Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.
Nat Commun
; 15(1): 4177, 2024 May 16.
Article
in En
| MEDLINE
| ID: mdl-38755196
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.
Full text:
1
Database:
MEDLINE
Main subject:
Signal Transduction
/
Interferons
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SARS-CoV-2
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COVID-19
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Antibodies, Viral
Limits:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Language:
En
Year:
2024
Type:
Article