LAUSR

Background COVID-19 has stronger infectivity and ahigherrisk forseverity than mostother contagious respiratory illnesses. Themechanisms underlying this difference remain unclear. Methods We compared the immunological landscape betweenCOVID-19 and two other contagious respiratory illnesses (influenza and respiratory syncytial virus (RSV)) by clustering analysis of the three diseases based on 27 immune signatures’ scores. Results We identified three immune subtypes: Immunity-H, Immunity-M, and Immunity-L, which displayed high, medium, and low immune signatures, respectively. We found 20%, 35.5%, and 44.5% of COVID-19 cases included in Immunity-H, Immunity-M, and Immunity-L, respectively; all influenza cases were included in Immunity-H; 66.7% and 33.3% of RSV cases belonged to Immunity-H and Immunity-L, respectively. These data indicate that most COVID-19 patients have weaker immune signatures than influenza and RSV patients, as evidenced by22 of the 27 immune signatures having lower enrichment scores in COVID-19 than in influenza and/or RSV.The Immunity-M COVID-19 patients had the highest expression levels of ACE2 and IL-6 and lowestviral loads and werethe youngest. In contrast, the Immunity-H COVID-19 patients had the lowest expression levels of ACE2 and IL-6 and highestviral loads and werethe oldest. Most immune signatures had lower enrichment levels in the intensive care unit(ICU) than in non-ICU patients. Gene ontology analysis showed that the innate and adaptive immune responses were significantly downregulated in COVID-19 versus healthy individuals. Conclusions Compared to influenza and RSV, COVID-19 displayed significantly different immunologicalprofiles. Elevated immune signatures are associated with better prognosis in COVID-19 patients.