Immune alterations during SARS-CoV-2-related acute respiratory distress syndrome

Bouadma, L.; Wiedemann, A.; Patrier, J.; Surenaud, M.; Wicky, P.-H.; Foucat, E.; Diehl, J.-L.; Hejblum, B. P.; Sinnah, F.; de Montmollin, E.; Lacabaratz, C.; Thiebaut, R.; Timsit, J.-F.; Levy, Y.

We report a longitudinal analysis of the immune response associated with a fatal case of COVID-19. This patient exhibited a rapid evolution towards multiorgan failure. SARS-CoV-2 was detected in multiple nasopharyngeal, blood, and pleural samples, despite antiviral and immunomodulator treatment. Clinical evolution in the blood was marked by an increase (2-3 fold) in differentiated effector T cells expressing exhaustion (PD-1) and senescence (CD57) markers, an expansion of antibody-secreting cells, a 15-fold increase in {gamma}{delta} T-cell and proliferating NK-cell populations, and the total disappearance of monocytes, suggesting lung trafficking. In the serum, waves of a proinflammatory cytokine storm, Th1 and Th2 activation, and markers of T-cell exhaustion, apoptosis, cell cytotoxicity, and endothelial activation were observed until the fatal outcome. This case underscores the need for well-designed studies to investigate complementary approaches to control viral replication, the source of the hyperinflammatory status, and immunomodulation to target the pathophysiological response.