Prevalence and Impact of Post-Exertional Malaise on Recovery in Adults with Post COVID-19 Condition. A Systematic Review with Meta-Analysis.

Abstract

Objective: To assess the prevalence of PEM in people with PCC; and the change in prevalence of PEM following rehabilitation interventions in people with PCC.

Data sources: We searched MEDLINE, Embase, Central, CINAHL, PsychINFO and Clinical Trial Registries from inception until January 12^th, 2024.

Study selection: 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 following 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. Any discrepancies were resolved by consensus.

Data extraction: 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 (ROB). Discrepancies were resolved with a senior research team member. For the prevalence studies we used the Cochrane Risk Of Bias In Non-randomized Studies - of Exposure (ROBINS-E) tool. For randomised controlled trials we used the Cochrane Risk of Bias tool II - (RoB2). For non-randomised interventional studies we used the Cochrane Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I)¹ to assess the non-randomised studies. We applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach to grade the quality of the evidence DATA SYNTHESIS: 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. This study is registered with PROSPERO (CRD42024516682).The prevalence of PEM in community-dwelling adults living with PCC was 36% (95% CI: 0.19 to 0.57; 2,263 participants). Two of the included studies (61 patients) found a decrease in the frequency and intensity of PEM episodes in adults with PCC following a tailored rehabilitation program centered on integrating pacing approaches. None of the included studies reported an increase of PEM symptoms' frequency and intensity following an individually tailored rehabilitation program with a therapeutic exercise component (5 studies; 892 patients).

Conclusions: Our research confirms that there is a large burden of PEM in adults living with PCC, highlighting a critical challenge for healthcare 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 that 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 non-validated, unstandardized tools to measure PEM in people with PCC, hence there is an urgent need to strengthen the methods of future trials.