Innate cell profiles during the acute and convalescent phase of SARS-CoV-2 infection in children

Abstract

Children have mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed disease (COVID-19) compared to adults and the immunological mechanisms underlying this difference remain unclear. Here, we report acute and convalescent innate immune responses in 48 children and 70 adults infected with, or exposed to, SARS-CoV-2. We find clinically mild SARS-CoV-2 infection in children is characterised by reduced circulating subsets of monocytes (classical, intermediate, non-classical), dendritic cells and natural killer cells during the acute phase. In contrast, SARS-CoV-2-infected adults show reduced proportions of non-classical monocytes only. We also observe increased proportions of CD63+ activated neutrophils during the acute phase to SARS-CoV-2 in infected children. Children and adults exposed to SARS-CoV-2 but negative on PCR testing display increased proportions of low-density neutrophils that we observe up to 7 weeks post exposure. This study characterises the innate immune response during SARS-CoV-2 infection and household exposure in children.

Fig. 1. Innate cell profiles of children infected with or exposed to SARS-CoV-2 during the acute and convalescent phase.

a Frequency of monocytes and subsets (classical, non-classical, intermediate), dendritic cells, NK cells and low-density immature neutrophils in PBMC samples of children during infection (SARS-CoV-2 positive n = 11, SARS-CoV-2 exposed n = 7) and in convalescence (SARS-CoV-2 positive n = 16, SARS-CoV-2 exposed n = 14). b Hierarchical clustering was performed on PBMC samples using FlowSOM and projected onto a UMAP plot. Frequencies of clusters corresponding to CD4 T, CD8 T, B cells, NK cells, classical monocytes, non-classical monocytes, dendritic cells and low-density neutrophils during acute (A) and convalescent (C) phase are reported. c Frequency of neutrophils and eosinophils in fresh whole blood (SARS-CoV-2 positive n = 11, SARS-CoV-2 exposed n = 7) and in convalescence (SARS-CoV-2 positive n = 13, SARS-CoV-2 exposed n = 9). Neutrophils were assessed for expression of activation marker CD63 (SARS-CoV-2 positive n = 11, SARS-CoV-2 exposed n = 6) and in convalescence (SARS-CoV-2 positive n = 13, SARS-CoV-2 exposed n = 9). d Hierarchical clustering was done on whole blood samples using FlowSOM and projected onto a UMAP plot, coloured by intensity of SSC-A expression in the first plot, and then by annotated granulocyte cell population. Frequencies of clusters corresponding to neutrophils and eosinophils are reported. P values by Kruskal-Wallis rank sum test and Dunn’s multiple comparison testing. All statistical tests were performed two-sided. Boxplots show the medians, the 1st and 3rd quartile as well as the smallest and largest values as whiskers.