Long COVID: mechanisms, risk factors and recovery

Rónan Astin; Amitava Banerjee; Mark R. Baker; Melanie Dani; Elizabeth Ford; James H. Hull; Phang Boon Lim; Melitta McNarry; Karl Morten; Oliver O'Sullivan; Etheresia Pretorius; Betty Raman; Demetris S. Soteropoulos; Maxime Taquet; Catherine N. Hall

doi:10.1113/ep090802

journal article Open Access Nov 22, 2022

Long COVID: mechanisms, risk factors and recovery

Rónan Astin Amitava Banerjee

Mark R. Baker Melanie Dani Elizabeth Ford

James H. Hull Phang Boon Lim Melitta McNarry Karl Morten Oliver O'Sullivan Etheresia Pretorius

Betty Raman

Demetris S. Soteropoulos Maxime Taquet Catherine N. Hall

Experimental Physiology Vol. 108 No. 1 pp. 12-27 · Wiley

View at Publisher Save 10.1113/ep090802

Abstract

AbstractLong COVID, the prolonged illness and fatigue suffered by a small proportion of those infected with SARS‐CoV‐2, is placing an increasing burden on individuals and society. A Physiological Society virtual meeting in February 2022 brought clinicians and researchers together to discuss the current understanding of long COVID mechanisms, risk factors and recovery. This review highlights the themes arising from that meeting. It considers the nature of long COVID, exploring its links with other post‐viral illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome, and highlights how long COVID research can help us better support those suffering from all post‐viral syndromes. Long COVID research started particularly swiftly in populations routinely monitoring their physical performance – namely the military and elite athletes. The review highlights how the high degree of diagnosis, intervention and monitoring of success in these active populations can suggest management strategies for the wider population. We then consider how a key component of performance monitoring in active populations, cardiopulmonary exercise training, has revealed long COVID‐related changes in physiology – including alterations in peripheral muscle function, ventilatory inefficiency and autonomic dysfunction. The nature and impact of dysautonomia are further discussed in relation to postural orthostatic tachycardia syndrome, fatigue and treatment strategies that aim to combat sympathetic overactivation by stimulating the vagus nerve. We then interrogate the mechanisms that underlie long COVID symptoms, with a focus on impaired oxygen delivery due to micro‐clotting and disruption of cellular energy metabolism, before considering treatment strategies that indirectly or directly tackle these mechanisms. These include remote inspiratory muscle training and integrated care pathways that combine rehabilitation and drug interventions with research into long COVID healthcare access across different populations. Overall, this review showcases how physiological research reveals the changes that occur in long COVID and how different therapeutic strategies are being developed and tested to combat this condition.

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References

144

[1]

10.1002/mus.27458

[2]

10.1152/ajpcell.00426.2020

[3]

10.1038/s41591-022-01840-0

[4]

10.1182/blood.2020008762

[5]

10.1136/annrheumdis-2020-217872

[6]

10.1007/s11306-015-0816-5

[7]

Assaf G. Davis H. McCorkell L. Wei H. O'Neil B. Akrami A. Low R. Mercier J. &Adetutu A.(2020).What Does COVID‐19 Recovery Actually Look Like? – Patient Led Research Collaborative; Covid‐19 Body Politic Slack Group. Available at:https://patientresearchcovid19.com/research/report‐1/

[8]

Ayoubkhani D. &Pawelek P.(2022).Prevalence of ongoing symptoms following coronavirus (COVID‐19) infection in the UK ‐ Office for National Statistics. Available at:https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/prevalenceofongoingsymptomsfollowingcoronaviruscovid19infectionintheuk/6may2022

[9]

Baker A. M. E. Maffitt N. J. Vecchio A. D. McKeating K. M. Baker M. R. Baker S. N. &Soteropoulos D. S.(2022).Neural dysregulation in post‐covid fatigue.medRxiv;https://doi.org/10.1101/2022.02.18.22271040medRxiv 10.1101/2022.02.18.22271040

[10]

Banerjee A. Heightman M. Murray E. &Lorgelly P.(n.d.).STIMULATE‐ICP: Understanding long COVID to improve diagnosis treatment and care. Available at:https://www.stimulate‐icp.org/about

[11]

10.1152/japplphysiol.00710.2020

[12]

10.1136/bjsports-2020-102596

[13]

10.1111/crj.12905

[14]

10.1007/s12026-021-09185-5

[15]

10.1164/rccm.202108-1903le

[16]

10.1038/s41577-021-00536-9

[17]

10.1038/s41591-022-01766-7

[18]

10.1371/journal.pone.0122982

[19]

10.1007/s00415-021-10735-y

[20]

10.1111/ijcp.14357

[21]

10.1136/bmj.316.7125.133

[22]

Persistent Symptoms in Patients After Acute COVID-19

Angelo Carfì, Roberto Bernabei, Francesco Landi

JAMA 10.1001/jama.2020.12603

[23]

10.1111/j.1365-2796.2011.02428.x

[24]

10.1016/j.eclinm.2021.101159

[25]

10.1089/ars.2014.6181

[26]

10.1016/j.clnu.2015.07.010

[27]

10.3390/healthcare9101290

[28]

10.1016/j.ijcard.2021.07.033

[29]

10.1016/j.chom.2020.11.003

[30]

Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa

Robert Dantzer

Physiological Reviews 10.1152/physrev.00039.2016

[31]

10.1038/s41584-021-00692-1

[32]

10.1136/bmjopen-2020-048391

[33]

10.1016/j.autrev.2022.103071

[34]

Effect of High-Intensity Inspiratory Muscle Training on Lung Volumes, Diaphragm Thickness, and Exercise Capacity in Subjects Who Are Healthy

Stephanie J Enright, Viswanath B Unnithan, Clare Heward et al.

Physical Therapy 10.1093/ptj/86.3.345

[35]

10.1155/2022/2466789

[36]

Falkingham BBC K. (2020).Long Covid: Oonagh Cousins GB rower on the effects ‐ BBC Sport. Available at:https://www.bbc.co.uk/sport/rowing/54702500

[37]

10.1186/s12959-021-00311-9

[38]

10.1016/j.ejim.2021.06.009

[39]

10.1038/s41598-021-97120-x

[40]

Fluge Ø. "Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome" JCI Insight (2017)

[41]

10.1016/j.cell.2021.03.012

[42]

10.1111/jth.15490

[43]

10.1016/s1081-1206(10)62595-1

[44]

10.1016/j.bjid.2021.101632

[45]

10.1515/labmed-2021-0134

[46]

10.1172/jci.insight.157621

[47]

10.15252/emmm.202013001

[48]

10.3389/fneur.2021.753284

[49]

10.1042/bsr20210611

[50]

10.3390/ijms21145168

Showing 50 of 144 references

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Metrics

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Citations

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References

Details

Published: Nov 22, 2022
Vol/Issue: 108(1)
Pages: 12-27
License: View

Authors

R

Rónan Astin

Department of Respiratory Medicine University College London Hospitals NHS Foundation Trust London UK; Centre for Human Health and Performance Institute for Sport Exercise and Health University College London London UK

A

Amitava Banerjee

Institute of Health Informatics University College London London UK; Department of Cardiology Barts Health NHS Trust London UK

M

Mark R. Baker

Faculty of Medical Sciences Newcastle University Newcastle upon Tyne UK

M

Melanie Dani

Imperial Syncope Unit Imperial College Healthcare NHS Trust London UK

E

Elizabeth Ford

Brighton and Sussex Medical School Falmer UK

J

James H. Hull

Institute of Sport Exercise and Health (ISEH) Division of Surgery and Interventional Science University College London London UK; Royal Brompton Hospital London UK

P

Phang Boon Lim

Imperial Syncope Unit Imperial College Healthcare NHS Trust London UK

M

Melitta McNarry

Applied Sports, Technology, Exercise and Medicine Research Centre Swansea University Swansea UK

K

Karl Morten

Applied Sports, Technology, Exercise and Medicine Research Centre Swansea University Swansea UK; Nuffield Department of Women's and Reproductive Health University of Oxford Oxford UK

O

Oliver O'Sullivan

Academic Department of Military Rehabilitation Defence Medical Rehabilitation Centre Stanford Hall Loughborough UK; School of Medicine University of Nottingham Nottingham UK

E

Etheresia Pretorius

Department of Physiological Sciences Faculty of Science Stellenbosch University Stellenbosch South Africa; Department of Biochemistry and Systems Biology Institute of Systems Molecular and Integrative Biology Faculty of Health and Life Sciences University of Liverpool Liverpool UK

B

Betty Raman

Radcliffe Department of Medicine Division of Cardiovascular Medicine University of Oxford Oxford UK; Radcliffe Department of Medicine Division of Cardiovascular Medicine Oxford University Hospitals NHS Foundation Trust Oxford UK

D

Demetris S. Soteropoulos

Faculty of Medical Sciences Newcastle University Newcastle upon Tyne UK

M

Maxime Taquet

Department of Psychiatry University of Oxford Oxford UK; Oxford Health NHS Foundation Trust Oxford UK

C

Catherine N. Hall

School of Psychology and Sussex Neuroscience University of Sussex Falmer UK

Funding

Medical Research Council Award: MR/S026495/1

UK Research and Innovation Award: KTP 11678

AstraZeneca

National Institute for Health Research Award: NIHR200937

ME Association

Cite This Article

Rónan Astin, Amitava Banerjee, Mark R. Baker, et al. (2022). Long COVID: mechanisms, risk factors and recovery. Experimental Physiology, 108(1), 12-27. https://doi.org/10.1113/ep090802

Long COVID: mechanisms, risk factors and recovery

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