Pouliopoulou Dimitra V, Hawthorne Myranda, MacDermid Joy C, Billias Nicole, Miller Erin, Quinn Kieran, Décary Simon, Razak Fahad A, Cheung Angela, Galiatsatos Panagis, Pereira Tiago V, Bobos Pavlos
School of Physical Therapy, Faculty of Health Science, Western University, London, ON, Canada; Department of Health and Rehabilitation Sciences, Faculty of Health Sciences, Western University, London, ON, Canada.
Department of Health and Rehabilitation Sciences, Faculty of Health Sciences, Western University, London, ON, Canada.
Arch Phys Med Rehabil. 2025 Feb 5. doi: 10.1016/j.apmr.2025.01.471.
To assess the prevalence of postexertional malaise (PEM) in people with post-COVID-19 condition (PCC); and the change in prevalence of PEM after rehabilitation interventions in people with PCC.
We searched MEDLINE, Embase, CENTRAL, CINAHL, PsychINFO, and clinical trial registries from inception until February 11, 2025.
We included observational studies that measured the prevalence of PEM in adults with PCC and interventional studies that measured the change in prevalence of PEM after rehabilitation interventions in adults with PCC. Two independent researchers screened titles and abstracts. Any discrepancies underwent full text review. Two independent researchers screened the articles included at the full text level.
Two independent researchers extracted data from eligible studies. We extracted point prevalence from the cross-sectional studies; and period prevalence from the longitudinal studies. Two independent reviewers assessed the risk of bias. Discrepancies were resolved with a senior research team member. For the prevalence studies we used the ROBINS-E tool. For randomized controlled trials we used the RoB2 tool. For non-randomized interventional studies we used the ROBINS-I tool to assess the non-randomized studies. We used the GRADE system to assess the certainty of the evidence.
We performed a single-arm proportional meta-analysis to synthesize prevalence estimates using logit transformation. We conducted a sensitivity analysis using multilevel-mixed-effects logistic regression. We used a random effects model. Results were reported as proportions with corresponding 95% confidence intervals (95% CI) or presented descriptively when statistical analysis was not applied. This study is registered with PROSPERO (CRD42024516682). The prevalence of PEM in community-dwelling adults living with PCC was 25% (95% CI: 0.17-0.36; 10 studies; 4,076 low certainty after the word participants). Five of the included studies (193 patients) found a decrease in the frequency and intensity of PEM episodes in adults with PCC after a tailored rehabilitation program centered on integrating pacing approaches. Eight studies (1080 patients) measured PEM as an adverse event following an individually tailored rehabilitation intervention with a therapeutic exercise component. Seven of these studies did not find indications of post exertional symptom exacerbation related to the exercise component of the intervention. All of the studies had high to very high risk of bias.
Our research confirms that there is a large burden of PEM in adults living with PCC, highlighting a critical challenge for health care systems and an urgent need for more inclusive and rigorous research, to offer safe and effective therapeutic solutions and meet the variable needs of people with PCC that experience PEM. There is a subgroup of patients with PCC who do not experience PEM; and there is limited evidence that supervised, individually tailored, symptom-titrated rehabilitation interventions with active exercise components may not trigger PEM in this subgroup of people with PCC. Our results are limited by the insufficient reporting of the percentage of PEM in the baseline before enrolling patients in the rehabilitation programs, and the large number of studies using nonvalidated, unstandardized tools to measure PEM in people with PCC; hence, there is an urgent need to strengthen the methods of future trials.
评估新冠后状况（PCC）患者中运动后不适（PEM）的患病率；以及PCC患者康复干预后PEM患病率的变化。
我们检索了MEDLINE、Embase、CENTRAL、CINAHL、PsychINFO以及临床试验注册库，检索时间从创建至2025年2月11日。
我们纳入了测量PCC成年患者中PEM患病率的观察性研究，以及测量PCC成年患者康复干预后PEM患病率变化的干预性研究。两名独立研究人员筛选标题和摘要。如有分歧，则进行全文审查。两名独立研究人员在全文层面筛选纳入的文章。
两名独立研究人员从符合条件的研究中提取数据。我们从横断面研究中提取时点患病率；从纵向研究中提取期间患病率。两名独立评审员评估偏倚风险。分歧由高级研究团队成员解决。对于患病率研究，我们使用ROBINS-E工具。对于随机对照试验，我们使用RoB2工具。对于非随机干预研究，我们使用ROBINS-I工具评估非随机研究。我们使用GRADE系统评估证据的确定性。
我们进行了单臂比例荟萃分析，使用对数转换来合成患病率估计值。我们使用多水平混合效应逻辑回归进行敏感性分析。我们使用随机效应模型。结果以比例及相应的95%置信区间（95%CI）报告，或在未进行统计分析时进行描述性呈现。本研究已在PROSPERO注册（CRD42024516682）。社区居住的PCC成年患者中PEM的患病率为25%（95%CI：0.17 - 0.36；10项研究；4076名参与者，证据确定性低）。纳入的5项研究（193名患者）发现，以整合 pacing 方法为中心的量身定制康复计划后，PCC成年患者PEM发作的频率和强度有所降低。8项研究（1080名患者）将PEM作为个体化量身定制的含治疗性运动成分的康复干预后的不良事件进行测量。其中7项研究未发现与干预的运动成分相关的运动后症状加重迹象。所有研究的偏倚风险均为高至非常高。
我们的研究证实，PCC成年患者中PEM负担沉重，凸显了医疗保健系统面临的重大挑战，以及迫切需要开展更具包容性和严谨性的研究，以提供安全有效的治疗方案，并满足经历PEM的PCC患者的多样化需求。有一部分PCC患者未经历PEM；且证据有限，表明有监督的、个体化量身定制的、症状滴定的含主动运动成分的康复干预可能不会在这部分PCC患者亚组中引发PEM。我们的结果受到以下因素限制：在将患者纳入康复计划之前，基线时PEM百分比的报告不足，以及大量研究使用未经验证、未标准化的工具来测量PCC患者的PEM；因此，迫切需要加强未来试验的方法。
