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<p>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 (<i>n</i> = 26; 10 subacute, 11 moderate and 5 severe disease; median age = 1.6 months) and matched controls (<i>n</i> = 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月16日

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  • 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,
  • Octavio Ramilo

摘要

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.