SARS-CoV-2 induced immune perturbations in infants vary with disease severity and differ from adults’ responses

Djamel Nehar-Belaid, Asunción Mejías, Zhaohui Xu, Radu Marches, Rushil Yerrabelli, Guo Chen, Sara Mertz, Fang Ye, Pablo J. Sánchez, John S. Tsang, Teresa Aydillo, Lisa Miorin, Anastasija Cupic, Adolfo García-Sastre, Duygu Ucar, Jacques F. Banchereau (), Virginia Pascual () and Octavio Ramilo ()
Additional contact information
Djamel Nehar-Belaid: The Jackson Laboratory for Genomic Medicine
Asunción Mejías: Nationwide Children’s Hospital and The Ohio State University College of Medicine
Zhaohui Xu: Abigail Wexner Research Institute at Nationwide Children’s Hospital
Radu Marches: The Jackson Laboratory for Genomic Medicine
Rushil Yerrabelli: The Jackson Laboratory for Genomic Medicine
Guo Chen: The Jackson Laboratory for Genomic Medicine
Sara Mertz: Abigail Wexner Research Institute at Nationwide Children’s Hospital
Fang Ye: Abigail Wexner Research Institute at Nationwide Children’s Hospital
Pablo J. Sánchez: Abigail Wexner Research Institute at Nationwide Children’s Hospital
John S. Tsang: Yale University
Teresa Aydillo: Icahn School of Medicine at Mount Sinai
Lisa Miorin: Icahn School of Medicine at Mount Sinai
Anastasija Cupic: Icahn School of Medicine at Mount Sinai
Adolfo García-Sastre: Icahn School of Medicine at Mount Sinai
Duygu Ucar: The Jackson Laboratory for Genomic Medicine
Jacques F. Banchereau: The Jackson Laboratory for Genomic Medicine
Virginia Pascual: Weill Cornell Medicine
Octavio Ramilo: Nationwide Children’s Hospital and The Ohio State University College of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-59411-z

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