TY - JOUR
T1 - COVID-19 is associated with distinct myopathic features in the diaphragm of critically ill patients
AU - Shi, Zhonghua
AU - Bogaards, Sylvia J. P.
AU - Conijn, Stefan
AU - Onderwater, Yeszamin
AU - Espinosa, Pedro
AU - Bink, Diewertje I.
AU - van den Berg, Marloes
AU - van de Locht, Martijn
AU - Bugiani, Marianna
AU - van der Hoeven, Hans
AU - Boon, Reinier A.
AU - Heunks, Leo
AU - Ottenheijm, Coen A. C.
N1 - Funding Information: Funding Research reported in this work was supported by a grant from the Publisher Copyright: © 2021 BMJ Publishing Group. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/9/20
Y1 - 2021/9/20
N2 - Introduction The diaphragm is the main muscle of inspiration, and its dysfunction contributes to adverse clinical outcomes in critically ill patients. We recently reported the infiltration of SARS-CoV-2, and the development of fibrosis, in the diaphragm of critically ill patients with COVID-19. In the current study, we aimed to characterise myofiber structure in the diaphragm of critically ill patients with COVID-19. Methods Diaphragm muscle specimens were collected during autopsy from patients who died of COVID-19 in three academic medical centres in the Netherlands in April and May 2020 (n=27). We studied diaphragm myofiber gene expression and structure and compared the findings obtained to those of deceased critically ill patients without COVID-19 (n=10). Results Myofibers of critically ill patients with COVID-19 showed on average larger cross-sectional area (slow-twitch myofibers: 2441±229 vs 1571±309 μm 2; fast-twitch myofibers: 1966±209 vs 1225±222 μm 2). Four critically ill patients with COVID-19 showed extremely large myofibers, which were splitting and contained many centralised nuclei. RNA-sequencing data revealed differentially expressed genes involved in muscle regeneration. Conclusion Diaphragm of critically ill patients with COVID-19 has distinct myopathic features compared with critically ill patients without COVID-19, which may contribute to the ongoing dyspnoea and fatigue in the patients surviving COVID-19 infection.
AB - Introduction The diaphragm is the main muscle of inspiration, and its dysfunction contributes to adverse clinical outcomes in critically ill patients. We recently reported the infiltration of SARS-CoV-2, and the development of fibrosis, in the diaphragm of critically ill patients with COVID-19. In the current study, we aimed to characterise myofiber structure in the diaphragm of critically ill patients with COVID-19. Methods Diaphragm muscle specimens were collected during autopsy from patients who died of COVID-19 in three academic medical centres in the Netherlands in April and May 2020 (n=27). We studied diaphragm myofiber gene expression and structure and compared the findings obtained to those of deceased critically ill patients without COVID-19 (n=10). Results Myofibers of critically ill patients with COVID-19 showed on average larger cross-sectional area (slow-twitch myofibers: 2441±229 vs 1571±309 μm 2; fast-twitch myofibers: 1966±209 vs 1225±222 μm 2). Four critically ill patients with COVID-19 showed extremely large myofibers, which were splitting and contained many centralised nuclei. RNA-sequencing data revealed differentially expressed genes involved in muscle regeneration. Conclusion Diaphragm of critically ill patients with COVID-19 has distinct myopathic features compared with critically ill patients without COVID-19, which may contribute to the ongoing dyspnoea and fatigue in the patients surviving COVID-19 infection.
KW - COVID-19
KW - respiratory muscles
UR - http://www.scopus.com/inward/record.url?scp=85115741361&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/bmjresp-2021-001052
DO - https://doi.org/10.1136/bmjresp-2021-001052
M3 - Article
C2 - 34544735
SN - 2052-4439
VL - 8
JO - BMJ Open Respiratory Research
JF - BMJ Open Respiratory Research
IS - 1
M1 - e001052
ER -