Refining long-COVID by a prospective multimodal evaluation of patients with long-term symptoms related to SARS-CoV-2 infection

SCHERLINGER, M.; Felten, R.; Gallais, F.; Nazon, C.; Chatelus, E.; Pijnenburg, L.; Mengin, A.; Gras, A.; Vidailhet, P.; Arnould-Michel, R.; Bibi-triki, S.; Carapito, R.; Bahram, S.; trouillet-assant, s.; Perret, M.; Belot, A.; Arnaud, L.; Gottenberg, J.-E.; Fafi-Kremer, S.; Sibilia, J.

Background: COVID-19 long-haulers or long-COVID represent 10% of COVID-19 patients and remain understudied. Methods: 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, psychological, virological, specific immunological assays and were followed longitudinally. Results The median age was 40 [interquartile range: 35-54] and 18 (60%) were female. After a median time of 152 [102-164] days after symptom onset, fever, cough and dyspnea were less frequently reported as 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 analogic scales were 7 [5-8] and 5 [2-6], respectively. Extensive biological studies were unremarkable, as were multiplex cytokine and ultra-sensitive interferon-a2 measurements. At this time, nasopharyngeal swab and stool RT-PCR were negative for all tested patients. Using SARS-CoV-2 serology and IFN-{gamma} ELISPOT, we found evidence of a previous SARS-CoV-2 infection in 50% (15/30) of patients, with objective evidence of lack or waning of immune response in two. 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. Conclusions Half of patients seeking medical help for long-COVID lack SARS-CoV-2 immunity. The presence of SARS-CoV-2 immunity did not cluster clinically or biologically long haulers, who reported severe fatigue, altered quality of life, and exhibited psychological distress.