Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.
Détails
Télécharger: 38755196.pdf (6183.08 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_B53A83071D51
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.
Périodique
Nature communications
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
16/05/2024
Peer-reviewed
Oui
Volume
15
Numéro
1
Pages
4177
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4 <sup>+</sup> T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.
Mots-clé
Humans, COVID-19/immunology, SARS-CoV-2/immunology, Antibodies, Viral/immunology, Antibodies, Viral/blood, Signal Transduction/immunology, Interferons/metabolism, Interferons/immunology, Female, Male, Middle Aged, Immunoglobulin G/blood, Immunoglobulin G/immunology, CD4-Positive T-Lymphocytes/immunology, Aged, Adult, Spike Glycoprotein, Coronavirus/immunology, Spike Glycoprotein, Coronavirus/metabolism, Spike Glycoprotein, Coronavirus/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
21/05/2024 13:58
Dernière modification de la notice
02/11/2024 7:10