Abstract
Long COVID continues to impose a significant burden on COVID-19 survivors, presenting with diverse symptoms and clinical uncertainty. This review synthesized evidence from 97 studies, including 26 randomized controlled trials and 15 non-randomized comparative studies, which explored the effectiveness, comparative effectiveness, and potential risks of proposed interventions for managing common long COVID symptoms: fatigue, neurocognitive symptoms, anxiety, depression, and sleep issues. Our comprehensive analysis, encompassing English-language articles, gray literature, and feedback from 14 Key Informants (i.e., patients, caregivers, clinicians, payors, and researchers), reveals a persistently weak body of evidence, characterized by high imprecision and considerable uncertainty regarding the benefits and harms of the interventions. The studies examined a wide array of treatment categories, including multi-component rehabilitation, supplements, complementary treatments, prescription medications, and the COVID-19 vaccine. Key informants emphasized the critical need for establishing robust diagnostic criteria and utilizing functional outcomes while also highlighting significant barriers to care, including dismissive attitudes from healthcare providers, inadequate insurance coverage, and restricted access to specialty care. Given the evolving definitions of long COVID and the variable mechanisms of its management, our findings underscore the pressing need for further rigorous research to refine and validate effective treatment protocols. Until more definitive evidence is available, both clinicians and patients face substantial uncertainty in treatment decisions, with many resorting to self-treatment using costly and potentially ineffective options.


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Acknowledgements:
The authors gratefully acknowledge the following individuals for their contributions to this project: Gowri Raman, MBBS, MS, Meghana Vijaysimha, MPH, Amanda Barbeau, MPH, Denise Bonds, MD, and William Lawrence, MD, MS, at PCORI for their support scoping the project and overall approach guidance; one group of experts for insight and reviewing our protocol, interview guides, and draft report (in alphabetical order): Charissa Fotinos, MD (Washington Health Care Authority); Rowena Ng, PhD (Kennedy Krieger Institute and Johns Hopkins University); Amy Price, PhD (Stanford University); Louise Walter, MD (University of California, San Francisco), and David Warburton, MD (University of Southern California and Children’s Hospital Los Angeles); second group of experts for insight into important interventions, outcomes, and disease burden (in alphabetical order): Alba Miranda Azola, MD (Johns Hopkins University), ZZ DeFonde; Dawn Jeanette Dore-Stites, PhD (C. S. Mott Children’s Hospital), Kurt Elward, MD, MPH (Virginia Department of Medical Assistance Services and Virginia Commonwealth University), Semhar Fisseha, MPH (Weill Cornell Medicine), Eric Herman, MD (Oregon Health & Science University), Katherine Tochtrop, David Weber, MD, MPH (University of North Carolina); ECRI members Allison Hedden-Gross, MS, MLS for developing search strategies, Helen Dunn for managing references, Kariann Hudson, Med for supporting gray literature search strategy development, and Britney Hall and Julia Barndt for editorial work; Lindsey Miller, DPT, PMP and Jesse Munn, MBA for project support; and Justin Zimmerman, MSME for providing the code to retrieve Reddit submissions.
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This report was conducted under contract to the PCORI, Washington, DC (contract MSA-SOW#05-ECRI-ENG-11-07-2022).
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Ivlev, I., Wagner, J., Phillips, T. et al. Interventions for Long COVID: A Narrative Review. J GEN INTERN MED (2025). https://doi.org/10.1007/s11606-024-09254-z
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DOI: https://doi.org/10.1007/s11606-024-09254-z