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.
- respiratory muscles
Data availability statement
Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information.
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Contributors CACO, LH, ZS and HvdH contributed to conception and design. ZS, SJPB, SC, YO, PE, DIB, MB, MvdL, MvdB and RAB contributed to acquisition and analysis of data. ZS, SJPB, MvdB, MvdL, RAB, CACO and LH contributed to interpretation of data. ZS, CACO, LH and HvdH contributed to drafting the manuscript. All authors reviewed, edited and approved the final manuscript.
Funding Research reported in this work was supported by a grant from the National Institutes of Health-Heart Lung and Blood Institute R01HL121500 (CACO).
Competing interests LH reports grants and personal fees from Liberate medical, personal fees from Getinge, personal fees from Fisher and Paykel, outside the submitted work.
Provenance and peer review Not commissioned; internally peer reviewed.
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