Post-exertional malaise prevalent in adults with long COVID

A systematic review and meta-analysis reports a high prevalence of post-exertional malaise (PEM) in individuals with post-COVID-19 condition (PCC).

“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 individuals with PCC who experience PEM,” the investigators said.

This review and meta-analysis included 41 studies (n=33,685). Data from 28 studies were used to evaluate PEM prevalence in individuals with PCC (mean age 46 years, 65 percent women), while data from 13 studies were used for the evaluation of PEM prevalence after rehabilitation, including a prescribed exercise component (mean age 49 years, 67 percent women).

The overall pooled prevalence estimate of PEM among community-dwelling adults living with PCC was 25 percent. [Arch Phys Med Rehabil 2025;106:1267-1278]

Five studies reported reductions in the frequency and intensity of PEM episodes in adults with PCC after participating in a tailored rehabilitation programme centred on integrating pacing approaches. “However, four of these studies did not have a control group, so it is uncertain whether the improvement was part of the natural cause of the disease or attributed to the rehabilitation programme,” the researchers noted.

Hallmark symptom of chronic fatigue syndrome

A subset of individuals with PCC also experiences PEM, which is characterized by severe and prolonged worsening of symptoms after minimal physical or cognitive exertion. [Work 2023;74:1187-1197] Even typical activities of daily living can be a challenge for them, leading to functional and social impairments, which could subsequently impact their overall health status and quality of life. [PLoS One 2018;13:e0197811]

“PEM is considered to be the hallmark symptom of myalgic encephalomyelitis, also known as chronic fatigue syndrome, but the pathophysiological mechanism of PEM in individuals with PCC is not yet fully understood,” the researchers noted. “Understanding and estimating the prevalence of PEM in adults with PCC is crucial for the planning and development of new health resources on a societal scale.”

Of note, most of the studies included in the analysis only included patients with a confirmed PCC diagnosis during the acute phase of COVID-19. According to the WHO, individuals with PCC are those with both confirmed and suspected prior COVID-19 infections, they said.

“[We] would like to highlight that it is concerning that individuals with suspected cases are excluded from PCC research. During the early stages of SARS-COV-2, there was a shortage in diagnostic tests, and a large number of individuals did not get a confirmed diagnosis,” said the researchers.

“Lack of research could further contribute to the current lack of referral and care pathways that individuals with a suspected COVID-19 diagnosis during the acute phase face nowadays; hence, we argue that there is an urgent need for more inclusive and pragmatic research studies,” they continued.

The investigators acknowledged that their findings are also limited by the inadequate reporting of PEM percentage at baseline prior to enrolment in rehabilitation programmes, and that most studies used non-validated, unstandardized tools to evaluate PEM in individuals with PCC. “[H]ence, there is an urgent need to strengthen the methods of future trials.”