Long Covid is defined by a wide range of symptoms that persist after the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Commonly reported symptoms include fatigue, weakness, postexertional malaise, and cognitive dysfunction, with many other symptoms reported. Symptom range, duration, and severity are highly variable and partially overlap with symptoms of myalgic encephalomyelitis/chronic fatigue syndrome and other post-acute infectious syndromes, highlighting opportunities to define shared mechanisms of pathogenesis. Potential mechanisms of Long Covid are diverse, including persistence of viral reservoirs, dysregulated immune responses, direct viral damage of tissues targeted by SARS-CoV-2, inflammation driven by reactivation of latent viral infections, vascular endothelium activation or dysfunction, and subsequent thromboinflammation, autoimmunity, metabolic derangements, microglial activation, and microbiota dysbiosis. The heterogeneity of symptoms and baseline characteristics of people with Long Covid, as well as the varying states of immunity and therapies given at the time of acute infection, have made etiologies of Long Covid difficult to determine. Here, we examine progress on preclinical models for Long Covid and review progress being made in clinical trials, highlighting the need for large human studies and further development of models to better understand Long Covid. Such studies will inform clinical trials that will define treatments to benefit those living with this condition.

中文翻译：

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将见解转化为长期 Covid 的疗法


Long Covid 的定义是在严重急性呼吸系统综合症冠状病毒 2 （SARS-CoV-2） 感染急性期后持续存在多种症状。常见报告的症状包括疲劳、虚弱、劳累后不适和认知功能障碍，还报告了许多其他症状。症状范围、持续时间和严重程度差异很大，并且与肌痛性脑脊髓炎/慢性疲劳综合征和其他急性感染后综合征的症状部分重叠，突出了确定共同发病机制的机会。Long Covid 的潜在机制多种多样，包括病毒库的持续存在、免疫反应失调、SARS-CoV-2 靶向组织的直接病毒损伤、由潜伏病毒感染再激活驱动的炎症、血管内皮激活或功能障碍，以及随后的血栓炎症、自身免疫、代谢紊乱、小胶质细胞激活和微生物群失调。Long Covid 患者的症状和基线特征的异质性，以及急性感染时免疫状态和治疗的不同，使得 Long Covid 的病因难以确定。在这里，我们研究了 Long Covid 临床前模型的进展，并回顾了临床试验的进展，强调了进行大型人体研究和进一步开发模型以更好地了解 Long Covid 的必要性。此类研究将为临床试验提供信息，这些试验将确定使患有这种疾病的人受益的治疗方法。