SARS-CoV-2 Productively Infects Primary Human Immune System Cells in Vitro and in COVID-19 Patients

The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection is associated with a hyperinflammatory state and lymphocytopenia,a hallmark that appears as both signature and prognosis of disease severity outcome.Although cytokine storm and a sustained inflammatory state are commonly associated with immune cell depletion,it is still unclear whether direct SARS-CoV-2 infection of immune cells could also play a role in this scenario by harboring viral replication.We found that monocytes,as well as both B and T lymphocytes,were susceptible to SARS-CoV-2 infection in vitro,accumulating double-stranded RNA consistent with viral RNA replication and ultimately leading to expressive T cell apoptosis.In addition,flow cytometry and immunofluorescence analysis revealed that SARS-CoV-2 was frequently detected in monocytes and B lymphocytes from coronavirus disease 2019(COVID-19)patients.The rates of SARS-CoV-2-infected monocytes in peripheral blood mononuclear cells from COVID-19 patients increased over time from symptom onset,with SARS-CoV-2-positive monocytes,B cells,and CD4+T lymphocytes also detected in postmortem lung tissue.These results indicated that SARS-CoV-2 infection of blood-circulating leukocytes in COVID-19 patients might have important implications for disease pathogenesis and progression,immune dysfunction,and virus spread within the host.