Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity
Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity
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- dc.contributor.author
- Brunet-Ratnasingham, Elsa
- Morin, Sacha
- Randolph, Haley E.
- Labrecque, Marjorie
- Bélair, Justin
- Lima-Barbosa, Raphaël
- Pagliuzza, Amélie
- Marchitto, Lorie
- Hultström, Michael
- Niessl, Julia
- Cloutier, Rose
- Sreng Flores, Alina M.
- Brassard, Nathalie
- Benlarbi, Mehdi
- Prévost, Jérémie
- Ding, Shilei
- Anand, Sai Priya
- Sannier, Gérémy
- Bareke, Eric
- Zeberg, Hugo
- Lipcsey, Miklos
- Frithiof, Robert
- Larsson, Anders
- Zhou, Sirui
- Nakanishi, Tomoko
- Morrison, David
- Vezina, Dani
- Bourassa, Catherine
- Gendron-Lepage, Gabrielle
- Medjahed, Halima
- Richard, Jonathan
- Larochelle, Catherine
- Prat, Alexandre
- Arbour, Nathalie
- Durand, Madeleine
- Richards, J. Brent
- Moon, Kevin
- Chomont, Nicolas
- Finzi, Andrés
- Tétreault, Martine
- Barreiro, Luis
- Wolf, Guy
- Kaufmann, Daniel E.
- Point, Floriane
- dc.date.accepted
- 2023-06-01
- dc.date.accessioned
- 2025-01-27T20:04:47Z
- dc.date.available
- 2025-01-27T20:04:47Z
- dc.date.issued
- 2023-06-20
- dc.description.abstract - en
- 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 COVID-19 patients. Integrated analysis using k-means reveal 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 are delineated by high and low antibody responses. 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+ 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.
- dc.description.sponsorship
- This study was funded by the American Foundation for AIDS Research (amfAR) grant 110068-68-RGCV (DEK, NC, AF); Canada s COVID-19 Immunity Task Force (CITF), in collaboration with the Canadian Institutes of Health Research (CIHR) grant VR2-173203 (DEK, AF); CIHR grant # 178344 (DEK, AF); CIHR grants 365825 and 409511 (JBR); Canada Foundation for Innovation (CFI): Exceptional Fund COVID-19 grant #41027 to AF, DEK, NC; CFI leader to JBR. The Symphony flow cytometer was funded by a John R. Evans Leaders Fund from the Canada Foundation for Innovation (#37521 to D.E.K) and the Fondation Sclerodermie Quebec. The Ministere de l Economie et de l Innovation du Quebec, Programme de soutien aux organismes de recherche et d innovation (AF), CRCHUM Foundation. The Biobanque Quebecoise de la COVID-19 (BQC19) is supported by the Fonds de recherche Quebec Sante (FRQS) Genome Quebec and the Public Health Agency of Canada. DEK and JBR are FRQS Merit Research Scholars. NC, MD, MC, JBR, CL and MT are supported by FRQS Salary Awards. AF and AP are recipients of Canada Research Chairs. EBR is recipient of a COVID-19 excellence scholarship from the Universite de Montreal (EBR); SM is recipient of an IVADO MSc Excellence scholarship and a Fonds de recherche du Quebec Nature et technologies (FRQNT) B1X scholarship (SM); HER is supported by a National Institutes of Health (NIH) Ruth L. Kirschstein National Research Service Award (F31-HL156419); SPA, J.P., M.B. were supported by CIHR fellowships; G.S is supported by a FRQS doctoral fellowship and by a scholarship from the Department of Microbiology, Infectious Disease, and Immunology of the University of Montreal. The Pronmed study was funded by the SciLifeLab/Knut and Alice Wallenberg national COVID-19 research program (M.H.: KAW 2020.0182, KAW 2020.0241), the Swedish Heart-Lung Foundation (M.H.: 20210089, 20190639, 20190637), the Swedish Research Council (R.F.: 2014-02569, 2014-07606), the Swedish Kidney Foundation (R.F.: F2020-0054) and the Swedish Society of Medicine (M.H.: SLS-938101).
- dc.identifier.doi
- https://doi.org/10.1101/2023.06.14.23290814
- dc.identifier.uri
- https://open-science.canada.ca/handle/123456789/3365
- dc.language.iso
- en
- dc.publisher - en
- medRxiv
- dc.relation.isreplacedby
- https://doi.org/10.1038/s41467-024-48556-y
- dc.rights - en
- Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
- dc.rights - fr
- Creative Commons Attribution - Pas d'utilisation commerciale - Pas de modification 4.0 International (CC BY-NC-ND 4.0)
- dc.rights.uri - en
- https://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.rights.uri - fr
- https://creativecommons.org/licenses/by-nc-nd/4.0/deed.fr
- dc.subject - en
- Health
- Coronavirus diseases
- dc.subject - fr
- Santé
- Maladie à coronavirus
- dc.subject.en - en
- Health
- Coronavirus diseases
- dc.subject.fr - fr
- Santé
- Maladie à coronavirus
- dc.title - en
- Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity
- dc.type - en
- Article
- dc.type - fr
- Article
- local.pagination
- 1-57
- local.peerreview - en
- No
- local.peerreview - fr
- Non
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