Department of Immunology and Allergy, Academic Center for Education, Culture, and Research, Tehran, Iran,
Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran,
Int Arch Allergy Immunol. 2020;181(6):467-475. doi: 10.1159/000508247. Epub 2020 May 11.
After the advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the outbreak of coronavirus disease 2019 (COVID-19) commenced across the world. Understanding the Immunopathogenesis of COVID-19 is essential for interrupting viral infectivity and preventing aberrant immune responses before a vaccine can be developed. In this review, we provide the latest insights into the roles of angiotensin-converting enzyme II (ACE2) and Ang II receptor-1 (AT1-R) in this disease. Novel therapeutic strategies, including recombinant ACE2, ACE inhibitors, AT1-R blockers, and Ang 1-7 peptides, may prevent or reduce viruses-induced pulmonary, cardiac, and renal injuries. However, more studies are needed to clarify the efficacy of these therapeutics. Furthermore, considering the common role of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in AT1-R expressed on peripheral tissues and cytokine receptors on the surface of immune cells, potential targeting of this pathway using JAK inhibitors (JAKinibs) is suggested as a promising approach in patients with COVID-19 who are admitted to hospitals. In addition to antiviral therapy, potential ACE2- and AT1-R-inhibiting strategies, and other supportive care, we suggest other potential JAKinibs and novel anti-inflammatory combination therapies that affect the JAK-STAT pathway in patients with COVID-19. Since the combination of MTX and baricitinib leads to outstanding clinical outcomes, the addition of baricitinib to MTX might be a potential strategy.
严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 出现后，2019 年冠状病毒病 (COVID-19) 在全球范围内爆发。了解 COVID-19 的免疫发病机制对于在开发疫苗之前阻断病毒感染力和防止异常免疫反应至关重要。在这篇综述中，我们提供了 ACE2 和 Ang II 受体-1 (AT1-R) 在这种疾病中作用的最新见解。新型治疗策略，包括重组 ACE2、ACE 抑制剂、AT1-R 阻滞剂和 Ang 1-7 肽，可能预防或减轻病毒引起的肺、心脏和肾脏损伤。然而，还需要更多的研究来阐明这些治疗方法的疗效。此外，鉴于 JAK-STAT 途径在周围组织表达的 AT1-R 和免疫细胞表面细胞因子受体中的共同作用，使用 JAK 抑制剂 (JAKinibs) 靶向该途径被建议作为 COVID-19 住院患者的一种有前途的方法。除了抗病毒治疗、潜在的 ACE2 和 AT1-R 抑制策略和其他支持性护理外，我们建议 COVID-19 患者使用其他潜在的 JAKinibs 和影响 JAK-STAT 途径的新型抗炎联合疗法。由于 MTX 和巴瑞替尼的联合使用导致了出色的临床结果，因此将巴瑞替尼添加到 MTX 中可能是一种潜在的策略。
