Remote weight management programme benefits individuals with overweight, long COVID

A remotely delivered structured weight management programme appears effective and safe in reducing symptoms that matter most among individuals with long COVID (LC) and overweight, findings from the wait-list-controlled open-label ReDIRECT trial suggest.

A total of 234 participants (mean age 46 years, 84.6 percent women, mean baseline weight 101.9 kg) were randomized 1:1 to the weight management programme (intervention arm) or usual care (control arm). Nearly half (46 percent) of the participants experienced weight gain following COVID infection, with about a third shifting weight class status.

Ninety-five percent (n=109) of participants in the intervention arm started the programme with total diet replacement. Three-quarters completed the programme at 6 months. [Nat Med 2025;doi:10.1038/s41591-024-03384-x]

Of the four main LC symptoms, fatigue was the symptom that most participants wanted to improve (54 percent), followed by breathlessness (16 percent), pain (12 percent), and anxiety/depression (1 percent). The prespecified primary outcome was based on participant-selected dominant LC symptom score.

Seventeen percent selected an alternative ‘other’ symptom apart from the four most frequently selected symptoms. A total of 816 ‘other’ symptoms were reported.

At 6 months, the adjusted between-group mean difference favoured the intervention over the control arm (intervention effect estimate, −0.34; p=0.0466). Of note, the effect estimate was more marked at 3 months (−0.90; p<0.0001).

Secondary outcomes, safety

Except for pain, the three LC symptoms improved with the intervention (treatment effect [TE], −1.41; p=0.1480).

For fatigue, the change* was greater in the intervention vs the control arm (−7.5 vs −3.7 points; TE, −3.64; p<0.0001), with similar TEs for both the physical (−2.56; p<0.0001) and mental fatigue subscales (−1.06; p=0.0032).

Similar patterns were seen for breathlessness* (−0.4 vs −0.2 points; TE, –0.27; p=0.0124) and anxiety and depression* (−2.9 vs −0.9 points; TE, −1.94; p=0.0249). The latter was mostly attributable to the depression subscale (TE, −1.44; p=0.0052).

Parallel improvements favouring the intervention over the control was also evident in terms of ‘other’ symptoms (−2 vs −1.4 points; TE, −0.82; p=0.0113) and quality of life (QoL; EQ-5D VAS**, 10.9 vs 2.3 points; TE, 7.55; p=0.0019).

The number of hours of work missed per week due to health problems dropped by 3.38 hours in the intervention group and 2.34 in the control group (TE, 2.44; p=0.0949). However, the researchers noted that this should be interpreted with caution, given the relatively weak evidence for a between-group difference at 6 months symptom-wise (p=0.095). Nonetheless, the difference in the number of work hours missed weekly may signal other benefits if the weight loss is sustained longer.

Month 6 also saw better improvements in mean body weight (−10.3 vs −0.7 kg; adjusted group difference, −9.79 kg; p<0.0001) and blood pressure (−6.6 vs −3.2 mm Hg; adjusted group difference, −4.16 mm Hg; p=0.0126 [systolic] and −4.7 vs −1.8 mm Hg; adjusted group difference, −2.73 mm Hg; p=0.0160) in the intervention vs the control arm.

There were no deaths reported. Of the 16 serious adverse events reported, six were severe, five moderate, four mild, and one unclassified. Two gallstone events were deemed intervention-related but were not unexpected.

Profound impact on various life aspects

“[The QoL and functional impairment due to LC] is compounded by the profound impact of the condition on other aspects of life, such as employment and livelihoods, relationships with family and friends, and community participation,” the researchers said.

“Our findings are important since very few interventions have been shown to help individuals with LC … Our work has genuine translational potential for offering personalized dietary weight management solutions under existing services to people living with LC and excess weight,” they said.

Of note was the TE decline between months 3 and 6 despite the well-maintained weight loss. “A follow-up analysis at 12 months will indicate the sustainability of benefits in the longer term,” they said. More studies may also shed light on the mechanisms for the observed benefits.