Acute respiratory distress syndrome (ARDS) is a form of progressive hypoxemia that can be brought on by a variety of cardiorespiratory or systemic disorders, such as coronavirus disease 2019 (COVID-19). The binding of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus spike protein to the cell membrane is mediated through its binding to angiotensin-converting enzyme 2 (ACE2) receptors, resulting in viral entry, replication, and induction of a signaling cascade inducing pro-inflammatory responses that are linked to a higher mortality rate and the progression of ARDS, leading to multi-organ failure in these patients. We aimed to analyze the relationships between circulating gene expression levels of ACE2, Toll-like receptor 4 (TLR4), and interleukin-17 (IL-17) and the clinical severity of COVID-19, as well as the associated pathogenic conditions, in hospitalized patients. Sixty COVID-19 patients (34 mild/moderate COVID-19 and 26 COVID-19 with severe ARDS manifestation) and 60 healthy controls were included. The patient group was also subdivided according to outcomes into 32 recoveries and 28 deaths. ACE2, TLR4, and IL-17 levels were assessed by quantitative polymerase chain reaction (qPCR) in addition to all routine baseline laboratory investigations, including complete blood count (CBC) with differential analysis and the levels of C-reactive protein (CRP), ferritin, and d-dimer. ACE2, TLR4, and IL-17 serum expression levels were significantly higher in the COVID-19 group and subgroups and were correlated with different laboratory and clinical parameters. The serum expression levels of ACE2, TLR4, and IL-17 were accurate in differentiating between the patient groups and controls, with 86.7%, 91.7%, and 95.0% sensitivity and 96.7%, 98.3%, and 98.3% specificity, respectively, and correlated with more severe disease courses in COVID-19 patients. Higher levels are associated with overwhelmingly distressing outcomes. Our results allow us to conclude that increased circulating gene expression levels of ACE2, TLR4, and IL-17 are important in assessing the severity of COVID-19. Consequently, targeting these biomarkers may offer additional therapeutic options for COVID-19 patients in the future.
急性呼吸窘迫综合征（ARDS）是一种进行性低氧血症，可由多种心呼吸系统或全身性疾病（如2019冠状病毒病（COVID-19））引发。严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）病毒刺突蛋白通过与细胞膜上的血管紧张素转化酶2（ACE2）受体结合，介导病毒进入细胞进行复制，并诱导信号级联反应，从而引发促炎反应。这些反应与更高的死亡率和ARDS的进展相关，最终导致患者出现多器官功能衰竭。本研究旨在分析循环中ACE2、Toll样受体4（TLR4）和白细胞介素-17（IL-17）基因表达水平与COVID-19疾病临床严重程度以及住院患者相关病理状况之间的关系。研究纳入了60名COVID-19患者（34名轻/中度和26名重度ARDS）和60名健康对照者。患者组还根据预后进一步细分为32名康复者和28名死亡者。除所有常规基线实验室检查（包括全血细胞计数及分类分析、C-反应蛋白（CRP）、铁蛋白和 d-二聚体）外，本研究还通过定量聚合酶链式反应（qPCR）评估了ACE2、TLR4和IL-17的水平。COVID-19组及其各亚组的ACE2、TLR4和IL-17血清表达水平均显著升高，并与不同的实验室和临床参数相关。ACE2、TLR4和IL-17的血清表达水平在区分患者组与对照组方面表现出良好的准确性，其灵敏度分别为86.7%、91.7%和95.0%，特异性分别为96.7%、98.3%和98.3%，并且与COVID-19患者更严重的病程相关。因此，针对这些生物标志物的研究可能为未来的新冠患者提供额外的治疗选择。.
Keywords: Acute respiratory distress syndrome (ARDS); Angiotensin-converting enzyme 2 (ACE2); Coronavirus disease 2019 (COVID-19); Intensive care unit (ICU); Interleukin-17 (IL-17); Polymerase chain reaction (PCR); Toll-like receptor 4 (TLR4).