Background. SARS-CoV-2 induces apoptosis and amplifies the immune response by continuously stressing the endoplasmic reticulum (ER) after invading cells. This study aimed to establish a protein-metabolic pathway associated with ER dysfunction based on the invasion mechanism of SARS-CoV-2. Methods. This study included 17 healthy people and 46 COVID-19 patients, including 38 mild patients and 8 severe patients. Proteomics and metabolomics were measured in the patient plasma collected at admission and one week after admission. The patients were further divided into the aggravation and remission groups based on disease progression within one week of admission. Results. Cross-sectional comparison showed that endoplasmic reticulum molecular chaperone-binding immunoglobulin protein (ERC-BiP), angiotensinogen (AGT), ceramide acid (Cer), and C-reactive protein (CRP) levels were significantly increased in COVID-19 patients, while the sphingomyelin (SM) level was significantly decreased . In addition, longitudinal comparative analysis found that the temporal fold changes of ERC-BiP, AGT, Cer, CRP, and SM were significantly different between the patients in the aggravation and remission groups . ERC-BiP, AGT, and Cer levels were significantly increased in aggravation patients, while SM was significantly decreased . Meanwhile, ERC-BiP was significantly correlated with AGT (r = 0.439; ). Conclusions. ERC-BiP can be used as a core index to reflect the degree of ER stress in COVID-19 patients, which is of great value for evaluating the functional state of cells. A functional pathway for AGT/ERC-BiP/glycolysis can directly assess the activation of unfolded protein reactions. The ERC-BiP pathway is closer to the intracellular replication pathway of SARS-CoV-2 and may help in the development of predictive protocols for COVID-19 exacerbation.

中文翻译：

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ERC-BiP 功能蛋白通路用于评估细胞侵袭后 SARS-CoV-2 复制诱导的内质网应激

背景。SARS-CoV-2 在入侵细胞后通过持续对内质网 (ER) 施加压力来诱导细胞凋亡并放大免疫反应。本研究旨在基于SARS-CoV-2的侵袭机制建立与内质网功能障碍相关的蛋白质代谢途径。方法。这项研究包括 17 名健康人和 46 名 COVID-19 患者，其中轻症患者 38 名，重症患者 8 名。对入院时和入院后一周收集的患者血浆进行蛋白质组学和代谢组学检测。根据入院一周内疾病进展情况将患者进一步分为加重组和缓解组。结果。横断面比较显示，COVID-19患者的内质网分子伴侣结合免疫球蛋白（ERC-BiP）、血管紧张素原（AGT）、神经酰胺酸（Cer）和C反应蛋白（CRP）水平显着升高，而鞘磷脂（SM）水平显着降低。此外，纵向对比分析发现，加重组和缓解组患者的ERC-BiP、AGT、Cer、CRP、SM的颞叶皱襞变化存在显着差异。。加重患者的ERC-BiP、AGT和Cer水平显着升高，而SM显着降低。同时，ERC-BiP与AGT显着相关（ r  =0.439；）。 结论。ERC-BiP可作为反映COVID-19患者内质网应激程度的核心指标，对于评估细胞的功能状态具有重要价值。AGT/ERC-BiP/糖酵解的功能途径可以直接评估未折叠蛋白质反应的激活。ERC-BiP 途径更接近 SARS-CoV-2 的细胞内复制途径，可能有助于制定 COVID-19 恶化的预测方案。