PT  - JOURNAL ARTICLE
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
TI  - COVID-19 is associated with distinct myopathic features in the diaphragm of critically ill patients
AID  - 10.1136/bmjresp-2021-001052
DP  - 2021 Sep 01
TA  - BMJ Open Respiratory Research
PG  - e001052
VI  - 8
IP  - 1
4099  - http://bmjopenrespres.bmj.com/content/8/1/e001052.short
4100  - http://bmjopenrespres.bmj.com/content/8/1/e001052.full
SO  - BMJ Open Resp Res2021 Sep 01; 8
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 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.Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information.