Fatigue Commonly Improved Under Specialist Long COVID Care; Adding Multi-Organ MRI Showed No Additional Benefit

Fatigue is one of the most common and difficult-to-manage symptoms of Long COVID. A large UK phase 3 trial now offers a more concrete answer about where healthcare resources should be directed: patients’ fatigue decreased overall after receiving specialist Long COVID services, but adding multi-organ magnetic resonance imaging (MRI) to existing care did not further improve fatigue or quality of life.

The STIMULATE-ICP trial was conducted at six National Health Service Long COVID clinics in England and enrolled 1,152 adults who had not been hospitalized for their initial infection and whose symptoms had persisted for at least four weeks. The study used cluster randomization across 122 primary care networks, incorporating multi-organ MRI, digital rehabilitation, both, or neither into local standard care pathways. All groups continued to receive specialist assessment, necessary tests, self-management advice, and multidisciplinary rehabilitation support, including activity pacing.

The median time from infection to enrollment was approximately 394 days, indicating that most participants were not in the natural recovery period shortly after infection. Overall Fatigue Assessment Scale scores fell from a mean of 35.8 to 31.3 within 12 weeks; among the 870 participants with complete baseline and 12-week data, 59% had a decrease of at least 3 points. However, because the trial did not include a control group that received no specialist care, this finding can only show that improvement occurred during the care period and cannot by itself prove that the improvement was entirely caused by specialist services.

Additional imaging did not change the primary outcome. Compared with participants who did not receive additional MRI, those who underwent multi-organ MRI had a difference of only 0.18 points in fatigue scores at 12 weeks, which was not statistically significant; there was also no clear advantage in fatigue or quality of life at 24 weeks. Among the 437 participants who actually underwent scanning, approximately 24% had results deemed abnormal by the hospital, but these findings did not translate into better fatigue outcomes. The research team concluded that, in the absence of specific treatments that can be undertaken based on scan results, current evidence does not support including comprehensive multi-organ MRI as a routine examination for Long COVID.

The signal for digital rehabilitation was more complex. The platform used a mobile app to collect symptoms, provide personalized self-management content, and allow clinicians to remotely monitor progress; however, at 12 weeks, it provided no significant additional benefit for the primary fatigue endpoint. By 24 weeks, fatigue scores in the digital rehabilitation group were 1.14 points lower than with usual care, and quality-of-life ratings were also slightly higher. However, both were secondary endpoints, the differences were small, and whether they were clinically sufficient for patients to perceive a meaningful change remains uncertain.

The trial used an open-label design, implementation may not have been entirely consistent across sites, some participants also joined a nested drug trial, and follow-up data were lost. Analyses of healthcare utilization and costs, which have not yet been published, will also affect decisions about service configuration. The study found no serious adverse events related to the care pathway interventions. Overall, the results more strongly support maintaining accessible multidisciplinary specialist services while carefully selecting expensive tests; whether digital rehabilitation can take over long-term care after intensive specialist support ends still requires confirmation through longer follow-up and independent trials.