Effects of specialized pro-resolving mediators and telerehabilitation on fatigue, dyspnea, and quality of life in post‑COVID‑19 condition: the ARACOV-02 randomized controlled trial

Abstract

Post‑COVID‑19 Condition (PCC) is characterized by persistent multisystem symptoms, with fatigue and dyspnea among the most disabling. Specialized pro‑resolving mediators (SPMs) may modulate chronic inflammation, while telerehabilitation has emerged as an accessible therapeutic strategy. This randomized controlled trial (ARACOV‑02) evaluated the combined effects of an SPM‑enriched nutritional supplement and a structured telerehabilitation program in individuals with PCC. A triple‑blind randomized controlled trial was conducted with 144 participants (mean age 50 ± 9 years; 82% women) experiencing PCC for more than 12 weeks. Participants were randomized 1:1 to receive either an SPM‑enriched marine oil supplement or placebo, both combined with a 12‑week asynchronous telerehabilitation program delivered via the HEFORA platform. The primary outcome was health‑related quality of life (EQ‑5D‑5 L). Secondary outcomes included fatigue (FSS), dyspnea (mMRC), respiratory muscle strength (MIP/MEP), functional capacity (6MWT), and limb strength (30‑s STST, 30‑s ACT). Analyses followed an intention‑to‑treat approach. No statistically significant between‑group differences were observed after 12 weeks ( p > .05). Both groups showed significant within‑group improvements. In the nutritional group, quality of life increased, fatigue decreased, and functional capacity improved (+ 37.82 m in 6MWT; p < .001). Strength and respiratory pressures also increased significantly. Similar improvements were observed in the placebo group, except for dyspnea. Exploratory adherence-stratified analyses showed larger improvements among participants with higher adherence. Although the SPM‑enriched supplement did not show superiority over placebo, adherence‑based analyses suggest potential benefits in highly compliant individuals. Improvements in fatigue, functional capacity, and respiratory strength were observed in both groups after the intervention period. Future biomarker‑guided studies are warranted to identify PCC phenotypes most likely to respond to pro‑resolving nutritional strategies. NCT06063031 (registration date: September 27, 2023).