Single Cell Profiling of Transcriptional and Epigenetic Differences Between Virus and Severity in Infants Infected with SARS-CoV-2 and RSV

This study compares the transcriptional and epigenetic immune responses to SARS-CoV-2 and RSV in infant PBMCs across different disease severities. Infants and young children hospitalized with SARS-CoV-2 (n=30) or RSV (n=19) were enrolled from February 2019 through January 2022. Blood samples were obtained within 24 hours for peripheral blood mononuclear cell isolation. Healthy controls (n=17) enrolled pre COVID-19 pandemic were also enrolled for baseline comparisons. Infants with COVID-19 were classified as subacute (n=9); moderate (n=12), or severe (n=9) based on level of clinical care, viral loads, and days post-exposure to COVID-19. Four of the five infants with severe COVID-19 were treated with dexamethasone and were reclassified as severe treated. Infants with RSV were classified as mild (n=5), moderate (n=7), or severe (n=7) based on an established clinical disease severity score designed for assessing severity in RSV. In total, 66 samples were included for scRNA-seq, and 51 samples were included for snATAC-seq. New data to be submitted from this study includes data for 27 scRNA-seq and 53 snATAC-seq. Note: Two additional samples (1 healthy control and 1 subacute COVID-19) were later determined to have signatures of viral infection (healthy control sample) or co-infection with another virus (subacute COVID-19 sample) during downstream analysis. These samples (adding up to the total of 68 scRNA-seq and 53 snATAC-seq) were included for reproducibility. ]]>
For RSV, children were excluded if they had any underlying conditions (i.e prematurity, congenital heart disease, chronic lung disease) or use of immunomodulatory drugs including systemic steroids >5 days within 2 weeks of presentation. All healthy controls were enrolled pre-pandemic. Healthy controls were typically enrolled in the operating room while undergoing minor scheduled surgical procedures not involving the respiratory tract, or at the primary care offices during well-child visits. ]]>