Document Type

Article

Publication Date

5-16-2025

Keywords

JGM, SS1, Humans, COVID-19, Infant, SARS-CoV-2, Adult, Female, Male, Severity of Illness Index, Interferons, Cytokines, Antibodies, Viral, Monocytes, CD4-Positive T-Lymphocytes, Leukocytes, Mononuclear, CD8-Positive T-Lymphocytes, Autoantibodies, B-Lymphocytes

JAX Source

Nat Commun. 2025;16(1):4562.

ISSN

2041-1723

PMID

40379618

DOI

https://doi.org/10.1038/s41467-025-59411-z

Grant

These shared services are supported in part by the JAX Cancer Center (P30 CA034196)

Abstract

Differences in immune profiles of children and adults with COVID-19 have been previously described. However, no systematic studies have been reported from infants hospitalized with severe disease. We applied a multidimensional approach to decipher the immune responses of SARS-CoV-2 infected infants (n = 26; 10 subacute, 11 moderate and 5 severe disease; median age = 1.6 months) and matched controls (n = 14; median age = 2 months). Single cell (scRNA-seq) profiling of PBMCs revealed substantial alterations in cell composition in SARS-CoV-2 infected infants; with most cell-types switching to an interferon-stimulated gene (ISGhi) state including: (i) CD14+ monocytes co-expressing ISGs and inflammasome-related molecules, (ii) ISGhi naive CD4+ T cells, (iii) ISGhi proliferating cytotoxic CD8+ T cells, and (iv) ISGhi naive and transitional B cells. We observe increased serum concentrations of both interferons and inflammatory cytokines in infected infants. Antibody responses to SARS-CoV-2 are also consistently detected in the absence of anti-IFN autoantibodies. Compared with infected adults, infants display a similar ISG signature in monocytes but a markedly enhanced ISG signature in T and B cells. These findings provide insights into the distinct immune responses to SARS-CoV-2 in the first year of life and underscore the importance of further defining the unique features of early life immunity.

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