학술논문
Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity
Document Type
article
Author
Elsa Brunet-Ratnasingham; Sacha Morin; Haley E. Randolph; Marjorie Labrecque; Justin Bélair; Raphaël Lima-Barbosa; Amélie Pagliuzza; Lorie Marchitto; Michael Hultström; Julia Niessl; Rose Cloutier; Alina M. Sreng Flores; Nathalie Brassard; Mehdi Benlarbi; Jérémie Prévost; Shilei Ding; Sai Priya Anand; Gérémy Sannier; Amanda Marks; Dick Wågsäter; Eric Bareke; Hugo Zeberg; Miklos Lipcsey; Robert Frithiof; Anders Larsson; Sirui Zhou; Tomoko Nakanishi; David Morrison; Dani Vezina; Catherine Bourassa; Gabrielle Gendron-Lepage; Halima Medjahed; Floriane Point; Jonathan Richard; Catherine Larochelle; Alexandre Prat; Janet L. Cunningham; Nathalie Arbour; Madeleine Durand; J. Brent Richards; Kevin Moon; Nicolas Chomont; Andrés Finzi; Martine Tétreault; Luis Barreiro; Guy Wolf; Daniel E. Kaufmann
Source
Nature Communications, Vol 15, Iss 1, Pp 1-19 (2024)
Subject
Language
English
ISSN
2041-1723
Abstract
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+ 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.