Brandenburg Antiinfektiva, c/o Forschungszentrum Borstel, Leibniz-Lungenzentrum, Parkallee 10, 23845 Borstel, Germany.
Department of Microbiology, University of Navarra, IdiSNA (Navarra Institute for Health Research), Irunlarrea 1, E-31008 Pamplona, Spain.
Int J Mol Sci. 2023 Oct 14;24(20):15169. doi: 10.3390/ijms242015169.
Sepsis is a life-threatening condition caused by the body's overwhelming response to an infection, such as pneumonia or urinary tract infection. It occurs when the immune system releases cytokines into the bloodstream, triggering widespread inflammation. If not treated, it can lead to organ failure and death. Unfortunately, sepsis has a high mortality rate, with studies reporting rates ranging from 20% to over 50%, depending on the severity and promptness of treatment. According to the World Health Organization (WHO), the annual death toll in the world is about 11 million. One of the main toxins responsible for inflammation induction are lipopolysaccharides (LPS, endotoxin) from Gram-negative bacteria, which rank among the most potent immunostimulants found in nature. Antibiotics are consistently prescribed as a part of anti-sepsis-therapy. However, antibiotic therapy (i) is increasingly ineffective due to resistance development and (ii) most antibiotics are unable to bind and neutralize LPS, a prerequisite to inhibit the interaction of endotoxin with its cellular receptor complex, namely Toll-like receptor 4 (TLR4)/MD-2, responsible for the intracellular cascade leading to pro-inflammatory cytokine secretion. The pandemic virus SARS-CoV-2 has infected hundreds of millions of humans worldwide since its emergence in 2019. The COVID-19 (Coronavirus disease-19) caused by this virus is associated with high lethality, particularly for elderly and immunocompromised people. As of August 2023, nearly 7 million deaths were reported worldwide due to this disease. According to some reported studies, upregulation of TLR4 and the subsequent inflammatory signaling detected in COVID-19 patients "mimics bacterial sepsis". Furthermore, the immune response to SARS-CoV-2 was described by others as "mirror image of sepsis". Similarly, the cytokine profile in sera from severe COVID-19 patients was very similar to those suffering from the acute respiratory distress syndrome (ARDS) and sepsis. Finally, the severe COVID-19 infection is frequently accompanied by bacterial co-infections, as well as by the presence of significant LPS concentrations. In the present review, we will analyze similarities and differences between COVID-19 and sepsis at the pathophysiological, epidemiological, and molecular levels.
脓毒症是一种危及生命的疾病，由身体对感染（如肺炎或尿路感染）的过度反应引起。当免疫系统将细胞因子释放到血液中，引发广泛的炎症时，就会发生这种情况。如果不加以治疗，它可能导致器官衰竭和死亡。不幸的是，脓毒症的死亡率很高，研究报告的死亡率范围从 20%到 50%以上，具体取决于严重程度和治疗的及时性。根据世界卫生组织（WHO）的数据，全球每年的死亡人数约为 1100 万。导致炎症诱导的主要毒素之一是革兰氏阴性菌的脂多糖（LPS，内毒素），它是自然界中发现的最有效的免疫刺激剂之一。抗生素一直被作为抗脓毒症治疗的一部分开出。然而，抗生素治疗（i）由于耐药性的发展而变得越来越无效，（ii）大多数抗生素无法结合和中和 LPS，而这是抑制内毒素与其细胞受体复合物（即 Toll 样受体 4（TLR4）/MD-2）相互作用的前提，该复合物负责导致促炎细胞因子分泌的细胞内级联反应。自 2019 年出现以来，SARS-CoV-2 病毒已感染了数亿人。由这种病毒引起的 COVID-19（冠状病毒病-19）与高死亡率相关，特别是对老年人和免疫功能低下的人。截至 2023 年 8 月，全球因这种疾病报告的死亡人数已接近 700 万。根据一些报告的研究，COVID-19 患者中检测到的 TLR4 上调和随后的炎症信号“类似于细菌性败血症”。此外，其他人将对 SARS-CoV-2 的免疫反应描述为“败血症的镜像”。同样，严重 COVID-19 患者血清中的细胞因子谱与患有急性呼吸窘迫综合征（ARDS）和败血症的患者非常相似。最后，严重的 COVID-19 感染常伴有细菌合并感染，以及存在大量 LPS 浓度。在本综述中，我们将分析 COVID-19 和脓毒症在病理生理学、流行病学和分子水平上的相似之处和差异。
