Cargando…

Low perforin expression in CD8+ T lymphocytes during the acute phase of severe SARS-CoV-2 infection predicts long COVID

T cell cytotoxicity plays a major role in antiviral immunity. Anti-SARS-CoV-2 immunity may determine acute disease severity, but also the potential persistence of symptoms (long COVID). We therefore measured the expression of perforin, a cytotoxic mediator, in T cells of patients recently hospitaliz...

Descripción completa

Detalles Bibliográficos
Autores principales: Kundura, Lucy, Cezar, Renaud, André, Sonia, Campos-Mora, Mauricio, Lozano, Claire, Vincent, Thierry, Muller, Laurent, Lefrant, Jean-Yves, Roger, Claire, Claret, Pierre-Géraud, Duvnjak, Sandra, Loubet, Paul, Sotto, Albert, Tran, Tu-Ahn, Estaquier, Jérôme, Corbeau, Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630742/
https://www.ncbi.nlm.nih.gov/pubmed/36341327
http://dx.doi.org/10.3389/fimmu.2022.1029006
_version_ 1784823672328945664
author Kundura, Lucy
Cezar, Renaud
André, Sonia
Campos-Mora, Mauricio
Lozano, Claire
Vincent, Thierry
Muller, Laurent
Lefrant, Jean-Yves
Roger, Claire
Claret, Pierre-Géraud
Duvnjak, Sandra
Loubet, Paul
Sotto, Albert
Tran, Tu-Ahn
Estaquier, Jérôme
Corbeau, Pierre
author_facet Kundura, Lucy
Cezar, Renaud
André, Sonia
Campos-Mora, Mauricio
Lozano, Claire
Vincent, Thierry
Muller, Laurent
Lefrant, Jean-Yves
Roger, Claire
Claret, Pierre-Géraud
Duvnjak, Sandra
Loubet, Paul
Sotto, Albert
Tran, Tu-Ahn
Estaquier, Jérôme
Corbeau, Pierre
author_sort Kundura, Lucy
collection PubMed
description T cell cytotoxicity plays a major role in antiviral immunity. Anti-SARS-CoV-2 immunity may determine acute disease severity, but also the potential persistence of symptoms (long COVID). We therefore measured the expression of perforin, a cytotoxic mediator, in T cells of patients recently hospitalized for SARS-CoV-2 infection. We recruited 54 volunteers confirmed as being SARS-CoV-2-infected by RT-PCR and admitted to Intensive Care Units (ICUs) or non-ICU, and 29 age- and sex-matched healthy controls (HCs). Amounts of intracellular perforin and granzyme-B, as well as cell surface expression of the degranulation marker CD107A were determined by flow cytometry. The levels of 15 cytokines in plasma were measured by Luminex. The frequency of perforin-positive T4 cells and T8 cells was higher in patients than in HCs (9.9 ± 10.1% versus 4.6 ± 6.4%, p = 0.006 and 46.7 ± 20.6% vs 33.3 ± 18.8%, p = 0.004, respectively). Perforin expression was neither correlated with clinical and biological markers of disease severity nor predictive of death. By contrast, the percentage of perforin-positive T8 cells in the acute phase of the disease predicted the onset of long COVID one year later. A low T8 cytotoxicity in the first days of SARS-CoV-2 infection might favor virus replication and persistence, autoimmunity, and/or reactivation of other viruses such as Epstein-Barr virus or cytomegalovirus, paving the way for long COVID. Under this hypothesis, boosting T cell cytotoxicity during the acute phase of the infection could prevent delayed sequelae.
format Online
Article
Text
id pubmed-9630742
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-96307422022-11-04 Low perforin expression in CD8+ T lymphocytes during the acute phase of severe SARS-CoV-2 infection predicts long COVID Kundura, Lucy Cezar, Renaud André, Sonia Campos-Mora, Mauricio Lozano, Claire Vincent, Thierry Muller, Laurent Lefrant, Jean-Yves Roger, Claire Claret, Pierre-Géraud Duvnjak, Sandra Loubet, Paul Sotto, Albert Tran, Tu-Ahn Estaquier, Jérôme Corbeau, Pierre Front Immunol Immunology T cell cytotoxicity plays a major role in antiviral immunity. Anti-SARS-CoV-2 immunity may determine acute disease severity, but also the potential persistence of symptoms (long COVID). We therefore measured the expression of perforin, a cytotoxic mediator, in T cells of patients recently hospitalized for SARS-CoV-2 infection. We recruited 54 volunteers confirmed as being SARS-CoV-2-infected by RT-PCR and admitted to Intensive Care Units (ICUs) or non-ICU, and 29 age- and sex-matched healthy controls (HCs). Amounts of intracellular perforin and granzyme-B, as well as cell surface expression of the degranulation marker CD107A were determined by flow cytometry. The levels of 15 cytokines in plasma were measured by Luminex. The frequency of perforin-positive T4 cells and T8 cells was higher in patients than in HCs (9.9 ± 10.1% versus 4.6 ± 6.4%, p = 0.006 and 46.7 ± 20.6% vs 33.3 ± 18.8%, p = 0.004, respectively). Perforin expression was neither correlated with clinical and biological markers of disease severity nor predictive of death. By contrast, the percentage of perforin-positive T8 cells in the acute phase of the disease predicted the onset of long COVID one year later. A low T8 cytotoxicity in the first days of SARS-CoV-2 infection might favor virus replication and persistence, autoimmunity, and/or reactivation of other viruses such as Epstein-Barr virus or cytomegalovirus, paving the way for long COVID. Under this hypothesis, boosting T cell cytotoxicity during the acute phase of the infection could prevent delayed sequelae. Frontiers Media S.A. 2022-10-20 /pmc/articles/PMC9630742/ /pubmed/36341327 http://dx.doi.org/10.3389/fimmu.2022.1029006 Text en Copyright © 2022 Kundura, Cezar, André, Campos-Mora, Lozano, Vincent, Muller, Lefrant, Roger, Claret, Duvnjak, Loubet, Sotto, Tran, Estaquier and Corbeau https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Kundura, Lucy
Cezar, Renaud
André, Sonia
Campos-Mora, Mauricio
Lozano, Claire
Vincent, Thierry
Muller, Laurent
Lefrant, Jean-Yves
Roger, Claire
Claret, Pierre-Géraud
Duvnjak, Sandra
Loubet, Paul
Sotto, Albert
Tran, Tu-Ahn
Estaquier, Jérôme
Corbeau, Pierre
Low perforin expression in CD8+ T lymphocytes during the acute phase of severe SARS-CoV-2 infection predicts long COVID
title Low perforin expression in CD8+ T lymphocytes during the acute phase of severe SARS-CoV-2 infection predicts long COVID
title_full Low perforin expression in CD8+ T lymphocytes during the acute phase of severe SARS-CoV-2 infection predicts long COVID
title_fullStr Low perforin expression in CD8+ T lymphocytes during the acute phase of severe SARS-CoV-2 infection predicts long COVID
title_full_unstemmed Low perforin expression in CD8+ T lymphocytes during the acute phase of severe SARS-CoV-2 infection predicts long COVID
title_short Low perforin expression in CD8+ T lymphocytes during the acute phase of severe SARS-CoV-2 infection predicts long COVID
title_sort low perforin expression in cd8+ t lymphocytes during the acute phase of severe sars-cov-2 infection predicts long covid
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630742/
https://www.ncbi.nlm.nih.gov/pubmed/36341327
http://dx.doi.org/10.3389/fimmu.2022.1029006
work_keys_str_mv AT kunduralucy lowperforinexpressionincd8tlymphocytesduringtheacutephaseofseveresarscov2infectionpredictslongcovid
AT cezarrenaud lowperforinexpressionincd8tlymphocytesduringtheacutephaseofseveresarscov2infectionpredictslongcovid
AT andresonia lowperforinexpressionincd8tlymphocytesduringtheacutephaseofseveresarscov2infectionpredictslongcovid
AT camposmoramauricio lowperforinexpressionincd8tlymphocytesduringtheacutephaseofseveresarscov2infectionpredictslongcovid
AT lozanoclaire lowperforinexpressionincd8tlymphocytesduringtheacutephaseofseveresarscov2infectionpredictslongcovid
AT vincentthierry lowperforinexpressionincd8tlymphocytesduringtheacutephaseofseveresarscov2infectionpredictslongcovid
AT mullerlaurent lowperforinexpressionincd8tlymphocytesduringtheacutephaseofseveresarscov2infectionpredictslongcovid
AT lefrantjeanyves lowperforinexpressionincd8tlymphocytesduringtheacutephaseofseveresarscov2infectionpredictslongcovid
AT rogerclaire lowperforinexpressionincd8tlymphocytesduringtheacutephaseofseveresarscov2infectionpredictslongcovid
AT claretpierregeraud lowperforinexpressionincd8tlymphocytesduringtheacutephaseofseveresarscov2infectionpredictslongcovid
AT duvnjaksandra lowperforinexpressionincd8tlymphocytesduringtheacutephaseofseveresarscov2infectionpredictslongcovid
AT loubetpaul lowperforinexpressionincd8tlymphocytesduringtheacutephaseofseveresarscov2infectionpredictslongcovid
AT sottoalbert lowperforinexpressionincd8tlymphocytesduringtheacutephaseofseveresarscov2infectionpredictslongcovid
AT trantuahn lowperforinexpressionincd8tlymphocytesduringtheacutephaseofseveresarscov2infectionpredictslongcovid
AT estaquierjerome lowperforinexpressionincd8tlymphocytesduringtheacutephaseofseveresarscov2infectionpredictslongcovid
AT corbeaupierre lowperforinexpressionincd8tlymphocytesduringtheacutephaseofseveresarscov2infectionpredictslongcovid