Comparisons of the immunological landscape between COVID-19, influenza, and respiratory syncytial virus patients by clustering analysis

[Display omitted] Hierarchical clustering of respiratory viruses combined data yields three immune subtypes based on 27 immune signatures’ enrichment scores. A majority of COVID-19 patients have weaker immune signatures compared to the patients infected with the other viruses. COVID-19 has stronger infectivity and ahigherrisk forseverity than mostother contagious respiratory illnesses. Themechanisms underlying this difference remain unclear. 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. 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 ofACE2andIL-6and lowestviral loads and werethe youngest. In contrast, the Immunity-H COVID-19 patients had the lowest expression levels ofACE2andIL-6and 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. Compared to influenza and RSV, COVID-19 displayed significantly different immunologicalprofiles. Elevated immune signatures are associated with better prognosis in COVID-19 patients.