IL-6 drives T cell death to participate in lymphopenia in COVID-19

Lymphopenia is a common observation in patients with COVID-19. To explore the cause of T cell lymphopenia in the disease, laboratory results of 64 hospitalized COVID-19 patients were retrospectively analyzed and six pa-tients were randomly selected to trace their changes of T lymphocytes and plasma concentration of IL-6 for the course of disease. Results confirmed that the T-cell lymphopenia, especially CD4(+) T cell reduction in COVID-19 patients, was a reliable indicator of severity and hospitalization in infected patients. And CD4(+) T cell count below 200 cells/mu L predicts critical illness in COVID-19 patients. In vitro assay supported that exposure to key contributors (IL-1(i, IL-6, TNF-alpha and IFN-gamma) of COVID-19 cytokine storm caused substantial death of activated T cells. Among these contributors, IL-6 level was found to probably reversely correlate with T cell counts in patients. And IL-6 alone was potent to induce T cell reduction by gasderminE-mediated pyroptosis, inferring IL-6 took a part in affecting the function and status of T cells in COVID-19 patients. Intervention of IL-6 mediated T cell pryprotosis may effectively delay disease progression, maintain normal immune status at an early stage of infection.