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.

中文翻译：

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COVID-19 与重症患者膈肌的明显肌病特征相关

简介 膈肌是吸气的主要肌肉，其功能障碍会导致危重患者的不良临床结果。我们最近报道了 SARS-CoV-2 在 COVID-19 重症患者的膈肌中的浸润和纤维化的发展。在目前的研究中，我们旨在表征 COVID-19 重症患者膈肌中的肌纤维结构。方法 2020 年 4 月和 5 月，在荷兰三个学术医疗中心（n=27）死于 COVID-19 的患者的尸检过程中收集了膈肌标本。我们研究了膈肌肌纤维基因的表达和结构，并将获得的结果与没有 COVID-19 的已故危重患者（n = 10）的结果进行了比较。结果 COVID-19 重症患者的肌纤维平均横截面积更大（慢肌纤维：2441±229 vs 1571±309 µm2；快肌纤维：1966±209 vs 1225±222 µm2）。四名患有 COVID-19 的危重患者显示出非常大的肌纤维，这些肌纤维正在分裂并包含许多集中的细胞核。RNA 测序数据揭示了参与肌肉再生的差异表达基因。结论 与没有 COVID-19 的危重患者相比，COVID-19 危重患者的膈肌具有明显的肌病特征，这可能导致 COVID-19 感染幸存患者的持续呼吸困难和疲劳。可应合理要求提供数据。与研究相关的所有数据都包含在文章中或作为在线补充信息上传。