Trial Report Remotely delivered weight management for people with long COVID and overweight: the randomized wait-list-controlled ReDIRECT trial, 2025, Combet et al

Remotely delivered weight management for people with long COVID and overweight: the randomized wait-list-controlled ReDIRECT trial

Emilie Combet, Laura Haag, Janice Richardson, Caroline E. Haig, Yvonne Cunningham, Heather L. Fraser, Naomi Brosnahan, Tracy Ibbotson, Jane Ormerod, Chris White, Emma McIntosh, Catherine A. O’Donnell, Naveed Sattar, Alex McConnachie, Michael E. J. Lean & David N. Blane

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Abstract
Long COVID (LC) is a complex multisymptom condition with no known disease-modifying treatments. This wait-list-controlled open-label trial tested whether a remotely delivered structured weight management program could improve respective LC symptoms in people living with overweight.

Adults with LC (symptoms >12 weeks) and body mass index >27 kg m−2 (>25 kg m−2 for South Asians) were randomized (n = 234, 1:1) to control (n = 116, usual care) or the remotely delivered structured weight management (n = 118, total diet replacement (850 kcal per day) for 12 weeks, followed by food reintroduction and weight loss maintenance support) via minimization and randomization (80:20) to balance dominant LC symptom, sex, age, ethnicity and postcode-based index of multiple deprivation between groups. The control group received the intervention after 6 months.

Participants selected the dominant LC symptom they would most like to improve (fatigue, breathlessness, pain, anxiety/depression or other) as the prespecified respective primary outcome. Individual symptoms were assessed using validated questionnaires and a visual analog scale for those without prespecified scales.

At 6 months, the primary outcome improved in the intervention group (change −1.16 (s.d. 1.42), n = 97 analyzed) compared with the control group (change −0.83 (s.d. 1.14), n = 117 analyzed) with a treatment effect of −0.34 (95% confidence interval −0.67 to −0.01), with no excess of serious adverse events.

Link | PDF (Nature Medicine) [Open Access]

 

Thread for protocol for this study:

The remote diet intervention to reduce Long COVID symptoms trial (ReDIRECT): protocol for a randomised controlled trial to determine the effectiveness and cost-effectiveness of a remotely delivered supported weight management programme for people with Long COVID and excess weight, with personalised improvement goals, 2023, Haag et al

 

"people with overweight" Is that a new thing? Bizarrely, I first saw this usage only this morning in the title of this article: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00355-1/fulltext

 

Post-hoc analyses
We explored the possible mediating role of weight loss as a key intervention component in primary outcome improvement, a post-hoc analysis not prespecified in our statistical analysis plan but suggested during the review process. There was no evidence of an interaction between weight loss at 3 or 6 months and the intervention effect on the primary outcome (Extended Data Fig. 3).



From discussion:
Indeed, given the lack of observed interaction in a crude post-hoc interaction analysis between weight loss and the primary outcome, other components of this complex intervention (for instance, the support provided by dietitians and peers) may be important mechanisms of symptom improvement.

My comment:
This important observation should have been mentioned in the abstract.

And the structure of this paper is horrendous..