T cell apoptosis characterizes severe Covid-19 disease

Sonia André; Morgane Picard; Renaud Cezar; Florence Roux-Dalvai; Aurélie Alleaume-Butaux; Calaiselvy Soundaramourty; André Santa Cruz; Ana Mendes-Frias; Clarisse Gotti; Mickaël Leclercq; Alexandre Nicolas; Alexandra Tauzin; Alexandre Carvalho; Carlos Capela; Jorge Pedrosa; António Gil Castro; Lucy Kundura; Paul Loubet; Albert Sotto; Laurent Muller; Jean Yves Lefrant; Claire Roger; Pierre Géraud Claret; Sandra Duvnjak; Tu Anh Tran; Gina Racine; Ouafa Zghidi-Abouzid; Pierre Nioche; Ricardo Silvestre; Arnaud Droit; Fabrizio Mammano; Pierre Corbeau; Jérôme Estaquier

doi:10.1038/s41418-022-00936-x

T cell apoptosis characterizes severe Covid-19 disease

Sonia André, Morgane Picard, Renaud Cezar, Florence Roux-Dalvai, Aurélie Alleaume-Butaux, Calaiselvy Soundaramourty, André Santa Cruz, Ana Mendes-Frias, Clarisse Gotti, Mickaël Leclercq, Alexandre Nicolas, Alexandra Tauzin, Alexandre Carvalho, Carlos Capela, Jorge Pedrosa, António Gil Castro, Lucy Kundura, Paul Loubet, Albert Sotto, Laurent MullerJean Yves Lefrant, Claire Roger, Pierre Géraud Claret, Sandra Duvnjak, Tu Anh Tran, Gina Racine, Ouafa Zghidi-Abouzid, Pierre Nioche, Ricardo Silvestre, Arnaud Droit, Fabrizio Mammano, Pierre Corbeau, Jérôme Estaquier

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

Abstract

Severe SARS-CoV-2 infections are characterized by lymphopenia, but the mechanisms involved are still elusive. Based on our knowledge of HIV pathophysiology, we hypothesized that SARS-CoV-2 infection-mediated lymphopenia could also be related to T cell apoptosis. By comparing intensive care unit (ICU) and non-ICU COVID-19 patients with age-matched healthy donors, we found a strong positive correlation between plasma levels of soluble FasL (sFasL) and T cell surface expression of Fas/CD95 with the propensity of T cells to die and CD4 T cell counts. Plasma levels of sFasL and T cell death are correlated with CXCL10 which is part of the signature of 4 biomarkers of disease severity (ROC, 0.98). We also found that members of the Bcl-2 family had modulated in the T cells of COVID-19 patients. More importantly, we demonstrated that the pan-caspase inhibitor, Q-VD, prevents T cell death by apoptosis and enhances Th1 transcripts. Altogether, our results are compatible with a model in which T-cell apoptosis accounts for T lymphopenia in individuals with severe COVID-19. Therefore, a strategy aimed at blocking caspase activation could be beneficial for preventing immunodeficiency in COVID-19 patients.

Original language	English
Pages (from-to)	1486-1499
Number of pages	14
Journal	Cell Death and Differentiation
Volume	29
Issue number	8
DOIs	https://doi.org/10.1038/s41418-022-00936-x
Publication status	Published - 1 Aug 2022
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41418-022-00936-x

Cite this

André, S., Picard, M., Cezar, R., Roux-Dalvai, F., Alleaume-Butaux, A., Soundaramourty, C., Cruz, A. S., Mendes-Frias, A., Gotti, C., Leclercq, M., Nicolas, A., Tauzin, A., Carvalho, A., Capela, C., Pedrosa, J., Castro, A. G., Kundura, L., Loubet, P., Sotto, A., ... Estaquier, J. (2022). T cell apoptosis characterizes severe Covid-19 disease. Cell Death and Differentiation, 29(8), 1486-1499. https://doi.org/10.1038/s41418-022-00936-x

@article{6910dae001954008a622ce0d2ff0e7e0,

title = "T cell apoptosis characterizes severe Covid-19 disease",

abstract = "Severe SARS-CoV-2 infections are characterized by lymphopenia, but the mechanisms involved are still elusive. Based on our knowledge of HIV pathophysiology, we hypothesized that SARS-CoV-2 infection-mediated lymphopenia could also be related to T cell apoptosis. By comparing intensive care unit (ICU) and non-ICU COVID-19 patients with age-matched healthy donors, we found a strong positive correlation between plasma levels of soluble FasL (sFasL) and T cell surface expression of Fas/CD95 with the propensity of T cells to die and CD4 T cell counts. Plasma levels of sFasL and T cell death are correlated with CXCL10 which is part of the signature of 4 biomarkers of disease severity (ROC, 0.98). We also found that members of the Bcl-2 family had modulated in the T cells of COVID-19 patients. More importantly, we demonstrated that the pan-caspase inhibitor, Q-VD, prevents T cell death by apoptosis and enhances Th1 transcripts. Altogether, our results are compatible with a model in which T-cell apoptosis accounts for T lymphopenia in individuals with severe COVID-19. Therefore, a strategy aimed at blocking caspase activation could be beneficial for preventing immunodeficiency in COVID-19 patients.",

author = "Sonia Andr{\'e} and Morgane Picard and Renaud Cezar and Florence Roux-Dalvai and Aur{\'e}lie Alleaume-Butaux and Calaiselvy Soundaramourty and Cruz, \{Andr{\'e} Santa\} and Ana Mendes-Frias and Clarisse Gotti and Micka{\"e}l Leclercq and Alexandre Nicolas and Alexandra Tauzin and Alexandre Carvalho and Carlos Capela and Jorge Pedrosa and Castro, \{Ant{\'o}nio Gil\} and Lucy Kundura and Paul Loubet and Albert Sotto and Laurent Muller and Lefrant, \{Jean Yves\} and Claire Roger and Claret, \{Pierre G{\'e}raud\} and Sandra Duvnjak and Tran, \{Tu Anh\} and Gina Racine and Ouafa Zghidi-Abouzid and Pierre Nioche and Ricardo Silvestre and Arnaud Droit and Fabrizio Mammano and Pierre Corbeau and J{\'e}r{\^o}me Estaquier",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = aug,

day = "1",

doi = "10.1038/s41418-022-00936-x",

language = "English",

volume = "29",

pages = "1486--1499",

journal = "Cell Death and Differentiation",

issn = "1350-9047",

number = "8",

}

André, S, Picard, M, Cezar, R, Roux-Dalvai, F, Alleaume-Butaux, A, Soundaramourty, C, Cruz, AS, Mendes-Frias, A, Gotti, C, Leclercq, M, Nicolas, A, Tauzin, A, Carvalho, A, Capela, C, Pedrosa, J, Castro, AG, Kundura, L, Loubet, P, Sotto, A, Muller, L, Lefrant, JY, Roger, C, Claret, PG, Duvnjak, S, Tran, TA, Racine, G, Zghidi-Abouzid, O, Nioche, P, Silvestre, R, Droit, A, Mammano, F, Corbeau, P & Estaquier, J 2022, 'T cell apoptosis characterizes severe Covid-19 disease', Cell Death and Differentiation, vol. 29, no. 8, pp. 1486-1499. https://doi.org/10.1038/s41418-022-00936-x

TY - JOUR

T1 - T cell apoptosis characterizes severe Covid-19 disease

AU - André, Sonia

AU - Picard, Morgane

AU - Cezar, Renaud

AU - Roux-Dalvai, Florence

AU - Alleaume-Butaux, Aurélie

AU - Soundaramourty, Calaiselvy

AU - Cruz, André Santa

AU - Mendes-Frias, Ana

AU - Gotti, Clarisse

AU - Leclercq, Mickaël

AU - Nicolas, Alexandre

AU - Tauzin, Alexandra

AU - Carvalho, Alexandre

AU - Capela, Carlos

AU - Pedrosa, Jorge

AU - Castro, António Gil

AU - Kundura, Lucy

AU - Loubet, Paul

AU - Sotto, Albert

AU - Muller, Laurent

AU - Lefrant, Jean Yves

AU - Roger, Claire

AU - Claret, Pierre Géraud

AU - Duvnjak, Sandra

AU - Tran, Tu Anh

AU - Racine, Gina

AU - Zghidi-Abouzid, Ouafa

AU - Nioche, Pierre

AU - Silvestre, Ricardo

AU - Droit, Arnaud

AU - Mammano, Fabrizio

AU - Corbeau, Pierre

AU - Estaquier, Jérôme

PY - 2022/8/1

Y1 - 2022/8/1

N2 - Severe SARS-CoV-2 infections are characterized by lymphopenia, but the mechanisms involved are still elusive. Based on our knowledge of HIV pathophysiology, we hypothesized that SARS-CoV-2 infection-mediated lymphopenia could also be related to T cell apoptosis. By comparing intensive care unit (ICU) and non-ICU COVID-19 patients with age-matched healthy donors, we found a strong positive correlation between plasma levels of soluble FasL (sFasL) and T cell surface expression of Fas/CD95 with the propensity of T cells to die and CD4 T cell counts. Plasma levels of sFasL and T cell death are correlated with CXCL10 which is part of the signature of 4 biomarkers of disease severity (ROC, 0.98). We also found that members of the Bcl-2 family had modulated in the T cells of COVID-19 patients. More importantly, we demonstrated that the pan-caspase inhibitor, Q-VD, prevents T cell death by apoptosis and enhances Th1 transcripts. Altogether, our results are compatible with a model in which T-cell apoptosis accounts for T lymphopenia in individuals with severe COVID-19. Therefore, a strategy aimed at blocking caspase activation could be beneficial for preventing immunodeficiency in COVID-19 patients.

AB - Severe SARS-CoV-2 infections are characterized by lymphopenia, but the mechanisms involved are still elusive. Based on our knowledge of HIV pathophysiology, we hypothesized that SARS-CoV-2 infection-mediated lymphopenia could also be related to T cell apoptosis. By comparing intensive care unit (ICU) and non-ICU COVID-19 patients with age-matched healthy donors, we found a strong positive correlation between plasma levels of soluble FasL (sFasL) and T cell surface expression of Fas/CD95 with the propensity of T cells to die and CD4 T cell counts. Plasma levels of sFasL and T cell death are correlated with CXCL10 which is part of the signature of 4 biomarkers of disease severity (ROC, 0.98). We also found that members of the Bcl-2 family had modulated in the T cells of COVID-19 patients. More importantly, we demonstrated that the pan-caspase inhibitor, Q-VD, prevents T cell death by apoptosis and enhances Th1 transcripts. Altogether, our results are compatible with a model in which T-cell apoptosis accounts for T lymphopenia in individuals with severe COVID-19. Therefore, a strategy aimed at blocking caspase activation could be beneficial for preventing immunodeficiency in COVID-19 patients.

U2 - 10.1038/s41418-022-00936-x

DO - 10.1038/s41418-022-00936-x

M3 - Article

C2 - 35066575

AN - SCOPUS:85123499233

SN - 1350-9047

VL - 29

SP - 1486

EP - 1499

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

IS - 8

ER -

T cell apoptosis characterizes severe Covid-19 disease

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this