Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada.
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada.
Brain Behav Immun. 2022 Mar;101:93-135. doi: 10.1016/j.bbi.2021.12.020. Epub 2021 Dec 29.
COVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome.
To quantify the proportion of individuals experiencing fatigue and cognitive impairment 12 or more weeks following COVID-19 diagnosis, and to characterize the inflammatory correlates and functional consequences of post-COVID-19 syndrome.
Systematic searches were conducted without language restrictions from database inception to June 8, 2021 on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, and select reference lists.
Primary research articles which evaluated individuals at least 12 weeks after confirmed COVID-19 diagnosis and specifically reported on fatigue, cognitive impairment, inflammatory parameters, and/or functional outcomes were selected.
DATA EXTRACTION & SYNTHESIS: Two reviewers independently extracted published summary data and assessed methodological quality and risk of bias. A meta-analysis of proportions was conducted to pool Freeman-Tukey double arcsine transformed proportions using the random-effects restricted maximum-likelihood model.
MAIN OUTCOMES & MEASURES: The co-primary outcomes were the proportions of individuals reporting fatigue and cognitive impairment, respectively, 12 or more weeks following COVID-19 infection. The secondary outcomes were inflammatory correlates and functional consequences associated with post-COVID-19 syndrome.
The literature search yielded 10,979 studies, and 81 studies were selected for inclusion. The fatigue meta-analysis comprised 68 studies, the cognitive impairment meta-analysis comprised 43 studies, and 48 studies were included in the narrative synthesis. Meta-analysis revealed that the proportion of individuals experiencing fatigue 12 or more weeks following COVID-19 diagnosis was 0.32 (95% CI, 0.27, 0.37; p < 0.001; n = 25,268; I = 99.1%). The proportion of individuals exhibiting cognitive impairment was 0.22 (95% CI, 0.17, 0.28; p < 0.001; n = 13,232; I = 98.0). Moreover, narrative synthesis revealed elevations in proinflammatory markers and considerable functional impairment in a subset of individuals.
CONCLUSIONS & RELEVANCE: A significant proportion of individuals experience persistent fatigue and/or cognitive impairment following resolution of acute COVID-19. The frequency and debilitating nature of the foregoing symptoms provides the impetus to characterize the underlying neurobiological substrates and how to best treat these phenomena.
PROSPERO (CRD42021256965).
尽管急性感染已得到缓解（即 COVID-19 后综合征），但 COVID-19 仍与临床显著症状相关。疲劳和认知障碍是 COVID-19 后综合征中最常见和最使人虚弱的症状。
量化 COVID-19 诊断后 12 周或更长时间出现疲劳和认知障碍的个体比例，并描述 COVID-19 后综合征的炎症相关性和功能后果。
从数据库创建之初到 2021 年 6 月 8 日，对 PubMed/MEDLINE、Cochrane 图书馆、PsycInfo、Embase、Web of Science、Google/Google Scholar 以及一些参考文献进行了系统搜索，搜索时未对语言进行限制。
选择了至少在确诊 COVID-19 后 12 周评估个体，并特别报告疲劳、认知障碍、炎症参数和/或功能结果的原始研究文章。
两位评审员独立提取已发表的汇总数据，并评估方法学质量和偏倚风险。使用随机效应受限最大似然模型，对 Freeman-Tukey 双反正弦变换比例进行了荟萃分析，以汇总比例。
共同主要结果是 COVID-19 感染后 12 周或更长时间报告疲劳和认知障碍的个体比例。次要结果是与 COVID-19 后综合征相关的炎症相关性和功能后果。
文献检索得到了 10979 项研究，其中 81 项研究被纳入。疲劳荟萃分析包括 68 项研究，认知障碍荟萃分析包括 43 项研究，叙述性综合分析包括 48 项研究。荟萃分析显示，COVID-19 诊断后 12 周或更长时间出现疲劳的个体比例为 0.32（95%CI，0.27，0.37；p<0.001；n=25268；I=99.1%）。出现认知障碍的个体比例为 0.22（95%CI，0.17，0.28；p<0.001；n=13232；I=98.0%）。此外，叙述性综合分析显示，一部分个体的促炎标志物升高，功能严重受损。
相当一部分个体在急性 COVID-19 痊愈后会持续出现疲劳和/或认知障碍。这些症状的频率和使人虚弱的性质为描述潜在的神经生物学基础以及如何最好地治疗这些现象提供了动力。
PROSPERO（CRD42021256965）。
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