%0 Journal Article
%A Brunet-Ratnasingham, Elsa
%A Morin, Sacha
%A Randolph, Haley E.
%A Labrecque, Marjorie
%A Bélair, Justin
%A Lima-Barbosa, Raphaël
%A Pagliuzza, Amélie
%A Marchitto, Lorie
%A Hultström, Michael
%A Niessl, Julia
%A Cloutier, Rose
%A Sreng Flores, Alina M.
%A Brassard, Nathalie
%A Benlarbi, Mehdi
%A Prévost, Jérémie
%A Ding, Shilei
%A Anand, Sai Priya
%A Sannier, Gérémy
%A Marks, Amanda
%A Wågsäter, Dick
%A Bareke, Eric
%A Zeberg, Hugo
%A Lipcsey, Miklos
%A Frithiof, Robert
%A Larsson, Anders
%A Zhou, Sirui
%A Nakanishi, Tomoko
%A Morrison, David
%A Vezina, Dani
%A Bourassa, Catherine
%A Gendron-Lepage, Gabrielle
%A Medjahed, Halima
%A Point, Floriane
%A Richard, Jonathan
%A Larochelle, Catherine
%A Prat, Alexandre
%A Cunningham, Janet L.
%A Arbour, Nathalie
%A Durand, Madeleine
%A Richards, J. Brent
%A Moon, Kevin
%A Chomont, Nicolas
%A Finzi, Andrés
%A Tétreault, Martine
%A Barreiro, Luis
%A Wolf, Guy
%A Kaufmann, Daniel E.
%+ Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
%T Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity : 
%G eng
%U https://hdl.handle.net/21.11116/0000-000F-58BB-C
%R 10.1038/s41467-024-48556-y
%7 2024-05-16
%D 2024
%8 16.05.2024
%* Review method: peer-reviewed
%X 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+ 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. © The Author(s) 2024.
%K Adult; Aged; Antibodies, Viral; CD4-Positive T-Lymphocytes; COVID-19; Female; Humans; Immunoglobulin G; Interferons; Male; Middle Aged; SARS-CoV-2; Signal Transduction; Spike Glycoprotein, Coronavirus
%J Nature Communications
%V 15
%] 4177
%@ 2041-1723