Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appears to have higher pathogenicity among patients with obesity. Obesity, termed as body mass index greater than 30 kg/m², has now been demonstrated to be important comorbidity for disease severity during coronavirus disease 2019 (COVID-19) pandemic and associated with adverse events. Unraveling mechanisms behind this phenomenon can assist scientists, clinicians, and policymakers in responding appropriately to the COVID-19 pandemic. In this review, we systemically delineated the potential mechanistic links between obesity and worsening COVID-19 from altered physiology, underlying diseases, metabolism, immunity, cytokine storm, and thrombosis. Problematic ventilation caused by obesity and preexisting medical disorders exacerbate organ dysfunction for patients with obesity. Chronic metabolic disorders, including dyslipidemia, hyperglycemia, vitamin D deficiency, and polymorphisms of metabolism-related genes in obesity, probably aid SARS-CoV-2 intrusion and impair antiviral responses. Obesity-induced inadequate antiviral immunity (interferon, natural killer cells, invariant natural killer T cell, dendritic cell, T cells, B cell) at the early stage of SARS-CoV-2 infection leads to delayed viral elimination, increased viral load, and expedited viral mutation. Cytokine storm, with the defective antiviral immunity, probably contributes to tissue damage and pathological progression, resulting in severe symptoms and poor prognosis. The prothrombotic state, driven in large part by endothelial dysfunction, platelet hyperactivation, hypercoagulability, and impaired fibrinolysis in obesity, also increases the risk of severe COVID-19. These mechanisms in the susceptibility to severe condition also open the possibility for host-directed therapies in population with obesity. By bridging work done in these fields, researchers can gain a holistic view of the paths forward and therapeutic opportunities to break the vicious cycle of obesity and its devastating complications in the next emerging pandemic.

中文翻译：

---

肥胖与 2019 年严重冠状病毒病：分子机制、前进道路和治疗机会

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 似乎在肥胖患者中具有更高的致病性。肥胖被称为体重指数大于 30 kg/m ²，现已被证明是 2019 年冠状病毒病 (COVID-19) 大流行期间疾病严重程度的重要合并症，并与不良事件相关。揭示这一现象背后的机制可以帮助科学家、临床医生和政策制定者适当应对 COVID-19 大流行。在这篇综述中，我们从生理学改变、基础疾病、代谢、免疫、细胞因子风暴和血栓形成等方面系统地描述了肥胖与 COVID-19 恶化之间的潜在机制联系。肥胖和先前存在的疾病引起的通气问题会加剧肥胖患者的器官功能障碍。慢性代谢紊乱，包括血脂异常、高血糖、维生素 D 缺乏和肥胖代谢相关基因多态性，可能会促进 SARS-CoV-2 入侵并损害抗病毒反应。SARS-CoV-2感染早期肥胖引起的抗病毒免疫（干扰素、自然杀伤细胞、恒定自然杀伤T细胞、树突状细胞、T细胞、B细胞）不足，导致病毒清除延迟、病毒载量增加，加速病毒突变。细胞因子风暴伴随抗病毒免疫缺陷，可能导致组织损伤和病理进展，导致严重症状和不良预后。血栓前状态在很大程度上是由内皮功能障碍、血小板过度活化、高凝状态和肥胖引起的纤溶受损引起的，也会增加患严重 COVID-19 的风险。这些对严重疾病易感性的机制也为肥胖人群的宿主导向治疗提供了可能性。通过整合在这些领域所做的工作，研究人员可以全面了解未来的发展道路和治疗机会，以打破肥胖的恶性循环及其在下一次新出现的流行病中的破坏性并发症。