International Journal of Molecular Sciences (Apr 2023)

The Immunological Profile of SARS-CoV-2 Infection in Children Is Linked to Clinical Severity and Age

  • Claudia Vanetti,
  • Vito Lampasona,
  • Marta Stracuzzi,
  • Claudio Fenizia,
  • Mara Biasin,
  • Irma Saulle,
  • Fiona Limanaqi,
  • Ahmed Abdelsalam,
  • Cristian Loretelli,
  • Laura Paradiso,
  • Emma Longoni,
  • Lucia Barcellini,
  • Lorenzo Piemonti,
  • Ilaria Marzinotto,
  • Stefania Dispinseri,
  • Antonella Amendola,
  • Clara Fappani,
  • Elisabetta Tanzi,
  • Mario Salvatore Clerici,
  • Gabriella Scarlatti,
  • Gian Vincenzo Zuccotti,
  • Vania Giacomet,
  • Daria Trabattoni

DOI
https://doi.org/10.3390/ijms24076779
Journal volume & issue
Vol. 24, no. 7
p. 6779

Abstract

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Coronavirus disease 19 (COVID-19) is clinically less severe in children, even if the wide variety and degree of severity of symptoms reported in children pose a still-unresolved challenge for clinicians. We performed an in-depth analysis of the immunological profiles of 18 hospitalized SARS-CoV-2-infected children, whose results were compared to those obtained from 13 age- and sex-matched healthy controls (HC). The patients were categorized as paucisymptomatic/moderate (55.6%) or severe/critical (44.5%) according to established diagnostic criteria and further stratified into the categories of infants (1–12 months), children (1–12 years), and adolescents (>12 years). We assessed SARS-CoV-2-specific RBD antibodies (Ab), neutralizing antibodies (nAb), and circulating cytokines/chemokines in the plasma, and the SARS-CoV-2-specific immune response was measured in PBMCs by gene expression and secretome analyses. Our results showed peculiar circulating cytokine/chemokine profiles among patients sharing a similar clinical phenotype. A cluster of patients consisting of infants with severe symptoms presented hyperinflammatory profiles, together with extremely polarized antibody profiles. In a second cluster consisting of paucisymptomatic patients, a less pronounced increase in the level of inflammatory cytokines, together with an association between the selected cytokines and humoral responses, was observed. A third cluster, again consisting of paucisymptomatic patients, showed a circulating cytokine/chemokine profile which overlapped with that of the HC. The SARS-CoV-2-stimulated production of pro-inflammatory proteins, T lymphocyte activation, and migration-specific proteins, were significantly increased in SARS-CoV-2-infected children compared to the HC. Our findings suggest that immune response activation in the course of SARS-CoV-2 infection in children is directly correlated with clinical severity and, to a lesser extent, age.

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