SARS-CoV-2 specific T cell responses are lower in children and increase with age and time after infection

Abstract

SARS-CoV-2 infection of children leads to a mild illness and the immunological differences with adults remains unclear. We quantified the SARS-CoV-2 specific T cell responses in adults and children (<13 years of age) with RT-PCR confirmed asymptomatic and symptomatic infection for long-term memory, phenotype and polyfunctional cytokines. Acute and memory CD4+ T cell responses to structural SARS-CoV-2 proteins significantly increased with age, whilst CD8+ T cell responses increased with time post infection. Infected children had significantly lower CD4+ and CD8+ T cell responses to SARS-CoV-2 structural and ORF1ab proteins compared to infected adults. SARS-CoV-2-specific CD8+ T cell responses were comparable in magnitude to uninfected negative adult controls. In infected adults CD4+ T cell specificity was skewed towards structural peptides, whilst children had increased contribution of ORF1ab responses. This may reflect differing T cell compartmentalisation for antigen processing during antigen exposure or lower recruitment of memory populations. T cell polyfunctional cytokine production was comparable between children and adults, but children had a lower proportion of SARS-CoV-2 CD4+ T cell effector memory. Compared to adults, children had significantly lower levels of antibodies to b-coronaviruses, indicating differing baseline immunity. Total T follicular helper responses was increased in children during acute infection indicating rapid co-ordination of the T and B cell responses. However total monocyte responses were reduced in children which may be reflective of differing levels of inflammation between children and adults. Therefore, reduced prior b-coronavirus immunity and reduced activation and recruitment of de novo responses in children may drive milder COVID-19 pathogenesis.

Strong anti-viral responses in pediatric COVID-19 patients in South Brazil

“…These studies support a relevant role for structural N protein as an immune target in SARS-CoV-2 infection. We found robust antibody responses in children both to the S RBD as well as to the N protein, while Weisberg et al (9) found antibodies to the S, but not the N protein; and Cohen et al (37) found lower responses in children in general. These differences, as well as a lower response to the S protein in general in our sample, may reflect differences in HLA between American and Brazilian populations, or even a difference in immunization history, given a tradition in vaccination program for children in Brazil.…”

Strong specific anti-viral responses in pediatric COVID-19 patients in South Brazil

“…These studies support a relevant role for structural N protein as an immune target in SARS-CoV-2 infection. We found robust antibody responses in children both to the S RBD as well as to the N protein, while Weisberg et al (9) found antibodies to the S, but not the N protein; and Cohen et al (38) found lower responses in children in general. These differences, as well as a lower response to the S protein in general in our sample, may reflect differences in HLA between American and Brazilian populations, or even a difference in immunization history, given a tradition in vaccination program for children in Brazil.…”

Pediatric COVID-19: Immunopathogenesis, Transmission and Prevention

“…In a recent larger cohort study, children and adolescents showed high and durable antibody responses to SARS-CoV-2, following mild or asymptomatic infection [62]. Regarding cell-mediated immunity, only a few reports describe a lower or similar magnitude of SARS-CoV-2-specific T cells in children [21,57,63]. As the magnitude of the adaptive immune response to SARS-CoV-2 is related to severity of symptoms, it is essential that studies compare adults and children with similar clinical presentations.…”