Post-COVID-19 fatigue: A systematic review

Jian Joli, Patrizia Buck, Stephan Zipfel, Andreas Stengel, Jian Joli, Patrizia Buck, Stephan Zipfel, Andreas Stengel

Abstract

Fatigue is recognized as one of the most commonly presented long-term complaints in individuals previously infected with SARS-CoV-2. This systematic review was performed to describe symptoms, etiology, possible risk factors related to post-COVID-19 fatigue and the therapeutic approaches used for the treatment of post-COVID-19 fatigue. For the systematic literature search the databases PubMed, Web of Science, Cochrane Library, and PsycInfo were used. All articles that met the inclusion criteria were analyzed for demographics, clinical data and treatment. Included were studies which focused on an adult population (18-65 years old); elderly patients and patients with chronic somatic diseases which can also cause fatigue were excluded. We identified 2,851, screened 2,193 and finally included 20 studies with moderate to high methodological quality, encompassing 5,629 participants. Potential risk factors for post-COVID-19 fatigue were old age, female sex, severe clinical status in the acute phase of infection, a high number of comorbidities, and a prediagnosis of depression/anxiety. Lastly, a possible autoimmune etiology was suspected. Several treatment approaches have been tested mostly in small and uncontrolled studies so far: a Chinese herbal formulation improved breathlessness and fatigue. Moreover, molecular hydrogen (H2) inhalation had beneficial health effects in terms of improved physical (6-min walking test) and respiratory function in patients with post-COVID-19. Patients also noticed improvement in fatigue after undergoing hyperbaric oxygen therapy (HBOT) and enhanced external counterpulsation (EECP). Lastly. muscle strength and physical function were improved after undergoing an 8-weeks biweekly physical therapy course including aerobic training, strengthening exercises, diaphragmatic breathing techniques, and mindfulness training. However, larger and controlled studies e.g., investigating the effect of physical and / or psychotherapy for patients with post-COVID-19 fatigue are urgently warranted.

Systematic review registration: Unique Identifier: CRD42022320676, https://www.crd.york.ac.uk/PROSPERO/.

Keywords: COVID-19; brain fog; etiology; long-COVID; post-COVID fatigue; psychosomatic; symptoms; therapy.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Joli, Buck, Zipfel and Stengel.

Figures

Figure 1
Figure 1
Prisma flow chart.
Figure 2
Figure 2
Additional symptoms experienced by patients with post-COVID-19 fatigue (Frequency: from %—to %).
Figure 3
Figure 3
Etiology and risk factors of post-COVID-19 fatigue.

References

    1. Nehme M, Braillard O, Chappuis F, Courvoisier DS., Guessous I,T. Covicare study, prevalence of symptoms more than seven months after diagnosis of symptomatic COVID-19 in an outpatient setting. Ann Intern Med. (2021) 174:1252–160. 10.7326/M21-0878
    1. Malik P, Patel K, Pinto C, Jaiswal R, Tirupathi R, Pillai S, et al. . Post-acute COVID-19 syndrome (PCS) and health-related quality of life (HRQoL)-a systematic review and meta-analysis. J Med Virol. (2022) 94:253–62. 10.1002/jmv.27309
    1. Stengel A, Malek N, Zipfel S, Goepel S. Long haulers-what is the evidence for post-COVID fatigue? Front Psychiatry. (2021) 12:677934. 10.3389/fpsyt.2021.677934
    1. Sivan M, Taylor S, NICE . guideline on long covid. BMJ. (2020) 371:m4938. 10.1136/bmj.m4938
    1. Rudroff T, Fietsam AC, Deters JR, Bryant AD, Kamholz J. Post-COVID-19 fatigue: potential contributing factors. Brain Sci. (2020) 10:1012. 10.3390/brainsci10121012
    1. Julian JT, Higgins PT, Chandler J, Cumpston M, Li T, Page M, et al. . Cochrane Handbook for Systematic Reviews of Interventions Version 60. Chichester: The Cochrane Collaboration; John Wiley and Sons; (2021).
    1. 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. 10.1136/bmj.n160
    1. Lopez-Leon S, Wegman-Ostrosky ST, 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. MedRxiv. (2021). 10.1101/2021.01.27.21250617. [Epub ahead of print].
    1. Sterne JA, Hernan MA, Reeves BC, Savovic J, Berkman ND, Viswanathan M, et al. . ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. (2016) 355:i4919. 10.1136/bmj.i4919
    1. Graham EL, Clark JR, Orban ZS, Lim PH, Szymanski AL, Taylor C, et al. . Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 “long haulers”. Ann Clin Transl Neurol. (2021) 8:1073–85. 10.1002/acn3.51350
    1. Elanwar R, Hussein M, Magdy R, Eid RA, Yassien A, Abdelsattar AS, et al. . Physical and mental fatigue in subjects recovered from COVID-19 infection: a case-control study. Neuropsychiatr dis treat. (2021) 17:2063–71. 10.2147/NDT.S317027
    1. Kamal M, Abo Omirah M, Hussein A, Saeed H. Assessment and characterisation of post-COVID-19 manifestations. Int J Clin Pract. (2021) 75:e13746. 10.1111/ijcp.13746
    1. Ganesh R, Ghosh AK, Nyman MA, Croghan IT, Grach SL, Anstine CV, et al. . PROMIS scales for assessment of persistent post-COVID symptoms: a cross sectional study. J Prim Care Community Health. (2021) 12:21501327211030413. 10.1177/21501327211030413
    1. Samir ES, Shokry D, Gomaa SH. Post-COVID-19 fatigue and anhedonia: a cross-sectional study and their correlation to post-recovery period. Neuropsychopharmacol Rep. (2021) 41:50–5. 10.1002/npr2.12154
    1. Townsend L, Dyer AH, McCluskey P, O'Brien PK, Dowds J, Laird E, et al. . Investigating the relationship between vitamin D and persistent symptoms following SARS-CoV-2 infection. Nutrients. (2021) 13:2430. 10.3390/nu13072430
    1. Townsend L, Dyer AH, Jones K, Dunne J, Mooney A, Gaffney F, et al. . Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection. PLoS ONE. (2020) 15:e0240784. 10.1371/journal.pone.0240784
    1. Townsend L, Moloney D, Finucane C, McCarthy K, Bergin C, Bannan C, et al. . Fatigue following COVID-19 infection is not associated with autonomic dysfunction. PLoS ONE. (2021) 16:e0247280. 10.1371/journal.pone.0247280
    1. Margalit I, Yelin D, Sagi M, Rahat MM, Sheena L, Mizrahi N, et al. . Risk factors and multidimensional assessment of long COVID fatigue: a nested case-control study. Clin Infect Dis. (2022) cia283. 10.1093/cid/ciac283. [Epub ahead of print].
    1. Dayrit JK, Verduzco-Gutierrez M, Teal A, Shah SA. Enhanced external counterpulsation as a novel treatment for post-acute COVID-19 sequelae. Cureus. (2021) 13:e14358. 10.7759/cureus.14358
    1. Mayer KP, Steele AK, Soper MK, Branton JD, Lusby ML, Kalema AG, et al. . Physical therapy management of an individual with post-COVID syndrome: a case report. Phys Ther. (2021) 101:pzab098. 10.1093/ptj/pzab098
    1. Bhaiyat AM, Sasson E, Wang Z, Khairy S, Ginzarly M, Qureshi U, et al. . Hyperbaric oxygen treatment for long coronavirus disease-19: a case report. J Med Case Rep. (2022) 16:80. 10.1186/s13256-022-03287-w
    1. Pang W, Yang F, Zhao Y, Dai E, Feng J, Huang Y, et al. . Granules for post-COVID-19 condition: a randomized clinical trial. J Evid Based Med. (2022) 15:30–8. 10.1111/jebm.12465
    1. Townsend L, Dowds J, O'Brien K, Sheill G, Dyer AH, O'Kelly B, et al. . Persistent poor health after COVID-19 is not associated with respiratory complications or initial disease severity. Ann Am Thorac Soc. (2021) 18:997–1003. 10.1513/AnnalsATS.202009-1175OC
    1. Augustin M, Schommers P, Stecher M, Dewald F, Gieselmann L, Gruell H, et al. . Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study. Lancet Reg Health Eur. (2021) 6:100122. 10.1016/j.lanepe.2021.100122
    1. Fernandez-de-Las-Penas C, Guijarro C, Plaza-Canteli S, Hernandez-Barrera V, Torres-Macho. Prevalence of post-COVID-19 cough one year after SARS-CoV-2 infection: a multicenter study. Lung. (2021) 199:249–53. 10.1007/s00408-021-0014450-w
    1. Vanichkachorn G, Newcomb R, Cowl CT, Murad MH, Breeher L, Miller S, et al. . Post-COVID-19 syndrome (Long Haul Syndrome): description of a multidisciplinary clinic at mayo clinic and characteristics of the initial patient cohort. Mayo Clin Proc. (2021) 96:1782–91. 10.1016/j.mayocp.2021.04.024
    1. Botek M, Krejci J, Valenta M, McKune A, Sladeckova B. Konecny Pet 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) 19:1992. 10.3390/ijerph19041992
    1. Schaeffer MR, Cowan J, Milne KM, Puyat JH, Voduc N, Corrales-Medina V, et al. . Cardiorespiratory physiology, exertional symptoms, and psychological burden in post-COVID-19 fatigue. Respir Physiol Neurobiol. (2022) 302:103898. 10.1016/j.resp.2022.103898
    1. Buccheri G, Ferrigno D, Tamburini M. Karnofsky and ECOG performance status scoring in lung cancer: a prospective, longitudinal study of 536 patients from a single institution. Eur J Cancer. (1996) 32A:1135–41. 10.1016/0959-8049(95)00664-8
    1. Hanson KE, Caliendo AM, Arias CA, Englund JA, Lee MJ, Loeb M, et al. . Infectious diseases society of america guidelines on the diagnosis of COVID-19. Clin Infect Dis. (2020). 10.1093/cid/ciab048. [Epub ahead of print].
    1. Lai JS, Cella D, Choi S, Junghaenel DU, Christodoulou C, Gershon R, et al. . How item banks and their application can influence measurement practice in rehabilitation medicine: a PROMIS fatigue item bank example. Arch Phys Med Rehabil. (2011) 92:S20–7. 10.1016/j.ampr.2010.08.033
    1. Gershon RC, Wagster MV, Hendrie HC, Fox NA, Cook KF, Nowinski CJ, et al. . toolbox for assessment of neurological and behavioral function. Neurology. (2013) 80:S2–6. 10.1212/WNL.0b13e3182872e5f
    1. Institute of Medicine Committee . Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness, Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. National Academies Press.
    1. Chalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, Wright D, et al. . Development of a fatigue scale. J Psychosom Res. (1993) 37:147–53. 10.1016/0022-3999(93)90081-P
    1. Ameringer SW, Elswick RK, Menzies V, Robins JLW, Starkweather AR, Walter JM, et al. . Psychometric evaluation of the patient-reported outcomes measurement information system fatigue-short form across diverse populations. Nursing Res. (2016) 65:279–89. 10.1097/NNR.0000000000000162
    1. Michielsen HJ, De Vries J, Van Heck GL. Psychometric qualities of a brief self-rated fatigue measure: the fatigue assessment scale. J Psychosom Res. (2003) 54:345–52. 10.1016/S0022-3999(02)00392-6
    1. Butler S, Chalder T, Ron M, Wessely S. Cognitive behaviour therapy in chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. (1991) 54:153–8. 10.1136/jnnp.54.2.153
    1. Ewing DJ, Martyn CN, Young RJ, Clarke BF. The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care. (1985) 8:491–8. 10.2337/diacare.8.5.491
    1. Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. (1982) 14:377–81. 10.1249/00005768-198205000-00012
    1. Weisman IM, Zeballos RJ. Clinical exercise testing. Clin Chest Med. (2001) 22:679–701. 10.1016/S0272-5231(05)70060-5
    1. Borg E, Borg G, Larsson K, Letzter M, Sundblad BM. An index for breathlessness and leg fatigue. Scand J Med Sci Sports. (2010) 20:644–50. 10.1111/j.1600-0838.2009.00985.x
    1. Raza A, Steinberg K, Tartaglia J, Frishman WH, Gupta T. Enhanced external counterpulsation therapy: past, present, and future. Cardiol Rev. (2017) 25:59–67. 10.1097/CRD.0000000000000122
    1. Zhen H. Health Commission of Hebei Province. Hebei Administration of Traditional Chinese Medicine, Rehabilitation Guidelines of Integrated Medicine for COVID-19 Patients in Hebei Province. Hebei Administration of Traditional Chinese Medicine; (2021).
    1. Lyu M, Fan G, Xiao G, Wang T, Xu D, Gao J, et al. . Traditional chinese medicine in COVID-19. Acta Pharm Sin B. (2021) 11:3337–63. 10.1016/j.apsb.2021.09.008
    1. Ichihara M, Sobue S, Ito M, Ito M, Hirayama M. K. Ohno K Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles. Med Gas Res. (2015) 5:12. 10.1186/s13618-015-0035-1
    1. Li TT, Sun T, Wang YZ, Wan Q, Li WZ, Yang WC. Molecular hydrogen alleviates lung injury after traumatic brain injury: pyroptosis and apoptosis. Eur J Pharmacol. (2022) 914:174664. 10.1016/j.ejphar.2021.174664
    1. Ara J, Fadriquela A, Ahmed MF, Bajgai J, Sajo MEJ, Lee SP, et al. . Hydrogen water drinking exerts antifatigue effects in chronic forced swimming mice via antioxidative and anti-inflammatory activities. Biomed Res Int. (2018) 2018:1–9. 10.1155/2018/2571269
    1. Bansal AS, Bradley AS, Bishop KN, Kiani-Alikhan S, Ford B. Chronic fatigue syndrome, the immune system and viral infection. Brain Behav Immun. (2012) 26:24–31. 10.1016/j.bbi.2011.06.016
    1. Weingartner AL, Stengel A. [Fatigue at long COVID]. Psychother Psychosom Med Psychol. (2021) 71:515–27. 10.1055/a-1544-8349
    1. Cabrera Martimbianco AL, Pacheco RL, Bagattini AM. R. Riera R Frequency, signs and symptoms, and criteria adopted for long COVID-19: a systematic review. Int J Clin Pract. (2021) 75:e14357. 10.1111/ijcp.14357
    1. Zhou Y, Fu B, Zheng X, Wang D, Zhao C, Qi Y, et al. . Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients. Natl Sci Rev. (2020) 7:998–1002. 10.1093/nsr/nwaa041
    1. Galecki P, Mossakowska-Wojcik J, Talarowska M. The anti-inflammatory mechanism of antidepressants - SSRIs, SNRIs. Prog Neuropsychopharmacol Biol Psychiatry. (2018) 80:291–4. 10.1016/j.pnpbp.2017.03.016
    1. Heckenberg RA, Eddy P, Kent S, Wright BJ. Do workplace-based mindfulness meditation programs improve physiological indices of stress? A systematic review and meta-analysis. J Psychosom Res. (2018) 114:62–71. 10.1016/j.jpsychores.2018.09.010
    1. Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, et al. . Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol. (2020) 5:1265–73. 10.1001/jamacardio.2020.3557
    1. Batra A, Clark JR, LaHaye K, Shlobin NA, Hoffman SC, Orban ZS, et al. . Transcranial doppler ultrasound evidence of active cerebral embolization in COVID-19. J Stroke Cerebrovasc Dis. (2021) 30:105542. 10.1016/j.jstrokecerebrovasdis.2020.105542
    1. 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 (Basel). (2020) 8:552. 10.3390/healthcare8040552

Source: PubMed

3
購読する