COVID-19 is associated with distinct myopathic features in the diaphragm of critically ill patients

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 t...

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Main Authors: Zhonghua Shi, Leo Heunks, Marianna Bugiani, Sylvia J P Bogaards, Stefan Conijn, Yeszamin Onderwater, Pedro Espinosa, Diewertje I Bink, Marloes van den Berg, Martijn van de Locht, Hans van der Hoeven, Reinier A Boon, Coen A C Ottenheijm
Format: Article
Language:English
Published: BMJ Publishing Group 2021-01-01
Series:BMJ Open Respiratory Research
Online Access:https://bmjopenrespres.bmj.com/content/8/1/e001052.full
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author Zhonghua Shi
Leo Heunks
Marianna Bugiani
Sylvia J P Bogaards
Stefan Conijn
Yeszamin Onderwater
Pedro Espinosa
Diewertje I Bink
Marloes van den Berg
Martijn van de Locht
Hans van der Hoeven
Reinier A Boon
Coen A C Ottenheijm
author_facet Zhonghua Shi
Leo Heunks
Marianna Bugiani
Sylvia J P Bogaards
Stefan Conijn
Yeszamin Onderwater
Pedro Espinosa
Diewertje I Bink
Marloes van den Berg
Martijn van de Locht
Hans van der Hoeven
Reinier A Boon
Coen A C Ottenheijm
author_sort Zhonghua Shi
collection DOAJ
description 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 µm2; fast-twitch myofibers: 1966±209 vs 1225±222 µm2). 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.
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spelling doaj-art-bfc23ce2954c4e40bccc44b9168519402025-08-20T02:22:20ZengBMJ Publishing GroupBMJ Open Respiratory Research2052-44392021-01-018110.1136/bmjresp-2021-001052COVID-19 is associated with distinct myopathic features in the diaphragm of critically ill patientsZhonghua Shi0Leo Heunks1Marianna Bugiani2Sylvia J P Bogaards3Stefan Conijn4Yeszamin Onderwater5Pedro Espinosa6Diewertje I Bink7Marloes van den Berg8Martijn van de Locht9Hans van der Hoeven10Reinier A Boon11Coen A C Ottenheijm12Department of Intensive Care Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, The NetherlandsDepartment of Intensive Care Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, The NetherlandsDepartment of Pathology, Amsterdam UMC Locatie VUmc, Amsterdam, The NetherlandsDepartment of Physiology, Amsterdam UMC Locatie VUmc, Amsterdam, The NetherlandsDepartment of Physiology, Amsterdam UMC Locatie VUmc, Amsterdam, The NetherlandsDepartment of Physiology, Amsterdam UMC Locatie VUmc, Amsterdam, The NetherlandsDepartment of Physiology, Amsterdam UMC Locatie VUmc, Amsterdam, The NetherlandsDepartment of Physiology, Amsterdam UMC Locatie VUmc, Amsterdam, The NetherlandsDepartment of Physiology, Amsterdam UMC Locatie VUmc, Amsterdam, The NetherlandsDepartment of Physiology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands2 Intensive Care, Radboudumc, Nijmegen, The NetherlandsDepartment of Physiology, Amsterdam UMC Locatie VUmc, Amsterdam, The NetherlandsDepartment of Physiology, Amsterdam UMC Locatie VUmc, Amsterdam, The NetherlandsIntroduction 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 µm2; fast-twitch myofibers: 1966±209 vs 1225±222 µm2). 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.https://bmjopenrespres.bmj.com/content/8/1/e001052.full
spellingShingle Zhonghua Shi
Leo Heunks
Marianna Bugiani
Sylvia J P Bogaards
Stefan Conijn
Yeszamin Onderwater
Pedro Espinosa
Diewertje I Bink
Marloes van den Berg
Martijn van de Locht
Hans van der Hoeven
Reinier A Boon
Coen A C Ottenheijm
COVID-19 is associated with distinct myopathic features in the diaphragm of critically ill patients
BMJ Open Respiratory Research
title COVID-19 is associated with distinct myopathic features in the diaphragm of critically ill patients
title_full COVID-19 is associated with distinct myopathic features in the diaphragm of critically ill patients
title_fullStr COVID-19 is associated with distinct myopathic features in the diaphragm of critically ill patients
title_full_unstemmed COVID-19 is associated with distinct myopathic features in the diaphragm of critically ill patients
title_short COVID-19 is associated with distinct myopathic features in the diaphragm of critically ill patients
title_sort covid 19 is associated with distinct myopathic features in the diaphragm of critically ill patients
url https://bmjopenrespres.bmj.com/content/8/1/e001052.full
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