SARS-CoV-2 productively infects primary human immune system cells <i>in vitro</i> and in COVID-19 patients
Marjorie Cornejo Pontelli, Ítalo A. Castro, Ronaldo B. Martins, Leonardo La Serra, Flávio P. Veras, Daniele C. Nascimento, Camila M. Silva, Ricardo de Souza Cardoso, Roberta Costa, Rogério Gomes, Thais M. Lima, Juliano P. Souza, Brenda Cristina Vitti, Diego B. Caetité, Mikhael Haruo Fernandes de Lima, Spencer Stumpf, Cassandra E. Thompson, Louis-Marie Bloyet, Juliana E. Toller-Kawahisa, Marcela C Giannini, Letícia Pastorelli Bonjorno, Maria Isabel Fernandes Lopes, Sabrina Setembre Batah, Li Siyuan, Rodrigo Luppino Assad, Sérgio C. L. Almeida, Fabíola Reis de Oliveira, Maíra Nilson Benatti, Lorena Lobo de Figueiredo‐Pontes, Rodrigo de Carvalho Santana, Fernando Crivelenti Vilar, Maria Auxiliadora‐Martins, Pei‐Yong Shi, Thiago M. Cunha, Rodrigo T. Calado, José C. Alves‐Filho, Dario S. Zamboni, Alexandre Todorovic Fabro, Paulo Louzada‐Júnior, Renê Donizeti Ribeiro de Oliveira, Sean P. J. Whelan, Fernando Q. Cunha, Eurico Arruda
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.