Extracellular ATP and Imbalance of CD4+ T Cell Compartment in Pediatric COVID-19

Abstract

Severe COVID-19 in children is rare, but the reasons underlying are unclear. Profoundalterations in T cell responses have been well characterized in the course of adult severeCOVID-19, but little is known about the T cell function in children with COVID-19. Here, wemade three major observations in a cohort of symptomatic children with acute COVID-19:1) a reduced frequency of circulating FoxP3+ regulatory T cells, 2) the prevalence of aTH17 polarizing microenvironment characterized by high plasma levels of IL-6, IL-23, andIL17A, and an increased frequency of CD4+ T cells expressing ROR-gt, the masterregulator of TH17 development, and 3) high plasma levels of ATP together with anincreased expression of the P2X7 receptor. Moreover, that plasma levels of ATP displayedan inverse correlation with the frequency of regulatory T cells but a positive correlation withthe frequency of CD4+ T cells positive for the expression of ROR-gt. Collectively, our dataindicate an imbalance in CD4+ T cell profiles during pediatric COVID-19 that might favorthe course of inflammatory processes. This finding also suggests a possible role for theextracellular ATP in the acquisition of an inflammatory signature by the T cell compartmentoffering a novel understanding of the involved mechanisms.