The immunological profile of SARS-CoV-2 infection in children is linked to clinical severity and age

Abstract

Abstract Coronavirus disease 19 (COVID-19) is clinically less severe in children, even if the large variety and degree of severity of symptoms reported in children pose a still unresolved challenge to clinicians. We performed an in-depth analysis of immunological profiles in 18 hospitalized SARS-CoV-2-infected children; results were compared to those obtained in 13 age- and sex-matched healthy controls (HC). Patients were categorized as paucisymptomatic/moderate (55.6%) or severe/critical (44.5%), according to established diagnostic criteria, and further stratified into infants (1–12 months, 39%), children (1–12 years, 44%), and adolescents (> 12 years, 17%). We assessed SARS-CoV-2-specific RBD antibodies (Ab), neutralizing antibodies (nAb) and circulating cytokines/chemokines in plasma; SARS-CoV-2-specific immune response was measured in peripheral blood mononuclear cells by gene expression and secretome analyses. Our results disclose peculiar circulating cytokine/chemokine profiles in patients sharing a similar clinical phenotype. A cluster of patients consisted of infants with severe symptoms who presented a hyperinflammatory profile, and extremely polarized antibody profiles, ranging from patients who were negative for Abs and nAbs to those who displayed very high levels of both. In a second cluster consisting of paucisymptomatic patients, a less pronounced increase of inflammatory cytokines along with an association between selected cytokines and humoral responses emerged. A third cluster still consisting of paucisymptomatic patients showed a circulating cytokine/chemokine profile which substantially overlapped with that of HC. SARS-CoV-2-stimulated production of pro-inflammatory proteins (IL-1β, IL-2, IL-4, IL-6, IL-7, IL-8, IL-17, MIP-1β, and TNF-α), as well as T lymphocytes activation and migration-specific proteins were significantly increased in SARS-CoV-2 infected children compared to HC. Our findings suggest that immune response activation is directly correlated to clinical severity and to a lesser extent to age.