Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.
Details
Serval ID
serval:BIB_B53A83071D51
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.
Journal
Nature communications
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
16/05/2024
Peer-reviewed
Oui
Volume
15
Number
1
Pages
4177
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Abstract
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.
Keywords
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
Yes
Create date
21/05/2024 13:58
Last modification date
02/11/2024 7:10