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

Abstract

Epidemiological evidence that COVID-19 manifests as a milder disease in children compared to adults has been reported by numerous studies, but the mechanisms underlying this phenomenon have not been characterized. It is still unclear how frequently children get infected, and/or generate immune responses to SARS-CoV-2. We have performed immune profiling of pediatric and adult COVID-19 patients in Brazil, producing over 38 thousand data points, asking if cellular or humoral immune responses could help explain milder disease in children. In this study, pediatric COVID-19 patients presented high viral titers. Though their non-specific immune profile was dominated by naive, non-activated lymphocytes, their dendritic cells expressed high levels of HLA-DR and were low in CX3CR1, indicating competence to generate immune responses that are not targeted to inflamed tissue. Finally, children formed strong specific antibody and T cell responses for viral structural proteins. Children s T cell responses differed from adults in that their CD8+ TNFα+ T cell responses were low for S peptide but significantly higher against N and M peptide pools. Altogether, our data support a scenario in which SARS-CoV-2 infected children may contribute to transmission, though generating strong and differential responses to the virus that might associate with protection in pediatric COVID-19 presentation.

Why Does the Severity of COVID-19 Differ With Age?

“…16,35,49,50 Results of T cell responses against N and membrane proteins are conflicting with some studies showing lower levels in children 50 and others higher levels. 16,35,49 Adults infected with SARS-CoV-2 typically have a decreased lymphocyte count, with reduced numbers of naïve CD4+ and CD8+, T regulatory and memory T cells. [51][52][53] One study reported that acute and memory SARS-CoV-2-specific CD4+ cells increase with age.…”

“…50 Furthermore, they have lower T cell responses to S and ORF1 proteins and reduced CD4+ T cell effector memory. 16,35,49,50 Results of T cell responses against N and membrane proteins are conflicting with some studies showing lower levels in children 50 and others higher levels. 16,35,49…”

“…47 Children with COVID-19 have higher lymphocyte counts, with a higher proportion of innate lymphoid and non-clonally expanded naïve T cells in the blood. 48,49 Children also have higher numbers of T follicular helper cells, which are important for an early antibody response. 50 Furthermore, they have lower T cell responses to S and ORF1 proteins and reduced CD4+ T cell effector memory.…”

“…16,35,49,50 Results of T cell responses against N and membrane proteins are conflicting with some studies showing lower levels in children 50 and others higher levels. 16,35,49…”

“…50 Furthermore, they have lower T cell responses to S and ORF1 proteins and reduced CD4+ T cell effector memory. 16,35,49,50 Results of T cell responses against N and membrane proteins are conflicting with some studies showing lower levels in children 50 and others higher levels. 16,35,49 Adults infected with SARS-CoV-2 typically have a decreased lymphocyte count, with reduced numbers of naïve CD4+ and CD8+, T regulatory and memory T cells.…”