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DYNamic Assessment of Multi‐Organ level dysfunction in patients recovering from COVID‐19: DYNAMO COVID‐19

Gupta, Ayushman; Nicholas, Rosemary; McGing, Jordan J.; Nixon, Aline V.; Mallinson, Joanne E.; McKeever, Tricia M.; Bradley, Christopher R.; Piasecki, Mathew; Cox, Eleanor F.; Bonnington, James; Lord, Janet M.; Brightling, Christopher E.; Evans, Rachael A.; Hall, Ian P.; Francis, Susan T.; Greenhaff, Paul L.; Bolton, Charlotte E.

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Authors

AYUSHMAN GUPTA AYUSHMAN.GUPTA@NOTTINGHAM.AC.UK
Clinical Assistant Professor Inrespiratory Medicine (Clinical Lecturer)

Jordan J. McGing

Aline V. Nixon

Joanne E. Mallinson

TRICIA MCKEEVER tricia.mckeever@nottingham.ac.uk
Professor of Epidemiology and Medical Statistics

Christopher R. Bradley

ELEANOR COX ELEANOR.COX@NOTTINGHAM.AC.UK
Senior Research Fellow

James Bonnington

Janet M. Lord

Christopher E. Brightling

Rachael A. Evans

IAN HALL IAN.HALL@NOTTINGHAM.AC.UK
Professor of Molecular Medicine

PAUL GREENHAFF PAUL.GREENHAFF@NOTTINGHAM.AC.UK
Professor of Muscle Metabolism



Abstract

We evaluated the impacts of COVID-19 on multi-organ and metabolic function in patients following severe hospitalised infection compared to controls. Patients (n = 21) without previous diabetes, cardiovascular or cerebrovascular disease were recruited 5–7 months post-discharge alongside controls (n = 10) with similar age, sex and body mass. Perceived fatigue was estimated (Fatigue Severity Scale) and the following were conducted: oral glucose tolerance (OGTT) alongside whole-body fuel oxidation, validated magnetic resonance imaging and spectroscopy during resting and supine controlled exercise, dual-energy X-ray absorptiometry, short physical performance battery (SPPB), intra-muscular electromyography, quadriceps strength and fatigability, and daily step-count. There was a greater insulin response (incremental area under the curve, median (inter-quartile range)) during the OGTT in patients [18,289 (12,497–27,448) mIU/min/L] versus controls [8655 (7948–11,040) mIU/min/L], P < 0.001. Blood glucose response and fasting and post-prandial fuel oxidation rates were not different. This greater insulin resistance was not explained by differences in systemic inflammation or whole-body/regional adiposity, but step-count (P = 0.07) and SPPB scores (P = 0.004) were lower in patients. Liver volume was 28% greater in patients than controls, and fat fraction adjusted liver T1, a measure of inflammation, was raised in patients. Patients displayed greater perceived fatigue scores, though leg muscle volume, strength, force-loss, motor unit properties and post-exercise muscle phosphocreatine resynthesis were comparable. Further, cardiac and cerebral architecture and function (at rest and on exercise) were not different. In this cross-sectional study, individuals without known previous morbidity who survived severe COVID-19 exhibited greater insulin resistance, pointing to a need for physical function intervention in recovery.

Citation

Gupta, A., Nicholas, R., McGing, J. J., Nixon, A. V., Mallinson, J. E., McKeever, T. M., Bradley, C. R., Piasecki, M., Cox, E. F., Bonnington, J., Lord, J. M., Brightling, C. E., Evans, R. A., Hall, I. P., Francis, S. T., Greenhaff, P. L., & Bolton, C. E. (2024). DYNamic Assessment of Multi‐Organ level dysfunction in patients recovering from COVID‐19: DYNAMO COVID‐19. Experimental Physiology, 109(8), 1274-1291. https://doi.org/10.1113/ep091590

Journal Article Type Article
Acceptance Date May 22, 2024
Online Publication Date Jun 24, 2024
Publication Date Aug 1, 2024
Deposit Date Sep 10, 2024
Publicly Available Date Sep 13, 2024
Journal Experimental Physiology
Print ISSN 0958-0670
Electronic ISSN 1469-445X
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 109
Issue 8
Pages 1274-1291
DOI https://doi.org/10.1113/ep091590
Public URL https://nottingham-repository.worktribe.com/output/36579953
Publisher URL https://physoc.onlinelibrary.wiley.com/doi/10.1113/EP091590
Additional Information Received: 2023-12-30; Accepted: 2024-05-22; Published: 2024-06-24

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