The Trans-omics Landscape of COVID-19

Abstract The outbreak of coronavirus disease 2019 (COVID-19) has been causing a global health emergency. Although previous studies investigated COVID-19 at different omics levels, the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here, we presented a trans-omics landscape for COVID-19 based on integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles from blood samples of 231 COVID-19 patients, ranging from asymptomatic to critically ill, importantly excluding those with any comorbidities. Notably, we found neutrophils heterogeneity existed between asymptomatic and critically ill patients. Expression discordance of inflammatory cytokines at mRNA and protein levels in asymptomatic patients could possibly be explained by post-transcriptional regulation by RNA binding proteins (RBPs) and microRNAs. Neutrophils over-activation, induced arginine depletion, and tryptophan metabolites accumulation contributed to T/NK cell dysfunction in critical patients. Anti-virus interferons were gradually suppressed along with disease severity. Overall, our study systematically revealed multi-omics characteristics of COVID-19, and the data we generated could hopefully help illuminate COVID-19 pathogenesis and provide valuable clues about potential therapeutic strategies for COVID-19.