Long COVID: Difference between revisions

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== Introduction ==
== Introduction ==
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease (COVID-19) <ref>World Health Organization. [https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it Naming the coronavirus disease (COVID-19) and the virus that causes it].  [Accessed 7 January 2021]</ref>. The effects of COVID-19 have been characterised across different time points:  
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease (COVID-19) <ref>World Health Organization. Naming the coronavirus disease (COVID-19) and the virus that causes it. Availabe from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it [Accessed 7 January 2021]</ref>. The effects of COVID-19 have been characterised across different time points:  
* acute COVID-19 infection with signs and symptoms of COVID-19 for up to 4 weeks.
* acute COVID-19 infection with signs and symptoms of COVID-19 for up to 4 weeks.
* ongoing symptomatic COVID-19 with signs and symptoms of COVID-19 from 4 weeks up to 12 weeks.
* ongoing symptomatic COVID-19 with signs and symptoms of COVID-19 from 4 weeks up to 12 weeks.
* long term consequences of COVID-19 which usually presents with clusters of symptoms, often overlapping, which can fluctuate and change over time and can affect any system in the body for more than 12 weeks.<ref name=":1">National Institute for Health and Care Excellence (NICE), [https://www.nice.org.uk/guidance/ng188/documents/final-scope COVID-19 guideline scope: management of the long-term effects of COVID-19]. 2020 [Accessed 7 January 2021].</ref>
* long-term consequences of COVID-19 which usually presents with clusters of symptoms, often overlapping, which can fluctuate and change over time and can affect any system in the body for more than 12 weeks.<ref name=":1">National Institute for Health and Care Excellence (NICE), COVID-19 guideline scope: management of the long-term effects of COVID-19. 2020. Available from: https://www.nice.org.uk/guidance/ng188/documents/final-scope [Accessed 7 January 2021].</ref>


<nowiki>**</nowiki> The name Long COVID acknowledges that the disease cause and course are as yet unknown, makes clear that “mild” COVID-19 is not necessarily mild, avoids “chronic,” “post” and “syndrome” that may delegitimise people's experiences, draws attention to morbidity, and centres people with disability.<ref name=":0">Perego E, Callard F, Stras L, Melville-Johannesson B, Pope R, Alwan N. [https://blogs.bmj.com/bmj/2020/10/01/why-we-need-to-keep-using-the-patient-made-term-long-covid/ Why we need to keep using the patient made term “Long Covid]. BMJ Opinion. 2020 Oct 1 [Accessed 7 January 2021].</ref>   
<nowiki>**</nowiki> The name Long COVID acknowledges that the disease cause and course are as yet unknown makes clear that “mild” COVID-19 is not necessarily mild, avoids “chronic,” “post” and “syndrome” that may delegitimise people's experiences, draws attention to morbidity, and centres people with disability.<ref name=":0">Perego E, Callard F, Stras L, Melville-Johannesson B, Pope R, Alwan N. Why we need to keep using the patient made term “Long Covid. BMJ Opinion. 2020.</ref>   


"People call Long COVID by many names, including post-COVID conditions, long-haul COVID, post-acute COVID-19, long-term effects of COVID, and chronic COVID."<ref>[https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html Long COVID or Post-COVID Conditions]. Updated Dec. 16, 2022. Centers for Disease Control and Prevention. </ref>   
"People call Long COVID by many names, including post-COVID conditions, long-haul COVID, post-acute COVID-19, long-term effects of COVID, and chronic COVID."<ref>Long COVID or Post-COVID Conditions. Updated Dec. 16, 2022. Centres for Disease Control and Prevention. Available From: https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html </ref>   
== What is Long COVID? ==
== What is Long COVID? ==
Long Covid has been preliminarily defined as the presence of signs and symptoms that develop during or following an infection consistent with COVID-19 which continue for 12-weeks or more and are not explained by an alternative diagnosis. This includes both ongoing symptomatic COVID-19 (from 4 to 12 weeks) and "Post-COVID Syndrome" (12-weeks or more).<ref name=":4">National Institute for Health and Care Excellence (NICE). [https://www.nice.org.uk/guidance/ng188 COVID-19 Rapid Guideline: Managing The Long-term Effects of COVID-19]. 2020 December 18 [Accessed 8 January 2021].</ref>
Long Covid has been preliminarily defined as the presence of signs and symptoms that develop during or following an infection consistent with COVID-19 which continue for 12 weeks or more and are not explained by an alternative diagnosis. This includes both ongoing symptomatic COVID-19 (from 4 to 12 weeks) and "Post-COVID Syndrome" (12 weeks or more).<ref name=":4">National Institute for Health and Care Excellence (NICE). COVID-19 Rapid Guideline: Managing The Long-term Effects of COVID-19. 2020. Available From: https://www.nice.org.uk/guidance/ng188 [Accessed 8 January 2021].</ref>


Long COVID affects people who have been hospitalised with acute COVID-19 and those who managed in a community setting. There is growing evidence to suggest that individuals who have had both mild or severe COVID-19 can experience prolonged symptoms or develop Long COVID.<ref>Public Health England. [https://www.gov.uk/government/publications/wuhan-novel-coronavirus-background-information/wuhan-novel-coronavirus-epidemiology-virology-and-clinical-features COVID-19: epidemiology, virology and clinical features]. February 18, 2021.  
Long COVID affects people who have been hospitalised with acute COVID-19 and those who managed in a community setting. There is growing evidence to suggest that individuals who have had both mild or severe COVID-19 can experience prolonged symptoms or develop Long COVID.<ref>Public Health England. COVID-19: epidemiology, virology and clinical features. 2021.  
</ref><ref>L.Townsend, J.Dowds, K.O'Brien, G.Sheill, AH.Dyer, B.O'Kelly, JP.Hynes, A.Mooney, J.Dunne, CN.Cheallaigh, C.O'Farrelly, NM.Bourke, N.Conlon, I.Martin-Loeches, C.Bergin, P.Nadarajan,C.Bannan. [https://www.atsjournals.org/doi/10.1513/AnnalsATS.202009-1175OC Persistent Poor Health Post-COVID-19 Is Not Associated with Respiratory Complications or Initial Disease Severity]. Annals of the American Thoracic Society, 2021.  
</ref><ref>Townsend L, Dowds J, O'Brien K, Sheill G, Dyer AH, O'Kelly B, Hynes JP, Mooney A, Dunne J, Ni Cheallaigh C, O'Farrelly C, Bourke NM, Conlon N, Martin-Loeches I, Bergin C, Nadarajan P, Bannan C. Persistent Poor Health after COVID-19 Is Not Associated with Respiratory Complications or Initial Disease Severity. Ann Am Thorac Soc. 2021;18(6):997-1003.
</ref><ref>EL.Graham, JR.Clark, ZS.Orban, PH.Lim, AL.Szymanski, C.Taylor, RM.DiBiase, DT.Jia, R.Balabanov, SU.Ho, A.Batra, EM.Liotta, IJ.Koralnik.[https://onlinelibrary.wiley.com/doi/10.1002/acn3.51350 Persistent neurologic symptoms and cognitive dysfunction in non‐hospitalized Covid‐19 “long haulers”]. Annals of Clinical and Translational Neurology, 2021.  
</ref><ref>Graham EL, Clark JR, Orban ZS, Lim PH, Szymanski AL, Taylor C, DiBiase RM, Jia DT, Balabanov R, Ho SU, Batra A, Liotta EM, Koralnik IJ. Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 "long haulers". Ann Clin Transl Neurol. 2021;8(5):1073-1085.
</ref><ref>P.Brodin. [https://www.nature.com/articles/s41591-020-01202-8 Immune determinants of COVID-19 disease presentation and severity]. Nature Medicine, 2021;27:28–33.  
</ref><ref>Brodin P. Immune determinants of COVID-19 disease presentation and severity. Nature Medicine, 2021;27:28–33.  
</ref><ref name=":25" /><ref>Augustin M, Schommers P, Stecher M, Dewald F, Gieselmann L, Gruell H, Horn C, Vanshylla K, Cristanziano VD, Osebold L, Roventa M. [https://www.medrxiv.org/content/10.1101/2021.03.11.21253207v1 Recovered not restored: Long-term health consequences after mild COVID-19 in non-hospitalized patients]. medRxiv. 2021 Mar 12:2021-03.  
</ref><ref name=":25" /><ref>Augustin M, Schommers P, Stecher M, Dewald F, Gieselmann L, Gruell H, Horn C, Vanshylla K, Cristanziano VD, Osebold L, Roventa M. Recovered not restored: Long-term health consequences after mild COVID-19 in non-hospitalized patients. MedRxiv. 2021;2021-03.  
</ref><ref name=":22" /><ref>Evans RA, McAuley H, Harrison EM, Shikotra A, Singapuri A, Sereno M, Elneima O, Docherty AB, Lone NI, Leavy OC, Daines L, Baillie JK, Brown JS, Chalder T, De Soyza A, Diar Bakerly N, Easom N, Geddes JR, Greening NJ, Hart N, Heaney LG, Heller S, Howard L, Hurst JR, Jacob J, Jenkins RG, Jolley C, Kerr S, Kon OM, Lewis K, Lord JM, McCann GP, Neubauer S, Openshaw PJM, Parekh D, Pfeffer P, Rahman NM, Raman B, Richardson M, Rowland M, Semple MG, Shah AM, Singh SJ, Sheikh A, Thomas D, Toshner M, Chalmers JD, Ho LP, Horsley A, Marks M, Poinasamy K, Wain LV, Brightling CE. Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study. Lancet Respir Med. 2021;9(11):1275-1287.  
</ref><ref name=":22" /><ref>Evans RA, McAuley H, Harrison EM, Shikotra A, Singapuri A, Sereno M, Elneima O, Docherty AB, Lone NI, Leavy OC, Daines L, Baillie JK, Brown JS, Chalder T, De Soyza A, Diar Bakerly N, Easom N, Geddes JR, Greening NJ, Hart N, Heaney LG, Heller S, Howard L, Hurst JR, Jacob J, Jenkins RG, Jolley C, Kerr S, Kon OM, Lewis K, Lord JM, McCann GP, Neubauer S, Openshaw PJM, Parekh D, Pfeffer P, Rahman NM, Raman B, Richardson M, Rowland M, Semple MG, Shah AM, Singh SJ, Sheikh A, Thomas D, Toshner M, Chalmers JD, Ho LP, Horsley A, Marks M, Poinasamy K, Wain LV, Brightling CE. Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study. Lancet Respir Med. 2021;9(11):1275-1287.  
</ref><ref name=":9" /> Long COVID is both common and debilitating.<ref name=":23">Rajan S, Khunti K, Alwan N, Steves C, MacDermott N, Morsella A, Angulo E, Winkelmann J, Bryndová L, Fronteira I, Gandré C, Or Z, Gerkens S, Sagan A, Simões J, Ricciardi W, de Belvis AG, Silenzi A, Bernal-Delgado E, Estupiñán-Romero F, McKee M. In the wake of the pandemic: Preparing for Long COVID [Internet]. Copenhagen (Denmark): European Observatory on Health Systems and Policies; 2021. PMID: 33877759. </ref>  
</ref><ref name=":9" /> Long COVID is both common and debilitating.<ref name=":23">Rajan S, Khunti K, Alwan N, Steves C, MacDermott N, Morsella A, Angulo E, Winkelmann J, Bryndová L, Fronteira I, Gandré C, Or Z, Gerkens S, Sagan A, Simões J, Ricciardi W, de Belvis AG, Silenzi A, Bernal-Delgado E, Estupiñán-Romero F, McKee M. In the wake of the pandemic: Preparing for Long COVID [Internet]. Copenhagen (Denmark): European Observatory on Health Systems and Policies; 2021. PMID: 33877759. </ref>  
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As of October 2021, the [https://www.who.int/publications/i/item/WHO-2019-nCoV-Post_COVID-19_condition-Clinical_case_definition-2021.1 World Health Organization (WHO)] has developed a case definition of post COVID-19 condition.  
As of October 2021, the [https://www.who.int/publications/i/item/WHO-2019-nCoV-Post_COVID-19_condition-Clinical_case_definition-2021.1 World Health Organization (WHO)] has developed a case definition of post COVID-19 condition.  


''"Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS- CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction but also others* and generally have an impact on everyday functioning. Symptoms may be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms may also fluctuate or relapse over time."''<ref>WHO [https://apps.who.int/iris/bitstream/handle/10665/345824/WHO-2019-nCoV-Post-COVID-19-condition-Clinical-case-definition-2021.1-eng.pdf Diaz JV, Soriano JB. A Delphi consensus to advance on a Clinical Case Definition for Post COVID-19 condition: A WHO protoco]l. 6.10.2021 Available: https://apps.who.int/iris/bitstream/handle/10665/345824/WHO-2019-nCoV-Post-COVID-19-condition-Clinical-case-definition-2021.1-eng.pdf (accessed11.10.2021)</ref>
''"Post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction but also others* and generally have an impact on everyday functioning. Symptoms may be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms may also fluctuate or relapse over time."''<ref>WHO Diaz JV, Soriano JB. A Delphi consensus to advance on a Clinical Case Definition for Post COVID-19 condition: A WHO protocol. 2021. Available from: https://apps.who.int/iris/bitstream/handle/10665/345824/WHO-2019-nCoV-Post-COVID-19-condition-Clinical-case-definition-2021.1-eng.pdf [Accessed 11th October 2021]</ref>


== Long COVID Symptoms ==
== Long COVID Symptoms ==
Long COVID usually presents as clusters of symptoms, often overlapping, which can fluctuate and change over time and can affect any system in the body. <ref name=":23" /><ref name=":4" /><ref name=":5">Davis HE, Assaf GS, McCorkell L, Wei H, Low RJ, Re'em Y, Redfield S, Austin JP, Akrami A. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021;38:101019.</ref><ref name=":18">Carfì A, Bernabei R, Landi F. Persistent Symptoms in Patients After Acute COVID-19. ''JAMA''. 2020;324(6):603-605.</ref><ref name=":6">Assaf G, Davis H, McCorkell L. [https://patientresearchcovid19.com/research/report-1/ Report: What Does COVID-19 Recovery Actually Look Like? An analysis of the prolonged COVID-19 symptoms survey by Patient-Led Research Team]. Patient-Led Research [online]. Patient-Led Research. 2020.</ref><ref>Salmon-Ceron D, Slama D, Broucker TD. [https://www.journalofinfection.com/article/S0163-4453(20)30762-3/fulltext Clinical, virological and imaging profile in patients with prolonged forms of COVID-19: A cross-sectional study]. J Infect. 2020.</ref><ref name=":14">Chaolin Huang, Lixue Huang, Yeming Wang, Xia Li, Lili Ren, Xiaoying Gu, Liang Kang, Li Guo, Min Liu, Xing Zhou, Jianfeng Luo, Zhenghui Huang, Shengjin Tu, Yue Zhao, Li Chen, Decui Xu, Yanping Li, Caihong Li, Lu Peng, Yong Li, Wuxiang Xie, Dan Cui, Lianhan Shang, Guohui Fan, Jiuyang Xu, Geng Wang, Ying Wang, Jingchuan Zhong, Prof Chen Wang, Prof Jianwei Wang, Dingyu Zhang, Prof Bin Cao. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32656-8/fulltext 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study]. The Lancet, 2021. </ref> including, but not limited to: pulmonary, cardiovascular, gastrointestinal, reproductive, genitourinary, endocrine, renal, dermatologic, musculoskeletal, neurological, neuropsychiatric, immunological, ophthalmic, and audiological.<ref name=":5" />   
Long COVID usually presents as clusters of symptoms, often overlapping, which can fluctuate and change over time and can affect any system in the body. <ref name=":23" /><ref name=":4" /><ref name=":5">Davis HE, Assaf GS, McCorkell L, Wei H, Low RJ, Re'em Y, Redfield S, Austin JP, Akrami A. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021;38:101019.</ref><ref name=":18">Carfì A, Bernabei R, Landi F. Persistent Symptoms in Patients After Acute COVID-19. ''JAMA''. 2020;324(6):603-605.</ref><ref name=":6">Assaf G, Davis H, McCorkell L, Wei H, Brooke O', Akrami A, Low R, Mercier J, Adetutu A. Report: What Does COVID-19 Recovery Look Like? An analysis of the prolonged COVID-19 symptoms survey by Patient-Led Research Team. Patient-Led Research [online]. Patient-Led Research. 2020.
</ref><ref>Salmon-Ceron D, Slama D, Broucker TD. Clinical, virological and imaging profile in patients with prolonged forms of COVID-19: A cross-sectional study. J Infect. 2020.</ref><ref name=":14">Huang C, Huang L, Wang Y, Li X, Ren L, Gu X, Kang L, Guo L, Liu M, Zhou X, Luo J, Huang Z, Tu S, Zhao Y, Chen L, Xu D, Li Y, Li C, Peng L, Li Y, Xie W, Cui D, Shang L, Fan G, Xu J, Wang G, Wang Y, Zhong J, Wang C, Wang J, Zhang D, Cao B. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021 Jan 16;397(10270):220-232. </ref> including, but not limited to pulmonary, cardiovascular, gastrointestinal, reproductive, genitourinary, endocrine, renal, dermatologic, musculoskeletal, neurological, neuropsychiatric, immunological, ophthalmic, and audiological.<ref name=":5" />   


The most common Long Covid symptom is fatigue.<ref name=":5" /><ref name=":18" /><ref>Tabacof L, Tosto-Mancuso J, Wood J, Cortes M, Kontorovich A, McCarthy D, Rizk D, Nasr L, Breyman E, Mohammadi N, Kellner C. [https://www.medrxiv.org/content/10.1101/2020.11.04.20226126v1 Post-acute COVID-19 syndrome negatively impacts health and wellbeing despite less severe acute infection]. medRxiv. 2020 Jan 1.</ref><ref>Centers for Disease Control and Prevention. [https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/late-sequelae.html Late Sequelae of COVID-19]. 2020 November 13 [Accessed 8 January 2021].</ref><ref name=":9">Dennis A, Wamil M, Alberts J, Oben J, Cuthbertson DJ, Wootton D, Crooks M, Gabbay M, Brady M, Hishmeh L, Attree E, Heightman M, Banerjee R, Banerjee A; COVERSCAN study investigators. Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome: a prospective, community-based study. BMJ Open. 2021;11(3).</ref><ref>Tenforde MW, Kim SS, Lindsell CJ, Rose EB, Shapiro NI, Files DC, Gibbs KW, Erickson HL, Steingrub JS, Smithline HA, Gong MN. [https://www.cdc.gov/mmwr/volumes/69/wr/mm6930e1.htm Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network—United States, March–June 2020]. Morbidity and Mortality Weekly Report. 2020 Jul 31;69(30):993.</ref><ref>Nehme M, Braillard O, Alcoba G, Aebischer Perone S, Courvoisier D, Chappuis F, Guessous I. [https://www.acpjournals.org/doi/10.7326/M20-5926 COVID-19 Symptoms: Longitudinal Evolution and Persistence in Outpatient Settings]. Annals of internal medicine. 2020 Dec 8.</ref><ref>Sudre CH, Murray B, Varsavsky T, Graham MS, Penfold RS, Bowyer RC, Pujol JC, Klaser K, Antonelli M, Canas LS, Molteni E. [https://www.nature.com/articles/s41591-021-01292-y?utm_medium=affiliate&utm_source=commission_junction&utm_campaign=3_nsn6445_deeplink_PID9237743&utm_content=deeplink&fbclid=IwAR1OaqtjXjqc6sFYJ7du39yAH_1zmutyXDK8K1qc4RQrBCIwqmOO0iL98HE Attributes and predictors of Long-COVID]. Nature Medicine, 2021. </ref><ref name=":25">Townsend L, Dyer AH, Jones K, Dunne J, Mooney A, Gaffney F, O'Connor L, Leavy D, O'Brien K, Dowds J, Sugrue JA. [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240784 Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection]. Plos one. 2020 Nov 9;15(11):e0240784.</ref><ref>S.Lopez-Leon, T.Wegman-Ostrosky, C.Perelman, R.Sepulveda, P.Rebolledo, A.Cuapio, S.Villapol. [https://www.medrxiv.org/content/10.1101/2021.01.27.21250617v1 More than 50 Long-term effects of COVID-19: a systematic review and meta-analysis]. MedRxiv, 2021.  
The most common Long Covid symptom is fatigue.<ref name=":5" /><ref name=":18" /><ref>Tabacof L, Tosto-Mancuso J, Wood J, Cortes M, Kontorovich A, McCarthy D, Rizk D, Nasr L, Breyman E, Mohammadi N, Kellner C. Post-acute COVID-19 syndrome negatively impacts health and wellbeing despite less severe acute infection. medRxiv. 2020.</ref><ref>Centers for Disease Control and Prevention. Late Sequelae of COVID-19. 2020. Available from: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/late-sequelae.html. [Accessed 8th January 2021].</ref><ref name=":9">Dennis A, Wamil M, Alberts J, Oben J, Cuthbertson DJ, Wootton D, Crooks M, Gabbay M, Brady M, Hishmeh L, Attree E, Heightman M, Banerjee R, Banerjee A; COVERSCAN study investigators. Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome: a prospective, community-based study. BMJ Open. 2021;11(3).</ref><ref>Tenforde MW, Kim SS, Lindsell CJ, Rose EB, Shapiro NI, Files DC, Gibbs KW, Erickson HL, Steingrub JS, Smithline HA, Gong MN. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network—United States, March–June 2020. Morbidity and Mortality Weekly Report. 2020;69(30):993.</ref><ref>Nehme M, Braillard O, Alcoba G, Aebischer Perone S, Courvoisier D, Chappuis F, Guessous I. COVID-19 Symptoms: Longitudinal Evolution and Persistence in Outpatient Settings. Annals of Internal Medicine. 2020.</ref><ref>Sudre CH, Murray B, Varsavsky T, Graham MS, Penfold RS, Bowyer RC, Pujol JC, Klaser K, Antonelli M, Canas LS, Molteni E. Attributes and predictors of Long-COVID. Nature Medicine 2021. </ref><ref name=":25">Townsend L, Dyer AH, Jones K, Dunne J, Mooney A, Gaffney F, O'Connor L, Leavy D, O'Brien K, Dowds J, Sugrue JA. Persistent fatigue following SARS-CoV-2 infection is common and independent of the severity of initial infection. Plos One. 2020;9:15(11).</ref><ref>Lopez-Leon S, Wegman-Ostrosky T, Perelman C, Sepulveda R, Rebolledo PA, Cuapio A, Villapol S. More than 50 Long-term effects of COVID-19: a systematic review and meta-analysis. medRxiv [Preprint]. 2021.  
</ref><ref>S.Lopez-Leon, T.Wegman-Ostrosky, C.Perelman, R.Sepulveda, P.A.Rebolledo, A.Cuapio, S.Villapol. [https://www.medrxiv.org/content/10.1101/2021.01.27.21250617v2 More than 50 Long-term effects of COVID-19: a systematic review and meta-analysis.] MedRxiv, 2021. <nowiki>https://doi.org/10.1101/2021.01.27.21250617</nowiki></ref><ref>E.Garrigues, P.Janvier, Y.Kherabi, A.Le Bot, A.Hamon, H.Gouze, L.Doucet, S.Berkani, E.Oliosi, E.Mallart, F.Corre, V.Zarrouk, JD.Moyer, A.Galy, V.Honsel, B.Fantin, Y.Nguyen. [https://www.journalofinfection.com/article/S0163-4453(20)30562-4/fulltext Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19]. Journal of Infection, 2020; 81(6):E4-E6. DOI:<nowiki>https://doi.org/10.1016/j.jinf.2020.08.029</nowiki>
</ref><ref>Lopez-Leon S, Wegman-Ostrosky T, Perelman C, Sepulveda R, Rebolledo PA, Cuapio A, Villapol S. More than 50 Long-term effects of COVID-19: a systematic review and meta-analysis. medRxiv [Preprint]. 2021.</ref><ref>Garrigues E, Janvier P, Kherabi Y, Le Bot A, Hamon A, Gouze H, Doucet L, Berkani S, Oliosi E, Mallart E, Corre F, Zarrouk V, Moyer JD, Galy A, Honsel V, Fantin B, Nguyen Y. Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. J Infect. 2020;81(6):e4-e6.
</ref><ref name=":19" /><ref name=":20">O.Moreno-Perez, E.Merino, JM.Leon-Ramirez, M.Andres, JM.Ramos, J.Arenas-Jimenez, S.Asensio, R.Sanchez, P.Ruiz-Torregrosa, I.Galan, A.Scholz, A.Amo, P.Gonzalez-delaAleja, V.Boix, J.Gil. [https://www.journalofinfection.com/article/S0163-4453(21)00009-8/fulltext Post-acute COVID-19 Syndrome. Incidence and risk factors: a Mediterranean cohort study]. Journal of Infection, 2021. DOI:<nowiki>https://doi.org/10.1016/j.jinf.2021.01.004</nowiki>
</ref><ref name=":19" /><ref name=":20">Moreno-Pérez O, Merino E, Leon-Ramirez JM, Andres M, Ramos JM, Arenas-Jiménez J, Asensio S, Sanchez R, Ruiz-Torregrosa P, Galan I, Scholz A, Amo A, González-delaAleja P, Boix V, Gil J; COVID19-ALC research group. Post-acute COVID-19 syndrome. Incidence and risk factors: A Mediterranean cohort study. J Infect. 2021;82(3):378-383.
</ref><ref name=":21">D.Munblit, P.Bobkova, E.Spiridonova, A.Shikhaleva, A.Gamirova, O.Blyuss, NA.Nekliudov, P.Bugaeva, M.Andreeva, A.DunnGalvin, P.Comberiati, C.Apfelbacher, J.Genuneit, S.Avdeev, V.Kapustina, A.Guekht, V.Fomin, AA.Svistunov,  P.Timashev, TM.Drake, S.Wulf Hanson, L.Merson, P.Horby, L.Sigfrid, JT.Scott, MG.Semple, JO.Warner, T.Vos, P.Olliaro, P.Glybochko, D.Butnaru. [https://www.medrxiv.org/content/10.1101/2021.02.17.21251895v1 Risk factors for long-term consequences of COVID-19 in hospitalised adults in Moscow using the ISARIC Global follow-up protocol: StopCOVID cohort study.] MedRxiv, 2021. doi: <nowiki>https://doi.org/10.1101/2021.02.17.21251895</nowiki></ref><ref name=":22">Logue JK, Franko NM, McCulloch DJ, McDonald D, Magedson A, Wolf CR, Chu HY. Sequelae in Adults at 6 Months After COVID-19 Infection. JAMA Netw Open. 2021;1:4(2).
</ref><ref name=":21">Munblit D, Bobkova P, Spiridonova E, Shikhaleva A, Gamirova A, Blyuss O, Nekliudov N, Bugaeva P, Andreeva M, DunnGalvin A, Comberiati P, Apfelbacher C, Genuneit J, Avdeev S, Kapustina V, Guekht A, Fomin V, Svistunov AA, Timashev P, Subbot VS, Royuk VV, Drake TM, Hanson SW, Merson L, Carson G, Horby P, Sigfrid L, Scott JT, Semple MG, Warner JO, Vos T, Olliaro P, Glybochko P, Butnaru D. Incidence and risk factors for persistent symptoms in adults previously hospitalized for COVID-19. Clin Exp Allergy. 2021;51(9):1107-1120.</ref><ref name=":22">Logue JK, Franko NM, McCulloch DJ, McDonald D, Magedson A, Wolf CR, Chu HY. Sequelae in Adults at 6 Months After COVID-19 Infection. JAMA Netw Open. 2021;1:4(2).
</ref><ref name=":24">D Menges; T.Ballouz; A.Anagnostopoulos; HE.Aschmann; A.Domenghino; JS.Fehr; MA.Puhan. [https://www.medrxiv.org/content/10.1101/2021.02.27.21252572v1 Estimating the burden of post-COVID-19 syndrome in a population-based cohort study of SARS-CoV-2 infected individuals: Implications for healthcare service planning]. MedRxiv, 2021. <nowiki>https://doi.org/10.1101/2021.02.27.21252572</nowiki>
</ref><ref name=":24">Menges D, Ballouz T, Anagnostopoulos A, Aschmann HE, Domenghino A, Fehr JS, Puhan MA. The burden of the post-COVID-19 syndrome and implications for healthcare service planning: A population-based cohort study. PLoS One. 2021;12:16(7).
</ref><ref>B.Osikomaiya, O.Erinoso, KO.Wright, AO.Odusola, B.Thomas, O.Adeyemi, A.Bowale, O.Adejumo, A.Falana, I.Abdus-salam, O.Ogboye, A.Osibogun, A.Abayomi. [https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-020-05716-x ‘Long COVID’: persistent COVID-19 symptoms in survivors managed in Lagos State, Nigeria]. BMC Infectious Diseases, 2021.  
</ref><ref>Osikomaiya B, Erinoso O, Wright KO, Odusola AO, Thomas B, Adeyemi O, Bowale A, Adejumo O, Falana A, Abdus-Salam I, Ogboye O, Osibogun A, Abayomi A. 'Long COVID': persistent COVID-19 symptoms in survivors managed in Lagos State, Nigeria. BMC Infect Dis. 2021;21(1):304.  
</ref> The most frequently reported Long COVID symptoms after 6 months include fatigue, post-exertion malaise, and cognitive dysfunction.<ref name=":5" /> Mental health symptoms associated with long COVID include anxiety (28% increase), increased presence of depression (13% increase), PTSD (20% increase), suicide ideation (10% increase) and decreased life satisfaction and daily functioning. Researchers and patients have distinguished more than 200 symptoms associated with long COVID.<ref name=":2">Thaweethai T, Jolley SE, Karlson EW, Levitan EB, Levy B, McComsey GA, McCorkell L, Nadkarni GN, Parthasarathy S, Singh U, Walker TA. [https://jamanetwork.com/journals/jama/fullarticle/2805540 Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection.] JAMA. 2023</ref> The most common symptoms include:
</ref> The most frequently reported Long COVID symptoms after 6 months include fatigue, post-exertion malaise, and cognitive dysfunction.<ref name=":5" /> Mental health symptoms associated with long COVID include anxiety (28% increase), increased presence of depression (13% increase), PTSD (20% increase), suicide ideation (10% increase) and decreased life satisfaction and daily functioning. Researchers and patients have distinguished more than 200 symptoms associated with long COVID.<ref name=":2">Thaweethai T, Jolley SE, Karlson EW, Levitan EB, Levy B, McComsey GA, McCorkell L, Nadkarni GN, Parthasarathy S, Singh U, Walker TA. Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection. JAMA. 2023;''329(22):1934-1946.''</ref> The most common symptoms include:


* tiredness
* tiredness
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* body aches
* body aches
* trouble sleeping
* trouble sleeping
* mood changes<ref>RECOVER: Researching COVID to Enhance Recovery.  The National Institutes of Health. 2023.  Available from:
* mood changes<ref>RECOVER: Researching COVID to Enhance Recovery.  The National Institutes of Health. 2023.  Available from:https://recovercovid.org/</ref>
 
https://recovercovid.org/</ref>
 
The multidimensional, episodic and often unpredictable nature of Long COVID has been described as "relapsing and remitting",<ref name=":6" /> whereby 86% of people with Long COVID report relapses over 7 months, with physical activity, stress, exercise and mental activity being the most common triggers of relapses.<ref name=":5" /> The trajectory of Long COVID is heterogenous with some improving over time, some worsening and others stable, with many experiencing ongoing fluctuating symptoms after 6 months.<ref name=":5" /><ref name=":27">J.Scott, L.Sigfrid, T.Drake, E.Pauley, E.Jesudason, WS.Lim, D.Munblit, C.Hastie, E.Harrison, A.Docherty, P.Olliaro, P.Openshaw, K.Baillie, C.Semple for ISARIC4C Investigators. [https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/968923/s1138-isaric4c-long-covid-preliminary-results.pdf Symptoms and quality of life following hospitalisation for COVID-19 (Post COVID-19 Syndrome/Long COVID) in the ISARIC WHO Clinical Characterisation Protocol UK: preliminary results]. 2021.</ref> Furthermore, outcomes are worse in working age females than males, with females under 50 being over five times more likely to report incomplete recovery, over five times more likely to report a new disability, more likely to have severe fatigue, and more than six times more likely to report increased breathlessness than males under 50.<ref name=":27" /> It is estimated that 30% of people not hospitalised with "mild" acute symptoms, continue to have symptoms 9 months after infection.<ref name=":22" /> Preliminary evidence suggests children also experience Long COVID symptoms similar to adults.<ref>D.Buonsenso, D.Munblit, C.De Rose, D.Sinatti, A.Ricchiuto, A.Carfi, P.Valentini. [https://www.medrxiv.org/content/10.1101/2021.01.23.21250375v1 Preliminary Evidence on Long COVID in children]. MedRxiv, 2021. <nowiki>https://doi.org/10.1101/2021.01.23.21250375</nowiki>
</ref> 
 
{{#ev:youtube|9fogPLrZoQc}}<ref>Darren Brown for Long COVID Physio. What are common Long COVID symptoms? Available from
https://youtu.be/9fogPLrZoQc [last accessed 22 March 2022]</ref>


The multidimensional, episodic and often unpredictable nature of Long COVID has been described as "relapsing and remitting",<ref name=":6" /> whereby 86% of people with Long COVID report relapses over 7 months, with physical activity, stress, exercise and mental activity being the most common triggers of relapses.<ref name=":5" /> The trajectory of Long COVID is heterogenous with some improving over time, some worsening and others stable, with many experiencing ongoing fluctuating symptoms after 6 months.<ref name=":5" /><ref name=":27">Sigfrid L, Drake TM, Pauley E, Jesudason EC, Olliaro P, Lim WS, Gillesen A, Berry C, Lowe DJ, McPeake J, Lone N, Munblit D, Cevik M, Casey A, Bannister P, Russell CD, Goodwin L, Ho A, Turtle L, O'Hara ME, Hastie C, Donohue C, Spencer RG, Donegan C, Gummery A, Harrison J, Hardwick HE, Hastie CE, Carson G, Merson L, Baillie JK, Openshaw P, Harrison EM, Docherty AB, Semple MG, Scott JT. Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol. Lancet Reg Health Eur. 2021;8:100186. </ref> Furthermore, outcomes are worse in working-age females than males, with females under 50 being over five times more likely to report incomplete recovery, over five times more likely to report a new disability, more likely to have severe fatigue, and more than six times more likely to report increased breathlessness than males under 50.<ref name=":27" /> It is estimated that 30% of people not hospitalised with "mild" acute symptoms, continue to have symptoms 9 months after infection.<ref name=":22" /> Preliminary evidence suggests children also experience Long COVID symptoms similar to adults.<ref>Buonsenso D, Munblit D, De Rose C, Sinatti D, Ricchiuto A, Carfi A, Valentini P. Preliminary evidence on long COVID in children. Acta Paediatr. 2021;110(7):2208-2211.
</ref>{{#ev:youtube|9fogPLrZoQc}}<ref>Darren Brown for Long COVID Physio. What are common Long COVID symptoms? Available from https://youtu.be/9fogPLrZoQc [last accessed 22 March 2022]</ref>
== Long COVID Prevalence ==
== Long COVID Prevalence ==
The COVID-19 Infection Survey<ref>Office for National Statistics. [https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/coronaviruscovid19infectionsurveypilot/previousReleases Coronavirus (COVID-19) Infection Survey, UK Statistical bulletins]. [Accessed 8 January 2021]</ref> is a nationally representative sample of the UK community population, from which it is has been estimated that around 1 in 5 people exhibit Long COVID symptoms for 5 weeks or longer, and around 1 in 10 exhibit Long COVID symptoms for 12 weeks or longer.<ref name=":7">Office for National Statistics. [https://www.ons.gov.uk/news/statementsandletters/theprevalenceoflongcovidsymptomsandcovid19complications The prevalence of long COVID symptoms and COVID-19 complications]. 2020 December 16 [Accessed 7 January 2021].</ref><ref>Office for National Statistics. [https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/healthandlifeexpectancies/adhocs/12788updatedestimatesoftheprevalenceoflongcovidsymptoms Updated estimates of the prevalence of long COVID symptoms]. Released 21 January 2021. Accessed 21 January 2021.  
The COVID-19 Infection Survey<ref>Office for National Statistics. Coronavirus (COVID-19) Infection Survey, UK Statistical bulletins. Available from:https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/coronaviruscovid19infectionsurveypilot/previousReleases [Accessed 8th January 2021].</ref> is a nationally representative sample of the UK community population, from which it has been estimated that around 1 in 5 people exhibit Long COVID symptoms for 5 weeks or longer, and around 1 in 10 exhibit Long COVID symptoms for 12 weeks or longer.<ref name=":7">Office for National Statistics. The prevalence of long COVID symptoms and COVID-19 complications. Available from: https://www.ons.gov.uk/news/statementsandletters/theprevalenceoflongcovidsymptomsandcovid19complications [Accessed 7th January 2021].</ref><ref>Office for National Statistics. Updated estimates of the prevalence of long COVID symptoms. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/prevalenceofongoingsymptomsfollowingcoronaviruscovid19infectionintheuk/2february2023 [Accessed 21st January 2021].  
</ref>  
</ref>  


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== Pathological Process  ==
== Pathological Process  ==


The aetiology and pathophysiological causes of Long COVID symptoms remains unknown. Initial hypothesis include: viral persistence,<ref>Hu F, Chen F, Ou Z, Fan Q, Tan X, Wang Y, Pan Y, Ke B, Li L, Guan Y, Mo X. [https://www.nature.com/articles/s41423-020-00550-2 A compromised specific humoral immune response against the SARS-CoV-2 receptor-binding domain is related to viral persistence and periodic shedding in the gastrointestinal tract]. Cellular & molecular immunology. 2020 Nov;17(11):1119-25.</ref><ref>Gaebler C, Wang Z, Lorenzi JC, Muecksch F, Finkin S, Tokuyama M, Ladinsky M, Cho A, Jankovic M, Schaefer-Babajew D, Oliveira TY. [https://www.nature.com/articles/s41586-021-03207-w?utm_source=twitter&utm_medium=social&utm_content=organic&utm_campaign=NGMT_USG_JC01_GL_Nature Evolution of Antibody Immunity to SARS-CoV-2]. Nature. 2021 Jan 18.</ref><ref>De Melo GD, Lazarini F, Levallois S, Hautefort C, Michel V, Larrous F, Verillaud B, Aparicio C, Wagner S, Gheusi G, Kergoat L. [https://www.biorxiv.org/content/10.1101/2020.11.18.388819v1.full COVID-19-associated olfactory dysfunction reveals SARS-CoV-2 neuroinvasion and persistence in the olfactory system]. bioRxiv. 2020 Jan 1.</ref><ref>Bussani R, Schneider E, Zentilin L, Collesi C, Ali H, Braga L, Volpe MC, Colliva A, Zanconati F, Berlot G, Silvestri F. [https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(20)30480-1/fulltext Persistence of viral RNA, pneumocyte syncytia and thrombosis are hallmarks of advanced COVID-19 pathology]. EBioMedicine. 2020 Nov 1;61:103104.</ref> continued hyperactive immune response,<ref>Afrin LB, Weinstock LB, Molderings GJ. [https://www.ijidonline.com/article/S1201-9712(20)30732-3/fulltext Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome]. International Journal of Infectious Diseases. 2020 Nov 1;100:327-32.</ref><ref>Woodruff MC, Ramonell RP, Lee FE, Sanz I. [https://www.medrxiv.org/content/10.1101/2020.10.21.20216192v2 Clinically identifiable autoreactivity is common in severe SARS-CoV-2 Infection]. medRxiv. 2020 Jan 1.</ref><ref>BK.Patterson, J.Guevara-Coto, R.Yogendra, E.Francisco, E.Long, A.Pise, H.Rodrigues, P.Parikh, J.Mora, RA.Mora-Rodríguez. [https://www.biorxiv.org/content/10.1101/2020.12.16.423122v1 Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning]. BioXriv, 2021. doi: <nowiki>https://doi.org/10.1101/2020.12.16.423122</nowiki>
The aetiology and pathophysiological causes of Long COVID symptoms remain unknown. Initial hypothesis includes: viral persistence,<ref>Hu F, Chen F, Ou Z, Fan Q, Tan X, Wang Y, Pan Y, Ke B, Li L, Guan Y, Mo X. A compromised specific humoral immune response against the SARS-CoV-2 receptor-binding domain is related to viral persistence and periodic shedding in the gastrointestinal tract. Cellular & molecular immunology. 2020;17(11):1119-25.</ref><ref>Gaebler C, Wang Z, Lorenzi JCC, Muecksch F, Finkin S, Tokuyama M, Cho A, Jankovic M, Schaefer-Babajew D, Oliveira TY, Cipolla M, Viant C, Barnes CO, Bram Y, Breton G, Hägglöf T, Mendoza P, Hurley A, Turroja M, Gordon K, Millard KG, Ramos V, Schmidt F, Weisblum Y, Jha D, Tankelevich M, Martinez-Delgado G, Yee J, Patel R, Dizon J, Unson-O'Brien C, Shimeliovich I, Robbiani DF, Zhao Z, Gazumyan A, Schwartz RE, Hatziioannou T, Bjorkman PJ, Mehandru S, Bieniasz PD, Caskey M, Nussenzweig MC. Evolution of antibody immunity to SARS-CoV-2. Nature. 2021;591(7851):639-644.</ref><ref>Gaebler C, Wang Z, Lorenzi JCC, Muecksch F, Finkin S, Tokuyama M, Cho A, Jankovic M, Schaefer-Babajew D, Oliveira TY, Cipolla M, Viant C, Barnes CO, Bram Y, Breton G, Hägglöf T, Mendoza P, Hurley A, Turroja M, Gordon K, Millard KG, Ramos V, Schmidt F, Weisblum Y, Jha D, Tankelevich M, Martinez-Delgado G, Yee J, Patel R, Dizon J, Unson-O'Brien C, Shimeliovich I, Robbiani DF, Zhao Z, Gazumyan A, Schwartz RE, Hatziioannou T, Bjorkman PJ, Mehandru S, Bieniasz PD, Caskey M, Nussenzweig MC. Evolution of antibody immunity to SARS-CoV-2. Nature. 2021;591(7851):639-644.</ref><ref>Bussani R, Schneider E, Zentilin L, Collesi C, Ali H, Braga L, Volpe MC, Colliva A, Zanconati F, Berlot G, Silvestri F, Zacchigna S, Giacca M. Persistence of viral RNA, pneumocyte syncytia and thrombosis are hallmarks of advanced COVID-19 pathology. EBioMedicine. 2020;61:103104.</ref> continued hyperactive immune response,<ref>Afrin LB, Weinstock LB, Molderings GJ. Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome. International Journal of Infectious Diseases. 2020;100:327-32.</ref><ref>Woodruff MC, Ramonell RP, Lee FE, Sanz I. Clinically identifiable autoreactivity is common in severe SARS-CoV-2 Infection. medRxiv. 2020.</ref><ref>Patterson BK, Guevara-Coto J, Yogendra R, Francisco EB, Long E, Pise A, Rodrigues H, Parikh P, Mora J, Mora-Rodríguez RA. Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning. Front Immunol. 2021;12:700782.
</ref> cellular metabolic dysfunction,<ref>Miller R, Wentzel AR, Richards GA. [https://www.sciencedirect.com/science/article/pii/S0306987720314742?via%3Dihub COVID-19: NAD+ deficiency may predispose the aged, obese and type2 diabetics to mortality through its effect on SIRT1 activity]. Medical Hypotheses. 2020 Nov 1;144:110044.</ref> auto-antibodies,<ref>Vlachoyiannopoulos PG, Magira E, Alexopoulos H, Jahaj E, Theophilopoulou K, Kotanidou A, Tzioufas AG. [https://ard.bmj.com/content/79/12/1661 Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19]. Annals of the Rheumatic Diseases. 2020 Dec 1;79(12):1661-3.</ref><ref>Wang EY, Mao T, Klein J, Dai Y, Huck JD, Liu F, Zheng NS, Zhou T, Israelow B, Wong P, Lucas C. [https://www.medrxiv.org/content/10.1101/2020.12.10.20247205v3 Diverse Functional Autoantibodies in Patients with COVID-19]. medRxiv. 2020 Jan 1.</ref> neurological dysfunction,<ref>Shin Jie Yong. [https://pubs.acs.org/doi/10.1021/acschemneuro.0c00793 Persistent Brainstem Dysfunction in Long-COVID: A Hypothesis]. ''ACS Chem. Neurosci.'' 2021.<nowiki>https://doi.org/10.1021/acschemneuro.0c00793</nowiki></ref><ref>E. Guedj, J. Y. Campion, P. Dudouet, E. Kaphan, F. Bregeon, H. Tissot-Dupont, S. Guis, F. Barthelemy, P. Habert, M. Ceccaldi, M. Million, D. Raoult, S. Cammilleri, C. Eldin. [https://link.springer.com/article/10.1007/s00259-021-05215-4 18F-FDG brain PET hypometabolism in patients with long COVID]. European Journal of Nuclear Medicine and Molecular Imaging, 2021. <nowiki>https://doi.org/10.1007/s00259-021-05215-4</nowiki>
</ref> cellular metabolic dysfunction,<ref>Miller R, Wentzel AR, Richards GA. COVID-19: NAD+ deficiency may predispose the aged, obese and type2 diabetics to mortality through its effect on SIRT1 activity. Medical Hypotheses. 2020;144:110044.</ref> auto-antibodies,<ref>Vlachoyiannopoulos PG, Magira E, Alexopoulos H, Jahaj E, Theophilopoulou K, Kotanidou A, Tzioufas AG. Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19. Annals of the Rheumatic Diseases. 2020;79(12):1661-3.</ref><ref>Wang EY, Mao T, Klein J, Dai Y, Huck JD, Liu F, Zheng NS, Zhou T, Israelow B, Wong P, Lucas C. Diverse Functional Autoantibodies in Patients with COVID-19. medRxiv. 2020.</ref> neurological dysfunction,<ref>Shin Jie Yong. Persistent Brainstem Dysfunction in Long-COVID: A Hypothesis. ''ACS Chem. Neurosci.'' 2021; 573–580.</ref><ref>Guedj E, Campion JY, Dudouet P, Kaphan E, Bregeon F, Tissot-Dupont H, Guis S, Barthelemy F, Habert P, Ceccaldi M, Million M, Raoult D, Cammilleri S, Eldin C. <sup>18</sup>F-FDG brain PET hypometabolism in patients with long COVID. Eur J Nucl Med Mol Imaging. 2021;48(9):2823-2833.  
</ref><ref>DW.Nauen, JE.Hooper, M.Stewart, IH.Solomon. [https://jamanetwork.com/journals/jamaneurology/fullarticle/2776455 Assessing Brain Capillaries in Coronavirus Disease 2019]. JAMA Neurology, 2021. doi:10.1001/jamaneurol.2021.0225
</ref><ref>Nauen DW, Hooper JE, Stewart CM, Solomon IH. Assessing Brain Capillaries in Coronavirus Disease 2019. JAMA Neurol. 2021;78(6):760-762.
</ref><ref>M.Boldrini, PD.Canoll, RS. Klein. [https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2778090?fbclid=IwAR0194M9z2ay35dc3NIpqWx4ZL2luCOW_w3wA-utxj12aY0j4QADWm49MV4 How COVID-19 Affects the Brain]. JAMA Psychiatry, 2021.  
</ref><ref>Boldrini M, Canoll PD, Klein RS. How COVID-19 Affects the Brain. JAMA Psychiatry. 2021;78(6):682-683.  
</ref> neuroimmunology,<ref>V.Mondelli, CM.Pariante. [https://academic.oup.com/ooim/article/2/1/iqab004/6131647 What can neuroimmunology teach us about the symptoms of long-COVID?] Oxford Open Immunology, 2021.  
</ref> neuroimmunology,<ref>Mondelli V, Pariante CM. What can neuroimmunology teach us about the symptoms of long-COVID? Oxf Open Immunol. 2021;10:2(1).  
</ref> neurological inflammation,<ref>J.Remsik, JA.Wilcox, NE.Babady, TA.McMillen, BA.Vachha, NA.Halpern, V.Dhawan, M.Rosenblum, CA.Iacobuzio-Donahue, EK.Avila, B.Santomasso, A.Boire. [https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00051-9 Inflammatory Leptomeningeal Cytokines Mediate COVID-19 Neurologic Symptoms in Cancer Patients]. Cancer Cell 2021, 39; 2: p276-283.2021. DOI: <nowiki>https://doi.org/10.1016/j.ccell.2021.01.007</nowiki>
</ref> neurological inflammation,<ref>Remsik J, Wilcox JA, Babady NE, McMillen TA, Vachha BA, Halpern NA, Dhawan V, Rosenblum M, Iacobuzio-Donahue CA, Avila EK, Santomasso B, Boire A. Inflammatory Leptomeningeal Cytokines Mediate COVID-19 Neurologic Symptoms in Cancer Patients. Cancer Cell. 2021;39(2):276-283.
</ref> and organ impairment,<ref name=":9" /> including cardiac impairment.<ref name=":9" /><ref>VO.Puntmann, M.Ludovica Carerj, I.Wieters, M.Fahim, C.Arendt, J.Hoffmann, A.Shchendrygina, F.Escher, M.Vasa-Nicotera, AM.Zeiher, M.Vehreschild, E.Nagel. [https://jamanetwork.com/journals/jamacardiology/fullarticle/2768916 Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19)]. JAMA Cardiol. 2020;5(11):1265-1273. doi:10.1001/jamacardio.2020.3557
</ref> and organ impairment,<ref name=":9" /> including cardiac impairment.<ref name=":9" /><ref>Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, Shchendrygina A, Escher F, Vasa-Nicotera M, Zeiher AM, Vehreschild M, Nagel E. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265-1273.  
</ref><ref>J.Abbasi. [https://jamanetwork.com/journals/jama/fullarticle/2776538 Researchers Investigate What COVID-19 Does to the Heart]. JAMA Network, 2021. doi:10.1001/jama.2021.0107
</ref><ref>Abbasi J. Researchers Investigate What COVID-19 Does to the Heart. ''JAMA.'' 2021;325(9):808–811.
</ref><ref>T.Kotecha, DS.Knight, Y.Razvi, K.Kumar, K.Vimalesvaran, G.Thornton, R.Patel, L.Chacko, JT.Brown, C.Coyle, D.Leith, A.Shetye, B.Ariff, R.Bell, G.Captur, M.Coleman, J.Goldring, D.Gopalan, M.Heightman, T.Hillman, L.Howard, M.Jacobs, PS.Jeetley, P.Kanagaratnam, O.Min Kon, LE.Lamb, CH.Manisty, P.Mathurdas, J.Mayet, R.Negus, N.Patel, I.Pierce, G.Russell, A.Wolff, H.Xue, P.Kellman, JC.Moon, TA.Treibel, GD.Cole, M.Fontana. [https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehab075/6140994 Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance]. European Heart Journal, 2021. <nowiki>https://doi.org/10.1093/eurheartj/ehab075</nowiki>
</ref><ref>Kotecha T, Knight DS, Razvi Y, Kumar K, Vimalesvaran K, Thornton G, Patel R, Chacko L, Brown JT, Coyle C, Leith D, Shetye A, Ariff B, Bell R, Captur G, Coleman M, Goldring J, Gopalan D, Heightman M, Hillman T, Howard L, Jacobs M, Jeetley PS, Kanagaratnam P, Kon OM, Lamb LE, Manisty CH, Mathurdas P, Mayet J, Negus R, Patel N, Pierce I, Russell G, Wolff A, Xue H, Kellman P, Moon JC, Treibel TA, Cole GD, Fontana M. Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance. Eur Heart J. 2021;42(19):1866-1878.  
</ref><ref>M.Imazio. [https://www.acc.org/latest-in-cardiology/articles/2021/02/05/19/37/covid-19-as-a-possible-cause-of-myocarditis-and-pericarditis?fbclid=IwAR3BttbdsngJ1J735wMkBuLDJhCBVDX4A6jaltU4TwOPi8g-ZMQ-eeb6xc8#.YDydzPdAYvU.twitter COVID-19 as a Possible Cause of Myocarditis and Pericarditis]. American College of Cardiology, Expert Analysis, Feb 05 2021.
</ref><ref>M.Imazio. COVID-19 as a Possible Cause of Myocarditis and Pericarditis. American College of Cardiology, Expert Analysis. 2021;19-37.
</ref><ref>[https://www.escardio.org/Education/COVID-19-and-Cardiology/ESC-COVID-19-Guidance European Society of Cardiology (ECS) Guidance for the Diagnosis and Management of Cardiovascular Disease (CV) during the COVID-19 Pandemic]. Last updated on 10 June 2020. </ref> Musculoskeletal short- and long-term consequences of COVID-19 are also discussed.<ref>SL.Ramani, J.Samet, CK.Franz, C.Hsieh, CV.Nguyen, C.Horbinski, S.Deshmukh. [https://link.springer.com/article/10.1007/s00256-021-03734-7 Musculoskeletal involvement of COVID-19: review of imaging.] Skeletal Radiology, 2021. <nowiki>https://doi.org/10.1007/s00256-021-03734-7</nowiki>
</ref><ref>Task Force for the management of COVID-19 of the European Society of Cardiology. European Society of Cardiology guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 1-epidemiology, pathophysiology, and diagnosis. Eur Heart J. 2022;43(11):1033-1058. </ref> Musculoskeletal short- and long-term consequences of COVID-19 are also discussed.<ref>Ramani SL, Samet J, Franz CK, Hsieh C, Nguyen CV, Horbinski C, Deshmukh S. Musculoskeletal involvement of COVID-19: review of imaging. Skeletal Radiol. 2021;50(9):1763-1773.  
</ref> More research is required to understand the mechanisms by which Long COVID develops.<ref name=":23" />   
</ref> More research is required to understand the mechanisms by which Long COVID develops.<ref name=":23" />   


== Long COVID Management  ==
== Long COVID Management  ==


At this time, there is no evidence from randomised controlled trials on the effectiveness of rehabilitation for Long COVID. Most recommendations from international guidance on rehabilitation for Long COVID are based on expert opinion or evidence from other diseases. Suggestions include patient-centred management with continuous follow-up to decrease the severity of current symptoms. Attention should be placed on creating therapeutic alliances and setting reasonable goals and expectations through discussions with patients and caregivers.<ref name=":3">Chuang HJ, Lin CW, Hsiao MY, Wang TG, Liang HW. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10101546/ Long COVID and rehabilitation]. Journal of the Formosan Medical Association. 2023 Apr 13.</ref>
Currently, there is no evidence from randomised controlled trials on the effectiveness of rehabilitation for Long COVID. Most recommendations from international guidance on rehabilitation for Long COVID are based on expert opinion or evidence from other diseases. Suggestions include patient-centred management with continuous follow-up to decrease the severity of current symptoms. Attention should be placed on creating therapeutic alliances and setting reasonable goals and expectations through discussions with patients and caregivers.<ref name=":3">Chuang HJ, Lin CW, Hsiao MY, Wang TG, Liang HW. Long COVID and rehabilitation. J Formos Med Assoc. 2023;S0929-6646(23)00107-9. </ref>


A multi-disciplinary approach to the assessment and management of Long COVID is essential.<ref name=":23" /> The team approach could include a rehabilitation physician along with multiple speciality physicians, occupational therapists, physiotherapists, pharmacists, nursing professionals, mental health experts, community workers and other health care professionals.<ref>Swarnakar R, Yadav SL. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9350732/ Rehabilitation in long COVID-19: A mini-review]. World Journal of Methodology. 2022 Jul 7;12(4):235.</ref> Encompassing a disability model could improve clinicians’ responses to Long COVID.<ref>VV.Altiery De Jesús, N.Alwan, F.Callard, Z.Berger. [https://osf.io/tfbnd/ Listening to Long COVID: Epistemic Injustice and COVID-19 morbidity]. OSFPrePrints, 2021. </ref>
A multi-disciplinary approach to the assessment and management of Long COVID is essential.<ref name=":23" /> The team approach could include a rehabilitation physician along with multiple speciality physicians, occupational therapists, physiotherapists, pharmacists, nursing professionals, mental health experts, community workers and other health care professionals.<ref>Swarnakar R, Yadav SL. Rehabilitation in long COVID-19: A mini-review. World Journal of Methodology. 2022;12(4):235.</ref> Encompassing a disability model could improve clinicians’ responses to Long COVID.<ref>Altiery De Jesús VV, Alwan N, Callard F, Berger Z. Listening to Long COVID: Epistemic Injustice and COVID-19 morbidity. OSFPrePrints, 2021. </ref>


Rehabilitation professionals should screen for cognitive, physical, emotional and social triggers. The focus of rehabilitation is optimising function, mitigating disability and establishing strategies to support living with a disability. Healthcare professionals need to support people living with Long COVID in managing and anticipating their own setbacks. Individuals living with Long COVID need to be heard and understood by their healthcare professionals. Thus, rehabilitation professionals should create a supportive environment, be non-judgmental and respectful that the Long COVID patient is the expert in their own health. It is important not to blame the patient for setbacks or exacerbations and to celebrate small successes.<ref>DeMars J, Brown DA, Angelidis I, Jones F, McGuire F, O’Brien KK, Oller D, Pemberton S, Tarrant R, Verduzco-Gutierrez M, Gross DP. [https://link.springer.com/article/10.1007/s10926-022-10075-2 What is Safe Long COVID Rehabilitation?.] Journal of Occupational Rehabilitation. 2022 Oct 31:1-4.</ref>
Rehabilitation professionals should screen for cognitive, physical, emotional and social triggers. The focus of rehabilitation is optimising function, mitigating disability and establishing strategies to support living with a disability. Healthcare professionals need to support people living with Long COVID in managing and anticipating their setbacks. Individuals living with Long COVID need to be heard and understood by their healthcare professionals. Thus, rehabilitation professionals should create a supportive environment, be non-judgmental and respectful that the Long COVID patient is the expert in their health. It is important not to blame the patient for setbacks or exacerbations and to celebrate small successes.<ref>DeMars J, Brown DA, Angelidis I, Jones F, McGuire F, O'Brien KK, Oller D, Pemberton S, Tarrant R, Verduzco-Gutierrez M, Gross DP. What is Safe Long COVID Rehabilitation? J Occup Rehabil. 2023;33(2):227-230. </ref>


=== Evaluation and Treatment ===
=== Evaluation and Treatment ===
Rehabilitation professionals should initiate evaluations by ruling out red flags such as exertional desaturation, cardiac impairment, PESE (post exertional symptom exacerbation) and orthostatic intolerance. PESE refers to the worsening of symptoms immediately or 12-72 hours after exertion and can last for hours to weeks. These symptoms can include fatigue, pain, dyspnoea and cognitive impairment. Individuals with PESE should monitor their duration, intensity and onset of symptom exacerbations and identify potential triggers. Energy conservation technique is suggested to decrease exacerbations. Increasing rehabilitation intensity without considering PESE should be avoided. Individuals with orthostatic intolerance symptoms such as dizziness, breathlessness, presyncope or syncope after a prolonged period in an upright position should be identified.<ref name=":3" />
Rehabilitation professionals should initiate evaluations by ruling out red flags such as exertional desaturation, cardiac impairment, PESE (post-exertional symptom exacerbation) and orthostatic intolerance. PESE refers to the worsening of symptoms immediately or 12-72 hours after exertion and can last for hours to weeks. These symptoms can include fatigue, pain, dyspnoea and cognitive impairment. Individuals with PESE should monitor their duration, intensity and onset of symptom exacerbations and identify potential triggers. An energy conservation technique is suggested to decrease exacerbations. Increasing rehabilitation intensity without considering PESE should be avoided. Individuals with orthostatic intolerance symptoms such as dizziness, breathlessness, presyncope or syncope after a prolonged period in an upright position should be identified.<ref name=":3" />


Mental health problems, psychological therapy, pharmacological therapy and sleep disorders are additional areas that can be addressed in treatment. Some techniques for these issues have included mindfulness-based stress reduction and exercise training. Cognitive impairments can be addressed with environmental modification, pacing and assistive tools as well as restorative cognitive exercise.<ref name=":3" />
Mental health problems, psychological therapy, pharmacological therapy and sleep disorders are additional areas that can be addressed in treatment. Some techniques for these issues have included mindfulness-based stress reduction and exercise training. Cognitive impairments can be addressed with environmental modification, pacing and assistive tools, and vital cognitive exercise.<ref name=":3" />


=== Exercise Therapy ===
=== Exercise Therapy ===
There is currently insufficient evidence on safe and effective interventions for the management of Long COVID symptoms and impairments or disability. But the World Health Organization has called on countries to offer people living with Long COVID more rehabilitation.<ref>J.Wise. [https://www.bmj.com/content/372/bmj.n405 Long covid: WHO calls on countries to offer patients more rehabilitation]. BMJ 2021;372:n405. doi: <nowiki>https://doi.org/10.1136/bmj.n405</nowiki>
There is currently insufficient evidence on safe and effective interventions for the management of Long COVID symptoms and impairments or disability. But the World Health Organization has called on countries to offer people living with Long COVID more rehabilitation.<ref>Wise J. Long covid: WHO calls on countries to offer patients more rehabilitation. BMJ 2021;372:n405.  
</ref>
</ref>


Rehabilitation must always be safe and effective for the patient. With Long COVID, we should note that exercise is not always medicine. Sometimes rest is medicine.<ref name=":8">Brown D, Patman S, Alghwiri A, Skipper L, Hossain K, Setchell J. Long Covid. (Discussion) June 2023. World Physiotherapy Congress Dubai 2023.</ref>
Rehabilitation must always be safe and effective for the patient. With Long COVID, we should note that exercise is not always medicine. Sometimes rest is medicine.<ref name=":8">Brown D, Patman S, Alghwiri A, Skipper L, Hossain K, Setchell J. Long Covid. (Discussion) June 2023. World Physiotherapy Congress Dubai 2023.</ref>


Physiotherapists often use graded exercise therapy (GET) to progress patients, but this may make post-exertion malaise worse.<ref name=":8" /> The National Institute for Health and Care Excellence (NICE) has, for instance, cautioned against the use of GET for managing post-viral fatigue<ref name=":13">Torjesen I. [https://www.bmj.com/content/370/bmj.m2912 NICE cautions against using graded exercise therapy for patients recovering from covid-19]. 2020 July 21 [Accessed 8 January 2021].</ref> in response to draft guidance updates on the management of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS).<ref name=":17">NICE. [https://www.nice.org.uk/news/article/nice-draft-guidance-addresses-the-continuing-debate-about-the-best-approach-to-the-diagnosis-and-management-of-me-cfs NICE draft guidance addresses the continuing debate about the best approach to the diagnosis and management of ME/CFS]. 2020 November 10 [Accessed 8 January 2020].</ref><ref>National Institute for Health and Care Excellence (NICE). [https://www.nice.org.uk/guidance/indevelopment/gid-ng10091 <nowiki>Myalgic encephalomyelitis (or encephalopathy) /chronic fatigue syndrome: diagnosis and management, In development [GID-NG10091]</nowiki>]                                    Expected publication date: <time>21 April 2021 [Accessed 8 January 2021].</time>               
Physiotherapists often use graded exercise therapy (GET) to progress patients, but this may make post-exertion malaise worse.<ref name=":8" /> The National Institute for Health and Care Excellence (NICE) has, for instance, cautioned against the use of GET for managing post-viral fatigue<ref name=":13">Torjesen I. NICE advises against using graded exercise therapy for patients recovering from covid-19. BMJ. 2020;370.</ref> in response to draft guidance updates on the management of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS).<ref name=":17">National Institute for Health and Care Excellence (NICE), NICE outlines steps needed to put ME/CFS guideline into practice. 2020. Available from: https://www.nice.org.uk/news/article/nice-outlines-steps-needed-to-put-me-cfs-guideline-into-practice [Accessed 8 January 2020].</ref><ref>National Institute for Health and Care Excellence (NICE). Myalgic encephalomyelitis (or encephalopathy) /chronic fatigue syndrome: diagnosis and management, In development [GID-NG10091] Expected publication date: <time>21 April 2021. Available from:</time> https://www.nice.org.uk/guidance/NG206 <time>[Accessed 8th January 2021].</time>               
</ref>
</ref>


* Substantial concerns exist regarding the potential for harm in respect to GET as an intervention for ME/CFS.<ref>Dialogues for a Neglected Illness (Dialogues for ME/CFS). [https://www.dialogues-mecfs.co.uk/films/graded-exercise-therapy/ Graded Exercise Therapy]. [Accessed 8 January 2021]</ref>
* Substantial concerns exist regarding the potential for harm with respect to GET as an intervention for ME/CFS.<ref>Dialogues for a Neglected Illness (Dialogues for ME/CFS). Graded Exercise Therapy. Available From: https://www.dialogues-mecfs.co.uk/ (Accessed 8 January 2021).</ref>
* Post-exertion malaise is a symptom experienced by people living with ME/CFS,<ref>Carruthers BM, van de Sande MI, De Meirleir KL, Klimas NG, Broderick G, Mitchell T, Staines D, Powles AP, Speight N, Vallings R, Bateman L. [https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2796.2011.02428.x Myalgic encephalomyelitis: international consensus criteria]. Journal of internal medicine. 2011 Oct;270(4):327-38.</ref> and is characterised as the worsening of symptoms by exertion including physical, cognitive and emotional activities,<ref>Stussman B, Williams A, Snow J, Gavin A, Scott R, Nath A, Walitt B. [https://www.frontiersin.org/articles/10.3389/fneur.2020.01025/full Characterization of Post–exertional Malaise in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]. Frontiers in Neurology. 2020 Sep 18;11:1025.</ref><ref>Stephens C. [https://meassociation.org.uk/wp-content/uploads/MEA-Research-Review-Assessing-PEM-in-MECFS-25.03.19.pdf?fbclid=IwAR1iT9TOYyOfdofaTsflQRdxkg_VEjY-0wFMOCLJJ9l8ZGQ1dgL3EI-MCeA MEA Summary Review: Assessing PEM (Post-exertional malaise)]. The ME Association. 2019 March 25 [Accessed 8 January 2021].</ref><ref>Chu L, Valencia IJ, Garvert DW, Montoya JG. [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197811 Deconstructing post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: A patient-centered, cross-sectional survey]. PloS one. 2018 Jun 1;13(6):e0197811.</ref> which would prohibit exercise interventions.
* Post-exertion malaise is a symptom experienced by people living with ME/CFS,<ref>Carruthers BM, van de Sande MI, De Meirleir KL, Klimas NG, Broderick G, Mitchell T, Staines D, Powles AP, Speight N, Vallings R, Bateman L. Myalgic encephalomyelitis: international consensus criteria. Journal of internal medicine. 2011;270(4):327-38.</ref> and is characterised as the worsening of symptoms by exertion including physical, cognitive and emotional activities,<ref>Stussman B, Williams A, Snow J, Gavin A, Scott R, Nath A, Walitt B. Characterization of Post–exertional Malaise in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Frontiers in Neurology. 2020;11:1025.</ref><ref>Stephens C. MEA Summary Review: Assessing
* '''Among a sample of 3,762 people living with Long COVID, post-exertion malaise was reported by 72.2%.'''<ref name=":17" /> Moreover, exercise is a common trigger for symptom relapses.<ref name=":5" /><ref name=":26">N.Ziauddeen, D.Gurdasani, ME.O’Hara, C.Hastie, P.Roderick, G.Yao, NA.Alwan. [https://www.medrxiv.org/content/10.1101/2021.03.21.21253968v1.full.pdf?fbclid=IwAR0pV8LBthvrj_USuO3wYe63pOUvIDIRsjKuBLvbh-pBsSTHQGE1P4MZGRM Characteristics of Long Covid: findings from a social media survey]. MedRxiv, 2021. </ref>


We must, therefore, be careful when using exercise as a rehabilitation intervention for Long COVID and people living with COVID-19. Groups representing people living with Long COVID have advocated for a risk stratification approach to exercise as a rehabilitation intervention. A focus is needed on assessing and excluding post-exertion malaise,<ref name=":15">Holtzman CS, Bhatia S, Cotler J, Jason LA. [https://www.mdpi.com/2075-4418/9/1/26 Assessment of post-exertional malaise (PEM) in patients with myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS): a patient-driven survey]. Diagnostics. 2019 Mar;9(1):26.</ref><ref name=":16" /> plus screening for potential cardiac involvement.<ref>Phelan D, Kim JH, Elliott MD, Wasfy MM, Cremer P, Johri AM et al. [https://www.sciencedirect.com/science/article/abs/pii/S1936878X20309098 Screening of Potential Cardiac Involvemenappt in Competitive Athletes Recovering from COVID-19: An Expert Consensus Statement]. JACC: Cardiovascular Imaging. 2020;13(12):2635-2652.</ref> We can use the DePaul Symptom Questionnaire to screen for post-exertion malaise.<ref name=":16">Jason LA, Sunnquist M. [https://www.frontiersin.org/articles/10.3389/fped.2018.00330/full The Development of the DePaul Symptom Questionnaire: Original, Expanded, Brief, and Pediatric Versions]. Frontiers in pediatrics. 2018 Nov 6;6:330.</ref> If this symptom is present, exercise may not be considered a safe rehabilitation intervention.<ref name=":17" />
PEM (Post-exertional malaise). The ME Association. 2019. Available from: https://meassociation.org.uk/wp-content/uploads/MEA-Research-Review-Assessing-PEM-in-MECFS-25.03.19.pdf [Accessed 8 January 2021].</ref><ref>Chu L, Valencia IJ, Garvert DW, Montoya JG. Deconstructing post-exertional malaise in myalgic encephalomyelitis/ chronic fatigue syndrome: A patient-centered, cross-sectional survey. PLoS One. 2018;13(6):e0197811. </ref> which would prohibit exercise interventions.
* '''Among a sample of 3,762 people living with Long COVID, post-exertion malaise was reported by 72.2%.'''<ref name=":17" /> Moreover, exercise is a common trigger for symptom relapses.<ref name=":5" /><ref name=":26">Ziauddeen N, Gurdasani D, O'Hara ME, Hastie C, Roderick P, Yao G, Alwan NA. Characteristics and impact of Long Covid: Findings from an online survey. PLoS One. 2022;17(3):e0264331. </ref>


Activity management or [https://longcovid.physio/pacing pacing] and [https://longcovid.physio/heart-rate-monitoring heart rate monitoring] are, however, likely to be a safe and effective interventions for managing fatigue and post-exertion malaise. Useful resources on specific rehabilitation ideas, pacing and heart rate monitoring are provided below:     
We must, therefore, be careful when using exercise as a rehabilitation intervention for Long COVID and people living with COVID-19. Groups representing people living with Long COVID have advocated for a risk stratification approach to exercise as a rehabilitation intervention. A focus is needed on assessing and excluding post-exertion malaise,<ref name=":15">Holtzman CS, Bhatia S, Cotler J, Jason LA. Assessment of Post-Exertional Malaise (PEM) in Patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS): A Patient-Driven Survey. Diagnostics. 2019;9(1):26.</ref><ref name=":16" /> plus screening for potential cardiac involvement.<ref>Phelan D, Kim JH, Elliott MD, Wasfy MM, Cremer P, Johri AM et al. Screening of Potential Cardiac Involvement in Competitive Athletes Recovering from COVID-19: An Expert Consensus Statement. JACC: Cardiovascular Imaging 2020;13(12):2635-2652.</ref> We can use the DePaul Symptom Questionnaire to screen for post-exertion malaise.<ref name=":16">Jason LA, Sunnquist M. The Development of the DePaul Symptom Questionnaire: Original, Expanded, Brief, and Pediatric Versions. Frontiers in paediatrics. 2018;6:330.</ref> If this symptom is present, exercise may not be considered a safe rehabilitation intervention.<ref name=":17" />
 
Activity management or [https://longcovid.physio/pacing pacing] and [https://longcovid.physio/heart-rate-monitoring heart rate monitoring] are, however, likely to be a safe and effective intervention for managing fatigue and post-exertion malaise. Useful resources on specific rehabilitation ideas, pacing and heart rate monitoring are provided below:     
*World Physiotherapy response to COVID-19: [https://world.physio/sites/default/files/2021-06/Briefing-Paper-9-Long-Covid-FINAL-2021.pdf Safe Rehabilitation Approaches for People Living with Long Covid: Physical Activity and exercise]. June 2021
*World Physiotherapy response to COVID-19: [https://world.physio/sites/default/files/2021-06/Briefing-Paper-9-Long-Covid-FINAL-2021.pdf Safe Rehabilitation Approaches for People Living with Long Covid: Physical Activity and exercise]. June 2021
* Royal College of Occupational Therapy (RCOT): "[https://www.rcot.co.uk/recovering-covid-19-post-viral-fatigue-and-conserving-energy Post viral fatigue and energy conservation]"
* Royal College of Occupational Therapy (RCOT): "[https://www.rcot.co.uk/recovering-covid-19-post-viral-fatigue-and-conserving-energy Post viral fatigue and energy conservation]"
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=== Outcome Measures ===
=== Outcome Measures ===
Some studies have performed a level of functional assessment, including:     
Some studies have performed a level of functional assessment, including:     
* Post-COVID-19 Functional Status Assessment (PCFS) <ref>Klok FA, Boon GJ, Barco S, Endres M, Geelhoed JM, Knauss S, Rezek SA, Spruit MA, Vehreschild J, Siegerink B. [https://erj.ersjournals.com/content/56/1/2001494 The Post-COVID-19 Functional Status scale: a tool to measure functional status over time after COVID-19]. European Respiratory Journal. 2020 Jul 1;56(1).</ref><ref>Mohamed-Hussein A, Galal I, Saad M, Zayan HE, Abdelsayed M, Moustafa M, Ezzat AR, Helmy R, Abd Elaal H, Aly K, Abderheem S. [https://www.medrxiv.org/content/10.1101/2020.08.26.20182618v1 Post-COVID-19 Functional Status: Relation to age, smoking, hospitalization and comorbidities]. medRxiv. 2020 Jan 1.</ref><ref name=":10">D'Cruz RF, Waller MD, Perrin F, Periselneris J, Norton S, Smith LJ, Patrick T, Walder D, Heitmann A, Lee K, Madula R. [https://openres.ersjournals.com/content/early/2020/10/15/23120541.00655-2020 Chest radiography is a poor predictor of respiratory symptoms and functional impairment in survivors of severe COVID-19 pneumonia]. ERJ Open Research. 2020 Jan 1.</ref><ref>FVC.Machado, R.Meys, JM.Delbressine, AW.Vaes, YMJ.Goërtz, M.van Herck, S.Houben-Wilke, GJAM.Boon, S.Barco, C.Burtin, A.van 't Hul, R.Posthuma, FME.Franssen, Y.Spies, H.Vijlbrief, F.Pitta, SA.Rezek, DJA.Janssen, B.Siegerink, FA.Klok, MA.Spruit. [https://hqlo.biomedcentral.com/articles/10.1186/s12955-021-01691-2 Construct validity of the Post-COVID-19 Functional Status Scale in adult subjects with COVID-19]. Health Qual Life Outcomes. 2021 Feb 3;19(1):40. doi: 10.1186/s12955-021-01691-2.
* Post-COVID-19 Functional Status Assessment (PCFS) <ref>Klok FA, Boon GJ, Barco S, Endres M, Geelhoed JM, Knauss S, Rezek SA, Spruit MA, Vehreschild J, Siegerink B. The Post-COVID-19 Functional Status scale: a tool to measure functional status over time after COVID-19. European Respiratory Journal 2020;56(1).</ref><ref>Mohamed Hussein AA, Saad M, Zayan HE, Abdelsayed M, Moustafa M, Ezzat AR, Helmy R, Abd-Elaal H, Aly K, Abdelrheem S, Sayed I. Post-COVID-19 functional status: Relation to age, smoking, hospitalization, and previous comorbidities. Ann Thorac Med. 2021;16(3):260-265. </ref><ref name=":10">D'Cruz RF, Waller MD, Perrin F, Periselneris J, Norton S, Smith LJ, Patrick T, Walder D, Heitmann A, Lee K, Madula R, McNulty W, Macedo P, Lyall R, Warwick G, Galloway JB, Birring SS, Patel A, Patel I, Jolley CJ. Chest radiography is a poor predictor of respiratory symptoms and functional impairment in survivors of severe COVID-19 pneumonia. ERJ Open Res. 2021;7(1):00655-2020.</ref><ref>Machado FVC, Meys R, Delbressine JM, Vaes AW, Goërtz YMJ, van Herck M, Houben-Wilke S, Boon GJAM, Barco S, Burtin C, van 't Hul A, Posthuma R, Franssen FME, Spies Y, Vijlbrief H, Pitta F, Rezek SA, Janssen DJA, Siegerink B, Klok FA, Spruit MA. Construct validity of the Post-COVID-19 Functional Status Scale in adult subjects with COVID-19. Health Qual Life Outcomes 2021;19(1):40.  
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</ref>
* [https://c19-yrs.com/ COVID-19 Yorkshire Rehabilitation Scale (C19-YRS)] <ref name=":23" /><ref>Sivan M, Halpin S, Gee J. [https://www.acnr.co.uk/2020/06/c19-yrs/ Assessing long-term rehabilitation needs in COVID-19 survivors using a telephone screening tool (C19-YRS tool)]. Advances in Clinical Neurosciences and Rehabilitation. 2020 Jun 29;19(4):14-7.</ref><ref name=":19">Halpin SJ, McIvor C, Whyatt G, Adams A, Harvey O, McLean L, Walshaw C, Kemp S, Corrado J, Singh R, Collins T. [https://onlinelibrary.wiley.com/doi/10.1002/jmv.26368 Postdischarge symptoms and rehabilitation needs in survivors of COVID‐19 infection: A cross‐sectional evaluation]. Journal of medical virology. 2020 Jul 30.</ref><ref>Sivan M. [https://link.springer.com/article/10.1007/s40520-020-01685-y Remote assessment for identifying COVID-19 post-acute care needs]. Aging Clinical and Experimental Research. 2020 Oct;32(10):2167-8.</ref>  
* [https://c19-yrs.com/ COVID-19 Yorkshire Rehabilitation Scale (C19-YRS)] <ref name=":23" /><ref>Sivan M, Halpin S, Gee J. [https://www.acnr.co.uk/2020/06/c19-yrs/ Assessing long-term rehabilitation needs in COVID-19 survivors using a telephone screening tool (C19-YRS tool)]. Advances in Clinical Neurosciences and Rehabilitation. 2020;19(4):14-7.</ref><ref name=":19">Halpin SJ, McIvor C, Whyatt G, Adams A, Harvey O, McLean L, Walshaw C, Kemp S, Corrado J, Singh R, Collins T, O'Connor RJ, Sivan M. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol. 2021;93(2):1013-1022.</ref><ref>Sivan M. Remote assessment for identifying COVID-19 post-acute care needs. Ageing Clinical and Experimental Research. 2020;32(10):2167-8.</ref>
*Core Outcome Measure for Recovery, which is a measure to define the absence of symptoms, resumption of usual daily activities, and return to the previous state of health prior to the illness using a 5-point Likert scale <ref>Tong A, Elliott JH, Azevedo LC, Baumgart A, Bersten A, Cervantes L, Chew DP, Cho Y, Cooper T, Crowe S, Douglas IS. [https://journals.lww.com/ccmjournal/Fulltext/2020/11000/Core_Outcomes_Set_for_Trials_in_People_With.10.aspx Core outcomes set for trials in people with coronavirus disease 2019]. Critical care medicine. 2020 Nov;48(11):1622.</ref><ref>A Tong, A Baumgart, Evangelidis N et al. [https://journals.lww.com/ccmjournal/Fulltext/2021/03000/Core_Outcome_Measures_for_Trials_in_People_With.11.aspx Core Outcome Measures for Trials in People With Coronavirus Disease 2019: Respiratory Failure, Multiorgan Failure, Shortness of Breath, and Recovery]. Critical Care Medicine, 2021; 49(3): 503-516. DOI: 10.1097/CCM.0000000000004817
*Core Outcome Measure for Recovery, which is a measure to define the absence of symptoms, resumption of usual daily activities, and return to the previous state of health before the illness using a 5-point Likert scale <ref>Tong A, Elliott JH, Azevedo LC, Baumgart A, Bersten A, Cervantes L, Chew DP, Cho Y, Cooper T, Crowe S, Douglas IS. Core outcomes set for trials in people with coronavirus disease 2019. Critical care medicine 2020;48(11):1622.</ref><ref>Tong A, Baumgart A, Evangelidis N, Viecelli AK, Carter SA, Azevedo LC, Cooper T, Bersten A, Cervantes L, Chew DP, Crowe S, Douglas IS, Flemyng E, Elliott JH, Hannan E, Horby P, Howell M, Ju A, Lee J, Lorca E, Lynch D, Manera KE, Marshall JC, Gonzalez AM, McKenzie A, Mehta S, Mer M, Morris AC, Needham DM, Nseir S, Povoa P, Reid M, Sakr Y, Shen N, Smyth AR, Simpson AJ, Snelling T, Strippoli GFM, Teixeira-Pinto A, Torres A, Turner T, Webb S, Williamson PR, Woc-Colburn L, Zhang J, Craig JC; COVID-19-Core Outcomes Set Investigators. Core Outcome Measures for Trials in People With Coronavirus Disease 2019: Respiratory Failure, Multiorgan Failure, Shortness of Breath, and Recovery. Crit Care Med. 2021;49(3):503-516.
</ref>   
</ref>
* Sit-to-stand tests <ref name=":10" /><ref name=":11">Arnold DT, Hamilton FW, Milne A, Morley AJ, Viner J, Attwood M, Noel A, Gunning S, Hatrick J, Hamilton S, Elvers KT. [https://www.medrxiv.org/content/10.1101/2020.08.12.20173526v1 Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: results from a prospective UK cohort]. Thorax. 2020 Dec 3.</ref><ref>R.Núñez-Cortés, G.Rivera-Lillo, M.Arias-Campoverde, D. Soto-García, R.García-Palomera, R.Torres-Castro. [https://journals.sagepub.com/doi/full/10.1177/1479973121999205 Use of sit-to-stand test to assess the physical capacity and exertional desaturation in patients post COVID-19]. Chronic Respiratory Disease, 2021.[https://doi.org/10.1177%2F1479973121999205 https://doi.org/10.1177/1479973121999205]
* Sit-to-stand tests <ref name=":10" /><ref name=":11">Arnold DT, Hamilton FW, Milne A, Morley AJ, Viner J, Attwood M, Noel A, Gunning S, Hatrick J, Hamilton S, Elvers KT, Hyams C, Bibby A, Moran E, Adamali HI, Dodd JW, Maskell NA, Barratt SL. Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: results from a prospective UK cohort. Thorax 2021;76(4):399-401. </ref><ref>Núñez-Cortés R, Rivera-Lillo G, Arias-Campoverde M, Soto-García D, García-Palomera R, Torres-Castro R. Use of sit-to-stand test to assess the physical capacity and exertional desaturation in patients post COVID-19. Chron Respir  Dis 2021;18:1479973121999205.
</ref>  
</ref>
* Gait speed tests<ref name=":14" /><ref name=":10" /><ref>Raman B, Cassar MP, Tunnicliffe EM, Filippini N, Griffanti L, Alfaro-Almagro F, Okell T, Sheerin F, Xie C, Mahmod M, Mózes FE. [https://www.medrxiv.org/content/10.1101/2020.10.15.20205054v1 Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge]. medRxiv. 2020 Jan 1.</ref><ref>Daher A, Balfanz P, Cornelissen C, Müller A, Bergs I, Marx N, Müller-Wieland D, Hartmann B, Dreher M, Müller T. [https://www.resmedjournal.com/article/S0954-6111(20)30337-1/fulltext Follow up of patients with severe coronavirus disease 2019 (COVID-19): Pulmonary and extrapulmonary disease sequelae]. Respiratory medicine. 2020 Nov 1;174:106197.</ref><ref>Huang Y, Tan C, Wu J, Chen M, Wang Z, Luo L et al. [https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-020-01429-6 Impact of Coronavirus Disease 2019 on Pulmonary Function in Early Convalescence Phase]. Respiratory Research. 2020;21:163.</ref><ref>Sonnweber T, Boehm A, Sahanic S, Pizzini A, Aichner M, Sonnweber B, Kurz K, Koppelstätter S, Haschka D, Petzer V, Hilbe R. [https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-020-01546-2 Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients’ performance: a prospective observational cohort study]. Respiratory research. 2020 Dec;21(1):1-9.</ref>  
* Gait speed tests<ref name=":14" /><ref name=":10" /><ref>Raman B, Cassar MP, Tunnicliffe EM, Filippini N, Griffanti L, Alfaro-Almagro F, Okell T, Sheerin F, Xie C, Mahmod M, Mózes FE, Lewandowski AJ, Ohuma EO, Holdsworth D, Lamlum H, Woodman MJ, Krasopoulos C, Mills R, McConnell FAK, Wang C, Arthofer C, Lange FJ, Andersson J, Jenkinson M, Antoniades C, Channon KM, Shanmuganathan M, Ferreira VM, Piechnik SK, Klenerman P, Brightling C, Talbot NP, Petousi N, Rahman NM, Ho LP, Saunders K, Geddes JR, Harrison PJ, Pattinson K, Rowland MJ, Angus BJ, Gleeson F, Pavlides M, Koychev I, Miller KL, Mackay C, Jezzard P, Smith SM, Neubauer S. Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge. EClinicalMedicine. 2021;31:100683. </ref><ref>Daher A, Balfanz P, Cornelissen C, Müller A, Bergs I, Marx N, Müller-Wieland D, Hartmann B, Dreher M, Müller T. Follow up of patients with severe coronavirus disease 2019 (COVID-19): Pulmonary and extrapulmonary disease sequelae. Respiratory Medicine 2020;174:106197.</ref><ref>Huang Y, Tan C, Wu J, Chen M, Wang Z, Luo L, Zhou X, Liu X, Huang X, Yuan S, Chen C, Gao F, Huang J, Shan H, Liu J. Impact of coronavirus disease 2019 on pulmonary function in early convalescence phase. Respir Res. 2020;21(1):163. </ref><ref>Sonnweber T, Boehm A, Satanic S, Pizzini A, Aichner M, Sonnweber B, Kurz K, Koppelstätter S, Haschka D, Petzer V, Hilbe R. Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients’ performance: a prospective observational cohort study. Respiratory Research 2020;21(1):1-9.</ref>
* Modified Rankin Score <ref>Savarraj JP, Burkett AB, Hinds SN, Paz AS, Assing AR, Juneja S, Colpo GD, Torres LF, Gusdon AM, McCullough L, Choi HA. [https://www.medrxiv.org/content/10.1101/2020.10.16.20211029v1 Three-month outcomes in hospitalized COVID-19 patients]. medRxiv. 2020 Jan 1.</ref>  
* Modified Rankin Score <ref>Savarraj JP, Burkett AB, Hinds SN, Paz AS, Assing AR, Juneja S, Colpo GD, Torres LF, Gusdon AM, McCullough L, Choi HA. Three-month outcomes in hospitalized COVID-19 patients. MedRxiv. 2020.</ref>
* [https://physio-pedia.com/EQ-5D?utm_source=physiopedia&utm_medium=search&utm_campaign=ongoing_internal EuroQOL EQ-5D-5L] <ref name=":14" />     
* [https://physio-pedia.com/EQ-5D?utm_source=physiopedia&utm_medium=search&utm_campaign=ongoing_internal EuroQOL EQ-5D-5L] <ref name=":14" />     
* [https://physio-pedia.com/36-Item_Short_Form_Survey_(SF-36)?utm_source=physiopedia&utm_medium=search&utm_campaign=ongoing_internal SF-36 questionnaire] <ref name=":11" />     
* [https://physio-pedia.com/36-Item_Short_Form_Survey_(SF-36)?utm_source=physiopedia&utm_medium=search&utm_campaign=ongoing_internal SF-36 questionnaire] <ref name=":11" />     
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== Peer Support ==
== Peer Support ==
Peer support involves people sharing knowledge, experience, or practical help with each other, often when living with the same or similar health conditions. Many online Long COVID peer support groups have been established for people living with Long COVID. These are safe spaces for people living with Long COVID to access peer support. Mutual respect and confidentiality is, therefore, requested in these groups. Many of these groups have outputs to share valuable information with allies. Long COVID Physio published [https://longcovid.physio/ blogs] with JOSPT highlighting the value of peer support. Long COVID groups include:
Peer support involves people sharing knowledge, experience, or practical help with each other, often when living with the same or similar health conditions. Many online Long COVID peer support groups have been established for people living with Long COVID. These are safe spaces for people living with Long COVID to access peer support. Mutual respect and confidentiality are, therefore, requested in these groups. Many of these groups have outputs to share valuable information with allies. Long COVID Physio published [https://longcovid.physio/ blogs] with JOSPT highlighting the value of peer support. Long COVID groups include:
* [https://longcovid.physio/ Long COVID Physio] - [https://twitter.com/LongCovidPhysio Twitter]  
* [https://longcovid.physio/ Long COVID Physio] - [https://twitter.com/LongCovidPhysio Twitter]  
* [https://linktr.ee/wearebodypolitic Body Politic] - [https://twitter.com/itsbodypolitic Twitter]
* [https://linktr.ee/wearebodypolitic Body Politic] - [https://twitter.com/itsbodypolitic Twitter]
Line 168: Line 165:
* [https://twitter.com/LongCovidNZ Long COVID New Zealand]     
* [https://twitter.com/LongCovidNZ Long COVID New Zealand]     
* [https://covid19-recovery.org/ COVID-19 Patient Stories / Recovery Collective] - [https://twitter.com/RecoveryCovid19 Twitter]  
* [https://covid19-recovery.org/ COVID-19 Patient Stories / Recovery Collective] - [https://twitter.com/RecoveryCovid19 Twitter]  
* [https://patientresearchcovid19.com/ Patient led research for Long COVID] - [https://twitter.com/patientled Twitter]  
* [https://patientresearchcovid19.com/ Patient-led research for Long COVID] - [https://twitter.com/patientled Twitter]  
* [https://twitter.com/LongCovidOT Long COVID OT] (Occupational Therapy) - [https://www.facebook.com/groups/685453145469418 Facebook]  
* [https://twitter.com/LongCovidOT Long COVID OT] (Occupational Therapy) - [https://www.facebook.com/groups/685453145469418 Facebook]  
* [https://twitter.com/longcovacademia Long COVID in Academia]  
* [https://twitter.com/longcovacademia Long COVID in Academia]  

Latest revision as of 17:10, 7 August 2023

Original Editor - Darren Brown Top Contributors - Darren Brown, Jess Bell, Olajumoke Ogunleye, Robin Tacchetti, Kim Jackson, Shwe Shwe U Marma, Tarina van der Stockt, Lucinda hampton, Candace Goh and Chelsea Mclene 

Introduction[edit | edit source]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease (COVID-19) [1]. The effects of COVID-19 have been characterised across different time points:

  • acute COVID-19 infection with signs and symptoms of COVID-19 for up to 4 weeks.
  • ongoing symptomatic COVID-19 with signs and symptoms of COVID-19 from 4 weeks up to 12 weeks.
  • long-term consequences of COVID-19 which usually presents with clusters of symptoms, often overlapping, which can fluctuate and change over time and can affect any system in the body for more than 12 weeks.[2]

** The name Long COVID acknowledges that the disease cause and course are as yet unknown makes clear that “mild” COVID-19 is not necessarily mild, avoids “chronic,” “post” and “syndrome” that may delegitimise people's experiences, draws attention to morbidity, and centres people with disability.[3]

"People call Long COVID by many names, including post-COVID conditions, long-haul COVID, post-acute COVID-19, long-term effects of COVID, and chronic COVID."[4]

What is Long COVID?[edit | edit source]

Long Covid has been preliminarily defined as the presence of signs and symptoms that develop during or following an infection consistent with COVID-19 which continue for 12 weeks or more and are not explained by an alternative diagnosis. This includes both ongoing symptomatic COVID-19 (from 4 to 12 weeks) and "Post-COVID Syndrome" (12 weeks or more).[5]

Long COVID affects people who have been hospitalised with acute COVID-19 and those who managed in a community setting. There is growing evidence to suggest that individuals who have had both mild or severe COVID-19 can experience prolonged symptoms or develop Long COVID.[6][7][8][9][10][11][12][13][14] Long COVID is both common and debilitating.[15]

As of October 2021, the World Health Organization (WHO) has developed a case definition of post COVID-19 condition.

"Post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction but also others* and generally have an impact on everyday functioning. Symptoms may be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms may also fluctuate or relapse over time."[16]

Long COVID Symptoms[edit | edit source]

Long COVID usually presents as clusters of symptoms, often overlapping, which can fluctuate and change over time and can affect any system in the body. [15][5][17][18][19][20][21] including, but not limited to pulmonary, cardiovascular, gastrointestinal, reproductive, genitourinary, endocrine, renal, dermatologic, musculoskeletal, neurological, neuropsychiatric, immunological, ophthalmic, and audiological.[17]

The most common Long Covid symptom is fatigue.[17][18][22][23][14][24][25][26][10][27][28][29][30][31][32][12][33][34] The most frequently reported Long COVID symptoms after 6 months include fatigue, post-exertion malaise, and cognitive dysfunction.[17] Mental health symptoms associated with long COVID include anxiety (28% increase), increased presence of depression (13% increase), PTSD (20% increase), suicide ideation (10% increase) and decreased life satisfaction and daily functioning. Researchers and patients have distinguished more than 200 symptoms associated with long COVID.[35] The most common symptoms include:

  • tiredness
  • brain fog
  • cough
  • loss of smell or change in taste
  • fever
  • body aches
  • trouble sleeping
  • mood changes[36]

The multidimensional, episodic and often unpredictable nature of Long COVID has been described as "relapsing and remitting",[19] whereby 86% of people with Long COVID report relapses over 7 months, with physical activity, stress, exercise and mental activity being the most common triggers of relapses.[17] The trajectory of Long COVID is heterogenous with some improving over time, some worsening and others stable, with many experiencing ongoing fluctuating symptoms after 6 months.[17][37] Furthermore, outcomes are worse in working-age females than males, with females under 50 being over five times more likely to report incomplete recovery, over five times more likely to report a new disability, more likely to have severe fatigue, and more than six times more likely to report increased breathlessness than males under 50.[37] It is estimated that 30% of people not hospitalised with "mild" acute symptoms, continue to have symptoms 9 months after infection.[12] Preliminary evidence suggests children also experience Long COVID symptoms similar to adults.[38]

[39]

Long COVID Prevalence[edit | edit source]

The COVID-19 Infection Survey[40] is a nationally representative sample of the UK community population, from which it has been estimated that around 1 in 5 people exhibit Long COVID symptoms for 5 weeks or longer, and around 1 in 10 exhibit Long COVID symptoms for 12 weeks or longer.[41][42]

Researchers have determined that Long COVID is more severe and common in individuals infected before the Omicron variant in 2021 and those who were unvaccinated. Additionally, reinfections were related to higher Long COVID severity and frequency compared to people who were only infected once.[35]

Pathological Process[edit | edit source]

The aetiology and pathophysiological causes of Long COVID symptoms remain unknown. Initial hypothesis includes: viral persistence,[43][44][45][46] continued hyperactive immune response,[47][48][49] cellular metabolic dysfunction,[50] auto-antibodies,[51][52] neurological dysfunction,[53][54][55][56] neuroimmunology,[57] neurological inflammation,[58] and organ impairment,[14] including cardiac impairment.[14][59][60][61][62][63] Musculoskeletal short- and long-term consequences of COVID-19 are also discussed.[64] More research is required to understand the mechanisms by which Long COVID develops.[15]

Long COVID Management[edit | edit source]

Currently, there is no evidence from randomised controlled trials on the effectiveness of rehabilitation for Long COVID. Most recommendations from international guidance on rehabilitation for Long COVID are based on expert opinion or evidence from other diseases. Suggestions include patient-centred management with continuous follow-up to decrease the severity of current symptoms. Attention should be placed on creating therapeutic alliances and setting reasonable goals and expectations through discussions with patients and caregivers.[65]

A multi-disciplinary approach to the assessment and management of Long COVID is essential.[15] The team approach could include a rehabilitation physician along with multiple speciality physicians, occupational therapists, physiotherapists, pharmacists, nursing professionals, mental health experts, community workers and other health care professionals.[66] Encompassing a disability model could improve clinicians’ responses to Long COVID.[67]

Rehabilitation professionals should screen for cognitive, physical, emotional and social triggers. The focus of rehabilitation is optimising function, mitigating disability and establishing strategies to support living with a disability. Healthcare professionals need to support people living with Long COVID in managing and anticipating their setbacks. Individuals living with Long COVID need to be heard and understood by their healthcare professionals. Thus, rehabilitation professionals should create a supportive environment, be non-judgmental and respectful that the Long COVID patient is the expert in their health. It is important not to blame the patient for setbacks or exacerbations and to celebrate small successes.[68]

Evaluation and Treatment[edit | edit source]

Rehabilitation professionals should initiate evaluations by ruling out red flags such as exertional desaturation, cardiac impairment, PESE (post-exertional symptom exacerbation) and orthostatic intolerance. PESE refers to the worsening of symptoms immediately or 12-72 hours after exertion and can last for hours to weeks. These symptoms can include fatigue, pain, dyspnoea and cognitive impairment. Individuals with PESE should monitor their duration, intensity and onset of symptom exacerbations and identify potential triggers. An energy conservation technique is suggested to decrease exacerbations. Increasing rehabilitation intensity without considering PESE should be avoided. Individuals with orthostatic intolerance symptoms such as dizziness, breathlessness, presyncope or syncope after a prolonged period in an upright position should be identified.[65]

Mental health problems, psychological therapy, pharmacological therapy and sleep disorders are additional areas that can be addressed in treatment. Some techniques for these issues have included mindfulness-based stress reduction and exercise training. Cognitive impairments can be addressed with environmental modification, pacing and assistive tools, and vital cognitive exercise.[65]

Exercise Therapy[edit | edit source]

There is currently insufficient evidence on safe and effective interventions for the management of Long COVID symptoms and impairments or disability. But the World Health Organization has called on countries to offer people living with Long COVID more rehabilitation.[69]

Rehabilitation must always be safe and effective for the patient. With Long COVID, we should note that exercise is not always medicine. Sometimes rest is medicine.[70]

Physiotherapists often use graded exercise therapy (GET) to progress patients, but this may make post-exertion malaise worse.[70] The National Institute for Health and Care Excellence (NICE) has, for instance, cautioned against the use of GET for managing post-viral fatigue[71] in response to draft guidance updates on the management of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS).[72][73]

  • Substantial concerns exist regarding the potential for harm with respect to GET as an intervention for ME/CFS.[74]
  • Post-exertion malaise is a symptom experienced by people living with ME/CFS,[75] and is characterised as the worsening of symptoms by exertion including physical, cognitive and emotional activities,[76][77][78] which would prohibit exercise interventions.
  • Among a sample of 3,762 people living with Long COVID, post-exertion malaise was reported by 72.2%.[72] Moreover, exercise is a common trigger for symptom relapses.[17][79]

We must, therefore, be careful when using exercise as a rehabilitation intervention for Long COVID and people living with COVID-19. Groups representing people living with Long COVID have advocated for a risk stratification approach to exercise as a rehabilitation intervention. A focus is needed on assessing and excluding post-exertion malaise,[80][81] plus screening for potential cardiac involvement.[82] We can use the DePaul Symptom Questionnaire to screen for post-exertion malaise.[81] If this symptom is present, exercise may not be considered a safe rehabilitation intervention.[72]

Activity management or pacing and heart rate monitoring are, however, likely to be a safe and effective intervention for managing fatigue and post-exertion malaise. Useful resources on specific rehabilitation ideas, pacing and heart rate monitoring are provided below:

Outcome Measures[edit | edit source]

Some studies have performed a level of functional assessment, including:

Peer Support[edit | edit source]

Peer support involves people sharing knowledge, experience, or practical help with each other, often when living with the same or similar health conditions. Many online Long COVID peer support groups have been established for people living with Long COVID. These are safe spaces for people living with Long COVID to access peer support. Mutual respect and confidentiality are, therefore, requested in these groups. Many of these groups have outputs to share valuable information with allies. Long COVID Physio published blogs with JOSPT highlighting the value of peer support. Long COVID groups include:

Video Resources for Patients[edit | edit source]

[98]
[99]
[100]

References[edit | edit source]

  1. ↑ World Health Organization. Naming the coronavirus disease (COVID-19) and the virus that causes it. Availabe from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it [Accessed 7 January 2021]
  2. ↑ National Institute for Health and Care Excellence (NICE), COVID-19 guideline scope: management of the long-term effects of COVID-19. 2020. Available from: https://www.nice.org.uk/guidance/ng188/documents/final-scope [Accessed 7 January 2021].
  3. ↑ Perego E, Callard F, Stras L, Melville-Johannesson B, Pope R, Alwan N. Why we need to keep using the patient made term “Long Covid. BMJ Opinion. 2020.
  4. ↑ Long COVID or Post-COVID Conditions. Updated Dec. 16, 2022. Centres for Disease Control and Prevention. Available From: https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html
  5. ↑ 5.0 5.1 National Institute for Health and Care Excellence (NICE). COVID-19 Rapid Guideline: Managing The Long-term Effects of COVID-19. 2020. Available From: https://www.nice.org.uk/guidance/ng188 [Accessed 8 January 2021].
  6. ↑ Public Health England. COVID-19: epidemiology, virology and clinical features. 2021.
  7. ↑ Townsend L, Dowds J, O'Brien K, Sheill G, Dyer AH, O'Kelly B, Hynes JP, Mooney A, Dunne J, Ni Cheallaigh C, O'Farrelly C, Bourke NM, Conlon N, Martin-Loeches I, Bergin C, Nadarajan P, Bannan C. Persistent Poor Health after COVID-19 Is Not Associated with Respiratory Complications or Initial Disease Severity. Ann Am Thorac Soc. 2021;18(6):997-1003.
  8. ↑ Graham EL, Clark JR, Orban ZS, Lim PH, Szymanski AL, Taylor C, DiBiase RM, Jia DT, Balabanov R, Ho SU, Batra A, Liotta EM, Koralnik IJ. Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 "long haulers". Ann Clin Transl Neurol. 2021;8(5):1073-1085.
  9. ↑ Brodin P. Immune determinants of COVID-19 disease presentation and severity. Nature Medicine, 2021;27:28–33.
  10. ↑ 10.0 10.1 Townsend L, Dyer AH, Jones K, Dunne J, Mooney A, Gaffney F, O'Connor L, Leavy D, O'Brien K, Dowds J, Sugrue JA. Persistent fatigue following SARS-CoV-2 infection is common and independent of the severity of initial infection. Plos One. 2020;9:15(11).
  11. ↑ Augustin M, Schommers P, Stecher M, Dewald F, Gieselmann L, Gruell H, Horn C, Vanshylla K, Cristanziano VD, Osebold L, Roventa M. Recovered not restored: Long-term health consequences after mild COVID-19 in non-hospitalized patients. MedRxiv. 2021;2021-03.
  12. ↑ 12.0 12.1 12.2 Logue JK, Franko NM, McCulloch DJ, McDonald D, Magedson A, Wolf CR, Chu HY. Sequelae in Adults at 6 Months After COVID-19 Infection. JAMA Netw Open. 2021;1:4(2).
  13. ↑ Evans RA, McAuley H, Harrison EM, Shikotra A, Singapuri A, Sereno M, Elneima O, Docherty AB, Lone NI, Leavy OC, Daines L, Baillie JK, Brown JS, Chalder T, De Soyza A, Diar Bakerly N, Easom N, Geddes JR, Greening NJ, Hart N, Heaney LG, Heller S, Howard L, Hurst JR, Jacob J, Jenkins RG, Jolley C, Kerr S, Kon OM, Lewis K, Lord JM, McCann GP, Neubauer S, Openshaw PJM, Parekh D, Pfeffer P, Rahman NM, Raman B, Richardson M, Rowland M, Semple MG, Shah AM, Singh SJ, Sheikh A, Thomas D, Toshner M, Chalmers JD, Ho LP, Horsley A, Marks M, Poinasamy K, Wain LV, Brightling CE. Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study. Lancet Respir Med. 2021;9(11):1275-1287.
  14. ↑ 14.0 14.1 14.2 14.3 Dennis A, Wamil M, Alberts J, Oben J, Cuthbertson DJ, Wootton D, Crooks M, Gabbay M, Brady M, Hishmeh L, Attree E, Heightman M, Banerjee R, Banerjee A; COVERSCAN study investigators. Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome: a prospective, community-based study. BMJ Open. 2021;11(3).
  15. ↑ 15.0 15.1 15.2 15.3 15.4 Rajan S, Khunti K, Alwan N, Steves C, MacDermott N, Morsella A, Angulo E, Winkelmann J, Bryndová L, Fronteira I, Gandré C, Or Z, Gerkens S, Sagan A, Simões J, Ricciardi W, de Belvis AG, Silenzi A, Bernal-Delgado E, Estupiñán-Romero F, McKee M. In the wake of the pandemic: Preparing for Long COVID [Internet]. Copenhagen (Denmark): European Observatory on Health Systems and Policies; 2021. PMID: 33877759.
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