Fig. 2

Potential mechanisms of SARS-CoV-2-induced immunopathology. a The potential mechanisms of depletion and exhaustion of lymphocytes. (1) ACE2 receptor expression on lymphocytes, especially on T cells, promotes SARS-CoV-2 entry into lymphocytes. (2) A concomitant increase in inflammatory cytokine levels promotes the depletion and exhaustion of T cells. (3) SARS-CoV-2 directly damages lymphatic organs, including the spleen and lymph nodes, inducing lymphopenia. (4) Increased lactic acid levels inhibit the proliferation and dysfunction of lymphocytes. b Lymphopenia may lead to infection with microbe, further promoting the activation and recruitment of neutrophils in the blood. c The potential mechanisms of cytokine storm induction. (1) CD4⁺ T cells can be rapidly activated into Th1 cells that secret GM-CSF, further inducing CD14⁺CD16⁺ monocytes with high IL-6 levels. (2) An increase in the CD14⁺IL-1β⁺ monocyte subpopulation promotes increased IL-1β production. (3) Th17 cells produce IL-17 to further recruit monocytes, macrophages, and neutrophils and stimulate other cytokine cascades, such as IL-1β and IL-6 among others. d A neutralizing monoclonal antibody targeting the virus can enhance virus entry into cells via the Fc region of the antibody bound to the Fc receptor (FcR) on cells; this is correlated with disease progression and poor outcomes of patients with COVID-19