T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID

BackgroundAs about 10% of patients with COVID-19 present sequelae, it is important to better understand the physiopathology of so-called long COVID.MethodTo this aim, we recruited 29 patients hospitalized for SARS-CoV-2 infection and, by Luminex®, quantified 19 soluble factors in their plasma and in...

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Main Authors: Renaud Cezar, Lucy Kundura, Sonia André, Claire Lozano, Thierry Vincent, Laurent Muller, Jean-Yves Lefrant, Claire Roger, Pierre-Géraud Claret, Sandra Duvnjak, Paul Loubet, Albert Sotto, Tu-Ahn Tran, Jérôme Estaquier, Pierre Corbeau
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-01-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1335352/full
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author Renaud Cezar
Lucy Kundura
Sonia André
Claire Lozano
Thierry Vincent
Laurent Muller
Jean-Yves Lefrant
Claire Roger
Pierre-Géraud Claret
Sandra Duvnjak
Paul Loubet
Albert Sotto
Tu-Ahn Tran
Jérôme Estaquier
Jérôme Estaquier
Pierre Corbeau
Pierre Corbeau
author_facet Renaud Cezar
Lucy Kundura
Sonia André
Claire Lozano
Thierry Vincent
Laurent Muller
Jean-Yves Lefrant
Claire Roger
Pierre-Géraud Claret
Sandra Duvnjak
Paul Loubet
Albert Sotto
Tu-Ahn Tran
Jérôme Estaquier
Jérôme Estaquier
Pierre Corbeau
Pierre Corbeau
author_sort Renaud Cezar
collection DOAJ
description BackgroundAs about 10% of patients with COVID-19 present sequelae, it is important to better understand the physiopathology of so-called long COVID.MethodTo this aim, we recruited 29 patients hospitalized for SARS-CoV-2 infection and, by Luminex®, quantified 19 soluble factors in their plasma and in the supernatant of their peripheral blood mononuclear cells, including inflammatory and anti-inflammatory cytokines and chemokines, Th1/Th2/Th17 cytokines, and endothelium activation markers. We also measured their T4, T8 and NK differentiation, activation, exhaustion and senescence, T cell apoptosis, and monocyte subpopulations by flow cytometry. We compared these markers between participants who developed long COVID or not one year later.ResultsNone of these markers was predictive for sequelae, except programmed T4 cell death. T4 lymphocytes from participants who later presented long COVID were more apoptotic in culture than those of sequelae-free participants at Month 12 (36.9 ± 14.7 vs. 24.2 ± 9.0%, p = 0.016).ConclusionsOur observation raises the hypothesis that T4 cell death during the acute phase of SARS-CoV-2 infection might pave the way for long COVID. Mechanistically, T4 lymphopenia might favor phenomena that could cause sequelae, including SARS-CoV-2 persistence, reactivation of other viruses, autoimmunity and immune dysregulation. In this scenario, inhibiting T cell apoptosis, for instance, by caspase inhibitors, could prevent long COVID.
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spelling doaj.art-d8b84236ac6c4142884fcaf274d018e32024-01-03T04:43:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011410.3389/fimmu.2023.13353521335352T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVIDRenaud Cezar0Lucy Kundura1Sonia André2Claire Lozano3Thierry Vincent4Laurent Muller5Jean-Yves Lefrant6Claire Roger7Pierre-Géraud Claret8Sandra Duvnjak9Paul Loubet10Albert Sotto11Tu-Ahn Tran12Jérôme Estaquier13Jérôme Estaquier14Pierre Corbeau15Pierre Corbeau16Immunology Department, Nîmes University Hospital, Nîmes, FranceInstitute of Human Genetics, UMR9002, Centre National de la Recherche Scientifique (CNRS) and Montpellier University, Montpellier, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM) U1124, Université de Paris, Paris, FranceImmunology Department, Montpellier University Hospital, Montpellier, FranceImmunology Department, Montpellier University Hospital, Montpellier, FranceSurgical Intensive Care Department, Nîmes University Hospital, Nîmes, FranceSurgical Intensive Care Department, Nîmes University Hospital, Nîmes, FranceSurgical Intensive Care Department, Nîmes University Hospital, Nîmes, FranceMedical and Surgical Emergency Department, Nîmes University Hospital, Nîmes, FranceGerontology Department, Nîmes University Hospital, Nîmes, FranceInfectious Diseases Department, Nîmes University Hospital, Nîmes, FranceInfectious Diseases Department, Nîmes University Hospital, Nîmes, FrancePediatrics Department, Nîmes University Hospital, Nîmes, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM) U1124, Université de Paris, Paris, France0Laval University Research Center, Quebec City, QC, CanadaImmunology Department, Nîmes University Hospital, Nîmes, FranceInstitute of Human Genetics, UMR9002, Centre National de la Recherche Scientifique (CNRS) and Montpellier University, Montpellier, FranceBackgroundAs about 10% of patients with COVID-19 present sequelae, it is important to better understand the physiopathology of so-called long COVID.MethodTo this aim, we recruited 29 patients hospitalized for SARS-CoV-2 infection and, by Luminex®, quantified 19 soluble factors in their plasma and in the supernatant of their peripheral blood mononuclear cells, including inflammatory and anti-inflammatory cytokines and chemokines, Th1/Th2/Th17 cytokines, and endothelium activation markers. We also measured their T4, T8 and NK differentiation, activation, exhaustion and senescence, T cell apoptosis, and monocyte subpopulations by flow cytometry. We compared these markers between participants who developed long COVID or not one year later.ResultsNone of these markers was predictive for sequelae, except programmed T4 cell death. T4 lymphocytes from participants who later presented long COVID were more apoptotic in culture than those of sequelae-free participants at Month 12 (36.9 ± 14.7 vs. 24.2 ± 9.0%, p = 0.016).ConclusionsOur observation raises the hypothesis that T4 cell death during the acute phase of SARS-CoV-2 infection might pave the way for long COVID. Mechanistically, T4 lymphopenia might favor phenomena that could cause sequelae, including SARS-CoV-2 persistence, reactivation of other viruses, autoimmunity and immune dysregulation. In this scenario, inhibiting T cell apoptosis, for instance, by caspase inhibitors, could prevent long COVID.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1335352/fullprogrammed cell deathpost-acute COVID-19 syndromeimmune activationhelper T lymphocyteSARS-CoV-2 infection sequelae
spellingShingle Renaud Cezar
Lucy Kundura
Sonia André
Claire Lozano
Thierry Vincent
Laurent Muller
Jean-Yves Lefrant
Claire Roger
Pierre-Géraud Claret
Sandra Duvnjak
Paul Loubet
Albert Sotto
Tu-Ahn Tran
Jérôme Estaquier
Jérôme Estaquier
Pierre Corbeau
Pierre Corbeau
T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID
Frontiers in Immunology
programmed cell death
post-acute COVID-19 syndrome
immune activation
helper T lymphocyte
SARS-CoV-2 infection sequelae
title T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID
title_full T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID
title_fullStr T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID
title_full_unstemmed T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID
title_short T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID
title_sort t4 apoptosis in the acute phase of sars cov 2 infection predicts long covid
topic programmed cell death
post-acute COVID-19 syndrome
immune activation
helper T lymphocyte
SARS-CoV-2 infection sequelae
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1335352/full
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