TY - JOUR 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 DO - 10.1136/bmjresp-2021-001052 VL - 8 IS - 1 SP - e001052 AU - Zhonghua Shi AU - Sylvia J P Bogaards AU - Stefan Conijn AU - Yeszamin Onderwater AU - Pedro Espinosa AU - Diewertje I Bink AU - Marloes van den Berg AU - Martijn van de Locht AU - Marianna Bugiani AU - Hans van der Hoeven AU - Reinier A Boon AU - Leo Heunks AU - Coen A C Ottenheijm Y1 - 2021/09/01 UR - http://bmjopenrespres.bmj.com/content/8/1/e001052.abstract 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 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. ER -