COVID19 is a heterogeneous medical condition involving a suite of underlying pathophysiological processes including hyperinflammation, endothelial damage, thrombotic microangiopathy, and end-organ damage. Limited knowledge about the molecular mechanisms driving these processes and lack of staging biomarkers hamper the ability to stratify patients for targeted therapeutics. We report here the results of a cross-sectional multi-omics analysis of hospitalized COVID19 patients revealing that seroconversion status associates with distinct underlying pathophysiological states. Seronegative COVID19 patients harbor hyperactive T cells and NK cells, high levels of IFN alpha, gamma and lambda ligands, markers of systemic complement activation, neutropenia, lymphopenia and thrombocytopenia. In seropositive patients, all of these processes are attenuated, observing instead increases in B cell subsets, emergency hematopoiesis, increased markers of platelet activation, and hypoalbuminemia. We propose that seroconversion status could potentially be used as a biosignature to stratify patients for therapeutic intervention and to inform analysis of clinical trial results in heterogenous patient populations.

中文翻译：

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血清转化将COVID19分为不同的病理生理状态

COVID19是一种异质性医学疾病，涉及一系列潜在的病理生理过程，包括过度炎症，内皮损伤，血栓性微血管病和终末器官损伤。对驱动这些过程的分子机制的了解有限，并且缺乏分期生物标志物，这妨碍了对患者进行针对性治疗的分层能力。我们在这里报告了住院COVID19患者的多组学横断面分析结果，该结果显示血清转化状态与独特的潜在病理生理状态相关。血清阴性的COVID19患者具有过度活跃的T细胞和NK细胞，高水平的IFNα，γ和λ配体，全身补体激活，中性粒细胞减少，淋巴细胞减少和血小板减少的标志物。在血清阳性患者中，所有这些过程都会减弱，而是观察B细胞亚群的增加，紧急造血，血小板活化标志物增加和低白蛋白血症。我们建议血清转化状态可以潜在地用作生物签名，以对患者进行治疗干预并为异类患者群体的临床试验结果提供信息。