text: Is the Endothelium the Missing Link in the Pathophysiology and Treatment of COVID 19 Complications Patients with COVID 19 present a wide spectrum of disease severity from asymptomatic cases in the majority to serious disease leading to critical care and even death Clinically four different scenarios occur within the typical disease timeline first an incubation and asymptomatic period second a stage with mild symptoms due mainly to the virus itself third in up to 20 of the patients a stage with severe symptoms where a hyperinflammatory response with a cytokine storm driven by host immunity induces acute respiratory distress syndrome and finally a post acute sequelae PASC phase which present symptoms that can range from mild or annoying to actually quite incapacitating Although the most common manifestation is acute respiratory failure of the lungs other organs are also frequently involved The clinical manifestations of the COVID 19 infection support a key role for endothelial dysfunction in the pathobiology of this condition The virus enters into the organism via its interaction with angiotensin converting enzyme 2 receptor that is present prominently in the alveoli but also in endothelial cells which can be directly infected by the virus Cytokine release syndrome can also drive endothelial damage independently Consequently a distinctive feature of SARS CoV 2 infection is vascular harm with severe endothelial injury widespread thrombosis microangiopathy and neo angiogenesis in response to endothelial damage Therefore endothelial dysfunction seems to be the pathophysiological substrate for severe COVID 19 complications Biomarkers of endothelial injury could constitute strong indicators of disease progression and severity In addition the endothelium could represent a very attractive target to both prevent and treat these complications To establish an adequate therapy the underlying pathophysiology and corresponding clinical stage should be clearly identified In this review the clinical features of COVID 19 the central role of the endothelium in COVID 19 and in other pathologies and the potential of specific therapies aimed at protecting the endothelium in COVID 19 patients are addressed 