ABSTRACT
Introduction: COVID-19 is a life-threatening disease leading to bilateral pneumonia and respiratory failure. The underlying reasons why a smaller percentage of patients present with severe pulmonary symptoms whereas the majority is only mildly affected, are to date not well understood. Methods: We analyzed immune cell dynamics in patients with mild (NIH Score 4+5) and severe (NIH Score 1-3) cases of SARS-CoV2 infection. Patients with mild courses presented with COVID-19 specific, mostly respiratory symptoms, however no one required treatment in the ICU, mechanical ventilation nor died due to COVID-19. Patients with a severe course of disease were treated in the ICU department of our hospital, all of them needed supplementary oxygen. Mortality rate of the cohort with severely ill patients was 33%. Results: Given that T cells play a critical role in the elimination of viral infections, we studied this lymphoid compartment in COVID-19 patients. Compared to healthy controls, patients with SARS-CoV2 infection presented increased T cell activation and proliferation and a decline of naive CD8 T-cells. Interestingly, activation markers on T cells were further enhanced in patients with severe courses of COVID-19 disease. Furthermore, the CD8 T-cell compartment in patients with mild COVID-19 exhibited a shift towards terminal differentiation. In contrast, severe cases showed an expansion of effector cells, which correlated with increased cell activation. To determine whether T-cells might be primed for homing to specific tissues during SARS-CoV-2 infection, we checked for particular chemokine receptors in our cohorts. We found the lung homing receptor CCR4 and the proinflammatory receptor CCR5 strongly upregulated on CD8 T-cells in patients with severe COVID-19 infection, mainly characterized by pulmonary failure and requirement of mechanical ventilation, however not in mild COVID-19 disease. Moreover, CD8 T-cells from patients with severe disease exhibited reduced CCR7 expression, pointing towards enhanced attracting to sites of inflammation and limited homing to secondary lymphoid organs. Further analysis revealed a linear relationship between CCR4 expression and CD8 T-cell activation and effector differentiation in patients with severe disease. Conclusion: Taken together, our data support the critical involvement of T cells in the pathogenesis of SARS-CoV2 infection and link clinical severity to T-cell hyperactivation and altered migratory capacity.