Journal
JOURNAL OF MOLECULAR CELL BIOLOGY
Volume 14, Issue 4, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jmcb/mjac021
Keywords
SARS-CoV-2; COVID-19; lymphocytopenia; peripheral blood mononuclear cell (PBMC); lymphocytes; monocytes; apoptosis
Categories
Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [310100/2017-8, 403201/2020-9, INCT 465539/2014-9]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2013/16349-2, 2014/02438-6]
- National Institutes of Health (NIH) [AI163019]
- CNPq [380849/2020-8]
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SARS-CoV-2 infection can lead to lymphocytopenia and infect immune cells such as monocytes, B cells, and T cells, resulting in T cell apoptosis. Additionally, SARS-CoV-2 is frequently detected in monocytes and B cells from 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.
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