Muscle abnormalities worsen after post-exertional malaise in long COVID

Brent Appelman; Braeden T Charlton; Richie P Goulding; Tom J Kerkhoff; Ellen A Breedveld; Wendy Noort; Carla Offringa; Frank W Bloemers; Michel van Weeghel; Bauke V Schomakers; Pedro Coelho; Jelle J Posthuma; Eleonora Aronica; W Joost Wiersinga; Michèle van Vugt; Rob C I Wüst

doi:10.1038/s41467-023-44432-3

Muscle abnormalities worsen after post-exertional malaise in long COVID

Brent Appelman, Braeden T Charlton, Richie P Goulding, Tom J Kerkhoff, Ellen A Breedveld, Wendy Noort, Carla Offringa, Frank W Bloemers, Michel van Weeghel, Bauke V Schomakers, Pedro Coelho, Jelle J Posthuma, Eleonora Aronica, W Joost Wiersinga, Michèle van Vugt, Rob C I Wüst

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear. With this longitudinal case-control study (NCT05225688), we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.

Original language	English
Article number	17
Pages (from-to)	17
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-44432-3
Publication status	Published - 4 Jan 2024

Bibliographical note

Funding

We particularly thank all participants for their time and dedication in participating in this study. We also would like to thank all staff of the post-COVID outpatient clinic of the Amsterdam UMC, in particular, Drs. Mooij-Kalverda and Huismans, for their support during this study. We also acknowledge the help of Dr. Eric Voorn in the data acquisition of the physical activity measurements, Onno van Driel in the analysis of the fiber type distribution, and Jos de Koning in supporting exercise data collection. This study was funded by own funding, the Patient-Led Research Collaborative for Long COVID (Grant ID: C1, [MvV]), the Talud Foundation for the Amsterdam UMC Corona Research Fund [WWJ], AMC Foundation [MvV], VU Foundation [RCIW], ZonMw Onderzoeksprogramma ME/CVS [RCIW], and the 2022 Ramsay Grant Program [RCIW].

Funders	Funder number
Patient-Led Research Collaborative for Long COVID
RCIW
Talud Foundation
ZonMw Onderzoeksprogramma ME
V Foundation for Cancer Research
Center for Visual Science
ACE Foundation

Keywords

Humans
Post-Acute COVID-19 Syndrome
SARS-CoV-2
Case-Control Studies
COVID-19/complications
Fatigue/etiology
Musculoskeletal Abnormalities
Muscle, Skeletal
Pain
Plaque, Amyloid

Access to Document

10.1038/s41467-023-44432-3

Persistent URL (handle)

Persistent link

Cite this

Appelman, B., Charlton, B. T., Goulding, R. P., Kerkhoff, T. J., Breedveld, E. A., Noort, W., Offringa, C., Bloemers, F. W., van Weeghel, M., Schomakers, B. V., Coelho, P., Posthuma, J. J., Aronica, E., Joost Wiersinga, W., van Vugt, M., & Wüst, R. C. I. (2024). Muscle abnormalities worsen after post-exertional malaise in long COVID. Nature Communications, 15(1), 17. Article 17. https://doi.org/10.1038/s41467-023-44432-3

@article{a0073faa649d4541b751c799908b3418,

title = "Muscle abnormalities worsen after post-exertional malaise in long COVID",

abstract = "A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear. With this longitudinal case-control study (NCT05225688), we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.",

keywords = "Humans, Post-Acute COVID-19 Syndrome, SARS-CoV-2, Case-Control Studies, COVID-19/complications, Fatigue/etiology, Musculoskeletal Abnormalities, Muscle, Skeletal, Pain, Plaque, Amyloid",

author = "Brent Appelman and Charlton, {Braeden T} and Goulding, {Richie P} and Kerkhoff, {Tom J} and Breedveld, {Ellen A} and Wendy Noort and Carla Offringa and Bloemers, {Frank W} and {van Weeghel}, Michel and Schomakers, {Bauke V} and Pedro Coelho and Posthuma, {Jelle J} and Eleonora Aronica and {Joost Wiersinga}, W and {van Vugt}, Mich{\`e}le and W{\"u}st, {Rob C I}",

note = "{\textcopyright} 2024. The Author(s).",

year = "2024",

month = jan,

day = "4",

doi = "10.1038/s41467-023-44432-3",

language = "English",

volume = "15",

pages = "17",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Appelman, B, Charlton, BT , Goulding, RP, Kerkhoff, TJ, Breedveld, EA, Noort, W, Offringa, C, Bloemers, FW, van Weeghel, M, Schomakers, BV, Coelho, P, Posthuma, JJ, Aronica, E, Joost Wiersinga, W, van Vugt, M & Wüst, RCI 2024, 'Muscle abnormalities worsen after post-exertional malaise in long COVID', Nature Communications, vol. 15, no. 1, 17, pp. 17. https://doi.org/10.1038/s41467-023-44432-3

TY - JOUR

T1 - Muscle abnormalities worsen after post-exertional malaise in long COVID

AU - Appelman, Brent

AU - Charlton, Braeden T

AU - Goulding, Richie P

AU - Kerkhoff, Tom J

AU - Breedveld, Ellen A

AU - Noort, Wendy

AU - Offringa, Carla

AU - Bloemers, Frank W

AU - van Weeghel, Michel

AU - Schomakers, Bauke V

AU - Coelho, Pedro

AU - Posthuma, Jelle J

AU - Aronica, Eleonora

AU - Joost Wiersinga, W

AU - van Vugt, Michèle

AU - Wüst, Rob C I

PY - 2024/1/4

Y1 - 2024/1/4

N2 - A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear. With this longitudinal case-control study (NCT05225688), we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.

AB - A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear. With this longitudinal case-control study (NCT05225688), we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.

KW - Humans

KW - Post-Acute COVID-19 Syndrome

KW - SARS-CoV-2

KW - Case-Control Studies

KW - COVID-19/complications

KW - Fatigue/etiology

KW - Musculoskeletal Abnormalities

KW - Muscle, Skeletal

KW - Pain

KW - Plaque, Amyloid

U2 - 10.1038/s41467-023-44432-3

DO - 10.1038/s41467-023-44432-3

M3 - Article

C2 - 38177128

SN - 2041-1723

VL - 15

SP - 17

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 17

ER -

Muscle abnormalities worsen after post-exertional malaise in long COVID

Abstract

Bibliographical note

Funding

Keywords

Access to Document

Persistent URL (handle)

Fingerprint

Cite this