Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Alfred Nobels Allé 8, 141 52, Stockholm, Sweden.
Science for Life Laboratory, Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden.
Respir Res. 2023 Feb 24;24(1):62. doi: 10.1186/s12931-023-02364-y.
COVID-19 remains a major public health challenge, requiring the development of tools to improve diagnosis and inform therapeutic decisions. As dysregulated inflammation and coagulation responses have been implicated in the pathophysiology of COVID-19 and sepsis, we studied their plasma proteome profiles to delineate similarities from specific features.
We measured 276 plasma proteins involved in Inflammation, organ damage, immune response and coagulation in healthy controls, COVID-19 patients during acute and convalescence phase, and sepsis patients; the latter included (i) community-acquired pneumonia (CAP) caused by Influenza, (ii) bacterial CAP, (iii) non-pneumonia sepsis, and (iv) septic shock patients.
We identified a core response to infection consisting of 42 proteins altered in both COVID-19 and sepsis, although higher levels of cytokine storm-associated proteins were evident in sepsis. Furthermore, microbiologic etiology and clinical endotypes were linked to unique signatures. Finally, through machine learning, we identified biomarkers, such as TRIM21, PTN and CASP8, that accurately differentiated COVID-19 from CAP-sepsis with higher accuracy than standard clinical markers.
This study extends the understanding of host responses underlying sepsis and COVID-19, indicating varying disease mechanisms with unique signatures. These diagnostic and severity signatures are candidates for the development of personalized management of COVID-19 and sepsis.
COVID-19 仍然是一个主要的公共卫生挑战，需要开发工具来改善诊断并为治疗决策提供信息。由于失调的炎症和凝血反应被认为与 COVID-19 和脓毒症的病理生理学有关，我们研究了它们的血浆蛋白质组谱，以描绘出相似之处和特定特征。
我们测量了 276 种参与炎症、器官损伤、免疫反应和凝血的血浆蛋白，这些蛋白存在于健康对照组、急性和恢复期的 COVID-19 患者以及脓毒症患者中；后者包括（i）流感引起的社区获得性肺炎（CAP），（ii）细菌性 CAP，（iii）非肺炎性脓毒症，和（iv）感染性休克患者。
我们确定了一个感染的核心反应，由 42 种在 COVID-19 和脓毒症中都改变的蛋白质组成，尽管在脓毒症中更明显的是细胞因子风暴相关蛋白质的水平更高。此外，微生物病因和临床终末类型与独特的特征有关。最后，通过机器学习，我们确定了生物标志物，如 TRIM21、PTN 和 CASP8，它们能够更准确地区分 COVID-19 与 CAP-脓毒症，比标准临床标志物的准确性更高。
这项研究扩展了对脓毒症和 COVID-19 中宿主反应的理解，表明了不同的疾病机制和独特的特征。这些诊断和严重程度特征是为 COVID-19 和脓毒症的个体化管理开发的候选者。
