Wendt Ralph, Lingitz Marie-Therese, Laggner Maria, Mildner Michael, Traxler Denise, Graf Alexandra, Krotka Pavla, Moser Bernhard, Hoetzenecker Konrad, Kalbitz Sven, Lübbert Christoph, Beige Joachim, Ankersmit Hendrik Jan
Department of Infectious Diseases, Tropical Medicine, Nephrology and Rheumatology, St. Georg Hospital, Delitzscher Str. 141, 04129 Leipzig, Germany.
Laboratory for Cardiac and Thoracic Diagnosis, Regeneration and Applied Immunology, Medical University of Vienna, Research Laboratories Vienna General Hospital, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Biology (Basel). 2021 Nov 15;10(11):1186. doi: 10.3390/biology10111186.
Although, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents one of the biggest challenges in the world today, the exact immunopathogenic mechanism that leads to severe or critical Coronavirus Disease 2019 (COVID-19) has remained incompletely understood. Several studies have indicated that high systemic plasma levels of inflammatory cytokines result in the so-called "cytokine storm", with subsequent development of microthrombosis, disseminated intravascular coagulation, and multiorgan-failure. Therefore, we reasoned those elevated inflammatory molecules might act as prognostic factors. Here, we analyzed 245 serum samples of patients with COVID-19, collected at hospital admission. We assessed the levels of heat shock protein 27 (HSP27), soluble suppressor of tumorigenicity-2 (sST2) and 20S proteasome at hospital admission and explored their associations with overall-, 30-, 60-, 90-day- and in-hospital mortality. Moreover, we investigated their association with the risk of ventilation. We demonstrated that increased serum sST2 was uni- and multivariably associated with all endpoints. Furthermore, we also identified 20S proteasome as independent prognostic factor for in-hospital mortality (sST2, AUC = 0.73; HSP27, AUC = 0.59; 20S proteasome = 0.67). Elevated sST2, HSP27, and 20S proteasome levels at hospital admission were univariably associated with higher risk of invasive ventilation (OR = 1.8; < 0.001; OR = 1.1; = 0.04; OR = 1.03, = 0.03, respectively). These findings could help to identify high-risk patients early in the course of COVID-19.
尽管严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是当今世界面临的最大挑战之一，但导致严重或危重型2019冠状病毒病（COVID-19）的确切免疫致病机制仍未完全明确。多项研究表明，全身血浆中炎症细胞因子水平升高会导致所谓的“细胞因子风暴”，随后会出现微血栓形成、弥散性血管内凝血和多器官功能衰竭。因此，我们推断这些升高的炎症分子可能作为预后因素。在此，我们分析了245例COVID-19患者入院时采集的血清样本。我们评估了入院时热休克蛋白27（HSP27）、可溶性肿瘤抑制因子2（sST2）和20S蛋白酶体的水平，并探讨了它们与总体、30天、60天、90天及住院死亡率的相关性。此外，我们还研究了它们与通气风险的相关性。我们发现血清sST2升高与所有终点均存在单变量和多变量相关性。此外，我们还确定20S蛋白酶体是住院死亡率的独立预后因素（sST2，曲线下面积 = 0.73；HSP27，曲线下面积 = 0.59；20S蛋白酶体 = 0.67）。入院时sST2、HSP27和20S蛋白酶体水平升高与有创通气风险增加单变量相关（比值比分别为1.8；P < 0.001；1.1；P = 0.04；1.03，P = 0.03）。这些发现有助于在COVID-19病程早期识别高危患者。
