Diar Bakerly Nawar, Smith Nikki, Darbyshire Julie L, Kwon Joseph, Bullock Emily, Baley Sareeta, Sivan Manoj, Delaney Brendan
Faculty of Science and Engineering, Manchester Metropolitan University, Manchester M15 6BH, UK.
Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, UK.
Int J Environ Res Public Health. 2024 Apr 12;21(4):473. doi: 10.3390/ijerph21040473.
Long COVID (LC) is a global public health crisis affecting more than 70 million people. There is emerging evidence of different pathophysiological mechanisms driving the wide array of symptoms in LC. Understanding the relationships between mechanisms and symptoms helps in guiding clinical management and identifying potential treatment targets.
This was a mixed-methods systematic review with two stages: Stage one (Review 1) included only existing systematic reviews (meta-review) and Stage two (Review 2) was a review of all primary studies. The search strategy involved Medline, Embase, Emcare, and CINAHL databases to identify studies that described symptoms and pathophysiological mechanisms with statistical analysis and/or discussion of plausible causal relationships between mechanisms and symptoms. Only studies that included a control arm for comparison were included. Studies were assessed for quality using the National Heart, Lung, and Blood Institute quality assessment tools.
19 systematic reviews were included in Review 1 and 46 primary studies in Review 2. Overall, the quality of reporting across the studies included in this second review was moderate to poor. The pathophysiological mechanisms with strong evidence were immune system dysregulation, cerebral hypoperfusion, and impaired gas transfer in the lungs. Other mechanisms with moderate to weak evidence were endothelial damage and hypercoagulation, mast cell activation, and auto-immunity to vascular receptors.
LC is a complex condition affecting multiple organs with diverse clinical presentations (or traits) underpinned by multiple pathophysiological mechanisms. A 'treatable trait' approach may help identify certain groups and target specific interventions. Future research must include understanding the response to intervention based on these mechanism-based traits.
长期新冠（LC）是一场全球公共卫生危机，影响着超过7000万人。越来越多的证据表明，不同的病理生理机制导致了长期新冠中出现的一系列广泛症状。了解这些机制与症状之间的关系有助于指导临床管理并确定潜在的治疗靶点。
这是一项混合方法的系统评价，分为两个阶段：第一阶段（综述1）仅包括现有的系统评价（元综述），第二阶段（综述2）是对所有原始研究的综述。检索策略涉及Medline、Embase、Emcare和CINAHL数据库，以识别那些通过统计分析和/或讨论机制与症状之间可能的因果关系来描述症状和病理生理机制的研究。仅纳入了包含对照组进行比较的研究。使用美国国立心肺血液研究所的质量评估工具对研究进行质量评估。
综述1纳入了19项系统评价，综述2纳入了46项原始研究。总体而言，本次二次综述中纳入的所有研究的报告质量为中等至较差。有充分证据的病理生理机制是免疫系统失调、脑灌注不足和肺气体交换受损。其他证据强度为中等至较弱的机制是内皮损伤和高凝状态、肥大细胞活化以及对血管受体的自身免疫。
长期新冠是一种复杂的病症，影响多个器官，有多种临床表现（或特征），由多种病理生理机制支撑。一种“可治疗特征”方法可能有助于识别特定群体并针对特定干预措施。未来的研究必须包括基于这些基于机制的特征来了解对干预的反应。
