In-depth phenotyping of human peripheral blood mononuclear cells in convalescent COVID-19 patients following a mild versus severe disease course

Chu, C.-F.; Sabath, F.; Sun, S.; Chao, Y.-Y.; Zielinski, C. E.

Background: Covid-19, the disease caused by infection with SARS-CoV-2, has developed to a pandemic causing more than 239, 000 deaths worldwide as of 6th May according to the World Health Organization (WHO). It presents with a highly variable disease course ranging from a large proportion of asymptomatic cases to severe respiratory failure in 17-29% of cases even in the absence of apparent comorbidities 1, 2. This implies a diverse host immune response to SARS-CoV-2. The immunological characteristics underlying these divergent disease courses, however, still remain elusive. While insights into abrogations of innate immunity begin to emerge, adaptive immune responses towards SARS-CoV-2 are poorly investigated, although they serve as immune signatures of protection and vaccine responses. We therefore set out to characterize immune signatures of convalescent COVID-19 patients stratified according to their disease severity. Methods: We performed high-dimensional flow cytometric profiling of peripheral blood mononuclear cells of convalescent COVID-19 patients who we stratified according to their disease severity by a physician-assisted questionnaire based assessment of COVID-19 symptoms. Results: Surprisingly, we did not observe any difference in the relative proportions of any major immune cell type in convalescent patients presenting with different severity of COVID-19 disease except for a reduction in monocytes. The frequency of Tnaive T cells was significantly reduced in CD4+ and CD8+ T cells, whereas other T cell differentiations states (TCM, TEM, TEMRA) remained relatively unaffected by COVID-19 severity as assessed approximately two weeks after infection. Conclusions In our COVID-19 patient cohort, which is characterized by absence of comorbidities and therapeutic interventions other than symptomatic antipyretics, the immunophenotype is similar irrespective of a highly variable disease severity. Convalescence is therefore associated with a rather uniform immune signature. Abrogations, which were previously identified in the innate and adaptive immune compartment of COVID-19 patients should be scrutinized for direct associations with a preconditioned immune system shaped and made vulnerable for SARS-CoV-2 by preexisting comorbidities.