Different polarization and functionality of CD4+ T helper subsets in people with post-COVID condition

Introduction: After mild COVID-19 that does not require hospitalization, some individuals develop persistent symptoms that may worsen over time, producing a multisystemic condition termed Post-COVID condition (PCC). Among other disorders, PCC is characterized by persistent changes in the immune syst...

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Autores: Sánchez-Menéndez, Clara, de la Calle-Jiménez, Olivia, Mateos, Elena, Vigon-Hernandez, Lorena, Fuertes, Daniel, Murciano-Antón, María Aranzazu, San José, Esther, García-Gutiérrez, Valentín, Cervero, Miguel, Torres, Montserrat, Coiras, Mayte
Formato: artículo
Fecha de publicación:2024
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/25373
Acesso em linha:https://hdl.handle.net/20.500.12105/25373
Access Level:acceso abierto
Palavra-chave:CD4+ T cells
T helper polarization
Th1
Th17
Th2
Cytokines
Post-covid condition
Adult
Aged
Male
Female
Humans
Middle Aged
CD4-Positive T-Lymphocytes
COVID-19
Post-Acute COVID-19 Syndrome
SARS-CoV-2
T-Lymphocytes, Helper-Inducer
Th1 Cells
Th17 Cells
Th2 Cells
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/25373
network_acronym_str ES
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repository_id_str
spelling Different polarization and functionality of CD4+ T helper subsets in people with post-COVID conditionSánchez-Menéndez, Clarade la Calle-Jiménez, OliviaMateos, ElenaVigon-Hernandez, LorenaFuertes, DanielMurciano-Antón, María AranzazuSan José, EstherGarcía-Gutiérrez, ValentínCervero, MiguelTorres, MontserratCoiras, MayteCD4+ T cellsT helper polarizationTh1Th17Th2CytokinesPost-covid conditionAdultAgedMaleFemaleHumansMiddle AgedCD4-Positive T-LymphocytesCOVID-19CytokinesPost-Acute COVID-19 SyndromeSARS-CoV-2T-Lymphocytes, Helper-InducerTh1 CellsTh17 CellsTh2 CellsIntroduction: After mild COVID-19 that does not require hospitalization, some individuals develop persistent symptoms that may worsen over time, producing a multisystemic condition termed Post-COVID condition (PCC). Among other disorders, PCC is characterized by persistent changes in the immune system that may not be solved several months after COVID-19 diagnosis. Methods: People with PCC were recruited to determine the distribution and functionality of CD4+ T helper (Th) subsets in comparison with individuals with mild, severe, and critical presentations of acute COVID-19 to evaluate their contribution as risk or protective factors for PCC. Results: People with PCC showed low levels of Th1 cells, similar to individuals with severe and critical COVID-19, although these cells presented a higher capacity to express IFNγ in response to stimulation. Th2/Th1 correlation was negative in individuals with acute forms of COVID-19, but there was no significant Th2/Th1 correlation in people with PCC. Th2 cells from people with PCC presented high capacity to express IL-4 and IL-13, which are related to low ventilation and death associated with COVID-19. Levels of proinflammatory Th9 and Th17 subsets were significantly higher in people with PCC in comparison with acute COVID-19, being Th1/Th9 correlation negative in these individuals, which probably contributed to a more pro-inflammatory than antiviral scenario. Th17 cells from approximately 50% of individuals with PCC had no capacity to express IL-17A and IL-22, similar to individuals with critical COVID-19, which would prevent clearing extracellular pathogens. Th2/Th17 correlation was positive in people with PCC, which in the absence of negative Th1/Th2 correlation could also contribute to the proinflammatory state. Finally, Th22 cells from most individuals with PCC had no capacity to express IL-13 or IL-22, which could increase tendency to reinfections due to impaired epithelial regeneration. Discussion: People with PCC showed skewed polarization of CD4+ Th subsets with altered functionality that was more similar to individuals with severe and critical presentations of acute COVID-19 than to people who fully recovered from mild disease. New strategies aimed at reprogramming the immune response and redirecting CD4+ Th cell polarization may be necessary to reduce the proinflammatory environment characteristic of PCC.Frontiers MediaMinisterio de Ciencia e Innovación (España)Instituto de Salud Carlos IIIUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal20242024-10-2920242024-01-0120242024-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/ziphttps://hdl.handle.net/20.500.12105/25373reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES PI22CIII 00059ES PID2022-141317OB-I00 Not availableES CB21 13ES CB21 13open accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/253732026-06-12T12:43:37Z
dc.title.none.fl_str_mv Different polarization and functionality of CD4+ T helper subsets in people with post-COVID condition
title Different polarization and functionality of CD4+ T helper subsets in people with post-COVID condition
spellingShingle Different polarization and functionality of CD4+ T helper subsets in people with post-COVID condition
Sánchez-Menéndez, Clara
CD4+ T cells
T helper polarization
Th1
Th17
Th2
Cytokines
Post-covid condition
Adult
Aged
Male
Female
Humans
Middle Aged
CD4-Positive T-Lymphocytes
COVID-19
Cytokines
Post-Acute COVID-19 Syndrome
SARS-CoV-2
T-Lymphocytes, Helper-Inducer
Th1 Cells
Th17 Cells
Th2 Cells
title_short Different polarization and functionality of CD4+ T helper subsets in people with post-COVID condition
title_full Different polarization and functionality of CD4+ T helper subsets in people with post-COVID condition
title_fullStr Different polarization and functionality of CD4+ T helper subsets in people with post-COVID condition
title_full_unstemmed Different polarization and functionality of CD4+ T helper subsets in people with post-COVID condition
title_sort Different polarization and functionality of CD4+ T helper subsets in people with post-COVID condition
dc.creator.none.fl_str_mv Sánchez-Menéndez, Clara
de la Calle-Jiménez, Olivia
Mateos, Elena
Vigon-Hernandez, Lorena
Fuertes, Daniel
Murciano-Antón, María Aranzazu
San José, Esther
García-Gutiérrez, Valentín
Cervero, Miguel
Torres, Montserrat
Coiras, Mayte
author Sánchez-Menéndez, Clara
author_facet Sánchez-Menéndez, Clara
de la Calle-Jiménez, Olivia
Mateos, Elena
Vigon-Hernandez, Lorena
Fuertes, Daniel
Murciano-Antón, María Aranzazu
San José, Esther
García-Gutiérrez, Valentín
Cervero, Miguel
Torres, Montserrat
Coiras, Mayte
author_role author
author2 de la Calle-Jiménez, Olivia
Mateos, Elena
Vigon-Hernandez, Lorena
Fuertes, Daniel
Murciano-Antón, María Aranzazu
San José, Esther
García-Gutiérrez, Valentín
Cervero, Miguel
Torres, Montserrat
Coiras, Mayte
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Instituto de Salud Carlos III
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal
dc.subject.none.fl_str_mv CD4+ T cells
T helper polarization
Th1
Th17
Th2
Cytokines
Post-covid condition
Adult
Aged
Male
Female
Humans
Middle Aged
CD4-Positive T-Lymphocytes
COVID-19
Cytokines
Post-Acute COVID-19 Syndrome
SARS-CoV-2
T-Lymphocytes, Helper-Inducer
Th1 Cells
Th17 Cells
Th2 Cells
topic CD4+ T cells
T helper polarization
Th1
Th17
Th2
Cytokines
Post-covid condition
Adult
Aged
Male
Female
Humans
Middle Aged
CD4-Positive T-Lymphocytes
COVID-19
Cytokines
Post-Acute COVID-19 Syndrome
SARS-CoV-2
T-Lymphocytes, Helper-Inducer
Th1 Cells
Th17 Cells
Th2 Cells
description Introduction: After mild COVID-19 that does not require hospitalization, some individuals develop persistent symptoms that may worsen over time, producing a multisystemic condition termed Post-COVID condition (PCC). Among other disorders, PCC is characterized by persistent changes in the immune system that may not be solved several months after COVID-19 diagnosis. Methods: People with PCC were recruited to determine the distribution and functionality of CD4+ T helper (Th) subsets in comparison with individuals with mild, severe, and critical presentations of acute COVID-19 to evaluate their contribution as risk or protective factors for PCC. Results: People with PCC showed low levels of Th1 cells, similar to individuals with severe and critical COVID-19, although these cells presented a higher capacity to express IFNγ in response to stimulation. Th2/Th1 correlation was negative in individuals with acute forms of COVID-19, but there was no significant Th2/Th1 correlation in people with PCC. Th2 cells from people with PCC presented high capacity to express IL-4 and IL-13, which are related to low ventilation and death associated with COVID-19. Levels of proinflammatory Th9 and Th17 subsets were significantly higher in people with PCC in comparison with acute COVID-19, being Th1/Th9 correlation negative in these individuals, which probably contributed to a more pro-inflammatory than antiviral scenario. Th17 cells from approximately 50% of individuals with PCC had no capacity to express IL-17A and IL-22, similar to individuals with critical COVID-19, which would prevent clearing extracellular pathogens. Th2/Th17 correlation was positive in people with PCC, which in the absence of negative Th1/Th2 correlation could also contribute to the proinflammatory state. Finally, Th22 cells from most individuals with PCC had no capacity to express IL-13 or IL-22, which could increase tendency to reinfections due to impaired epithelial regeneration. Discussion: People with PCC showed skewed polarization of CD4+ Th subsets with altered functionality that was more similar to individuals with severe and critical presentations of acute COVID-19 than to people who fully recovered from mild disease. New strategies aimed at reprogramming the immune response and redirecting CD4+ Th cell polarization may be necessary to reduce the proinflammatory environment characteristic of PCC.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-10-29
2024
2024-01-01
2024
2024-01-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.12105/25373
url https://hdl.handle.net/20.500.12105/25373
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv ES PI22CIII 00059
ES PID2022-141317OB-I00 Not available
ES CB21 13
ES CB21 13
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/zip
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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