Mechanisms underlying exercise intolerance in long COVID: An accumulation of multisystem dysfunction

Alexandra Jamieson; Lamia Al Saikhan; Lamis Alghamdi; Lee Hamill Howes; Helen Purcell; Toby Hillman; Melissa Heightman; Thomas Treibel; Michele Orini; Robert Bell; Marie Scully; Mark Hamer; Nishi Chaturvedi; Hugh Montgomery; Alun D. Hughes; Ronan Astin; Siana Jones

doi:10.14814/phy2.15940

Mechanisms underlying exercise intolerance in long COVID: An accumulation of multisystem dysfunction

Alexandra Jamieson^*, Lamia Al Saikhan, Lamis Alghamdi, Lee Hamill Howes, Helen Purcell, Toby Hillman, Melissa Heightman, Thomas Treibel, Michele Orini, Robert Bell, Marie Scully, Mark Hamer, Nishi Chaturvedi, Hugh Montgomery, Alun D. Hughes, Ronan Astin, Siana Jones^*

^*Corresponding author for this work

Biomedical Engineering Department

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

Abstract

The pathogenesis of exercise intolerance and persistent fatigue which can follow an infection with the SARS-CoV-2 virus (“long COVID”) is not fully understood. Cases were recruited from a long COVID clinic (N = 32; 44 ± 12 years; 10 (31%) men), and age-/sex-matched healthy controls (HC) (N = 19; 40 ± 13 years; 6 (32%) men) from University College London staff and students. We assessed exercise performance, lung and cardiac function, vascular health, skeletal muscle oxidative capacity, and autonomic nervous system (ANS) function. Key outcome measures for each physiological system were compared between groups using potential outcome means (95% confidence intervals) adjusted for potential confounders. Long COVID participant outcomes were compared to normative values. When compared to HC, cases exhibited reduced oxygen uptake efficiency slope (1847 (1679, 2016) vs. 2176 (1978, 2373) mL/min, p = 0.002) and anaerobic threshold (13.2 (12.2, 14.3) vs. 15.6 (14.4, 17.2) mL/kg/min, p < 0.001), and lower oxidative capacity, measured using near infrared spectroscopy (τ: 38.7 (31.9, 45.6) vs. 24.6 (19.1, 30.1) s, p = 0.001). In cases, ANS measures fell below normal limits in 39%. Long COVID is associated with reduced measures of exercise performance and skeletal muscle oxidative capacity in the absence of evidence of microvascular dysfunction, suggesting mitochondrial pathology. There was evidence of attendant ANS dysregulation in a significant proportion. These multisystem factors might contribute to impaired exercise tolerance in long COVID sufferers.

Original language	English
Article number	e15940
Journal	Physiological Reports
Volume	12
Issue number	3
DOIs	https://doi.org/10.14814/phy2.15940
Publication status	Published - Feb 2024

Keywords

cardiopulmonary fitness
exercise intolerance
long COVID
skeletal muscle

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.14814/phy2.15940

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Jamieson, A., Al Saikhan, L., Alghamdi, L., Hamill Howes, L., Purcell, H., Hillman, T., Heightman, M., Treibel, T., Orini, M., Bell, R., Scully, M., Hamer, M., Chaturvedi, N., Montgomery, H., Hughes, A. D., Astin, R., & Jones, S. (2024). Mechanisms underlying exercise intolerance in long COVID: An accumulation of multisystem dysfunction. Physiological Reports, 12(3), Article e15940. https://doi.org/10.14814/phy2.15940

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title = "Mechanisms underlying exercise intolerance in long COVID: An accumulation of multisystem dysfunction",

abstract = "The pathogenesis of exercise intolerance and persistent fatigue which can follow an infection with the SARS-CoV-2 virus (“long COVID”) is not fully understood. Cases were recruited from a long COVID clinic (N = 32; 44 ± 12 years; 10 (31%) men), and age-/sex-matched healthy controls (HC) (N = 19; 40 ± 13 years; 6 (32%) men) from University College London staff and students. We assessed exercise performance, lung and cardiac function, vascular health, skeletal muscle oxidative capacity, and autonomic nervous system (ANS) function. Key outcome measures for each physiological system were compared between groups using potential outcome means (95% confidence intervals) adjusted for potential confounders. Long COVID participant outcomes were compared to normative values. When compared to HC, cases exhibited reduced oxygen uptake efficiency slope (1847 (1679, 2016) vs. 2176 (1978, 2373) mL/min, p = 0.002) and anaerobic threshold (13.2 (12.2, 14.3) vs. 15.6 (14.4, 17.2) mL/kg/min, p < 0.001), and lower oxidative capacity, measured using near infrared spectroscopy (τ: 38.7 (31.9, 45.6) vs. 24.6 (19.1, 30.1) s, p = 0.001). In cases, ANS measures fell below normal limits in 39%. Long COVID is associated with reduced measures of exercise performance and skeletal muscle oxidative capacity in the absence of evidence of microvascular dysfunction, suggesting mitochondrial pathology. There was evidence of attendant ANS dysregulation in a significant proportion. These multisystem factors might contribute to impaired exercise tolerance in long COVID sufferers.",

keywords = "cardiopulmonary fitness, exercise intolerance, long COVID, skeletal muscle",

author = "Alexandra Jamieson and Lamia Al Saikhan and Lamis Alghamdi and Lee Hamill Howes and Helen Purcell and Toby Hillman and Melissa Heightman and Thomas Treibel and Michele Orini and Robert Bell and Marie Scully and Mark Hamer and Nishi Chaturvedi and Hugh Montgomery and Hughes, {Alun D.} and Ronan Astin and Siana Jones",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.",

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Jamieson, A, Al Saikhan, L, Alghamdi, L, Hamill Howes, L, Purcell, H, Hillman, T, Heightman, M, Treibel, T, Orini, M, Bell, R, Scully, M, Hamer, M, Chaturvedi, N, Montgomery, H, Hughes, AD, Astin, R & Jones, S 2024, 'Mechanisms underlying exercise intolerance in long COVID: An accumulation of multisystem dysfunction', Physiological Reports, vol. 12, no. 3, e15940. https://doi.org/10.14814/phy2.15940

TY - JOUR

T1 - Mechanisms underlying exercise intolerance in long COVID

T2 - An accumulation of multisystem dysfunction

AU - Jamieson, Alexandra

AU - Al Saikhan, Lamia

AU - Alghamdi, Lamis

AU - Hamill Howes, Lee

AU - Purcell, Helen

AU - Hillman, Toby

AU - Heightman, Melissa

AU - Treibel, Thomas

AU - Orini, Michele

AU - Bell, Robert

AU - Scully, Marie

AU - Hamer, Mark

AU - Chaturvedi, Nishi

AU - Montgomery, Hugh

AU - Hughes, Alun D.

AU - Astin, Ronan

AU - Jones, Siana

PY - 2024/2

Y1 - 2024/2

N2 - The pathogenesis of exercise intolerance and persistent fatigue which can follow an infection with the SARS-CoV-2 virus (“long COVID”) is not fully understood. Cases were recruited from a long COVID clinic (N = 32; 44 ± 12 years; 10 (31%) men), and age-/sex-matched healthy controls (HC) (N = 19; 40 ± 13 years; 6 (32%) men) from University College London staff and students. We assessed exercise performance, lung and cardiac function, vascular health, skeletal muscle oxidative capacity, and autonomic nervous system (ANS) function. Key outcome measures for each physiological system were compared between groups using potential outcome means (95% confidence intervals) adjusted for potential confounders. Long COVID participant outcomes were compared to normative values. When compared to HC, cases exhibited reduced oxygen uptake efficiency slope (1847 (1679, 2016) vs. 2176 (1978, 2373) mL/min, p = 0.002) and anaerobic threshold (13.2 (12.2, 14.3) vs. 15.6 (14.4, 17.2) mL/kg/min, p < 0.001), and lower oxidative capacity, measured using near infrared spectroscopy (τ: 38.7 (31.9, 45.6) vs. 24.6 (19.1, 30.1) s, p = 0.001). In cases, ANS measures fell below normal limits in 39%. Long COVID is associated with reduced measures of exercise performance and skeletal muscle oxidative capacity in the absence of evidence of microvascular dysfunction, suggesting mitochondrial pathology. There was evidence of attendant ANS dysregulation in a significant proportion. These multisystem factors might contribute to impaired exercise tolerance in long COVID sufferers.

AB - The pathogenesis of exercise intolerance and persistent fatigue which can follow an infection with the SARS-CoV-2 virus (“long COVID”) is not fully understood. Cases were recruited from a long COVID clinic (N = 32; 44 ± 12 years; 10 (31%) men), and age-/sex-matched healthy controls (HC) (N = 19; 40 ± 13 years; 6 (32%) men) from University College London staff and students. We assessed exercise performance, lung and cardiac function, vascular health, skeletal muscle oxidative capacity, and autonomic nervous system (ANS) function. Key outcome measures for each physiological system were compared between groups using potential outcome means (95% confidence intervals) adjusted for potential confounders. Long COVID participant outcomes were compared to normative values. When compared to HC, cases exhibited reduced oxygen uptake efficiency slope (1847 (1679, 2016) vs. 2176 (1978, 2373) mL/min, p = 0.002) and anaerobic threshold (13.2 (12.2, 14.3) vs. 15.6 (14.4, 17.2) mL/kg/min, p < 0.001), and lower oxidative capacity, measured using near infrared spectroscopy (τ: 38.7 (31.9, 45.6) vs. 24.6 (19.1, 30.1) s, p = 0.001). In cases, ANS measures fell below normal limits in 39%. Long COVID is associated with reduced measures of exercise performance and skeletal muscle oxidative capacity in the absence of evidence of microvascular dysfunction, suggesting mitochondrial pathology. There was evidence of attendant ANS dysregulation in a significant proportion. These multisystem factors might contribute to impaired exercise tolerance in long COVID sufferers.

KW - cardiopulmonary fitness

KW - exercise intolerance

KW - long COVID

KW - skeletal muscle

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DO - 10.14814/phy2.15940

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AN - SCOPUS:85185115785

SN - 2051-817X

VL - 12

JO - Physiological Reports

JF - Physiological Reports

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ER -

Mechanisms underlying exercise intolerance in long COVID: An accumulation of multisystem dysfunction

Abstract

Keywords

UN SDGs

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