Preschool-Age Children Maintain a Distinct Memory CD4+ T Cell and Memory B Cell Response After SARS-CoV-2 Infection

The purpose of this study was to characterize virus-specific T- and B-cell responses against SARS-CoV-2 comparing children and adults and to gain insight on how the immune system responds in children younger than 5 years.The study included uninfected children and adults and SARS-CoV-2–infected preschoolers, children, and adults. Participants were divided into groups based on their age—preschoolers (<5 years), older children (>5 and <18 years), and adults (>18 years)—and by disease severity in adults, namely, mild cases vs hospitalized. Vaccinated individuals were excluded. Patients who had documented reinfection between the initial SARS-CoV-2 infection and the memory time point were also excluded.The samples were obtained from March 2020 to June 2021 and collected before, during (day 0 to day 45 after positive diagnosis), and after (11 ± 3 months after positive diagnosis) the infection. To characterize SARS-CoV-2–reactive CD4+ T cells, a sensitive antigen-reactive T-cell assay and multiparametric flow cytometry were used.The results support that the participants younger than 5 years had a lower antiviral CD4+ T-cell response compared with children older than 5 years and adults, who had a similar virus-reactive CD4+ T-cell response. Adults with severe disease were noted to have a stronger response with higher frequencies of virus-reactive proinflammatory and cytotoxic T cells. Children younger than 5 years maintained neutralizing SARS-CoV-2 antibodies like the adult population but had fewer virus-reactive memory B cells compared with older children and adults. They also had memory T-cell activity displaying high inflammatory features and signals that assist with migration toward ongoing inflammation.The findings from this study show that preschoolers mounted a distinct memory CD4+ T-cell and memory B-cell response to natural SARS-CoV-2 infection compared with older children and adults.This study examines immune profile differences across preschoolers, older children, and adults. The findings from this study suggests that preschool-aged children may develop robust and possibly long-lasting immunity through infection, implying that age-specific vaccination strategies could be optimized based on these distinct immune memory patterns.