Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.
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Brunet-Ratnasingham E, Morin S, Randolph HE, Labrecque M, Bélair J, Lima-Barbosa R, Pagliuzza A, Marchitto L, Hultström M, Niessl J, Cloutier R, Sreng Flores AM, Brassard N, Benlarbi M, Prévost J, Ding S, Anand SP, 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 JL, Arbour N, Durand M, Richards JB, Moon K, Chomont N, Finzi A, Tétreault M, Barreiro L, Wolf G, Kaufmann DE
Nat Commun 15 (1) 4177
[2024-05-16; online 2024-05-16]
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.
Category: Genomics & transcriptomics
Funder: KAW/SciLifeLab National COVID program
PubMed 38755196
DOI 10.1038/s41467-024-48556-y
Crossref 10.1038/s41467-024-48556-y
pii: 10.1038/s41467-024-48556-y