The Long-COVIDiet Study: Protocol for a Randomized Controlled Trial Evaluating the Effectiveness of Diet Quality on Fatigue, Physical Function, and Inflammation in Older Adults with Long COVID

<ns3:p> Introduction Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent or new symptoms lasting three months or more after acute infection. Approximately 4% of U.S. adults are affected, with fatigue and muscle weakness among the most common symptoms. Chronic inflammation and nutritional imbalances are thought to contribute to long-COVID symptomatology. The Long-COVIDiet Study was designed to test the effectiveness of a whole-diet approach—grounded in the <ns3:italic>Dietary Guidelines for Americans, 2020–2025</ns3:italic> —that emphasizes nutrient-dense, anti-inflammatory foods and select supplements. The trial evaluates the impact of this dietary intervention, quantified through a diet quality score, on fatigue, muscle strength, physical function, and biomarkers of nutritional and inflammatory status in older adults with long COVID. Methods and analysis Fifty-six participants aged ≥50 years with long COVID, moderate-to-severe fatigue, and suboptimal diet quality will be recruited from the Baltimore, Maryland area. Participants will be randomized 1:1 to either a dietary intervention arm or an attention-control arm. The intervention includes individualized dietary counseling (eight biweekly sessions) and 16 weekly online group sessions with a registered dietitian, emphasizing anti-inflammatory and nutrient-rich foods. The control group attends matched weekly sessions on non-dietary healthy aging topics. Primary outcomes are fatigue and diet quality, assessed at baseline, 12 weeks, and 16 weeks. Secondary outcomes include muscle mass, grip strength, and physical function; exploratory outcomes include nutritional and inflammatory biomarkers. Analyses will follow the intention-to-treat principle, with linear regression and mixed-effects models evaluating changes across timepoints. Ethics and dissemination The study was approved by the University of Maryland, Baltimore Institutional Review Board (HP-00106745). Written informed consent will be obtained from all participants. Results will be disseminated through peer-reviewed publications, scientific conferences, and plain-language summaries on the study website. Trial registration number ClinicalTrials.gov Identifier: <ns3:bold>NCT05977179</ns3:bold> . </ns3:p>