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

Autor: 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, Marks, Amanda, Wågsäter, Dick
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Zdroj: Nature Communications; 10/29/2024, Vol. 15 Issue 1, p1-19, 19p
Abstrakt: 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 role of IFN signaling in SARS-CoV-2 infection and outcome is still debated. Here, the authors longitudinally profiled plasma samples from hospitalized patients and show that a persistent inflammatory response is linked to delayed generation of adaptive immunity and increased risk of death when coupled with severe infection. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index