Abstract
While numerous studies have already compared the immune responses against SARS-CoV-2 in severely and mild-to-moderately ill COVID-19 patients, longitudinal trajectories are still scarce. We therefore set out to analyze serial blood samples from mild-to-moderately ill patients in order to define the immune landscapes for differently progressed disease stages. Twenty-two COVID-19 patients were subjected to consecutive venipuncture within seven days after diagnosis or admittance to hospital. Flow cytometry was performed to analyze peripheral blood immune cell compositions and their activation as were plasma levels of cytokines and SARS-CoV-2 specific immunoglobulins. Healthy donors served as controls. Integrating the kinetics of plasmablasts and SARS-CoV-2 specific antibodies allowed for the definition of three disease stages of early COVID-19. The incubation phase was characterized by a sharp increase in pro-inflammatory monocytes and terminally differentiated cytotoxic T cells. The latter correlated significantly with elevated concentrations of IP-10. Early acute infection featured a peak in PD-1+ cytotoxic T cells, plasmablasts and increasing titers of virus specific antibodies. During late acute infection, immature neutrophils were enriched, whereas all other parameters returned to baseline. Our findings will help to define landmarks that are indispensable for the refinement of new anti-viral and anti-inflammatory therapeutics, and may also inform clinicians to optimize treatment and prevent fatal outcomes.
Highlights
The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a highly infectious and rapidly transmittable β-coronavirus that led to the global pandemic of coronavirus disease 2019 (COVID-19)
Even though mild-to-moderate COVID-19 does not seem to be associated with a fulminant immune activation, more and more data point to long lasting infection related sequelae including persisting nausea, fatigue and loss of smell and taste in up to 30% of patients who recovered from COVID-19 [10,11,12]
PD-1+ cytotoxic T cells was mostly restricted to the incubation phase and early acute infection, respectively, we found the activation marker CD38 to be overexpressed during all disease phases
Summary
The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a highly infectious and rapidly transmittable β-coronavirus that led to the global pandemic of coronavirus disease 2019 (COVID-19). COVID-19 is characterized by a diverse collection of isolated or combined symptoms ranging from mild to severe to life-threatening. While mild disease may proceed asymptomatic or show mere signs of a common cold, moderate and severe COVID-19 present with symptoms that range from fever, malaise and fatigue to neurological, dermatological, gastrointestinal and pulmonary manifestations [5]. Even though mild-to-moderate COVID-19 does not seem to be associated with a fulminant immune activation, more and more data point to long lasting infection related sequelae including persisting nausea, fatigue and loss of smell and taste in up to 30% of patients who recovered from COVID-19 [10,11,12]. Even non-severe COVID-19 may pose a considerable hazard for global health and the international economy
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