Multi-omic analysis resolves coordinated immune responses to mild, moderate and severe COVID-19

We present an integrated analysis of the clinical measurements, immune cells and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple novel immune cell phenotypes emerge and amplify with increasing disease severity. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to SARS-CoV-2. This immune-response axis independently aligns with the major plasma composition changes, with clinical metrics of blood clotting, and with the sharp transition between mild and moderate disease. This study suggests that moderate disease may provide the most effective setting for therapeutic intervention.

本研究对139名涵盖各疾病严重程度层级的新型冠状病毒肺炎（COVID-19）患者开展整合分析，分析对象包括其临床检测指标、免疫细胞及血浆多组学数据，样本均取自确诊后感染首周的系列血液标本。研究发现轻症与中型新型冠状病毒肺炎之间存在显著的表型转变节点：在此节点，炎症信号通路活化程度升高，同时伴随特定类别代谢物及代谢过程的缺失。在中型新型冠状病毒肺炎患者所处的应激血浆微环境中，多种新型免疫细胞表型出现，并随疾病严重程度升高而扩增。本研究将超过120000个免疫特征整合为单一分析轴，用以刻画不同免疫细胞类群在应对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）时的协同调控模式。该免疫应答轴可独立对应主要的血浆组分变化、凝血功能临床指标，以及轻症与中型新型冠状病毒肺炎之间的显著表型转变。本研究提示，中型新型冠状病毒感染阶段或许是开展治疗干预的最优窗口。