1. Patients with severe COVID-19 demonstrated a unique diaphragm myopathic phenotype compared to non-COVID-19 ICU patients.
2. It is unclear whether or not myopathy is a direct result of COVID-19.
Evidence Rating Level: 2 (Good)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has well-known respiratory implications as well as extrapulmonary manifestations. Adverse effects of severe COVID-19 on respiratory muscles, however, have not been studied to-date. This study across three medical centers in the Netherlands investigated the effects of severe COVID-19 on the diaphragm in critically ill patients. Muscle specimens were collected through autopsy of 26 patients who had been hospitalized in the ICUs with severe COVID-19 (median [IQR] age = 71 [61 to 74] years, 81% male). A total of 24 of these patients had undergone invasive mechanical ventilation for a median of 12 days (IQR 6 to 25 days). Specimens from the left midcostal diaphragm were used for subsequent analyses. These patients also had higher BMIs than those without COVID-19 and were less likely to be treated with steroids. SARS-CoV-2 viral RNA was found in four patients (15.4%), localized inside diaphragm myofibers. Angiotensin-converting enzyme 2 (ACE-2) primarily localizes at the myofiber membrane, which can serve as an entry point for severe infection of the diaphragm. Further RNA sequencing determined the upregulation of 315 genes and downregulation of 281 genes in the diaphragm of COVID-19 patients compared to non-COVID-19 ICU patients. Further, epimysial and permysial fibrosis was greater than two times higher in COVID-19 diaphragms than the controls. Overall, this study demonstrated unique differences in myopathic phenotype among patients with severe COVID-19, though it is unclear whether or not diaphragm myopathy is a direct effect of SARS-CoV-2 or related to other processes. However, diaphragm weakness associated with myopathy could result in fatigue, dyspnea, and ventilator weaning failure.
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