text: Refining Long COVID by a Prospective Multimodal Evaluation of Patients with Long Term Symptoms Attributed to SARS CoV 2 Infection COVID 19 long haulers also decribed as having long COVID or post acute COVID 19 syndrome represent 10 of COVID 19 patients and remain understudied In this prospective study we recruited 30 consecutive patients seeking medical help for persistent symptoms 30 days attributed to COVID 19 All reported a viral illness compatible with COVID 19 The patients underwent a multi modal evaluation including clinical psychologic virologic and specific immunologic assays and were followed longitudinally A group of 17 convalescent COVID 19 individuals without persistent symptoms were included as a comparison group The median age was 40 interquartile range 35 54 years and 18 60 were female At a median time of 152 102 164 days after symptom onset fever cough and dyspnea were less frequently reported compared with the initial presentation but paresthesia and burning pain emerged in 18 60 and 13 43 patients respectively The clinical examination was unremarkable in all patients although the median fatigue and pain visual analog scales were 7 5 8 and 5 2 6 respectively Extensive biologic studies were unremarkable and multiplex cytokines and ultra sensitive interferon α2 measurements were similar between long haulers and convalescent COVID 19 individuals without persistent symptoms Using SARS CoV 2 serology and IFN γ ELISPOT we found evidence of a previous SARS CoV 2 infection in 50 15 30 of patients with evidence of a lack of immune response or a waning immune response in two patients Finally psychiatric evaluation showed that 11 36 7 13 43 3 and 9 30 patients had a positive screening for anxiety depression and post traumatic stress disorder respectively Half of patients seeking medical help for post acute COVID 19 syndrome lack SARS CoV 2 immunity The presence of SARS CoV 2 immunity or not had no consequence on the clinical or biologic characteristics of post acute COVID 19 syndrome patients all of whom reported severe fatigue altered quality of life and psychologic distress 