Respiratory and Critical Care Research Group, Southampton NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
Antioxid Redox Signal. 2021 Nov 10;35(14):1226-1268. doi: 10.1089/ars.2021.0017. Epub 2021 Jun 29.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19), affects every aspect of human life by challenging bodily, socioeconomic, and political systems at unprecedented levels. As vaccines become available, their distribution, safety, and efficacy against emerging variants remain uncertain, and specific treatments are lacking. Initially affecting the lungs, COVID-19 is a complex multisystems disease that disturbs the whole-body redox balance and can be long-lasting (Long-COVID). Numerous risk factors have been identified, but the reasons for variations in susceptibility to infection, disease severity, and outcome are poorly understood. The reactive species interactome (RSI) was recently introduced as a framework to conceptualize how cells and whole organisms sense, integrate, and accommodate stress. We here consider COVID-19 as a redox disease, offering a holistic perspective of its effects on the human body, considering the vulnerability of complex interconnected systems with multiorgan/multilevel interdependencies. Host/viral glycan interactions underpin SARS-CoV-2's extraordinary efficiency in gaining cellular access, crossing the epithelial/endothelial barrier to spread along the vascular/lymphatic endothelium, and evading antiviral/antioxidant defences. An inflammation-driven "oxidative storm" alters the redox landscape, eliciting epithelial, endothelial, mitochondrial, metabolic, and immune dysfunction, and coagulopathy. Concomitantly reduced nitric oxide availability renders the sulfur-based redox circuitry vulnerable to oxidation, with eventual catastrophic failure in redox communication/regulation. Host nutrient limitations are crucial determinants of resilience at the individual and population level. While inflicting considerable damage to health and well-being, COVID-19 may provide the ultimate testing ground to improve the diagnosis and treatment of redox-related stress diseases. "Redox phenotyping" of patients to characterize whole-body RSI status as the disease progresses may inform new therapeutic approaches to regain redox balance, reduce mortality in COVID-19 and other redox diseases, and provide opportunities to tackle Long-COVID. . 35, 1226-1268.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）是导致 2019 年冠状病毒病（COVID-19）的病毒，它通过以前所未有的水平挑战人体、社会经济和政治系统的各个方面，影响着人类生活的方方面面。随着疫苗的问世，其分配、安全性以及对新兴变异株的有效性仍然不确定，并且缺乏特定的治疗方法。最初影响肺部的 COVID-19 是一种复杂的多系统疾病，它会扰乱全身的氧化还原平衡，并且可能持续存在（长 COVID）。已经确定了许多危险因素，但对感染易感性、疾病严重程度和结果的差异的原因还了解甚少。活性氧相互作用组（RSI）最近被引入作为一个概念框架，用于理解细胞和整个生物体如何感知、整合和适应压力。 我们在这里将 COVID-19 视为一种氧化还原疾病，提供了对其对人体影响的整体视角，考虑了具有多器官/多层次相互依存关系的复杂互联系统的脆弱性。宿主/病毒聚糖相互作用是 SARS-CoV-2 获得细胞进入、穿过上皮/内皮屏障沿着血管/淋巴管内皮扩散以及逃避抗病毒/抗氧化防御的非凡效率的基础。炎症驱动的“氧化应激”改变了氧化还原状态，引发上皮、内皮、线粒体、代谢和免疫功能障碍以及凝血功能障碍。同时，一氧化氮供应的减少使基于硫的氧化还原电路易受氧化，最终导致氧化还原通讯/调节灾难性故障。宿主营养限制是个体和人群层面恢复力的关键决定因素。 虽然 COVID-19 给健康和福祉造成了相当大的损害，但它可能为改善氧化还原相关应激疾病的诊断和治疗提供了最终的测试平台。随着疾病的进展，对患者进行“氧化还原表型分析”以描述全身 RSI 状态，可以为恢复氧化还原平衡提供新的治疗方法，降低 COVID-19 和其他氧化还原疾病的死亡率，并提供解决长 COVID 的机会。 35, 1226-1268.
