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

Marjorie C. Pontelli; Ítalo A. Castro; Ronaldo B. Martins; Leonardo La Serra; Flávio P. Veras; Daniele C. Nascimento; Camila M. Silva; Ricardo S. Cardoso; Roberta Rosales; Rogerio Gomes; Thais M. Lima; Juliano P. Souza; Brenda C. Vitti; Diego B. Caetite; Mikhael H.F. De Lima; Spencer D. Stumpf; Cassandra E. Thompson; Louis Marie Bloyet; Juliana E. Toller-Kawahisa; Marcela C. Giannini; Letícia P. Bonjorno; Maria I.F. Lopes; Sabrina S. Batah; Li Siyuan; Rodrigo Luppino-Assad; Fabiola R. Oliveira; Maíra N. Benatti; Lorena L.F. Pontes; Rodrigo C. Santana; Fernando C. Vilar; Maria Auxiliadora-Martins; Pei Yong Shi; Thiago M. Cunha; Rodrigo T. Calado; Jose C. Alves-Filho; Dario S. Zamboni; Alexandre T. Fabro; Paulo Louzada-Junior; Rene D.R. Oliveira; Sean P.J. Whelan; Fernando Q. Cunha; Eurico Arruda

doi:10.1093/jmcb/mjac021

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

Marjorie C. Pontelli, Ítalo A. Castro, Ronaldo B. Martins, Leonardo La Serra, Flávio P. Veras, Daniele C. Nascimento, Camila M. Silva, Ricardo S. Cardoso, Roberta Rosales, Rogerio Gomes, Thais M. Lima, Juliano P. Souza, Brenda C. Vitti, Diego B. Caetite, Mikhael H.F. De Lima, Spencer D. Stumpf, Cassandra E. Thompson, Louis Marie Bloyet, Juliana E. Toller-Kawahisa, Marcela C. GianniniLetícia P. Bonjorno, Maria I.F. Lopes, Sabrina S. Batah, Li Siyuan, Rodrigo Luppino-Assad, Fabiola R. Oliveira, Maíra N. Benatti, Lorena L.F. Pontes, Rodrigo C. Santana, Fernando C. Vilar, Maria Auxiliadora-Martins, Pei Yong Shi, Thiago M. Cunha, Rodrigo T. Calado, Jose C. Alves-Filho, Dario S. Zamboni, Alexandre T. Fabro, Paulo Louzada-Junior, Rene D.R. Oliveira, Sean P.J. Whelan, Fernando Q. Cunha, Eurico Arruda

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	mjac021
Journal	Journal of Molecular Cell Biology
Volume	14
Issue number	4
DOIs	https://doi.org/10.1093/jmcb/mjac021
State	Published - Apr 1 2022

Keywords

COVID-19
SARS-CoV-2
apoptosis
lymphocytes
lymphocytopenia
monocytes
peripheral blood mononuclear cell (PBMC)

ASJC Scopus subject areas

General Medicine

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10.1093/jmcb/mjac021

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Pontelli, M. C., Castro, Í. A., Martins, R. B., La Serra, L., Veras, F. P., Nascimento, D. C., Silva, C. M., Cardoso, R. S., Rosales, R., Gomes, R., Lima, T. M., Souza, J. P., Vitti, B. C., Caetite, D. B., De Lima, M. H. F., Stumpf, S. D., Thompson, C. E., Bloyet, L. M., Toller-Kawahisa, J. E., ... Arruda, E. (2022). SARS-CoV-2 productively infects primary human immune system cells in vitro and in COVID-19 patients. Journal of Molecular Cell Biology, 14(4), Article mjac021. https://doi.org/10.1093/jmcb/mjac021

Pontelli, MC, Castro, ÍA, Martins, RB, La Serra, L, Veras, FP, Nascimento, DC, Silva, CM, Cardoso, RS, Rosales, R, Gomes, R, Lima, TM, Souza, JP, Vitti, BC, Caetite, DB, De Lima, MHF, Stumpf, SD, Thompson, CE, Bloyet, LM, Toller-Kawahisa, JE, Giannini, MC, Bonjorno, LP, Lopes, MIF, Batah, SS, Siyuan, L, Luppino-Assad, R, Oliveira, FR, Benatti, MN, Pontes, LLF, Santana, RC, Vilar, FC, Auxiliadora-Martins, M, Shi, PY, Cunha, TM, Calado, RT, Alves-Filho, JC, Zamboni, DS, Fabro, AT, Louzada-Junior, P, Oliveira, RDR, Whelan, SPJ, Cunha, FQ & Arruda, E 2022, 'SARS-CoV-2 productively infects primary human immune system cells in vitro and in COVID-19 patients', Journal of Molecular Cell Biology, vol. 14, no. 4, mjac021. https://doi.org/10.1093/jmcb/mjac021

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title = "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 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)",

author = "Pontelli, {Marjorie C.} and Castro, {{\'I}talo A.} and Martins, {Ronaldo B.} and {La Serra}, Leonardo and Veras, {Fl{\'a}vio P.} and Nascimento, {Daniele C.} and Silva, {Camila M.} and Cardoso, {Ricardo S.} and Roberta Rosales and Rogerio Gomes and Lima, {Thais M.} and Souza, {Juliano P.} and Vitti, {Brenda C.} and Caetite, {Diego B.} and {De Lima}, {Mikhael H.F.} and Stumpf, {Spencer D.} and Thompson, {Cassandra E.} and Bloyet, {Louis Marie} and Toller-Kawahisa, {Juliana E.} and Giannini, {Marcela C.} and Bonjorno, {Let{\'i}cia P.} and Lopes, {Maria I.F.} and Batah, {Sabrina S.} and Li Siyuan and Rodrigo Luppino-Assad and Oliveira, {Fabiola R.} and Benatti, {Ma{\'i}ra N.} and Pontes, {Lorena L.F.} and Santana, {Rodrigo C.} and Vilar, {Fernando C.} and Maria Auxiliadora-Martins and Shi, {Pei Yong} and Cunha, {Thiago M.} and Calado, {Rodrigo T.} and Alves-Filho, {Jose C.} and Zamboni, {Dario S.} and Fabro, {Alexandre T.} and Paulo Louzada-Junior and Oliveira, {Rene D.R.} and Whelan, {Sean P.J.} and Cunha, {Fernando Q.} and Eurico Arruda",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s) (2022). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.",

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doi = "10.1093/jmcb/mjac021",

language = "English (US)",

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T1 - SARS-CoV-2 productively infects primary human immune system cells in vitro and in COVID-19 patients

AU - Pontelli, Marjorie C.

AU - Castro, Ítalo A.

AU - Martins, Ronaldo B.

AU - La Serra, Leonardo

AU - Veras, Flávio P.

AU - Nascimento, Daniele C.

AU - Silva, Camila M.

AU - Cardoso, Ricardo S.

AU - Rosales, Roberta

AU - Gomes, Rogerio

AU - Lima, Thais M.

AU - Souza, Juliano P.

AU - Vitti, Brenda C.

AU - Caetite, Diego B.

AU - De Lima, Mikhael H.F.

AU - Stumpf, Spencer D.

AU - Thompson, Cassandra E.

AU - Bloyet, Louis Marie

AU - Toller-Kawahisa, Juliana E.

AU - Giannini, Marcela C.

AU - Bonjorno, Letícia P.

AU - Lopes, Maria I.F.

AU - Batah, Sabrina S.

AU - Siyuan, Li

AU - Luppino-Assad, Rodrigo

AU - Oliveira, Fabiola R.

AU - Benatti, Maíra N.

AU - Pontes, Lorena L.F.

AU - Santana, Rodrigo C.

AU - Vilar, Fernando C.

AU - Auxiliadora-Martins, Maria

AU - Shi, Pei Yong

AU - Cunha, Thiago M.

AU - Calado, Rodrigo T.

AU - Alves-Filho, Jose C.

AU - Zamboni, Dario S.

AU - Fabro, Alexandre T.

AU - Louzada-Junior, Paulo

AU - Oliveira, Rene D.R.

AU - Whelan, Sean P.J.

AU - Cunha, Fernando Q.

AU - Arruda, Eurico

PY - 2022/4/1

Y1 - 2022/4/1

N2 - 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.

AB - 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.

KW - COVID-19

KW - SARS-CoV-2

KW - apoptosis

KW - lymphocytes

KW - lymphocytopenia

KW - monocytes

KW - peripheral blood mononuclear cell (PBMC)

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U2 - 10.1093/jmcb/mjac021

DO - 10.1093/jmcb/mjac021

M3 - Article

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AN - SCOPUS:85136909910

SN - 1674-2788

VL - 14

JO - Journal of Molecular Cell Biology

JF - Journal of Molecular Cell Biology

IS - 4

M1 - mjac021

ER -

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

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Keywords

ASJC Scopus subject areas

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