Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.

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State: Public
Version: Final published version
License: CC BY 4.0
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
Author(s)
Brunet-Ratnasingham E., Morin S., Randolph H.E., Labrecque M., Bélair J., Lima-Barbosa R., Pagliuzza A., Marchitto L., Hultström M., Niessl J., Cloutier R., Sreng Flores A.M., Brassard N., Benlarbi M., Prévost J., Ding S., Anand S.P., Sannier G., Marks A., Wågsäter D., Bareke E., Zeberg H., Lipcsey M., Frithiof R., Larsson A., Zhou S., Nakanishi T., Morrison D., Vezina D., Bourassa C., Gendron-Lepage G., Medjahed H., Point F., Richard J., Larochelle C., Prat A., Cunningham J.L., Arbour N., Durand M., Richards J.B., Moon K., Chomont N., Finzi A., Tétreault M., Barreiro L., Wolf G., Kaufmann D.E.
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
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
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