Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients

The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1-3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 hours of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28 days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention.

IMPACC队列由1000余名住院新型冠状病毒肺炎（COVID-19）参与者组成，在急性感染期（首28天）内包含5种疾病轨迹组（TGs），疾病严重程度从轻症（TG1~TG3）逐步升级为重症病程（TG4）乃至死亡结局（TG5）。本研究针对该队列中的540名参与者，采用14种独立检测方法，对15000余份纵向采集的血液与鼻腔样本开展深度免疫表型分析及特征谱解析。通过上述无偏倚分析，本研究鉴定出入院72小时内即可检测到的细胞与分子特征标签，可有效区分中度、重度及致死性COVID-19患者。尤为关键的是，细胞与分子状态还可进一步区分两类重症参与者：一类在28天内恢复或病情趋于稳定，另一类则进展为致死性结局（TG4 vs TG5）。此外，本研究的纵向设计揭示，此类生物学状态呈现出与临床结局密切相关的独特时间动态模式。针对宿主免疫应答与疾病进程异质性的特征解析，可为临床预后判断及干预策略的开发提供科学依据。