tetano
Editor, Senior Moderator
Nat Commun
. 2025 May 16;16(1):4562.
doi: 10.1038/s41467-025-59411-z. SARS-CoV-2 induced immune perturbations in infants vary with disease severity and differ from adults' responses
Djamel Nehar-Belaid[SUP] #[/SUP][SUP] 1 [/SUP], Asunción Mejías[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Zhaohui Xu[SUP] 3 4 [/SUP], Radu Marches[SUP] 1 [/SUP], Rushil Yerrabelli[SUP] 1 [/SUP], Guo Chen[SUP] 1 [/SUP], Sara Mertz[SUP] 3 [/SUP], Fang Ye[SUP] 3 [/SUP], Pablo J Sánchez[SUP] 5 [/SUP], John S Tsang[SUP] 6 7 8 [/SUP], Teresa Aydillo[SUP] 9 10 [/SUP], Lisa Miorin[SUP] 9 10 [/SUP], Anastasija Cupic[SUP] 9 10 [/SUP], Adolfo García-Sastre[SUP] 9 10 11 12 13 14 15 [/SUP], Duygu Ucar[SUP] 1 [/SUP], Jacques F Banchereau[SUP] 16 17 [/SUP], Virginia Pascual[SUP] 18 [/SUP], Octavio Ramilo[SUP] 19 20 21 [/SUP]
Affiliations
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[SUP]hi[/SUP]) state including: (i) CD14[SUP]+[/SUP] monocytes co-expressing ISGs and inflammasome-related molecules, (ii) ISG[SUP]hi[/SUP] naive CD4[SUP]+[/SUP] T cells, (iii) ISG[SUP]hi[/SUP] proliferating cytotoxic CD8[SUP]+[/SUP] T cells, and (iv) ISG[SUP]hi[/SUP] 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.
. 2025 May 16;16(1):4562.
doi: 10.1038/s41467-025-59411-z. SARS-CoV-2 induced immune perturbations in infants vary with disease severity and differ from adults' responses
Djamel Nehar-Belaid[SUP] #[/SUP][SUP] 1 [/SUP], Asunción Mejías[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Zhaohui Xu[SUP] 3 4 [/SUP], Radu Marches[SUP] 1 [/SUP], Rushil Yerrabelli[SUP] 1 [/SUP], Guo Chen[SUP] 1 [/SUP], Sara Mertz[SUP] 3 [/SUP], Fang Ye[SUP] 3 [/SUP], Pablo J Sánchez[SUP] 5 [/SUP], John S Tsang[SUP] 6 7 8 [/SUP], Teresa Aydillo[SUP] 9 10 [/SUP], Lisa Miorin[SUP] 9 10 [/SUP], Anastasija Cupic[SUP] 9 10 [/SUP], Adolfo García-Sastre[SUP] 9 10 11 12 13 14 15 [/SUP], Duygu Ucar[SUP] 1 [/SUP], Jacques F Banchereau[SUP] 16 17 [/SUP], Virginia Pascual[SUP] 18 [/SUP], Octavio Ramilo[SUP] 19 20 21 [/SUP]
Affiliations
- PMID: 40379618
- PMCID: PMC12084365
- DOI: 10.1038/s41467-025-59411-z
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[SUP]hi[/SUP]) state including: (i) CD14[SUP]+[/SUP] monocytes co-expressing ISGs and inflammasome-related molecules, (ii) ISG[SUP]hi[/SUP] naive CD4[SUP]+[/SUP] T cells, (iii) ISG[SUP]hi[/SUP] proliferating cytotoxic CD8[SUP]+[/SUP] T cells, and (iv) ISG[SUP]hi[/SUP] 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.