Title | SARS-CoV-2 induced immune perturbations in infants vary with disease severity and differ from adults' responses. |
Publication Type | Journal Article |
Year of Publication | 2025 |
Authors | Nehar-Belaid D, Mejias A, Xu Z, Marches R, Yerrabelli R, Chen G, Mertz S, Ye F, Sánchez PJ, Tsang JS, Aydillo T, Miorin L, Cupic A, García-Sastre A, Ucar D, Banchereau JF, Pascual V, Ramilo O |
Journal | Nat Commun |
Volume | 16 |
Issue | 1 |
Pagination | 4562 |
Date Published | 2025 May 16 |
ISSN | 2041-1723 |
Keywords | Adult, Antibodies, Viral, Autoantibodies, B-Lymphocytes, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, COVID-19, Cytokines, Female, Humans, Infant, Interferons, Leukocytes, Mononuclear, Male, Monocytes, SARS-CoV-2, Severity of Illness Index |
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. |
DOI | 10.1038/s41467-025-59411-z |
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Alternate Journal | Nat Commun |
PubMed ID | 40379618 |
PubMed Central ID | PMC12084365 |
Grant List | U01AI131386 / / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) / |