Children have reduced severity of COVID-19 compared to adults and typically have mild or asymptomatic disease. The immunological mechanisms underlying these age-related differences in clinical outcomes remain unexplained. Here, we quantify 23 immune cell populations in 141 samples from children and adults with mild COVID-19 and their PCR-negative close household contacts at acute and convalescent time points. Children with COVID-19 displayed marked reductions in myeloid cells during infection, most prominent in children under the age of five. Recovery from infection in both children and adults was characterised by the generation of CD8 TCM and CD4 TCM up to 9 weeks post infection. SARS-CoV-2-exposed close contacts also had immunological changes over time despite no evidence of confirmed SARS-CoV-2 infection on PCR testing. This included an increase in low-density neutrophils during convalescence in both exposed children and adults, as well as increases in CD8 TCM and CD4 TCM in exposed adults. In comparison to children with other common respiratory viral infections, those with COVID-19 had a greater change in innate and T cell-mediated immune responses over time. These findings provide new mechanistic insights into the immune response during and after recovery from COVID-19 in both children and adults.
COVID-19 is associated with haemostatic dysregulation, 1 with thromboembolism occurring in 25% of hospitalised COVID-19 patients and microvascular thrombi reported at autopsy. 2 Platelets are activated in COVID-19 patients requiring intensive care, 3 while limited data in mild COVID-19 shows no changes in platelet phenotype. 4 Children have low-risk of severe COVID-19 and thrombosis. 5 If haemostasis is fundamental to COVID-19 pathogenesis, then age-related haemostatic differences may protect children from COVID-19. While there is evidence of changes in leucocyte populations of non-hospitalised children and adults infected and exposed to SARS-CoV-2, 6 the effect on paediatric platelets is unknown.We investigated platelet surface-markers in adults and children who were SARS-CoV-2-positive and their household contacts. We aimed to establish whether SARS-CoV-2 induced changes in platelet phenotype in individuals with mild COVID-19.Participants were recruited from the Respiratory Infection Clinic at The Royal Children's Hospital (RCH), Melbourne, using the enrollment protocol and participant pool previously described. 6 Upon a positive SARS-CoV-2 polymerase chain reaction (PCR) test, blood collection was arranged for family members at two time points: 'acute', within two weeks of post-test and 'convalescent', 4-7 weeks posttest. Individuals were classified 'SARS-CoV-2-positive' if they tested positive, and 'SARS-CoV-2-exposed' if they tested negative on repeated tests but remained in close household contact with individuals who tested positive. All participants recovered at home. This study was approved by the RCH Human Research Ethics Committee (QA/63666/ RCHM-2020).
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