Functional SARS-CoV-2 cross-reactive CD4+ T cells established in early childhood decline with age

Significance Our results provide evidence that functional pre-existing SARS-CoV-2-reactive memory CD4+ T cells are elicited in early childhood and linked to seroconversion with the seasonal coronavirus OC43 but not many other viral infections. Compared to other viruses, the high OC43 seroprevalence at age two indicates that memory responses to coronaviruses develop at a young age. The distinct age-dependent profiles of the responding T cells suggest that cross-reactive T cells can contribute to the different clinical outcomes of COVID-19 in children and the elderly. The present results provide important advances regarding antigen-specific memory CD4+ T cell development and maturation, which can help guide future vaccine and therapeutic interventions relating to specificity, function, and phenotype of memory T cell responses throughout the human life span.