Abstract
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.
Keywords: COVID-19; SARS-CoV-2; apoptosis; lymphocytes; lymphocytopenia; monocytes; peripheral blood mononuclear cell (PBMC).
【저자키워드】 COVID-19, Monocytes, SARS-CoV-2, Apoptosis, Lymphocytes, lymphocytopenia, Peripheral blood mononuclear cell (PBMC), 【초록키워드】 coronavirus disease, Monocytes, Apoptosis, Coronavirus disease 2019, Cytokine storm, coronavirus, Lymphocytes, Prognosis, SARS-COV-2 infection, disease severity, Infection, B cells, progression, in vitro, outcome, severe acute respiratory syndrome Coronavirus, flow cytometry, monocyte, Peripheral blood, Replication, T cell, Viral, viral replication, lymphocytopenia, Peripheral blood mononuclear cells, immune cells, PBMC, Viral RNA, T lymphocytes, respiratory, patients, B lymphocyte, COVID-19 patients, leukocytes, double-stranded RNA, hyperinflammatory state, immune dysfunction, Immune cell, COVID-19 patient, inflammatory state, B lymphocytes, mononuclear cells, leukocyte, mononuclear cell, symptom onset, disease pathogenesis, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, SARS-CoV-2 infection in vitro, virus spread, lung tissue, immunofluorescence analysis, hallmark, circulating leukocytes, Host, implication, susceptible, B and T lymphocytes, indicated, addition, appear, sustained, accumulating, CD4+ T lymphocyte, expressive, 【제목키워드】 in vitro, Human immune system, COVID-19 patient, infect, Cell,