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

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 co...

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Vydané v:	Journal of molecular cell biology Ročník 14; číslo 4
Hlavní autori:	Pontelli, Marjorie C, Castro, Ítalo A, Martins, Ronaldo B, La Serra, Leonardo, Veras, Flávio P, Nascimento, Daniele C, Silva, Camila M, Cardoso, Ricardo S, Rosales, Roberta, Gomes, Rogério, Lima, Thais M, Souza, Juliano P, Vitti, Brenda C, Caetité, Diego B, de Lima, Mikhael H F, Stumpf, Spencer D, Thompson, Cassandra E, Bloyet, Louis-Marie, Toller-Kawahisa, Juliana E, Giannini, Marcela C, Bonjorno, Letícia P, Lopes, Maria I F, Batah, Sabrina S, Siyuan, Li, Luppino-Assad, Rodrigo, Almeida, Sergio C L, Oliveira, Fabiola R, Benatti, Maíra N, Pontes, Lorena L F, Santana, Rodrigo C, Vilar, Fernando C, Auxiliadora-Martins, Maria, Shi, Pei-Yong, Cunha, Thiago M, Calado, Rodrigo T, Alves-Filho, José C, Zamboni, Dario S, Fabro, Alexandre T, Louzada-Junior, Paulo, Oliveira, Rene D R, Whelan, Sean P J, Cunha, Fernando Q, Arruda, Eurico
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Oxford University Press 17.08.2022 Oxford UP
Predmet:	COVID-19 Cytokine Release Syndrome Humans Leukocytes, Mononuclear Life Sciences Microbiology and Parasitology Monocytes SARS-CoV-2 Virology COVID-19 monocytes SARS-CoV-2 lymphocytes apoptosis lymphocytopenia peripheral blood mononuclear cell (PBMC) Tropism Immune cells
ISSN:	1674-2788, 1759-4685, 1759-4685
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Abstract	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.
AbstractList	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. 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. 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. 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.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.
Author	Lopes, Maria I F Veras, Flávio P Souza, Juliano P Gomes, Rogério Caetité, Diego B Toller-Kawahisa, Juliana E de Lima, Mikhael H F Luppino-Assad, Rodrigo Whelan, Sean P J Castro, Ítalo A Calado, Rodrigo T Oliveira, Rene D R Martins, Ronaldo B Bloyet, Louis-Marie Almeida, Sergio C L Vitti, Brenda C Vilar, Fernando C Shi, Pei-Yong Giannini, Marcela C Alves-Filho, José C Fabro, Alexandre T Cunha, Fernando Q Siyuan, Li Pontes, Lorena L F Benatti, Maíra N La Serra, Leonardo Cardoso, Ricardo S Auxiliadora-Martins, Maria Louzada-Junior, Paulo Pontelli, Marjorie C Bonjorno, Letícia P Nascimento, Daniele C Silva, Camila M Rosales, Roberta Thompson, Cassandra E Arruda, Eurico Stumpf, Spencer D Batah, Sabrina S Lima, Thais M Santana, Rodrigo C Zamboni, Dario S Oliveira, Fabiola R Cunha, Thiago M
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Snippet	Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a hyperinflammatory state and lymphocytopenia, a... The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a hyperinflammatory state and lymphocytopenia, a hallmark that... Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a hyperinflammatory state and lymphocytopenia, a...
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SubjectTerms	COVID-19 Cytokine Release Syndrome Humans Leukocytes, Mononuclear Life Sciences Microbiology and Parasitology Monocytes SARS-CoV-2 Virology
Title	SARS-CoV-2 productively infects primary human immune system cells in vitro and in COVID-19 patients
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