Department of Paediatric Haematology/Oncology and of Cell and Gene Therapy, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Int J Mol Sci. 2021 Feb 8;22(4):1705. doi: 10.3390/ijms22041705.
Patients with coronavirus disease 2019 (COVID-19) have a wide variety of clinical outcomes ranging from asymptomatic to severe respiratory syndrome that can progress to life-threatening lung lesions. The identification of prognostic factors can help to improve the risk stratification of patients by promptly defining for each the most effective therapy to resolve the disease. The etiological agent causing COVID-19 is a new coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that enters cells via the ACE2 receptor. SARS-CoV-2 infection causes a reduction in ACE2 levels, leading to an imbalance in the renin-angiotensin system (RAS), and consequently, in blood pressure and systemic vascular resistance. ERAP1 and ERAP2 are two RAS regulators and key components of MHC class I antigen processing. Their polymorphisms have been associated with autoimmune and inflammatory conditions, hypertension, and cancer. Based on their involvement in the RAS, we believe that the dysfunctional status of ERAP1 and ERAP2 enzymes may exacerbate the effect of SARS-CoV-2 infection, aggravating the symptomatology and clinical outcome of the disease. In this review, we discuss this hypothesis.
新型冠状病毒肺炎（COVID-19）患者的临床表现多种多样，从无症状到可进展为危及生命肺部病变的严重呼吸系统综合征不等。识别预后因素有助于通过及时为每位患者确定最有效的治疗方法来改善患者的风险分层，从而解决疾病。导致 COVID-19 的病原体是一种新型冠状病毒，称为严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2），它通过 ACE2 受体进入细胞。SARS-CoV-2 感染导致 ACE2 水平降低，导致肾素-血管紧张素系统（RAS）失衡，进而导致血压和全身血管阻力升高。ERAP1 和 ERAP2 是两种 RAS 调节剂和 MHC Ⅰ类抗原加工的关键组成部分。它们的多态性与自身免疫和炎症性疾病、高血压和癌症有关。基于它们在 RAS 中的参与，我们认为 ERAP1 和 ERAP2 酶的功能障碍状态可能会加剧 SARS-CoV-2 感染的影响，使疾病的症状和临床结果恶化。在这篇综述中，我们讨论了这一假设。
