SARS-CoV-2 productively infects primary human immune system cells in vitro and in COVID-19 patients

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Pontelli, Marjorie | Castro, Ítalo | Martins, Ronaldo | La Serra, Leonardo | Veras, Flávio | Nascimento, Daniele | Silva, Camila | Cardoso, Ricardo | Rosales, Roberta | Gomes, Rogério | Lima, Thais | Souza, Juliano | Vitti, Brenda | Caetité, Diego | de Lima, Mikhael | Stumpf, Spencer | Thompson, Cassandra | Bloyet, Louis-Marie | Toller-Kawahisa, Juliana | Giannini, Marcela | Bonjorno, Letícia | Lopes, Maria | Batah, Sabrina | Siyuan, Li | Luppino-Assad, Rodrigo | Almeida, Sergio | Oliveira, Fabiola | Benatti, Maíra | Pontes, Lorena | Santana, Rodrigo | Vilar, Fernando | Auxiliadora-Martins, Maria | Shi, Pei-Yong | Cunha, Thiago | Calado, Rodrigo | Alves-Filho, José | Zamboni, Dario | Fabro, Alexandre | Louzada-Junior, Paulo | Oliveira, Rene | Whelan, Sean | Cunha, Fernando | Arruda, Eurico

Edité par CCSD ; Oxford UP -

International audience. 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.

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