Severe SARS-CoV-2 infections associated with immune-mediated myopathy

1. Most people who died with COVID-19 showed myositis of various severities.

2. Patients who died with COVID-19 had greater overall pathology and inflammation than those who died without COVID-19.

Evidence Rating Level: 2 (Good)

Study Rundown: Myalgia is commonly reported among those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with estimates ranging from 30% to 60%. Elevated levels of creatine kinase were also found in patients experiencing myalgia while infected with SARS-CoV-2. The association between SARS-CoV-2 and myopathy, however, is largely unexplored outside of case studies.

This case-control autopsy study examined individuals who died with SARS-CoV-2 or other critical illnesses between March 2020 and February 2021. Skeletal muscle samples showed higher overall pathology and inflammation in those with COVID-19, compared to those without COVID-19. These levels were associated with disease duration and severity of COVID-19 symptoms.

Overall, this study found that most people who died with COVID-19 showed myositis of various severities. Further, there was significantly greater overall pathology and skeletal muscle inflammation in those with COVID-19, compared to those without COVID-19. These findings suggest that SARS-CoV-2 may be related to a postinfectious, immune-mediated myopathy.

Click to read the study in JAMA Neurology

Relevant Reading: COVID-19-Associated Myopathy Caused by Type I Interferonopathy

In-Depth [ case-control study]:

SARS-CoV-2, or COVID-19, infections result in an array of system disruption and symptoms. One understudied area is related to myopathy, ranging from myositis to severe rhabdomyolysis. Given that between 30% and 60% of COVID-19-infected patients experience myalgia, it is worth considering whether or not COVID-19 is associated with skeletal muscle and myocardial inflammation among those who passed away with COVID-19.

A total of 54 patients were examined following death, 43 of whom had COVID-19 (median ([IQR] age = 72 [16] years, 28% female) and 11 did not have COVID-19 (median [IQR] age = 71 [5] years, 36% female). Samples of cryopreserved tissue of deltoid and quadriceps muscles, along with cryopreserved or formalin-fixed paraffin-embedded samples of heart and lung tissue were obtained from those who died with COVID-19. Patients who died with COVID-19 showed higher skeletal muscle inflammation (M [SD] = 3.5 [2.1] vs 1.0 [0.6], 95% CI 0.0 to 4.0, p<.001) and higher overall pathology (M [SD] = 3.4 [1.8] vs 1.5 [1.0], 95% CI 0.0 to 3.0, p<.001). Relevant expression of MHC class I antigens on the sarcolemma was found in 55% of COVID-19 patients and 17% of COVID-19 patients showed upregulation of MHC class II antigens, none of which were detected in individuals without COVID-19. The number f natural killer cells was also increased in those with COVID_19 (difference 5 cells per 10 high-power fields, 95% CI 1 to 10 cells per 10 high-power fields, p<.001). Those with a chronic course of COVID-19 had more pronounced inflammation than those with a less serious course of illness.

Image: PD

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