time, the urgency to identify drugs that could alter the inflammatory storm, thus protecting the vessel wall.

There is some evidence that Covid 19 pneumonia is associated with prothrombotic status and increased risk of venous thromboembolic events (deep venous thrombosis and pulmonary embolism).,Over a two-week period we admitted in our Unit 25 patients with Covid-19 pneumonia, of these pulmonary embolism was diagnosed using computed tomography angiography in 7.,We report on clinical and biochemical features of these patients.,They were all males, with a mean age of 70.3 years (range 58-84); traditional risk factors for venous thromboembolism were identified in the majority of patients with pulmonary embolism, however not differently from those without pulmonary embolism.,Clinical presentation of pulmonary embolism patients was usually characterized by persistence or worsening of respiratory symptoms, with increasing oxygen requirement.,D-dimer levels were several fold higher than the upper threshold of normal; in patients in whom PE was recognized during hospital stay, a rapid and relevant increase of D-dimer levels was observed.,Computed tomographic findings ranged from massive acute pulmonary embolism to a segmental or sub-segmental pattern; furthermore, thrombosis of sub-segmental pulmonary arteries within lung infiltrates were occasionally seen, suggesting local mechanisms.,Six out of 7 patients were treated with unfractionated or low molecular weight heparin with clinical benefit within few days; one patient needed systemic thrombolysis (death from hemorrhagic complication).,•Pulmonary embolism seems to be a not infrequent complication of Covid19 pneumonia.,•Standard prophylaxis with low-dose enoxaparine (or similar) seems to lack efficacy.,•Respiratory worsening and relevant increase of D-dimer may enhance clinical suspect.,•Thrombosis of segmental/subsegmental arteries within lung infiltrates was occasionally seen on computed tomography.,Pulmonary embolism seems to be a not infrequent complication of Covid19 pneumonia.,Standard prophylaxis with low-dose enoxaparine (or similar) seems to lack efficacy.,Respiratory worsening and relevant increase of D-dimer may enhance clinical suspect.,Thrombosis of segmental/subsegmental arteries within lung infiltrates was occasionally seen on computed tomography.

The evolution and progression of multiple myeloma and its precursors over time is poorly understood.,Here, we investigate the landscape and timing of mutational processes shaping multiple myeloma evolution in a large cohort of 89 whole genomes and 973 exomes.,We identify eight processes, including a mutational signature caused by exposure to melphalan.,Reconstructing the chronological activity of each mutational signature, we estimate that the initial transformation of a germinal center B-cell usually occurred during the first 2nd-3rd decades of life.,We define four main patterns of activation-induced deaminase (AID) and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) mutagenesis over time, including a subset of patients with evidence of prolonged AID activity during the pre-malignant phase, indicating antigen-responsiveness and germinal center reentry.,Our findings provide a framework to study the etiology of multiple myeloma and explore strategies for prevention and early detection.,The initial mutational processes and how these lead to progression in multiple myeloma (MM) are unclear.,Here, the authors identify mutational signatures that occur over time in a large cohort of MM patients and suggest features that may help in early diagnosis.

The multiple myeloma (MM) genome is heterogeneous and evolves through preclinical and post-diagnosis phases.,Here we report a catalog and hierarchy of driver lesions using sequences from 67 MM genomes serially collected from 30 patients together with public exome datasets.,Bayesian clustering defines at least 7 genomic subgroups with distinct sets of co-operating events.,Focusing on whole genome sequencing data, complex structural events emerge as major drivers, including chromothripsis and a novel replication-based mechanism of templated insertions, which typically occur early.,Hyperdiploidy also occurs early, with individual trisomies often acquired in different chronological windows during evolution, and with a preferred order of acquisition.,Conversely, positively selected point mutations, whole genome duplication and chromoplexy events occur in later disease phases.,Thus, initiating driver events, drawn from a limited repertoire of structural and numerical chromosomal changes, shape preferred trajectories of evolution that are biologically relevant but heterogeneous across patients.,Multiple myeloma evolves continuously.,Here the authors chronologically reconstruct driver events in multiple myeloma, noting a limited repertoire of initiating driver events that shape the evolutionary trajectory of the disease.

Giant cell arteritis (GCA) is a common form of primary systemic vasculitis in adults, with no reliable indicators of prognosis or treatment responses.,We used single cell technologies to comprehensively map immune cell populations in the blood of patients with GCA and identified the CD66b+CD15+CD10lo/-CD64- band neutrophils and CD66bhiCD15+CD10lo/-CD64+/bright myelocytes/metamyelocytes to be unequivocally associated with both the clinical phenotype and response to treatment.,Immature neutrophils were resistant to apoptosis, remained in the vasculature for a prolonged period of time, interacted with platelets, and extravasated into the tissue surrounding the temporal arteries of patients with GCA.,We discovered that immature neutrophils generated high levels of extracellular reactive oxygen species, leading to enhanced protein oxidation and permeability of endothelial barrier in an in vitro coculture system.,The same populations were also detected in other systemic vasculitides.,These findings link functions of immature neutrophils to disease pathogenesis, establishing a clinical cellular signature of GCA and suggesting different therapeutic approaches in systemic vascular inflammation.,Bona fide immature neutrophil subsets produce unchecked extracellular ROS that contributes to vascular pathologies.

Giant-cell arteritis (GCA) is considered a T helper (Th)1- and Th17-mediated disease.,Interleukin (IL)-12 is a heterodimeric cytokine (p35/p40) involved in Th1 differentiation.,When combining with p19 subunit, p40 compose IL-23, a powerful pro-inflammatory cytokine that maintains Th17 response.,The aims of this study were to investigate p40, p35, and p19 subunit expression in GCA lesions and their combinations to conform different cytokines, to assess the effect of glucocorticoid treatment on subunit expression, and to explore functional roles of p40 by culturing temporal artery sections with a neutralizing anti-human IL-12/IL-23p40 antibody.,p40 and p19 mRNA concentrations measured by real-time RT-PCR were significantly higher in temporal arteries from 50 patients compared to 20 controls (4.35 ± 4.06 vs 0.51 ± 0.75; p < 0.0001 and 20.32 ± 21.78 vs 4.17 ± 4.43 relative units; p < 0.0001, respectively).,No differences were found in constitutively expressed p35 mRNA.,Contrarily, p40 and p19 mRNAs were decreased in temporal arteries from 16 treated GCA patients vs those from 34 treatment-naïve GCA patients.,Accordingly, dexamethasone reduced p40 and p19 expression in cultured arteries.,Subunit associations to conform IL-12 and IL-23 were confirmed by proximity-ligation assay in GCA lesions.,Immunofluorescence revealed widespread p19 and p35 expression by inflammatory cells, independent from p40.,Blocking IL-12/IL-23p40 tended to reduce IFNγ and IL-17 mRNA production by cultured GCA arteries and tended to increase Th17 inducers IL-1β and IL-6.,IL-12 and IL-23 heterodimers are increased in GCA lesions and decrease with glucocorticoid treatment. p19 and p35 subunits are much more abundant than p40, indicating an independent role for these subunits or their potential association with alternative subunits.,The modest effect of IL-12/IL-23p40 neutralization may indicate compensation by redundant cytokines or cytokines resulting from alternative combinations.

Severe acute respiratory syndrome coronavirus 2 causes acute myocardial damage and arrhythmia in coronavirus disease 2019 (COVID‐19) patients.,Studying the changes of electrocardiogram is of great significance for the diagnosis of patients with COVID‐19.,A retrospective analysis method was adopted to compare the electrocardiogram changes between COVID‐19 critically severe and severe patients.,Univariate and multivariate logistic regression were used to analyze the correlation of the levels of serum indexes and past medical history with ST‐T changes and atrial fibrillation.,And the correlation of ECG parameters with in‐hospital death and ventilator use were investigated by using the same methods.,The incidence of male, stroke, elevated cardiac troponin I (cTnI), N‐terminal of the prohormone brain natriuretic peptide (NT‐proBNP), d‐dimer, high‐sensitivity C‐reactive protein (hs‐CRP), hyperkalemia, and hypocalcemia in the critically ill patients was higher than that in severe patients.,There were differences in ST‐T changes, sinus tachycardia, atrial fibrillation, and atrial tachycardia between the two groups.,Multivariate logistic regression analysis showed that elevated cTnI and NT‐proBNP were the independent risk factors of ST‐T changes.,Elevated NT‐proBNP and age were the independent risk factors of atrial fibrillation.,Sinus tachycardia and atrial fibrillation were the independent risk factors of in‐hospital death and ventilator use.,ST‐T changes, sinus tachycardia, and atrial fibrillation are with great significance in the diagnosis of the severity, myocardia injury, and cardiac insufficiency of COVID‐19 patients.,Sinus tachycardia and atrial fibrillation could be used as independent variables predicting in‐hospital death and ventilator use.

Data on the impact of COVID‐19 in chronic heart failure (CHF) patients and its potential to trigger acute heart failure (AHF) are lacking.,The aim of this work was to study characteristics, cardiovascular outcomes and mortality in patients with confirmed COVID‐19 infection and a prior diagnosis of heart failure (HF).,Further aims included the identification of predictors and prognostic implications for AHF decompensation during hospital admission and the determination of a potential correlation between the withdrawal of HF guideline‐directed medical therapy (GDMT) and worse outcomes during hospitalization.,Data for a total of 3080 consecutive patients with confirmed COVID‐19 infection and follow‐up of at least 30 days were analysed.,Patients with a previous history of CHF (n = 152, 4.9%) were more prone to the development of AHF (11.2% vs.,2.1%; P < 0.001) and had higher levels of N‐terminal pro brain natriuretic peptide.,In addition, patients with previous CHF had higher mortality rates (48.7% vs.,19.0%; P < 0.001).,In contrast, 77 patients (2.5%) were diagnosed with AHF, which in the vast majority of cases (77.9%) developed in patients without a history of HF.,Arrhythmias during hospital admission and CHF were the main predictors of AHF.,Patients developing AHF had significantly higher mortality (46.8% vs.,19.7%; P < 0.001).,Finally, the withdrawal of beta‐blockers, mineralocorticoid receptor antagonists and angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant increase in in‐hospital mortality.,Patients with COVID‐19 have a significant incidence of AHF, which is associated with very high mortality rates.,Moreover, patients with a history of CHF are prone to developing acute decompensation after a COVID‐19 diagnosis.,The withdrawal of GDMT was associated with higher mortality.,Heart failure in COVID‐19 patients: prevalence, incidence and prognostic implications.

The COVID-19 outbreak has had an unclear impact on the treatment and outcomes of patients with ST-segment elevation myocardial infarction (STEMI).,The aim of this study was to assess changes in STEMI management during the COVID-19 outbreak.,Using a multicenter, nationwide, retrospective, observational registry of consecutive patients who were managed in 75 specific STEMI care centers in Spain, we compared patient and procedural characteristics and in-hospital outcomes in 2 different cohorts with 30-day follow-up according to whether the patients had been treated before or after COVID-19.,Suspected STEMI patients treated in STEMI networks decreased by 27.6% and patients with confirmed STEMI fell from 1305 to 1009 (22.7%).,There were no differences in reperfusion strategy (> 94% treated with primary percutaneous coronary intervention in both cohorts).,Patients treated with primary percutaneous coronary intervention during the COVID-19 outbreak had a longer ischemic time (233 [150-375] vs 200 [140-332] minutes, P < .001) but showed no differences in the time from first medical contact to reperfusion.,In-hospital mortality was higher during COVID-19 (7.5% vs 5.1%; unadjusted OR, 1.50; 95%CI, 1.07-2.11; P < .001); this association remained after adjustment for confounders (risk-adjusted OR, 1.88; 95%CI, 1.12-3.14; P = .017).,In the 2020 cohort, there was a 6.3% incidence of confirmed SARS-CoV-2 infection during hospitalization.,The number of STEMI patients treated during the current COVID-19 outbreak fell vs the previous year and there was an increase in the median time from symptom onset to reperfusion and a significant 2-fold increase in the rate of in-hospital mortality.,No changes in reperfusion strategy were detected, with primary percutaneous coronary intervention performed for the vast majority of patients.,The co-existence of STEMI and SARS-CoV-2 infection was relatively infrequent.

To evaluate the impact of COVID‐19 pandemic migitation measures on of ST‐elevation myocardial infarction (STEMI) care.,We previously reported a 38% decline in cardiac catheterization activations during the early phase of the COVID‐19 pandemic mitigation measures.,This study extends our early observations using a larger sample of STEMI programs representative of different US regions with the inclusion of more contemporary data.,Data from 18 hospitals or healthcare systems in the US from January 2019 to April 2020 were collecting including number activations for STEMI, the number of activations leading to angiography and primary percutaneous coronary intervention (PPCI), and average door to balloon (D2B) times.,Two periods, January 2019-February 2020 and March-April 2020, were defined to represent periods before (BC) and after (AC) initiation of pandemic mitigation measures, respectively.,A generalized estimating equations approach was used to estimate the change in response variables at AC from BC.,Compared to BC, the AC period was characterized by a marked reduction in the number of activations for STEMI (29%, 95% CI:18-38, p < .001), number of activations leading to angiography (34%, 95% CI: 12-50, p = .005) and number of activations leading to PPCI (20%, 95% CI: 11-27, p < .001).,A decline in STEMI activations drove the reductions in angiography and PPCI volumes.,Relative to BC, the D2B times in the AC period increased on average by 20%, 95%CI (−0.2 to 44, p = .05).,The COVID‐19 Pandemic has adversely affected many aspects of STEMI care, including timely access to the cardiac catheterization laboratory for PPCI.

Electrocardiographic characteristics in COVID‐19‐related mortality have not yet been reported, particularly in racial/ethnic minorities.,We reviewed demographics, laboratory and cardiac tests, medications, and cardiac rhythm proximate to death or initiation of comfort care for patients hospitalized with a positive SARS‐CoV‐2 reverse‐transcriptase polymerase chain reaction in three New York City hospitals between March 1 and April 3, 2020 who died.,We described clinical characteristics and compared factors contributing toward arrhythmic versus nonarrhythmic death.,Of 1258 patients screened, 133 died and were enrolled.,Of these, 55.6% (74/133) were male, 69.9% (93/133) were racial/ethnic minorities, and 88.0% (117/133) had cardiovascular disease.,The last cardiac rhythm recorded was VT or fibrillation in 5.3% (7/133), pulseless electrical activity in 7.5% (10/133), unspecified bradycardia in 0.8% (1/133), and asystole in 26.3% (35/133).,Most 74.4% (99/133) died receiving comfort measures only.,The most common abnormalities on admission electrocardiogram included abnormal QRS axis (25.8%), atrial fibrillation/flutter (14.3%), atrial ectopy (12.0%), and right bundle branch block (11.9%).,During hospitalization, an additional 17.6% developed atrial ectopy, 14.7% ventricular ectopy, 10.1% atrial fibrillation/flutter, and 7.8% a right ventricular abnormality.,Arrhythmic death was confirmed or suspected in 8.3% (11/133) associated with age, coronary artery disease, asthma, vasopressor use, longer admission corrected QT interval, and left bundle branch block (LBBB).,Conduction, rhythm, and electrocardiographic abnormalities were common during COVID‐19‐related hospitalization.,Arrhythmic death was associated with age, coronary artery disease, asthma, longer admission corrected QT interval, LBBB, ventricular ectopy, and usage of vasopressors.,Most died receiving comfort measures.

To study whether combining vital signs and electrocardiogram (ECG) analysis can improve early prognostication.,This study analyzed 1258 adults with coronavirus disease 2019 who were seen at three hospitals in New York in March and April 2020.,Electrocardiograms at presentation to the emergency department were systematically read by electrophysiologists.,The primary outcome was a composite of mechanical ventilation or death 48 hours from diagnosis.,The prognostic value of ECG abnormalities was assessed in a model adjusted for demographics, comorbidities, and vital signs.,At 48 hours, 73 of 1258 patients (5.8%) had died and 174 of 1258 (13.8%) were alive but receiving mechanical ventilation with 277 of 1258 (22.0%) patients dying by 30 days.,Early development of respiratory failure was common, with 53% of all intubations occurring within 48 hours of presentation.,In a multivariable logistic regression, atrial fibrillation/flutter (odds ratio [OR], 2.5; 95% CI, 1.1 to 6.2), right ventricular strain (OR, 2.7; 95% CI, 1.3 to 6.1), and ST segment abnormalities (OR, 2.4; 95% CI, 1.5 to 3.8) were associated with death or mechanical ventilation at 48 hours.,In 108 patients without these ECG abnormalities and with normal respiratory vitals (rate <20 breaths/min and saturation >95%), only 5 (4.6%) died or required mechanical ventilation by 48 hours versus 68 of 216 patients (31.5%) having both ECG and respiratory vital sign abnormalities.,The combination of abnormal respiratory vital signs and ECG findings of atrial fibrillation/flutter, right ventricular strain, or ST segment abnormalities accurately prognosticates early deterioration in patients with coronavirus disease 2019 and may assist with patient triage.

Supplemental Digital Content is available in the text.,Severe acute respiratory syndrome corona virus 2 infection causes severe pneumonia (coronavirus disease 2019 [COVID-19]), but the mechanisms of subsequent respiratory failure and complicating renal and myocardial involvement are poorly understood.,In addition, a systemic prothrombotic phenotype has been reported in patients with COVID-19.,A total of 62 subjects were included in our study (n=38 patients with reverse transcriptase polymerase chain reaction-confirmed COVID-19 and n=24 non-COVID-19 controls).,We performed histopathologic assessment of autopsy cases, surface marker-based phenotyping of neutrophils and platelets, and functional assays for platelet, neutrophil functions, and coagulation tests, as well.,We provide evidence that organ involvement and prothrombotic features in COVID-19 are linked by immunothrombosis.,We show that, in COVID-19, inflammatory microvascular thrombi are present in the lung, kidney, and heart, containing neutrophil extracellular traps associated with platelets and fibrin.,Patients with COVID-19 also present with neutrophil-platelet aggregates and a distinct neutrophil and platelet activation pattern in blood, which changes with disease severity.,Whereas cases of intermediate severity show an exhausted platelet and hyporeactive neutrophil phenotype, patients severely affected with COVID-19 are characterized by excessive platelet and neutrophil activation in comparison with healthy controls and non-COVID-19 pneumonia.,Dysregulated immunothrombosis in severe acute respiratory syndrome corona virus 2 pneumonia is linked to both acute respiratory distress syndrome and systemic hypercoagulability.,Taken together, our data point to immunothrombotic dysregulation as a key marker of disease severity in COVID-19.,Further work is necessary to determine the role of immunothrombosis in COVID-19.

Thromboembolic disease is common in coronavirus disease-2019 (COVID-19).,There is limited evidence on the association of in-hospital anticoagulation (AC) with outcomes and postmortem findings.,The purpose of this study was to examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies.,This retrospective analysis examined the association of AC with mortality, intubation, and major bleeding.,Subanalyses were also conducted on the association of therapeutic versus prophylactic AC initiated ≤48 h from admission.,Thromboembolic disease was contextualized by premortem AC among consecutive autopsies.,Among 4,389 patients, median age was 65 years with 44% women.,Compared with no AC (n = 1,530; 34.9%), therapeutic AC (n = 900; 20.5%) and prophylactic AC (n = 1,959; 44.6%) were associated with lower in-hospital mortality (adjusted hazard ratio [aHR]: 0.53; 95% confidence interval [CI]: 0.45 to 0.62 and aHR: 0.50; 95% CI: 0.45 to 0.57, respectively), and intubation (aHR: 0.69; 95% CI: 0.51 to 0.94 and aHR: 0.72; 95% CI: 0.58 to 0.89, respectively).,When initiated ≤48 h from admission, there was no statistically significant difference between therapeutic (n = 766) versus prophylactic AC (n = 1,860) (aHR: 0.86; 95% CI: 0.73 to 1.02; p = 0.08).,Overall, 89 patients (2%) had major bleeding adjudicated by clinician review, with 27 of 900 (3.0%) on therapeutic, 33 of 1,959 (1.7%) on prophylactic, and 29 of 1,530 (1.9%) on no AC.,Of 26 autopsies, 11 (42%) had thromboembolic disease not clinically suspected and 3 of 11 (27%) were on therapeutic AC.,AC was associated with lower mortality and intubation among hospitalized COVID-19 patients.,Compared with prophylactic AC, therapeutic AC was associated with lower mortality, although not statistically significant.,Autopsies revealed frequent thromboembolic disease.,These data may inform trials to determine optimal AC regimens.

This case series reports a systematic assessment of deep vein thrombosis among patients in an intensive care unit in France with severe coronavirus disease 2019 (COVID-19).

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.

Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19).,We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.,In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis.,The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.,This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.,The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met.,Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58).,The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2).,The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort.,Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis.,In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis.,(ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.)

Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE.

We assessed the impact of the coronavirus disease 19 (COVID-19) pandemic on code stroke activations in the emergency department, stroke unit admissions, and referrals to the stroke prevention clinic at London’s regional stroke center, serving a population of 1.8 million in Ontario, Canada.,We found a 20% drop in the number of code strokes in 2020 compared to 2019, immediately after the first cases of COVID-19 were officially confirmed.,There were no changes in the number of stroke admissions and there was a 22% decrease in the number of clinic referrals, only after the provincial lockdown.,Our findings suggest that the decrease in code strokes was mainly driven by patient-related factors such as fear to be exposed to the SARS-CoV-2, while the reduction in clinic referrals was largely explained by hospital policies and the Government lockdown.

Spain has been one of the countries heavily stricken by COVID-19.,But this epidemic has not affected all regions equally.,We analyzed the impact of the COVID-19 pandemic on hospital stroke admissions and in-hospital mortality in tertiary referral hospitals from North-West Spain.,Spanish multicenter retrospective observational study based on data from tertiary hospitals of the NORDICTUS network.,We recorded the number of patients admitted for ischemic stroke between 30 December 2019 and 3 May 2020, the number of IVT and EVT procedures, and in-hospital mortality.,In the study period, 2737 patients were admitted with ischemic stroke.,There was a decrease in the weekly mean admitted patients during the pandemic (124 vs. 173, p<0.001).,In-hospital mortality of stroke patients increased significantly (9.9% vs.,6.5%, p = 0.003), but there were no differences in the proportion of IVT (17.3% vs.,16.1%, p = 0.405) or EVT (22% vs. 23%, p = 0.504).,We found a decrease in the number of ischemic stroke admissions and an increase in in-hospital mortality during the COVID-19 epidemic in this large study from North-West Spain.,There were regional changes within the network, not fully explained by the severity of the pandemic in different regions.

There are concerns that the coronavirus disease 2019 (COVID-19) outbreak negatively affects the quality of care for acute cardiovascular conditions.,We assessed the impact of the COVID-19 outbreak on trends in hospital admissions and workflow parameters of acute stroke care in Amsterdam, The Netherlands.,We used data from the three hospitals that provide acute stroke care for the Amsterdam region.,We compared two 7-week periods: one during the peak of the COVID-19 outbreak (March 16th-May 3th 2020) and one prior to the outbreak (October 21st-December 8th 2019).,We included consecutive patients who presented to the emergency departments with a suspected stroke and assessed the change in number of patients as an incidence-rate ratio (IRR) using a Poisson regression analysis.,Other outcomes were the IRR for stroke subtypes, change in use of reperfusion therapy, treatment times, and in-hospital complications.,During the COVID-19 period, 309 patients presented with a suspected stroke compared to 407 patients in the pre-COVID-19 period (IRR 0.76 95%CI 0.65-0.88).,The proportion of men was higher during the COVID-19 period (59% vs. 47%, p < 0.001).,There was no change in the proportion of stroke patients treated with intravenous thrombolysis (28% vs. 30%, p = 0.58) or endovascular thrombectomy (11% vs 12%, p = 0.82) or associated treatment times.,Seven patients (all ischemic strokes) were diagnosed with COVID-19.,We observed a 24% decrease in suspected stroke presentations during the COVID-19 outbreak, but no evidence for a decrease in quality of acute stroke care.

Little is known about the effect of the Coronavirus disease 2019 pandemic on stroke care and the impact of the epidemic on acute stroke hospitalizations has not been described.,We analyze the stroke admission rate in three hospitals in New York City from January 1, 2020 through April 17, 2020, identifying all cases of acute ischemic stroke, intraparenchymal hemorrhage and subarachnoid hemorrhage.,We confirmed 518 cases of out-of-hospital stroke.,During the baseline period up to February 25, 2020, the daily stroke admission rate was stable, with the slope of the regression describing the number of admissions over time equal to -0.33 (se = 1.21), not significantly different from 0 (p = 0.79), with daily admissions averaging 41.,During the pandemic period, the slope was -4.4 (se = 1.00); i.e., the number of stroke admissions decreased an average of 4.4 per week, (p = 0.005), with weekly admissions averaging 23, a reduction of 44% versus baseline.,This general result was not different by patient age, sex, or race/ethnicity.,The weekly stroke admission rate started declining two weeks prior to the local surge of coronavirus admissions.,The consequences of lack of diagnosis and treatment of a large proportion of acute stroke patients are likely severe and lasting.

Triglyceride Glucose (TyG) index has been associated with an increased risk in cardiovascular events.,Silent coronary disease is common in patients with type 2 diabetes.,In Vietnam, a low-middle income country, the burden of cardiovascular disease is growing simultaneously with the epidemiologic transition.,Our aim was to assess the prevalence of coronary stenoses (CS) in patients with type 2 diabetes and no history or symptom of cardiovascular disease and to investigate the association between TyG index and cardiovascular risk factors and both the presence and severity of CS.,Futhermore, we assessed the value of TyG index in predicting subclinical CS.,This was a cross-sectional observational study.,We recruited 166 patients at Ninh Thuan General Hospital, Vietnam.,TyG index and HOMA-IR were calculated, and a coronary computed tomography angiography (CCTA) was performed.,The population was classified according to tertiles of TyG index.,The highest TyG values were associated with higher BMI, waist circumference, total cholesterol, LDL-cholesterol, triglycerides, plasma glucose, HbA1c levels and HOMA-IR, lower HDL-cholesterol, a higher incidence of metabolic syndrome and less frequent physical activity (p < 0.05 to < 0.0001).,TyG index correlated with logHOMA-IR (p < 0.0001).,CS ≥ 50% were present in 60 participants and 32 had coronary artery stenosis ≥ 70%.,TyG index and HOMA-IR were significantly higher in patients with CS ≥ 70%.,The number of narrowed coronary arteries and the degree of stenosis were associated with higher TyG index levels (p = 0.04 and < 0.005 respectively).,A TyG index ≥ 10 was significantly associated with an increased risk of multiple coronary artery disease and of more severe CS.,After adjusting for confounding factors, including logHOMA-IR, these risks remained mostly significant.,A TyG index threshold at 10 resulted in 57% sensitivity and 75% specificity for predicting the presence of CS ≥ 70%.,In subgroup analysis TyG index ≥ 10 was associated with an increased risk in CS ≥ 70% in patients treated with statin or antiplatelet therapy.,More than one third of asymptomatic patients with type 2 diabetes had significant CS on CCTA.,TyG index may be considered as a marker for insulin resistance and increased TyG index could identify patients with high risk of coronary artery stenoses and is associated with the number and the severity of artery stenoses.

The triglyceride glucose (TyG) index is a useful surrogate marker for insulin resistance, which is an important risk factor for coronary artery disease (CAD).,However, data on the relationship of the TyG index and coronary plaque characteristics are limited.,This study included 2840 participants with near-normal renal function who underwent coronary computed tomography angiography.,CAD was defined as the presence of any plaques, and obstructive CAD was defined as the presence of plaques with ≥50% stenosis.,The relationship between the TyG index and noncalcified plaque (NCP), calcified or mixed plaque (CMP), and coronary artery calcium score (CACS) was evaluated.,All participants were stratified into 4 groups based on the quartiles of the TyG index.,The prevalence of CAD and obstructive CAD significantly increased with increasing quartiles.,The risk for NCP and obstructive NCP was not different among all groups.,However, compared with group I (lowest quartile), the risk for CMP was higher in groups III (odds ratio [OR]: 1.438) and IV (highest quartile) (OR: 1.895) (P < .05), and that for obstructive CMP was higher in groups II (OR: 1.469), III (OR: 1.595), and IV (OR: 2.168) (P < .05).,Multivariate regression analysis showed that the TyG index was associated with an increased risk for CAD (OR: 1.700), obstructive CAD (OR: 1.692), and CACS >400 (OR: 1.448) (P < .05).,The TyG index was independently associated with the presence and severity of CAD due to an increased risk for CMP.

A significant amount of clinical and research interest in thrombosis is focused on large vessels (eg, stroke, myocardial infarction, deep venous thrombosis, etc.); however, thrombosis is often present in the microcirculation in a variety of significant human diseases, such as disseminated intravascular coagulation, thrombotic microangiopathy, sickle cell disease, and others.,Further, microvascular thrombosis has recently been demonstrated in patients with COVID-19, and has been proposed to mediate the pathogenesis of organ injury in this disease.,In many of these conditions, microvascular thrombosis is accompanied by inflammation, an association referred to as thromboinflammation.,In this review, we discuss endogenous regulatory mechanisms that prevent thrombosis in the microcirculation, experimental approaches to induce microvascular thrombi, and clinical conditions associated with microvascular thrombosis.,A greater understanding of the links between inflammation and thrombosis in the microcirculation is anticipated to provide optimal therapeutic targets for patients with diseases accompanied by microvascular thrombosis.

The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide.,However, little is known about the causes of death and the virus's pathologic features.,To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests.,Prospective cohort study.,Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19.,The first 12 consecutive COVID-19-positive deaths.,Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed.,Clinical data and medical course were evaluated.,Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2).,Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively).,Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients.,Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients.,In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart.,Limited sample size.,The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy.,Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it.,University Medical Center Hamburg-Eppendorf.,Little is known of the pathologic changes that lead to death in patients with COVID-19.,This study reports the autopsy findings of consecutive patients who died with a diagnosis of COVID-19.

Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications.,To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19.,Single‐center cohort study of 198 hospitalized patients with COVID‐19.,Seventy‐five patients (38%) were admitted to the intensive care unit (ICU).,At time of data collection, 16 (8%) were still hospitalized and 19% had died.,During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis.,The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively.,For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36).,VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5).,The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days).,The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE.,Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated by a significant coagulopathy, that likely manifests in the form of both microthrombosis and VTE.,This recognition has led to the urgent need for practical guidance regarding prevention, diagnosis, and treatment of VTE.,A group of approved panelists developed key clinical questions by using the PICO (Population, Intervention, Comparator, Outcome) format that addressed urgent clinical questions regarding the prevention, diagnosis, and treatment of VTE in patients with COVID-19.,MEDLINE (via PubMed or Ovid), Embase, and Cochrane Controlled Register of Trials were systematically searched for relevant literature, and references were screened for inclusion.,Validated evaluation tools were used to grade the level of evidence to support each recommendation.,When evidence did not exist, guidance was developed based on consensus using the modified Delphi process.,The systematic review and critical analysis of the literature based on 13 Population, Intervention, Comparator, Outcome questions resulted in 22 statements.,Very little evidence exists in the COVID-19 population.,The panel thus used expert consensus and existing evidence-based guidelines to craft the guidance statements.,The evidence on the optimal strategies to prevent, diagnose, and treat VTE in patients with COVID-19 is sparse but rapidly evolving.

Venous thromboembolism (VTE) may complicate the course of Coronavirus Disease 2019 (COVID-19).,To evaluate the incidence of VTE in patients with COVID-19.,MEDLINE, EMBASE, and PubMed were searched up to 24th June 2020 for studies that evaluated the incidence of VTE, including pulmonary embolism (PE) and/or deep vein thrombosis (DVT), in patients with COVID-19.,Pooled proportions with corresponding 95% confidence intervals (CI) and prediction intervals (PI) were calculated by random-effect meta-analysis.,3487 patients from 30 studies were included.,Based on very low-quality evidence due to heterogeneity and risk of bias, the incidence of VTE was 26% (95% PI, 6%-66%).,PE with or without DVT occurred in 12% of patients (95% PI, 2%-46%) and DVT alone in 14% (95% PI, 1%-75%).,Studies using standard algorithms for clinically suspected VTE reported PE in 13% of patients (95% PI, 2%-57%) and DVT in 6% (95% PI, 0%-60%), compared to 11% (95% PI, 2%-46%) and 24% (95% PI, 2%-85%) in studies using other diagnostic strategies or patient sampling.,In patients admitted to intensive care units, VTE occurred in 24% (95% PI, 5%-66%), PE in 19% (95% PI, 6%-47%), and DVT alone in 7% (95% PI, 0%-69%).,Corresponding values in general wards were respectively 9% (95% PI, 0%-94%), 4% (95% PI, 0%-100%), and 7% (95% CI, 1%-49%).,VTE represents a frequent complication in hospitalized COVID-19 patients and often occurs as PE.,The threshold for clinical suspicion should be low to trigger prompt diagnostic testing.,•Incidence of venous thromboembolism (VTE) in Coronavirus Disease-2019 (COVID-19) is unclear.,•A total of 3487 patients with COVID-19 were included in 30 observational studies.,•VTE incidence varied due to differences in diagnostic protocols and hospital setting.,•VTE risk was higher in intensive care units, but seemed also substantial in general wards despite prophylaxis.,Incidence of venous thromboembolism (VTE) in Coronavirus Disease-2019 (COVID-19) is unclear.,A total of 3487 patients with COVID-19 were included in 30 observational studies.,VTE incidence varied due to differences in diagnostic protocols and hospital setting.,VTE risk was higher in intensive care units, but seemed also substantial in general wards despite prophylaxis.

Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE.

Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19).,We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.,In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care.,The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.,The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation.,Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis).,The median value for organ support-free days was 1 (interquartile range, −1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, −1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%).,The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11).,Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis.,In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis.,(REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.)

Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease.,In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis.,Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated.,Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19.,Further, we review other agents, including immunomodulators, that may have antithrombotic properties.,It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.

The trimethylamine N-oxide (TMAO) pathway is related to intestinal microbiota and has been associated to risk of cardiovascular disease (CVD).,We investigated associations between four plasma metabolites in the TMAO pathway and risk of all-cause mortality, CVD and deterioration in renal function in individuals with type 2-diabetes (T2D) and albuminuria.,Plasma concentrations of TMAO, choline, carnitine, and betaine were measured by liquid chromatography-tandem mass spectrometry at baseline in 311 individuals with T2D and albuminuria.,Information on all-cause mortality and fatal/non-fatal CVD during follow-up was obtained from registries.,The association of each metabolite, and a weighted sum score of all four metabolites, with the endpoints were examined.,Serum creatinine was measured at follow-up visits and the renal endpoint was defined as eGFR-decline of ≥30%.,Associations were analysed using proportional hazards models adjusted for traditional risk factors.,Baseline mean(SD) age was 57.2(8.2) years and 75% were males.,Follow-up was up to 21.9 years (median (IQR) follow-up 6.8 (6.1-15.5) years for mortality and 6.5 (5.5-8.1) years for CVD events).,The individual metabolites and the weighted sum score were not associated with all-cause mortality (n = 106) or CVD (n = 116) (adjusted p≥0.09).,Higher choline, carnitine and the weighted sum score of the four metabolites were associated with higher risk of decline in eGFR (n = 106) (adjusted p = 0.001, p = 0.03 and p<0.001, respectively).,In individuals with T2D and albuminuria, higher choline, carnitine and a weighted sum of four metabolites from the TMAO pathway were risk markers for deterioration in renal function during long-term follow-up.,Metabolites from the TMAO pathway were not independently related to risk of all-cause mortality or CVD.

Several epidemiological studies have examined the association between trimethylamine N-Oxide (TMAO) and stroke risk; however, the results are still inconclusive.,The purpose of this meta-analysis was to evaluate the relationship between TMAO concentrations and stroke risk.,PubMed, Scopus, Cochrane and ProQuest search engines were systematically searched up to 18 June 2019.,All of the studies that evaluated the relationship between TMAO and stroke were included in the systematic review and eligible studies were included into the meta-analysis.,Meta-regression and subgroup analysis were also employed to find the source of heterogeneity.,Eight studies (two cross-sectional studies, two cohort studies, three case-control studies and one nested case-control study) with a total of 6150 participants were included in the meta-analysis.,The overall result showed that being in the highest category of TMAO increased the odds of stroke by 68% (OR: 1.675; CI: 0.866-3.243; P = 0.047) and mean TMAO concentrations was 2.201 μmol/L higher in patients with stroke rather than non-stroke controls (weighted mean difference (WMD): 2.20; CI: 1.213-3.188; P < 0.001).,Furthermore, we observed revealed a non-linear association between increased TMAO levels and increased odds of stroke (P- for nonlinearity < 0.001).,In addition, visual inspection of the funnel plot revealed a significant asymmetry among studies examining the differences in TMAO in patients with stroke versus control group.,This is the first meta-analysis to show positive dose-dependent relations between circulating TMAO concentration and stroke risk.,However, further interventional studies and long-term studies are needed to better explain causality.

Coronavirus disease 2019 (COVID-19) may have a wide spectrum of clinical presentations, leading in some cases to a critical condition with poor long-term outcomes and residual disability requiring post-acute rehabilitation.,A major concern in severe COVID-19 is represented by a concomitant prothrombotic state.,However, contrasting data are available about the prevalence of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and/or pulmonary embolism (PE).,A detailed search on the association of COVID-19 with thromboembolic complications was conducted in the main electronic databases (PubMed, Web of Science, and Scopus) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.,The weighted mean prevalence (WMP) with 95% confidence interval (95% CI) was calculated with the random-effects model.,Twenty studies enrolling 1,988 COVID-19 patients were included.,The WMP of VTE was 31.3% (95% CI: 24.3-39.2%).,The WMP of DVT was 19.8% (95% CI: 10.5-34.0%), whereas the WMP of PE was 18.9% (95% CI: 14.4-24.3%).,Similar results were obtained when specifically analyzing studies on patients admitted to intensive care units and those on patients under antithrombotic prophylaxis.,Regression models showed that an increasing age was associated with a higher prevalence of VTE (Z-score: 3.11, p = 0.001), DVT (Z-score: 2.33, p = 0.002), and PE (Z-score: 3.03, p = 0.002), while an increasing body mass index was associated with an increasing prevalence of PE (Z-score = 2.01, p = 0.04).,Male sex did not impact the evaluated outcomes.,The rate of thromboembolic complications in COVID-19 patients is definitely high.,Considering the risk of fatal and disabling complications, adequate screening procedures and antithrombotic strategies should be implemented.

The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide.,However, little is known about the causes of death and the virus's pathologic features.,To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests.,Prospective cohort study.,Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19.,The first 12 consecutive COVID-19-positive deaths.,Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed.,Clinical data and medical course were evaluated.,Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2).,Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively).,Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients.,Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients.,In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart.,Limited sample size.,The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy.,Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it.,University Medical Center Hamburg-Eppendorf.,Little is known of the pathologic changes that lead to death in patients with COVID-19.,This study reports the autopsy findings of consecutive patients who died with a diagnosis of COVID-19.

Triglyceride-glucose (TyG) index was recently suggested to be a reliable surrogate marker of insulin resistance.,We aim to investigate the associations between baseline and long-term TyG index with subsequent stroke and its subtypes in a community-based cohort.,A total of 97,653 participants free of history of stroke in the Kailuan Study were included.,TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2).,Baseline TyG index was measured during 2006-2007.,Updated cumulative average TyG index used all available TyG index from baseline to the outcome events of interest or the end of follow up.,The outcome was the first occurrence of stroke, including ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage.,The associations of TyG index with outcomes were explored with Cox regression.,During a median of 11.02 years of follow-up, 5122 participants developed stroke of whom 4277 were ischemic stroke, 880 intracerebral hemorrhage, and 144 subarachnoid hemorrhage.,After adjusting for confounding variables, compared with participants in the lowest quartile of baseline TyG index, those in the third and fourth quartile were associated with an increased risk of stroke (adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.12-1.33, and adjusted HR 1.32, 95% CI 1.21-1.44, respectively, P for trend < 0.001).,We also found a linear association between baseline TyG index with stroke.,Similar results were found for ischemic stroke.,However, no significant associations were observed between baseline TyG index and risk of intracranial hemorrhage.,Parallel results were observed for the associations of updated cumulative average TyG index with outcomes.,Elevated levels of both baseline and long-term updated cumulative average TyG index can independently predict stroke and ischemic stroke but not intracerebral hemorrhage in the general population during an 11-year follow-up.

The triglyceride glucose (TyG) index has been suggested as a simple surrogate marker of insulin resistance.,However, there are limited data regarding the association between the TyG index and arterial stiffness in adults.,Therefore, we evaluated the relationship between the TyG index and arterial stiffness as measured based on brachial ankle pulse wave velocity (baPWV) in Korean adults.,A total of 3587 subjects were enrolled in this study.,Anthropometric and cardiovascular risk factors were measured.,The TyG index was calculated as ln[fasting triglycerides(mg/dl) × fasting glucose(mg/dl)/2], and the insulin resistance index of homeostasis model assessment (HOMA-IR) was estimated.,Arterial stiffness was determined by measuring baPWV.,The subjects were stratified into four groups based on the TyG index.,There were significant differences in cardiovascular parameters among the groups; the mean baPWV increased significantly with increasing TyG index.,According to the logistic regression analysis after adjusting for multiple risk factors, the odds ratio (95% CI) for increased baPWV (> 75th percentile) for the highest and lowest quartiles of the TyG index was 2.92 (1.92-4.44) in men and 1.84 (1.15-2.96) in women, and the odds ratio for increased baPWV for the highest and lowest quartiles of the HOMA-IR was 1.80 (1.17-2.78) in men and 1.46 (1.06-2.47) in women, respectively.,The TyG index is more independently associated with increased arterial stiffness than HOMA-IR in Korean adults.

The ongoing COVID-19 pandemic has caused significant morbidity and mortality worldwide, as well as profound effects on society.,COVID-19 patients have an increased risk of thromboembolic (TE) complications, which develop despite pharmacological thromboprophylaxis.,The mechanism behind COVID-19-associated coagulopathy remains unclear.,Mannose-binding lectin (MBL), a pattern recognition molecule that initiates the lectin pathway of complement activation, has been suggested as a potential amplifier of blood coagulation during thromboinflammation.,Here we describe data from a cohort of critically ill COVID-19 patients ( n = 65) treated at a tertiary hospital center intensive care unit (ICU).,A subset of patients had strongly elevated MBL plasma levels, and activity upon ICU admission, and patients who developed symptomatic TE (14%) had significantly higher MBL levels than patients without TE.,MBL was strongly correlated to plasma D-dimer levels, a marker of COVID-19 coagulopathy, but showed no relationship to degree of inflammation or other organ dysfunction.,In conclusion, we have identified complement activation through the MBL pathway as a novel amplification mechanism that contributes to pathological thrombosis in critically ill COVID-19 patients.,Pharmacological targeting of the MBL pathway could be a novel treatment option for thrombosis in COVID-19.,Laboratory testing of MBL levels could be of value for identifying COVID-19 patients at risk for TE events.

Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications.,To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19.,Single‐center cohort study of 198 hospitalized patients with COVID‐19.,Seventy‐five patients (38%) were admitted to the intensive care unit (ICU).,At time of data collection, 16 (8%) were still hospitalized and 19% had died.,During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis.,The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively.,For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36).,VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5).,The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days).,The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE.,Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

Despite its clinical significance, the risk of severe infection requiring hospitalization among outpatients with severe acute respiratory syndrome coronavirus 2 infection who receive angiotensin‐converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) remains uncertain.,In a propensity score-matched outpatient cohort (January-May 2020) of 2263 Medicare Advantage and commercially insured individuals with hypertension and a positive outpatient SARS‐CoV‐2, we determined the association of ACE inhibitors and ARBs with COVID‐19 hospitalization.,In a concurrent inpatient cohort of 7933 hospitalized with COVID‐19, we tested their association with in‐hospital mortality.,The robustness of the observations was assessed in a contemporary cohort (May-August).,In the outpatient study, neither ACE inhibitors (hazard ratio [HR], 0.77; 0.53-1.13, P=0.18) nor ARBs (HR, 0.88; 0.61-1.26, P=0.48) were associated with hospitalization risk.,ACE inhibitors were associated with lower hospitalization risk in the older Medicare group (HR, 0.61; 0.41-0.93, P=0.02), but not the younger commercially insured group (HR, 2.14; 0.82-5.60, P=0.12; P‐interaction 0.09).,Neither ACE inhibitors nor ARBs were associated with lower hospitalization risk in either population in the validation cohort.,In the primary inpatient study cohort, neither ACE inhibitors (HR, 0.97; 0.81-1.16; P=0.74) nor ARBs (HR, 1.15; 0.95-1.38, P=0.15) were associated with in‐hospital mortality.,These observations were consistent in the validation cohort.,ACE inhibitors and ARBs were not associated with COVID‐19 hospitalization or mortality.,Despite early evidence for a potential association between ACE inhibitors and severe COVID‐19 prevention in older individuals, the inconsistency of this observation in recent data argues against a role for prophylaxis.

The effect of chronic use of renin-angiotensin-aldosterone system (RAAS) inhibitors on the severity of COVID-19 infection is still unclear in patients with hypertension.,We aimed to investigate the association between chronic use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and COVID-19 related outcomes in hypertensive patients.,A single center study was conducted on 133 consecutive hypertensive subjects presenting to the Emergency Department with acute respiratory symptoms and/or fever who were diagnosed with COVID-19 infection between 9th and 31st March 2020.,All patients were grouped according to their chronic antihypertensive medications (ACEIs, N=40; ARBs, N=42; not on RAAS inhibitors, N=51).,There was no statistical difference between ACEIs and ARBs groups in terms of hospital admission rate, oxygen therapy and need for non-invasive ventilation.,Patients chronically treated with RAAS inhibitors showed a significantly lower rate of admission to semi-intensive/intensive care units, when compared to the non-RAAS population (odds ratio [OR] 0.25, CI95% 0.09-0.66 p=0.006).,Similarly, the risk of mortality was lower in the former group, although not reaching statistical significance (OR 0.56, CI95% 0.17-1.83, p=0.341).,Our data suggest that chronic use of RAAS inhibitors does not negatively affect clinical course of COVID-19 in hypertensive patients.,Further studies are needed to confirm this finding and determine whether RAAS inhibitors may have a protective effect on COVID 19-related morbidity and mortality.

Myocarditis is well known to be caused by viral infections such as Coxsackie virus group B, human herpes virus 6 and parvovirus B19.,However, during the current emerging outbreak of SARS-CoV-2, there have been few case reports describing myocarditis as a possible presentation.,In our case report we describe, early cardiac manifestations of SARS-CoV-2 in a UK District General Hospital.,A 44-year-old Caucasian woman without any comorbidities presented with SARS-CoV-2 related fulminant myocarditis without initial respiratory symptoms.,Patient underwent treatment with milrinone and methylprednisolone that showed reduction in myocardial inflammation and significantly improved myocardial contractility.,This was then followed by a second phase of SARS-CoV-2 associated pneumonia and renal failure requiring ventilatory support and haemofiltration.,Although, not described in the literature, we have found conjunctive use of milrinone and methylprednisolone effective in patient with SARS-CoV-2 fulminant myocarditis.

COVID-19 became a global pandemic in early 2020.,While well known for its pulmonary manifestations, the virus also has a number of cardiac manifestations as well.,Takotsubo syndrome has scarcely been reported in patients with COVID-19, but it is possible that the cytokine storm associated with the infection can trigger Takotsubo syndrome in patients with underlying risk factors for Takotsubo (emotional distress, physical distress, history of psychiatric disorders).

Autopsies of deceased with a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can provide important insights into the novel disease and its course.,Furthermore, autopsies are essential for the correct statistical recording of the coronavirus disease 2019 (COVID-19) deaths.,In the northern German Federal State of Hamburg, all deaths of Hamburg citizens with ante- or postmortem PCR-confirmed SARS-CoV-2 infection have been autopsied since the outbreak of the pandemic in Germany.,Our evaluation provides a systematic overview of the first 80 consecutive full autopsies.,A proposal for the categorisation of deaths with SARS-CoV-2 infection is presented (category 1: definite COVID-19 death; category 2: probable COVID-19 death; category 3: possible COVID-19 death with an equal alternative cause of death; category 4: SARS-CoV-2 detection with cause of death not associated to COVID-19).,In six cases, SARS-CoV-2 infection was diagnosed postmortem by a positive PCR test in a nasopharyngeal or lung tissue swab.,In the other 74 cases, SARS-CoV-2 infection had already been known antemortem.,The deceased were aged between 52 and 96 years (average 79.2 years, median 82.4 years).,In the study cohort, 34 deceased were female (38%) and 46 male (62%).,Overall, 38% of the deceased were overweight or obese.,All deceased, except for two women, in whom no significant pre-existing conditions were found autoptically, had relevant comorbidities (in descending order of frequency): (1) diseases of the cardiovascular system, (2) lung diseases, (3) central nervous system diseases, (4) kidney diseases, and (5) diabetes mellitus.,A total of 76 cases (95%) were classified as COVID-19 deaths, corresponding to categories 1-3.,Four deaths (5%) were defined as non-COVID-19 deaths with virus-independent causes of death.,In eight cases, pneumonia was combined with a fulminant pulmonary artery embolism.,Peripheral pulmonary artery embolisms were found in nine other cases.,Overall, deep vein thrombosis has been found in 40% of the cases.,This study provides the largest overview of autopsies of SARS-CoV-2-infected patients presented so far.

Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE.

Coronavirus disease‐2019 (COVID‐19) has a deleterious effect on several systems, including the cardiovascular system.,We aim to systematically explore the association of COVID‐19 severity and mortality rate with the history of cardiovascular diseases and/or other comorbidities and cardiac injury laboratory markers.,The standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CIs) were applied to estimate pooled results from the 56 studies.,The prognostic performance of cardiac markers for predicting adverse outcomes and to select the best cutoff threshold was estimated by receiver operating characteristic curve analysis.,Decision tree analysis by combining cardiac markers with demographic and clinical features was applied to predict mortality and severity in patients with COVID‐19.,A meta‐analysis of 17 794 patients showed patients with high cardiac troponin I (OR = 5.22, 95% CI = 3.73‐7.31, P < .001) and aspartate aminotransferase (AST) levels (OR = 3.64, 95% CI = 2.84‐4.66, P < .001) were more likely to develop adverse outcomes.,High troponin I more than 13.75 ng/L combined with either advanced age more than 60 years or elevated AST level more than 27.72 U/L was the best model to predict poor outcomes.,COVID‐19 severity and mortality are complicated by myocardial injury.,Assessment of cardiac injury biomarkers may improve the identification of those patients at the highest risk and potentially lead to improved therapeutic approaches.,COVID‐19 severity and mortality are complicated by myocardial injury.Patients with high cardiac troponin I and AST levels were more likely to develop adverse outcomes.High troponin I combined with either advanced age or elevated AST level was the best model to predict poor outcomes.Assessment of cardiac injury biomarkers may improve identification of COVID‐19 patients at the highest risk.,COVID‐19 severity and mortality are complicated by myocardial injury.,Patients with high cardiac troponin I and AST levels were more likely to develop adverse outcomes.,High troponin I combined with either advanced age or elevated AST level was the best model to predict poor outcomes.,Assessment of cardiac injury biomarkers may improve identification of COVID‐19 patients at the highest risk.

The Coronavirus Disease 2019 (COVID-19) is now a global pandemic with millions affected and millions more at risk for contracting the infection.,The COVID-19 virus, SARS-CoV-2, affects multiple organ systems, especially the lungs and heart.,Elevation of cardiac biomarkers, particularly high-sensitivity troponin and/or creatine kinase MB, is common in patients with COVID-19 infection.,In our review of clinical analyses, we found that in 26 studies including 11,685 patients, the weighted pooled prevalence of acute myocardial injury was 20% (ranged from 5% to 38% depending on the criteria used).,The plausible mechanisms of myocardial injury include, 1) hyperinflammation and cytokine storm mediated through pathologic T-cells and monocytes leading to myocarditis, 2) respiratory failure and hypoxemia resulting in damage to cardiac myocytes, 3) down regulation of ACE2 expression and subsequent protective signaling pathways in cardiac myocytes, 4) hypercoagulability and development of coronary microvascular thrombosis, 5) diffuse endothelial injury and ‘endotheliitis’ in several organs including the heart, and, 6) inflammation and/or stress causing coronary plaque rupture or supply-demand mismatch leading to myocardial ischemia/infarction.,Cardiac biomarkers can be used to aid in diagnosis as well as risk stratification.,In patients with elevated hs-troponin, clinical context is important and myocarditis as well as stress induced cardiomyopathy should be considered in the differential, along with type I and type II myocardial infarction.,Irrespective of etiology, patients with acute myocardial injury should be prioritized for treatment.,Clinical decisions including interventions should be individualized and carefully tailored after thorough review of risks/benefits.,Given the complex interplay of SARS-CoV-2 with the cardiovascular system, further investigation into potential mechanisms is needed to guide effective therapies.,Randomized trials are urgently needed to investigate treatment modalities to reduce the incidence and mortality associated with COVID-19 related acute myocardial injury.

To evaluate the prevalence of acute pulmonary embolism (APE) in non-hospitalized COVID-19 patients referred to CT pulmonary angiography (CTPA) by the emergency department.,From March 14 to April 6, 2020, 72 non-hospitalized patients referred by the emergency department to CTPA for COVID-19 pneumonia were retrospectively identified.,Relevant clinical and laboratory data and CT scan findings were collected for each patient.,CTPA scans were reviewed by two radiologists to determinate the presence or absence of APE.,Clinical classification, lung involvement of COVID-19 pneumonia, and CT total severity score were compared between APE group and non-APE group.,APE was identified in 13 (18%) CTPA scans.,The mean age and D-dimer of patients from the APE group were higher in comparison with those from the non-APE group (74.4 vs.,59.6 years, p = 0.008, and 7.29 vs.,3.29 μg/ml, p = 0.011).,There was no significant difference between APE and non-APE groups concerning clinical type, COVID-19 pneumonia lung lesions (ground-glass opacity: 85% vs. 97%; consolidation: 69% vs. 68%; crazy paving: 38% vs. 37%; linear reticulation: 69% vs.,78%), CT severity score (6.3 vs.,7.1, p = 0.365), quality of CTPA (1.8 vs.,2.0, p = 0.518), and pleural effusion (38% vs. 19%, p = 0.146).,Non-hospitalized patients with COVID-19 pneumonia referred to CT scan by the emergency departments are at risk of APE.,The presence of APE was not limited to severe or critical clinical type of COVID-19 pneumonia.,• Acute pulmonary embolism was found in 18% of non-hospitalized COVID-19 patients referred by the emergency department to CTPA.,Two (15%) patients had main, four (30%) lobar, and seven (55%) segmental acute pulmonary embolism.,• Five of 13 (38%) patients with acute pulmonary embolism had a moderate clinical type.,• Severity and radiological features of COVID-19 pneumonia showed no significant difference between patients with or without acute pulmonary embolism.

Acute respiratory distress syndrome development in patients with coronavirus disease 2019 (COVID-19) pneumonia is associated with a high mortality rate and is the main cause of death in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [1].,Myocardial injury has also been reported to be significantly associated with fatal outcome, with a 37% mortality rate in patients without prior cardiovascular disease but elevated troponin levels [2].,A D-dimer level of >1 μg·mL−1 has been clearly identified as a risk factor for poor outcome in SARS-Cov-2 infection [3], with recent reports highlighting a high incidence of thrombotic events in intensive care unit (ICU) patients [4].,A normal D-dimer level allows the safe exclusion of pulmonary embolism (PE) in outpatients with a low or intermediate clinical probability of PE, but there is no recommendation to use D-dimer as a positive marker of thrombosis because of lack of specificity.,This study reports an overall 24% (95% CI 17-32%) cumulative incidence of pulmonary embolism in patients with COVID-19 pneumonia, 50% (30-70%) in ICU and 18% (12-27%) in other patientshttps://bit.ly/35s7hjm

Data on the relationship between the triglyceride glucose (TyG) index and coronary artery calcification (CAC) progression is limited.,This longitudinal study evaluated the association of TyG index with CAC progression in asymptomatic adults.,We enrolled 12,326 asymptomatic Korean adults who had at least two CAC evaluations.,The TyG index was determined using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2).,CAC progression was defined as a difference ≥ 2.5 between the square roots (√) of the baseline and follow-up coronary artery calcium score (CACS) (Δ√transformed CACS).,Annualized Δ√transformed CACS was defined as Δ√transformed CACS divided by the inter-scan period.,During a mean 3.3 years, the overall incidence of CAC progression was 30.6%.,The incidence of CAC progression (group I [lowest]: 22.7% versus [vs.] group II: 31.7% vs. group III [highest]: 37.5%, P < 0.001) and annualized Δ√transformed CACS (group I: 0.46 ± 1.44 vs. group II: 0.71 ± 2.02 vs. group III: 0.87 ± 1.75, P < 0.001) were markedly elevated with increasing TyG index tertiles.,Multivariate linear regression analysis showed that TyG index was associated with annualized Δ√transformed CACS (β = 0.066, P = 0.036).,In multivariate logistic regression analysis, the TyG index was significantly associated with CAC progression in baseline CACS ≤ 100.,The TyG index is an independent predictor of CAC progression, especially in adults without heavy baseline CAC.

Non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is the leading cause of morbidity and mortality from cardiovascular disease worldwide.,Several recent studies have shown the relationship between the triglyceride-glucose (TyG) index and vascular disease; however, the role of the TyG index in NSTE-ACS has not been extensively assessed.,Thus, we aimed to investigate the association of the TyG index with cardiovascular risk factors and outcomes in NSTE-ACS.,Overall, 438 patients with NSTE-ACS were enrolled to examine the association of the TyG index with the SYNTAX score and major adverse cardiovascular events (MACEs).,The TyG index was calculated as ln (fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2).,The severity of coronary lesions was quantified by the SYNTAX score.,MACEs included cardiac death, nonfatal myocardial infarction, target vessel revascularization, congestive heart failure, and nonfatal stroke.,All the patients underwent a 12-month follow-up for MACEs after admission.,Multivariate regression analysis identified metabolic risk factors as independent parameters correlated with the TyG index.,The prevalence of glucose metabolism disorder, metabolic syndrome, and MACEs increased with increasing TyG index.,The TyG index showed a strong diagnostic performance for cardiovascular risk factors and was independently associated with the SYNTAX score (OR 6.055, 95% CI 2.915-12.579, P < 0.001).,The risk of MACEs (12.8% and 22.8% for the low TyG index and high TyG index groups, respectively; adjusted HR = 1.791, 95% CI 1.045-3.068, P = 0.034) significantly increased in the high TyG index group as compared with the low TyG index group.,The multivariate Cox regression analysis further revealed that the TyG index was an independent predictor of MACEs (HR 1.878, 95% CI 1.130-3.121, P = 0.015).,In conclusion, the TyG index might be an independent predictor of coronary artery disease severity and cardiovascular outcomes in NSTE-ACS.

With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke.,However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19.,We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic.,We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls).,In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls).,During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke.,Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P=0.003) and historical controls (25.0%, P<0.001).,When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels.,When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate.,Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls.,We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19.,Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased.,Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.

To investigate the incidence and spectrum of neuroimaging findings and their prognostic role in hospitalized COVID-19 patients in New York City.,This is a retrospective cohort study of 3218 COVID-19 confirmed patients admitted to a major healthcare system (three hospitals) in New York City between March 1, 2020 and April 13, 2020.,Clinical data were extracted from electronic medical records, and particularly data of all neurological symptoms were extracted from the imaging reports.,Four neuroradiologists evaluated all neuroimaging studies for acute neuroimaging findings related to COVID-19.,14.1% of admitted COVID-19 patients had neuroimaging and this accounted for only 5.5% of the total imaging studies.,Acute stroke was the most common finding on neuro-imaging, seen in 92.5% of patients with positive neuro-imaging studies, and present in 1.1% of hospitalized COVID-19 patients.,Patients with acute large ischemic and hemorrhagic stroke had much higher mortality risk adjusted for age, BMI and hypertension compared to those COVID-19 patients without neuroimaging.,(Odds Ratio 6.02 by LR; Hazard Ratio 2.28 by CRR).,Our study demonstrates acute stroke is the most common neuroimaging finding among hospitalized COVID-19 patients.,Detection of an acute stroke is a strong prognostic marker of poor outcome.,Our study also highlights the fact there is limited use of neuroimaging in these patients due to multiple logistical constraints.