Effectiveness of physical, psychological, and alternative interventions for post-COVID-19 condition: a systematic review
DOI:
https://doi.org/10.2340/jrm.v58.46279Keywords:
exercise therapy, fatigue, post-acute COVID-19 syndrome, quality of life, rehabilitationAbstract
Objective: To evaluate supervised physical, psycho-logical, and alternative non-pharmacological interventions for improving patient-reported and objective functional outcomes in adults with post-COVID-19 condition.
Design: Systematic review of randomized controlled trials.
Methods: PubMed, Web of Science Core Collection, APA PsycInfo, and Scopus were searched from 1 January 2020 to 29 January 2026. Eligible studies were supervised, face-to-face trials evaluating physical, psychological, or alternative non-pharmacological interventions against usual care, placebo/sham, or active comparators in adults with World Health Organization defined post-COVID-19 condition. Risk of bias was assessed using Cochrane RoB 2. Due to clinical and methodological heterogeneity, a narrative synthesis was performed.
Results: 27 trials (1,998 participants) were included and evaluated physical, psychological, and alternative therapies. Supervised cardiopulmonary rehabilitation and multimodal exercise consistently improved cardiorespiratory fitness and walking capacity. Cognitive-behavioural therapy and lifestyle adjustments significantly reduced fatigue and subjective concentration complaints. Findings for neuromodulation, complementary, and oxygen therapies were heterogeneous, often showing no benefit over placebo. Only 18.5% of trials had low risk of bias, limited by small samples, unblinding, and short follow-ups.
Conclusion: Supervised physical rehabilitation and CBT show promising evidence for improving functional capacity and symptoms in post-COVID-19 condition. Larger trials with longer follow-up are needed to confirm effectiveness and inform clinical guidelines.
Downloads
References
Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV, WHO Clinical Case Definition Working Group on Post-COVID-19 Condition. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis 2022; 22: e102–e107.
Al-Aly Z, Davis H, McCorkell L, Soares L, Wulf-Hanson S, Iwasaki A, et al. Long COVID science, research and policy. Nat Med 2024; 30: 2148–2164.
g/10.1038/s41591-024-03173-6
a systematic review and meta-analysis. JAMA Intern Med 2023; 183: 566–580.
Davis HE, Assaf GS, McCorkell L, Wei H, Low RJ, Re‘em Y, et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine 2021; 38: 101019.
Lopez-Leon S, Wegman-Ostrosky T, Perelman C, Sepulveda R, Rebolledo PA, Cuapio A, et al. More than 50 long-term effects of COVID-19: a systematic review and meta-analysis. Sci Rep 2021; 11: 16144–16151.
Ottiger M, Poppele I, Sperling N, Schlesinger T, Müller K. Work ability and return-to-work of patients with post-COVID-19: a systematic review and meta-analysis. BMC Public Health 2024; 24: 1811.
Pollini E, Lazzarini SG, Cordani C, Del Furia MJ, Kiekens C, Negrini S, et al. Effectiveness of rehabilitation interventions on adults with COVID-19 and post-COVID-19 condition: a systematic review with meta-analysis. Arch Phys Med Rehabil 2024; 105: 138–149.
Pouliopoulou DV, Macdermid JC, Saunders E, Peters S, Brunton L, Miller E, et al. Rehabilitation interventions for physical capacity and quality of life in adults with post-COVID-19 condition: a systematic review and meta-analysis. JAMA Netw Open 2023; 6: e2333838.
Ortiz-Ortigosa L, Gálvez-Álvarez P, Viñolo-Gil MJ, Rodriguez-Huguet M, Góngora-Rodríguez J, Martín-Valero R. Effectiveness of pulmonary rehabilitation programmes and/or respiratory muscle training in patients with post-COVID conditions: a systematic review. Respir Res 2024; 25: 248.
Martínez-Pozas O, Meléndez-Oliva E, Rolando LM, Rico JAQ, Corbellini C, Sánchez Romero EA. The pulmonary rehabilitation effect on long covid-19 syndrome: a systematic review and meta-analysis. Physiother Res Int 2024; 29: e2077.
Markser A, Vöckel J, Schneider A, Baumeister-Lingens L, Sigrist C, Koenig J. Non-invasive brain stimulation for post-COVID-19 conditions: a systematic review. Am J Med 2025; 138: 681–697.
Chen X, Lu C, Wang Q, Pan X, Zhang Y, Wang J, et al. Traditional, complementary and integrative medicine for fatigue post COVID-19 infection: a systematic review of randomized controlled trials. Integr Med Res 2024; 13: 101039.
Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ 2021; 372: n160.
Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan: a web and mobile app for systematic reviews. Syst Rev 2016; 5: 210.
Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019; 366: l4898.
Haddaway NR, Page MJ, Pritchard CC, McGuinness LA. PRISMA2020: an R package and Shiny app for producing PRISMA 2020-compliant flow diagrams, with interactivity for optimised digital transparency and open synthesis. Campbell Syst Rev 2022; 18: e1230.
Ahmad AM, Mohamed Awad Allah SA, Abd Elhaseeb GA, Elsharawy DE, Ahmed HS, Mohamed Abdelwahab MA. Effects of conventional versus virtual reality-simulated treadmill exercise on fatigue, cognitive function, and participant satisfaction in post-COVID-19 subjects: a randomized trial. J Exerc Sci Fit 2024; 22: 316–321.
Omarova I, Akanova A, Kurmanova A, Kurmanova G, Glushkova N, Seidanova A, et al. Acupuncture as an additional method of rehabilitation post-COVID-19: a randomized controlled trial. J Pharmacopuncture 2023; 26: 238–246.
Cherkasova AN, Ikonnikova ES, Lyukmanov RK, Kirichenko OA, Mokienko OA, Konyshev VA, et al. Biofeedback training in rehabilitation of patients with neurological disorders in post-Covid syndrome: a randomized controlled trial. Ann Clin Exp Neurol 2025; 19: 14–26.
Bobowik P, Gajewski J, Wiszomirska I, Maciejewska-Skrendo A, Leźnicka K, Kaczmarczyk K. The impact of resistance training on equilibrium abilities and quality of life in older adults after SARS-CoV-2 survival. J Clin Med 2024; 13: 2747.
Bai B, Xu M, Zhou H, Liao Y, Liu F, Liu Y, et al. Effects of aerobic training on cardiopulmonary fitness in patients with long COVID-19: a randomized controlled trial. Trials 2024; 25: 649.
Kjellberg A, Hassler A, Boström E, El Gharbi S, Al-Ezerjawi S, Schening A, et al. Ten sessions of hyperbaric oxygen versus sham treatment in patients with long covid (HOT-LoCO): a randomised, placebo-controlled, double-blind, phase II trial. BMJ Open 2025; 15: e094386.
Zha S, Liu X, Yao Y, He Y, Wang Y, Zhang Q, et al. Short-term intermittent hypoxia exposure for dyspnea and fatigue in post-acute sequelae of COVID-19: a randomized controlled study. Respir Med 2024; 232: 107763.
Kuut TA, Müller F, Csorba I, Braamse A, Aldenkamp A, Appelman B, et al. Efficacy of cognitive-behavioral therapy targeting severe fatigue following coronavirus disease 2019: results of a randomized controlled trial. Clin Infect Dis 2023; 77: 687–695.
Ahmad AM, Allah S, Abd Elhaseeb GA, Elsharawy DE, Ahmed HS, Abdelwahab M. Effects of conventional versus virtual reality-simulated treadmill exercise on fatigue, cognitive function, and participant satisfaction in post-COVID-19 subjects: a randomized trial. J Exerc Sci Fit 2024; 22: 316–321.
Jimeno-Almazán A, Buendía-Romero Á, Martínez-Cava A, Franco-López F, Sánchez-Alcaraz BJ, Courel-Ibáñez J, et al. Effects of a concurrent training, respiratory muscle exercise, and self-management recommendations on recovery from post-COVID-19 conditions: the RECOVE trial. J Appl Physiol 2023; 134: 95–104.
Polat M, Oba P, Karadağ A. Effect of motion-controlled video games-based virtual reality exercise on patients with post-COVID-19 condition: a randomized controlled trial. Healthcare (Basel) 2025; 13: 2914.
Santana K, França E, Sato J, Silva A, Queiroz M, de Farias J, et al. Non-invasive brain stimulation for fatigue in post-acute sequelae of SARS-CoV-2 (PASC). Brain Stimul 2023; 16: 100–107.
Sick J, Steinbacher V, Kotnik D, König F, Recking T, Bengsch D, et al. Exercise rehabilitation in post COVID-19 patients: a randomized controlled trial of different training modalities. Eur J Phys Rehabil Med 2025; 61: 130–140.
Volckaerts T, Ruttens D, Quadflieg K, Burtin C, Cops D, de Soomer K, et al. Improved functional exercise capacity after primary care pulmonary rehabilitation in patients with long COVID (PuRe-COVID): a pragmatic randomised controlled trial. BMJ Open Respir Res 2025; 12: e003379.
Zha S, Liu X, Yao Y, He Y, Wang Y, Zhang Q, et al. Short-term intermittent hypoxia exposure for dyspnea and fatigue in post-acute sequelae of COVID-19: a randomized controlled study. Respir Med 2024; 232: 107763.
Barz A, Berger J, Speicher M, Morsch A, Wanjek M, Rissland J, et al. Effects of a symptom-titrated exercise program on fatigue and quality of life in people with post-COVID condition: a randomized controlled trial. Sci Rep 2024; 14: 30511.
Gomes Dos Santos EG, Vieira da Costa K, Cordeiro de Souza IT, Victor Dos Santos Felix J, Furtado Brandão CB, Michelle de Souza Fernandes V, et al. Effects of a cardiopulmonary rehabilitation protocol on functional capacity, dyspnea, fatigue, and body composition in individuals with post-COVID-19 syndrome: a randomized controlled trial. Physiother Res Int 2024; 29: e2086.
Kuut TA, Müller F, Csorba I, Braamse A, Aldenkamp A, Appelman B, et al. Efficacy of cognitive-behavioral therapy targeting severe fatigue following coronavirus disease 2019: results of a randomized controlled trial. Clin Infect Dis 2023; 77: 687–695.
Kaddoussi R, Rejeb H, Kalai A, Zaara E, Rouetbi N, Salah Frih ZB, et al. Effects of a cardiopulmonary rehabilitation programme on submaximal exercise in Tunisian patients with long-COVID19: a randomized clinical trial. Biol Sport 2024; 41: 197–217.
Besnier F, Malo J, Mohammadi H, Clavet S, Klai C, Martin N, et al. Effects of cardiopulmonary rehabilitation on cardiorespiratory fitness and clinical symptom burden in long COVID: results from the COVID-Rehab randomized controlled trial. Am J Phys Med Rehabil 2025; 104: 163–171.
Sirydakis M, Danielevicz A, de Melo P, Bregalda J, Constantini MI, Pelliciari G, et al. Improving quality of life, sleep and mental health through multicomponent training versus Brazilian recommendations of physical activity in post-COVID-19 patients: CORE-study – a randomized controlled trial. Ment Health Phys Act 2024; 27: 100615.
D’hoore L, Germonpré P, Rinia B, Caeyers L, Stevens N, Balestra C. Effect of normobaric and hyperbaric hyperoxia treatment on symptoms and cognitive capacities in long COVID patients: a randomised placebo-controlled, prospective, double-blind trial. Diving Hyperb Med 2025; 55: 104–113.
Cabello Fernandez C, Didone V, Lesoinne A, Slama H, Fery P, Rousseau AF, et al. Cognitive and affective psychoeducation for long COVID: a randomized controlled trial. Brain Commun 2025; 7: fcaf447.
Navas-Otero A, Calvache-Mateo A, Calles-Plata I, Valenza-Peña G, Hernández-Hernández S, Ortiz-Rubio A, et al. A lifestyle adjustments program in long COVID-19 improves symptomatic severity and quality of life: a randomized control trial. Patient Educ Couns 2024; 122: 108180.
Ovejero D, Ribes A, Villar-García J, Trenchs-Rodriguez M, Lopez D, Nogués X, et al. Balneotherapy for the treatment of post-COVID syndrome: a randomized controlled trial. BMC Complement Med Ther 2025; 25: 37.
Zilberman-Itskovich S, Catalogna M, Sasson E, Elman-Shina K, Hadanny A, Lang E, et al. Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial. Sci Rep 2022; 12: 11252.
Kroll D, Gloeckl R, Schneeberger T, Jarosch I, Klefenz I, Hitzl W, et al. Effects of cranial electrotherapy stimulation in patients with post-COVID-19 condition on anxiety symptoms: a randomised controlled trial. Respiration 2025; 104: 956–962.
Maritescu A, Crisan AF, Pescaru CC, Stoicescu ER, Oancea C, Iacob D. Effectiveness of combined pulmonary rehabilitation and progressive muscle relaxation in treating long-term COVID-19 symptoms: a randomized controlled trial. J Clin Med 2024; 13: 6237.
Mooren JM, Garbsch R, Schäfer H, Kotewitsch M, Waranski M, Teschler M, et al. Medical rehabilitation of patients with post-COVID-19 syndrome: a comparison of aerobic interval and continuous training. J Clin Med 2023; 12: 6739.
Rutkowski S, Bogacz K, Rutkowska A, Szczegielniak J, Casaburi R. Inpatient post-COVID-19 rehabilitation program featuring virtual reality: preliminary results of randomized controlled trial. Front Public Health 2023; 11: 1121554.
Gaudreau-Majeau F, Gagnon C, Djedaa SC, Bérubé B, Malo J, Iglesies-Grau J, et al. Cardiopulmonary rehabilitation’s influence on cognitive functions, psychological state, and sleep quality in long COVID-19 patients: a randomized controlled trial. Neuropsychol Rehabil 2025; 35: 345–361.
Jimeno-Almazán A, Franco-López F, Buendía-Romero Á, Martínez-Cava A, Sánchez-Agar JA, Sánchez-Alcaraz Martínez BJ, et al. Rehabilitation for post-COVID-19 condition through a supervised exercise intervention: a randomized controlled trial. Scand J Med Sci Sports 2022; 32: 1791–1801.
Pouliopoulou DV, Macdermid JC, Saunders E, Peters S, Brunton L, Miller E, et al. Rehabilitation interventions for physical capacity and quality of life in adults with post-COVID-19 condition. JAMA Netw Open 2023; 6: e2333838.
Pollini E, Lazzarini SG, Cordani C, Del Furia MJ, Kiekens C, Negrini S, et al. Effectiveness of rehabilitation interventions on adults with COVID-19 and post-COVID-19 condition: a systematic review with meta-analysis. Arch Phys Med Rehabil 2024; 105: 138–149.
Li S, Dai B, Hou Y, Zhang L, Liu J, Hou H, et al. Effect of pulmonary rehabilitation for patients with long COVID-19: a systematic review and meta-analysis of randomized controlled trials. Ther Adv Respir Dis 2025; 19: 17534666251323482.
Silveira JM, Nakaishi APM, da Silva MG, Dos Santos DO, Gastaldi AC. Effects of exercise-based pulmonary rehabilitation in patients with long COVID: a systematic review and meta-analysis. Adv Respir Med 2026; 94: 25.
Meléndez-Oliva E, Martínez-Pozas O, Cuenca-Zaldívar JN, Villafañe JH, Jiménez-Ortega L, Sánchez-Romero EA. Efficacy of pulmonary rehabilitation in post-COVID-19: a systematic review and meta-analysis. Biomedicines 2023; 11: 2213.
Calvache-Mateo A, Navas-Otero A, Raya-Benítez J, Martín-Núñez J, Heredia-Ciuró A, Ortiz-Rubio A, et al. Effectiveness of a pain informed movement program in individuals with post-COVID-19 condition: a randomized controlled trial. Arch Phys Med Rehabil 2025; 106: 1636–1644.
Downloads
Additional Files
Published
How to Cite
License
Copyright (c) 2026 Akram Negm, Maike Stolz, Christian Krauth

This work is licensed under a Creative Commons Attribution 4.0 International License.
All digitalized JRM contents is available freely online. The Foundation for Rehabilitation Medicine owns the copyright for all material published until volume 40 (2008), as from volume 41 (2009) authors retain copyright to their work and as from volume 49 (2017) the journal has been published Open Access, under CC-BY-NC licences (unless otherwise specified). The CC-BY-NC licenses allow third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for non-commercial purposes, provided proper attribution to the original work.
From 2024, articles are published under the CC-BY licence. This license permits sharing, adapting, and using the material for any purpose, including commercial use, with the condition of providing full attribution to the original publication.