T1 The local and systemic response to SARS-CoV-2 infection in children and adults

Introduction and ObjectivesSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic. Whilst a substantial proportion of adults infected with SARS-CoV-2 progress to develop severe disease, children rarely manifest respiratory complications. However, the underlying mechanism behind this disparity remains largely unknown. Understanding the differences in the local and systemic response to SARS-CoV-2 infection at single cell resolution between children and adults may offer key clues about the pathogenesis of SARS-CoV-2 infection, providing guidance for future therapies and treatments.MethodsTo address this we generated a healthy reference multi-omics single cell data set from children (n=30) from infancy to adulthood (n=11). Here we profiled triple matched samples: nasal and tracheal brushings and PBMCs for single cell analysis, where we tracked the developmental changes for 59 airway and 45 blood cell populations at both transcriptomic and proteomic level. These were then contrasted with equivalent data from paediatric and adult COVID-19+ patients collected across a range of disease severities (total n=32), enabling age and disease-specific variances to be analysed at single cell level.ResultsStriking differences within the paediatric and adult immune responses in COVID-19 were observed, including an overall weaker interferon-response signature, with fewer interferon-stimulated immune cell subpopulations within children infected by SARS-CoV-2 compared to adults. In peripheral blood, a greater proportion of naïve cell populations was observed with disease, with the response in adults primarily dominated by the adaptive immune system. In the airway epithelium, we found the highest viral load in goblet and ciliated cells in infected adults and most notably, described a novel inflammatory epithelial cell population, enriched within our COVID-19 patients, representing a transitional regenerative state between secretory and ciliated cells. Through the integration of matched blood and airway samples we were able to investigate the dynamics between local and systemic response to COVID-19, finding marked differences.Abstract T1 Figure 1ConclusionsOverall, this largest paediatric single cell COVID-19 study to date showed significant differences in response to SARS-CoV-2 between children and adults, reflecting the changes of the immune landscape over developmental time, which in children are