The trans-omics landscape of COVID-19

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19.2019冠状病毒病（COVID-19, Coronavirus Disease 2019）的暴发属于全球卫生紧急事件。目前已有多项针对COVID-19的组学（omics）研究成果被报道，但COVID-19的分子特征，尤其是无合并症患者的分子特征，尚未得到充分探究。本研究收集了231名COVID-19患者的血液样本，预先筛选排除了存在特定合并症的受试者，其临床症状覆盖无症状至危重的全谱系。通过对基因组（genomic）、转录组（transcriptomic）、蛋白质组（proteomic）、代谢组（metabolomic）及脂质组（lipidomic）谱学数据的整合分析，我们构建了COVID-19的跨组学（trans-omics）图谱。分析结果显示，无症状患者与危重患者之间存在中性粒细胞异质性；同时，危重患者体内的中性粒细胞过度激活、精氨酸耗竭以及色氨酸代谢产物蓄积，均与T细胞功能障碍存在显著相关性。本研究获取的多组学数据及对COVID-19患者外周血的特征解析，可为阐明COVID-19的病理生理学机制及开发潜在治疗策略提供重要线索。