Author(s):
Martins, Catarina ; Ângelo-Dias, Miguel ; Chasqueira, Maria-Jesus ; Brito, Maria João ; Silva, Tiago Milheiro ; Matos, Maria Vitória ; Lopes, Maria Teresa ; Crespo, Hélio ; Mata, Mariana ; BORREGO, LUIS MIGUEL ; Paixão, Paulo
Date: 2025
Persistent ID: http://hdl.handle.net/10362/189226
Origin: Repositório Institucional da UNL
Subject(s): Humans; COVID-19/immunology; Child; Male; Female; SARS-CoV-2/immunology; Adolescent; Child, Preschool; Antibodies, Viral/blood; T-Lymphocytes/immunology; Infant; Host-Pathogen Interactions/immunology; B-Lymphocytes/immunology; Immunity, Cellular; Memory B Cells/immunology; Lymphocyte Activation
Description
Children with COVID-19 typically experience milder symptoms and lower hospitalization rates, though severe cases do occur. Understanding age-related immune responses is crucial for future preparedness. We characterized immune response dynamics to SARS-CoV-2 in 145 samples from 119 pediatric patients (<18 years) with confirmed infection, assessed at four distinct time points: <14 days, 14 days-3 months, 3-6 months, and 6-12 months post-infection. At infection, patients presented increased activated T-cells, higher levels of exhaustion (i.e., PD-1 +), lower numbers of unswitched memory B-cells, and increased antibody-secreting cells (ASCs). Both humoral and cellular anti-SARS-CoV-2 responses increased over time (all patients showed measurable responses in the last assessment). Asymptomatic/mildly symptomatic patients (58.6%) showed increased specific cellular responses from infection onwards, along with enriched memory B-cell subsets (but not ASCs), and distinct T-cell activation profiles. Children with severe disease were younger, predominantly boys, displayed altered T/B-cell ratios, and reduced PHA responses when infected. Compared to adolescents, younger children showed lower antibody titers and weaker cellular responses to SARS-CoV-2, possibly underlining the higher prevalence of severe manifestations in younger children. Our study illustrates important age-, gender-, and disease severity-dependent variations in immune responses to SARS-CoV-2, which can be helpful in improving patient management and immunization strategies adjusted to age groups.
