Journal Article

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

Nehar-Belaid, Djamel, García-Sastre, Adolfo, Marches, Radu, Ye, Fang, Mejías, Asunción, Xu, Zhaohui, Yerrabelli, Rushil, Banchereau, Jacques F., Mertz, Sara, Tsang, John S., Cupic, Anastasija, Ucar, Duygu, Miorin, Lisa, Chen, Guo, Sánchez, Pablo J., Aydillo, Teresa, Ramilo, Octavio, Pascual, Virginia

2025

Overview

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 (ISG hi ) state including: (i) CD14 + monocytes co-expressing ISGs and inflammasome-related molecules, (ii) ISG hi naive CD4 + T cells, (iii) ISG hi proliferating cytotoxic CD8 + T cells, and (iv) ISG hi 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. This work identified immune signatures of COVID-19 including broad Interferon signatures that are unique to infants. Compared with infected adults, infants display similar Interferon signatures in monocytes but enhanced signatures in T and B cells.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38 / 38/1 / 631/250/255 / 631/250/255/2514 / 631/326/596/4130 / 692/420/254 / Adult / Adults / Age / Antibodies, Viral - blood / Antibodies, Viral - immunology / Autoantibodies / Autoantibodies - blood / Autoantibodies - immunology / B-Lymphocytes - immunology / CD14 antigen / CD4 antigen / CD4-Positive T-Lymphocytes - immunology / CD8 antigen / CD8-Positive T-Lymphocytes - immunology / COVID-19 / COVID-19 - immunology / COVID-19 - virology / Cytokines / Cytokines - blood / Cytokines - immunology / Cytotoxicity / Dendritic cells / Female / Genes / Hospitalization / Humanities and Social Sciences / Humans / Immune response / Immune system / Infant / Infants / Infections / Inflammasomes / Interferon / Interferons - blood / Interferons - immunology / Leukocytes, Mononuclear - immunology / Lymphocytes / Lymphocytes B / Lymphocytes T / Male / Monocytes / Monocytes - immunology / multidisciplinary / Pandemics / Pediatrics / SARS-CoV-2 - immunology / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Severity of Illness Index / Signatures