RT Journal Article SR Electronic T1 COVID-19 is associated with distinct myopathic features in the diaphragm of critically ill patients JF BMJ Open Respiratory Research JO BMJ Open Resp Res FD British Thoracic Society SP e001052 DO 10.1136/bmjresp-2021-001052 VO 8 IS 1 A1 Shi, Zhonghua A1 Bogaards, Sylvia J P A1 Conijn, Stefan A1 Onderwater, Yeszamin A1 Espinosa, Pedro A1 Bink, Diewertje I A1 van den Berg, Marloes A1 van de Locht, Martijn A1 Bugiani, Marianna A1 van der Hoeven, Hans A1 Boon, Reinier A A1 Heunks, Leo A1 Ottenheijm, Coen A C YR 2021 UL http://bmjopenrespres.bmj.com/content/8/1/e001052.abstract 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.