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

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. International Standard Randomised Controlled Trial Number Registry registration: ISRCTN 12595520 .

Fig. 1. Participant flow through the ReDIRECT study.

Trial profile showing the number of patients screened for eligibility, enrolled, randomized, allocated to treatment or control, and included in the intention-to-treat analysis at 6 months.

Fig. 2. Change in the primary outcome (continuous measure derived from the symptom score for the most important LC symptom as selected by each participant at baseline (fatigue, breathlessness, pain, anxiety/depression or other)).

The data are presented as means, with the shaded areas representing the 95% CIs. Two-sided P values (linear regression) represent the treatment effect at 3 months (P < 0.0001, n = 219) and 6 months (P = 0.0466, n = 214) compared with baseline. No adjustment is made for multiple comparisons.

Fig. 3. Change in LC symptoms as secondary outcomes.

a–d, Fatigue (a), breathlessness (b), pain (c) and anxiety/depression (d). The data are presented as means, with the shaded areas representing the 95% CIs. Two-sided P values (linear regression) represent the treatment effect compared with baseline at 3 months for fatigue (P < 0.0001, n = 217), breathlessness (P = 0.0204, n = 218), pain (P = 0.0154, n = 217) and anxiety/depression (P < 0.0001, n = 217) and 6 months for fatigue (P < 0.0001, n = 214), breathlessness (P = 0.0124, n = 214), pain (P = 0.1480, n = 214) and anxiety/depression (P = 0.0249, n = 214). No adjustment is made for multiple comparisons.

Fig. 4. Change in LC symptoms as secondary outcomes at 6 months.

a–f, Physical (a) and mental (b) fatigue; HADS anxiety (c) and depression (d); quality of life (EQ-5D visual scale (e) and utility (f)); systolic (g) and diastolic (h) blood pressure. The data are presented as means, with the shaded areas representing the 95% CIs. Two-sided P values (linear regression) represent the treatment effect compared with baseline: at 3 months for physical fatigue (P < 0.0001, n = 217), mental fatigue, (P < 0.0001, n = 217), HADS anxiety (P = 0.0167, n = 217), HADS depression, (P < 0.0001, n = 217), EQ-5D visual scale (P = 0.0023, n = 217), EQ-5D utility (P = 0.0041, n = 217), SBP (P < 0.0001, n = 216), DBP (P = 0.0378, n = 216) at 6 months for physical fatigue (P < 0.0001, n = 214), mental fatigue, (P = 0.0032, n = 214), HADS anxiety (P = 0.2947, n = 214), HADS depression, (P = 0.0052, n = 214), EQ-5D visual scale (P = 0.0019, n = 214), EQ-5D utility (P = 0.0725, n = 214), SBP (P = 0.0126, n = 212), DBP (P = 0.0160, n = 212). No adjustment is made for multiple comparisons.

Extended Data Fig. 1. Change in weight at 6 months.

Change from baseline in kg (A) or % of baseline weight (B).

Extended Data Fig. 2. Difference in treatment effect based on age, deprivation level (IMD), baseline body mass index (BMI), sex, primary symptom selected (and whether this included fatigue or not).

Data are presented as means with 95% confidence intervals. Two-sided p-values represent the interaction between subgroup and treatment (linear regression/ANCOVA), exploring age ( < 42.1: n = 71, 42.2 to 51.4: n = 69, >51.4: n = 74, p = 0.5750), IMD (1st to 5th decile: n = 86, 6th to 10th decile: n = 128, p = 0.3191), BMI (Below 30: n = 31, 30 or above: n = 183, p = 0.0861), sex (female: n = 182, male: n = 31, p = 0.2255), primary symptom selected (Pain: n = 26, Breathlessness: n = 35, Fatigue: n = 115, Other: n = 37, p = 0.6053), and fatigue as a primary symptom (Yes: n = 115, No: n = 99, p = 0.3696).

Extended Data Fig. 3. Crude interaction analysis between change in weight and effect of the intervention on the primary outcome.

Data are presented as means with shaded areas representing 95% confidence intervals at 3 months with n = 216 (A) and 6 months with n = 212 (B). Estimates and p-values (two-tailed, linear regression) are given per 10 kg change in weight change, and no adjustments are made for multiple comparisons.