Background

Physicians treating patients with coronavirus disease 2019 (COVID-19) increasingly believe that the hyperinflammatory acute stage of COVID-19 results in a cytokine storm. The circulating biomarkers seen across the spectrum of COVID-19 have not been characterized compared with healthy controls, but such analyses are likely to yield insights into the pursuit of interventions that adequately reduce the burden of these cytokine storms.

Objective

To identify and characterize the host inflammatory response to severe acute respiratory syndrome coronavirus 2 infection, we assessed levels of proteins related to immune responses and cardiovascular disease in patients stratified as mild, moderate, and severe versus matched healthy controls.

Methods

Blood samples from adult patients hospitalized with COVID-19 were analyzed using high-throughput and ultrasensitive proteomic platforms and compared with age- and sex-matched healthy controls to provide insights into differential regulation of 185 markers.

Results

Results indicate a dominant hyperinflammatory milieu in the circulation and vascular endothelial damage markers within patients with COVID-19, and strong biomarker association with patient response as measured by Ordinal Scale. As patients progress, we observe statistically significant dysregulation of IFN-γ, IL-1RA, IL-6, IL-10, IL-19, monocyte chemoattractant protein (MCP)-1, MCP-2, MCP-3, CXCL9, CXCL10, CXCL5, ENRAGE, and poly (ADP-ribose) polymerase 1. Furthermore, in a limited series of patients who were sampled frequently, confirming reliability and reproducibility of our assays, we demonstrate that intervention with baricitinib attenuates these circulating biomarkers associated with the cytokine storm.

Conclusions

These wide-ranging circulating biomarkers show an association with increased disease severity and may help stratify patients and selection of therapeutic options. They also provide insights into mechanisms of severe acute respiratory syndrome coronavirus 2 pathogenesis and the host response.

中文翻译：

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细胞因子风暴的特征反映了COVID-19中的炎症性内皮功能异常。

背景

治疗冠状病毒病患者2019（COVID-19）的医师越来越相信，COVID-19的高炎症急性期会导致细胞因子风暴。与健康对照相比，未在COVID-19光谱中观察到的循环生物标志物有任何特征，但此类分析可能会为深入了解采取干预措施以充分减轻这些细胞因子风暴的负担提供见识。

目的

为了鉴定和表征宿主对严重急性呼吸系统综合症冠状病毒2感染的炎症反应，我们对分层为轻度，中度和重度与匹配健康对照的患者评估了与免疫反应和心血管疾病相关的蛋白质水平。

方法

使用高通量和超灵敏的蛋白质组学平台分析了住院COVID-19的成年患者的血样，并与年龄和性别相匹配的健康对照进行了比较，以了解185种标记物的差异调控。

结果

结果表明，在有COVID-19的患者中，循环和血管内皮损伤标记物中存在显着的高炎症环境，并且通过序号量表测量到与患者反应密切相关的生物标记物。随着患者的进展，我们观察到IFN-γ，IL-1RA，IL-6，IL-10，IL-19，单核细胞趋化蛋白（MCP）-1，MCP-2，MCP-3，CXCL9，CXCL10的统计学显着失调，CXCL5，ENRAGE和聚（ADP-核糖）聚合酶1。此外，在一系列经常采样的患者中，证实了我们测定的可靠性和可重复性，我们证明了使用Baricitinib进行干预可减弱这些与细胞因子相关的循环生物标志物风暴。

结论

这些广泛的循环生物标志物显示出疾病严重程度增加，可能有助于对患者进行分层和治疗选择的选择。他们还提供了有关严重急性呼吸系统综合症冠状病毒2发病机理和宿主反应的机制的见解。