A Review Article on Exercise Intolerance in Long COVID: Unmasking the Causes and Optimizing Treatment Strategies

. 2023 Oct 28 ; 29 () : e941079. [epub] 20231028

Jazyk angličtina Země Spojené státy americké Médium electronic

Typ dokumentu přehledy, časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid37897034

There is a growing body of research on SARS-CoV-2 (PASC), previously known as the post-COVID syndrome, a chronic condition characterized by symptoms that persist after SARS-CoV-2 infection. Among these symptoms, feelings of physical exhaustion and prolonged fatigue are particularly prevalent and can significantly impact patients' quality of life. These symptoms are associated with reduced overall physical capacity, decreased daily physical activity, malaise after intense training, and intolerance to physical activity (IFA). IFA, described as a reduced ability to perform physical activities typical for the patient's age, can often lead to a sedentary lifestyle. Prolonged physical inactivity can cause deterioration in the overall physical condition and disrupt mitochondrial function, triggering a vicious cycle of gradual symptom worsening. The underlying causes of PASC remain unclear; however, several biochemical mechanisms have been discussed to explain the body's energy depletion, and a multidisciplinary approach that combines physical and cognitive rehabilitation and lifestyle interventions such as exercise and diet modifications has been suggested to improve the overall health and well-being of PASC patients. This critical review aims to review the existing research on the possible causes and links among chronic fatigue, reduced physical activity, and exercise intolerance in patients with PASC. Further research into the underlying causes and treatment of PASC and the importance of developing individualized treatment is needed to address each patient's unique health requirements.

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Chen C, Haupert SR, Zimmermann L, et al. Global prevalence of post-coronavirus disease 2019 (COVID-19) condition or long COVID: A meta-analysis and systematic review. J Infect Dis. 2022;226(9):1593–607. PubMed PMC

Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601–15. PubMed PMC

Townsend L, Moloney D, Finucane C, et al. Fatigue following COVID-19 infection is not associated with autonomic dysfunction. PLoS One. 2021;16(2):e0247280. PubMed PMC

Anaya JM, Rojas M, Salinas ML, et al. Post-COVID syndrome. A case series and comprehensive review. Autoimmun Rev. 2021;20(11):102947. PubMed PMC

Hao F, Tam W, Hu X, et al. A quantitative and qualitative study on the neuropsychiatric sequelae of acutely ill COVID-19 inpatients in isolation facilities. Transl Psychiatry. 2020;10(1):355. PubMed PMC

Lorkiewicz P, Waszkiewicz N. Biomarkers of post-COVID depression. J Clin Med. 2021;10(18):4142. PubMed PMC

Batiha GES, Al-kuraishy HM, Al-Gareeb AI, Welson NN. Pathophysiology of post-COVID syndromes: A new perspective. Virol J. 2022;19(1):158. PubMed PMC

Shanbehzadeh S, Tavahomi M, Zanjari N, et al. Physical and mental health complications post-COVID-19: Scoping review. J Psychosom Res. 2021;147:110525. PubMed PMC

Joseph P, Singh I, Oliveira R, et al. Exercise pathophysiology in myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of SARS-CoV-2. Chest. 2023 [article in press] PubMed PMC

Afari N, Buchwald D. Chronic fatigue syndrome: A review. Am J Psychiatry. 2003;160(2):221–236. PubMed

Sandler CX, Wyller VBB, Moss-Morris R, et al. Long COVID and post-infective fatigue syndrome: A review. Open Forum Infect Dis. 2021;8(10):ofab440. PubMed PMC

Sukocheva OA, Maksoud R, Beeraka NM, et al. Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome. J Adv Res. 2022;40:179–96. PubMed PMC

Komaroff AL, Lipkin WI. Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome. Trends Mol Med. 2021;27(9):895–906. PubMed PMC

Wood E, Hall KH, Tate W. Role of mitochondria, oxidative stress and the response to antioxidants in myalgic encephalomyelitis/chronic fatigue syndrome: A possible approach to SARS-CoV-2 ‘long-haulers’? Chronic Dis Transl Med. 2021;7(1):14–26. PubMed PMC

Jason LA, Katz BZ, Shiraishi Y, et al. Predictors of post-infectious chronic fatigue syndrome in adolescents. Health Psychol Behav Med. 2014;2(1):41–51. PubMed PMC

Hunt J, Blease C, Geraghty KJ. Long COVID at the crossroads: Comparisons and lessons from the treatment of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) J Health Psychol. 2022;27(14):3106–20. PubMed

Komaroff AL, Bateman L. Will COVID-19 lead to myalgic encephalomyelitis/chronic fatigue syndrome? Front Med. 2021;7:606824. PubMed PMC

Twomey R, DeMars J, Franklin K, et al. Chronic fatigue and postexertional malaise in people living with long COVID: An observational study. Phys Ther. 2022;102(4):pzac005. PubMed PMC

Poenaru S, Abdallah SJ, Corrales-Medina V, Cowan J. COVID-19 and post-infectious myalgic encephalomyelitis/chronic fatigue syndrome: A narrative review. Ther Adv Infect Dis. 2021;8:204993612110093. PubMed PMC

Lim EJ, Son CG. Review of case definitions for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) J Transl Med. 2020;18(1):289. PubMed PMC

Evengård B, Gräns H, Wahlund E, Erik Nord C. Increased number of Candida albicans in the faecal microflora of chronic fatigue syndrome patients during the acute phase of illness. Scand J Gastroenterol. 2007;42(12):1514–15. PubMed

Stengel A, Malek N, Zipfel S, Goepel S. Long haulers – what is the evidence for post-COVID fatigue? Front Psychiatry. 2021;12:677934. PubMed PMC

Büttiker P, Weissenberger S, Ptacek R, Stefano GB. Interoception, trait anxiety, and the gut microbiome: A cognitive and physiological model. Med Sci Monit. 2021;27:931962. PubMed PMC

Wong TL, Weitzer DJ. Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) – a systemic review and comparison of clinical presentation and symptomatology. Medicina (Mex) 2021;57(5):418. PubMed PMC

Vink M, Vink-Niese A. Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe. Re-analysis of a Cochrane review. Health Psychol Open. 2018;5(2):205510291880518. PubMed PMC

Davenport TE, Lehnen M, Stevens SR, et al. Chronotropic intolerance: An overlooked determinant of symptoms and activity limitation in myalgic encephalomyelitis/chronic fatigue syndrome? Front Pediatr. 2019;7:82. PubMed PMC

Li Z, Liu J, Deng H, et al. SARS-CoV-2-specific T cell memory is long-lasting in the majority of convalescent COVID-19 individuals. Microbiology. 2020;2020:383463.

Katz BZ, Jason LA. Chronic fatigue syndrome following infections in adolescents. Curr Opin Pediatr. 2013;25(1):95–102. PubMed

Tleyjeh IM, Saddik B, Ramakrishnan RK, et al. Long-term predictors of breathlessness, exercise intolerance, chronic fatigue and well-being in hospitalized patients with COVID-19: A cohort study with 4 months median follow-up. J Infect Public Health. 2022;15(1):21–28. PubMed PMC

Singh I, Joseph P, Heerdt PM, et al. Persistent exertional intolerance after COVID-19. Chest. 2022;161(1):54–63. PubMed PMC

Halpin SJ, McIvor C, Whyatt G, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol. 2021;93(2):1013–22. PubMed

Prasannan N, Heightman M, Hillman T, et al. Impaired exercise capacity in post-COVID-19 syndrome: The role of VWF-ADAMTS13 axis. Blood Adv. 2022;6(13):4041–48. PubMed PMC

Jammes Y, Steinberg JG, Delliaux S. Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins: Infection and sport practice in CFS. J Intern Med. 2012;272(1):74–84. PubMed

Armstrong CW, McGregor NR, Lewis DP, et al. Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients. Metabolomics. 2015;11(6):1626–39.

Tarnopolsky MA, Raha S. Mitochondrial myopathies: Diagnosis, exercise intolerance, and treatment options. Med Sci Sports Exerc. 2005;37(12):2086–93. PubMed

Hu B, Huang S, Yin L. The cytokine storm and COVID-19. J Med Virol. 2021;93(1):250–56. PubMed PMC

Astin R, Banerjee A, Baker MR, et al. Long COVID: Mechanisms, risk factors and recovery. Exp Physiol. 2023;108(1):12–27. PubMed PMC

Guntur VP, Nemkov T, De Boer E, et al. Signatures of mitochondrial dysfunction and impaired fatty acid metabolism in plasma of patients with post-acute sequelae of COVID-19 (PASC) Metabolites. 2022;12(11):1026. PubMed PMC

Tomas C, Elson JL, Newton JL, Walker M. Substrate utilisation of cultured skeletal muscle cells in patients with CFS. Sci Rep. 2020;10(1):18232. PubMed PMC

Varesi A, Deumer US, Ananth S, Ricevuti G. The emerging role of gut microbiota in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Current evidence and potential therapeutic applications. J Clin Med. 2021;10(21):5077. PubMed PMC

König RS, Albrich WC, Kahlert CR, et al. The gut microbiome in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) Front Immunol. 2022;12:628741. PubMed PMC

Zhang F, Lau RI, Liu Q, et al. Gut microbiota in COVID-19: Key microbial changes, potential mechanisms and clinical applications. Nat Rev Gastroenterol Hepatol. 2023;20(5):323–37. PubMed PMC

Zuo T, Wu X, Wen W, Lan P. Gut microbiome alterations in COVID-19. Genomics Proteomics Bioinformatics. 2021;19(5):679–88. PubMed PMC

Petracek LS, Suskauer SJ, Vickers RF, et al. Adolescent and young adult ME/CFS after confirmed or probable COVID-19. Front Med. 2021;8:668944. PubMed PMC

Sattar N, Valabhji J. Obesity as a risk factor for severe COVID-19: Summary of the best evidence and implications for health care. Curr Obes Rep. 2021;10(3):282–89. PubMed PMC

Dalton A, Mermier C, Zuhl M. Exercise influence on the microbiome–gut–brain axis. Gut Microbes. 2019;10(5):555–68. PubMed PMC

Nieman DC. Exercise is medicine for immune function: Implication for COVID-19. Curr Sports Med Rep. 2021;20(8):395–401. PubMed

Wright J, Astill S, Sivan M. The relationship between physical activity and long COVID: A cross-sectional study. Int J Environ Res Public Health. 2022;19(9):5093. PubMed PMC

Guidetti M, Averna A, Castellini G, et al. Physical activity during COVID-19 lockdown: Data from an Italian Survey. Healthcare. 2021;9(5):513. PubMed PMC

Buizza C, Bazzoli L, Ghilardi A. Changes in college students mental health and lifestyle during the COVID-19 pandemic: A systematic review of longitudinal studies. Adolesc Res Rev. 2022;7(4):537–50. PubMed PMC

Belcher BR, Zink J, Azad A, et al. The roles of physical activity, exercise, and fitness in promoting resilience during adolescence: Effects on mental well-being and brain development. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021;6(2):225–37. PubMed PMC

Dale LP, Vanderloo L, Moore S, Faulkner G. Physical activity and depression, anxiety, and self-esteem in children and youth: An umbrella systematic review. Ment Health Phys Act. 2019;16:66–79.

Scheffer DDL, Latini A. Exercise-induced immune system response: Anti-inflammatory status on peripheral and central organs. Biochim Biophys Acta Mol Basis Dis. 2020;1866(10):165823. PubMed PMC

Davis HE, Assaf GS, McCorkell L, et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. eClinicalMedicine. 2021;38:101019. PubMed PMC

Cash A, Kaufman DL. Oxaloacetate treatment for mental and physical fatigue in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long-COVID fatigue patients: A non-randomized controlled clinical trial. J Transl Med. 2022;20(1):295. PubMed PMC

Wilkins HM, Harris JL, Carl SM, et al. Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis. Hum Mol Genet. 2014;23(24):6528–41. PubMed PMC

Kumar P, Osahon O, Vides DB, et al. Severe glutathione deficiency, oxidative stress and oxidant damage in adults hospitalized with COVID-19: Implications for GlyNAC (glycine and N-acetylcysteine) supplementation. Antioxidants. 2021;11(1):50. PubMed PMC

Paul BD, Lemle MD, Komaroff AL, Snyder SH. Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome. Proc Natl Acad Sci. 2021;118(34):e2024358118. PubMed PMC

Golanski J, Szymanska P, Rozalski M. Effects of Omega-3 polyunsaturated fatty acids and their metabolites on haemostasis – current perspectives in cardiovascular disease. Int J Mol Sci. 2021;22(5):2394. PubMed PMC

Su KP, Lai HC, Yang HT, et al. Omega-3 fatty acids in the prevention of interferon-alpha-induced depression: Results from a randomized, controlled trial. Biol Psychiatry. 2014;76(7):559–66. PubMed

Su KP, Tseng PT, Lin PY, et al. Association of use of Omega-3 polyunsaturated fatty acids with changes in severity of anxiety symptoms: A systematic review and meta-analysis. JAMA Netw Open. 2018;1(5):e182327. PubMed PMC

Maes M, Mihaylova I, Leunis JC. In chronic fatigue syndrome, the decreased levels of Omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation. Neuro Endocrinol Lett. 2005;26(6):745–51. PubMed

Weill P, Plissonneau C, Legrand P, et al. May Omega-3 fatty acid dietary supplementation help reduce severe complications in COVID-19 patients? Biochimie. 2020;179:275–80. PubMed PMC

Yang CP, Chang CM, Yang CC, et al. Long COVID and long chain fatty acids (LCFAs): psychoneuroimmunity implication of Omega-3 LCFAs in delayed consequences of COVID-19. Brain Behav Immun. 2022;103:19–27. PubMed PMC

Contreras-Briceño F, Espinosa-Ramírez M, Rozenberg D, Reid WD. Eccentric training in pulmonary rehabilitation of post-COVID-19 patients: An alternative for improving the functional capacity, inflammation, and oxidative stress. Biology. 2022;11(10):1446. PubMed PMC

Peñailillo L, Diaz-Reiher M, Gurovich A, Flores-Opazo M. A short-term eccentric HIIT induced greater reduction in cardio-metabolic risk markers in comparison with concentric HIIT in sedentary overweight men. Res Q Exerc Sport. 2023;94(2):547–59. PubMed

Rajit JS. Chronic fatigue syndrome and epigenetics: The case for hyperbaric oxygen therapy in biomarker identification. J Pulmonol Respir Res. 2021;5(1):027–030.

Akarsu S, Tekin L, Ay H, et al. The efficacy of hyperbaric oxygen therapy in the management of chronic fatigue syndrome. Undersea Hyperb Med J Undersea Hyperb Med Soc Inc. 2013;40(2):197–200. PubMed

Robbins T, Gonevski M, Clark C, et al. Hyperbaric oxygen therapy for the treatment of long COVID: Early evaluation of a highly promising intervention. Clin Med. 2021;21(6):e629–e32. PubMed PMC

Zilberman-Itskovich S, Catalogna M, Sasson E, et al. Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: Randomized controlled trial. Sci Rep. 2022;12(1):11252. PubMed PMC

Rossi Ferrario S, Panzeri A, Cerutti P, Sacco D. The psychological experience and intervention in post-acute COVID-19 inpatients. Neuropsychiatr Dis Treat. 2021;17:413–22. PubMed PMC

Vink M, Vink-Niese A. Could cognitive behavioural therapy be an effective treatment for long COVID and post COVID-19 fatigue syndrome? Lessons from the Qure study for Q-fever fatigue syndrome. Healthcare. 2020;8(4):552. PubMed PMC

Porter N, Jason LA. Mindfulness meditation interventions for long COVID: Biobehavioral gene expression and neuroimmune functioning. Neuropsychiatr Dis Treat. 2022;18:2599–26. PubMed PMC

Botek M, Krejčí J, Valenta M, et al. Molecular hydrogen positively affects physical and respiratory function in acute post-COVID-19 patients: A new perspective in rehabilitation. Int J Environ Res Public Health. 2022;19(4):1992. PubMed PMC

Alwazeer D, Liu FFC, Wu XY, LeBaron TW. Combating oxidative stress and inflammation in COVID-19 by molecular hydrogen therapy: Mechanisms and perspectives. Oxid Med Cell Longev. 2021;2021:5513868. PubMed PMC

Sathyamoorthy M, Verduzco-Gutierrez M, Varanasi S, et al. Enhanced external counterpulsation for management of symptoms associated with long COVID. Am Heart J Plus Cardiol Res Pract. 2022;13:100105. PubMed PMC

Wagner B, Steiner M, Markovic L, Crevenna R. Successful application of pulsed electromagnetic fields in a patient with post-COVID-19 fatigue: A case report. Wien Med Wochenschr. 2022;172(9–10):227–32. PubMed PMC

Liebert A, Bicknell B, Markman W, Kiat H. A potential role for photobiomodulation therapy in disease treatment and prevention in the era of COVID-19. Aging Dis. 2020;11(6):1352. PubMed PMC

De Matos BTL, Buchaim DV, Pomini KT, et al. Photobiomodulation therapy as a possible new approach in COVID-19: A systematic review. Life. 2021;11(6):580. PubMed PMC

Nunn AVW, Guy GW, Brysch W, Bell JD. Understanding long COVID; mitochondrial health and adaptation – old pathways, new problems. Biomedicines. 2022;10(12):3113. PubMed PMC

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