by Antonella Macerollo
For September 2021, we have selected:
- Aschman A et al. Association Between SARS-CoV-2 Infection and Immune-Mediated Myopathy in Patients Who Have Died. JAMA Neurol 2021; 78:948-960. doi: 10.1001/jamaneurol.2021.2004.
- Suh J et al. Skeletal Muscle and Peripheral Nerve Histopathology in COVID-19. Neurology. 2021; 97:e849-e858. doi: 10.1212/WNL.0000000000012344.
Our Covid-19 papers of the month are focused on the possible neuromuscular impact of Covid-19.
Aschman et al. investigated the skeletal muscle and myocardial inflammation in patients with COVID-19 who had died. The authors conducted a case-control autopsy series in a university hospital as a multidisciplinary postmortem investigation. Patients with COVID-19 or other critical illnesses who had died between March 2020 and February 2021 and on whom an autopsy was performed were included.
Individuals who were infected with SARS-CoV-2 per polymerase chain reaction test results and had clinical features suggestive of COVID-19 were compared with individuals with negative SARS-CoV-2 polymerase chain reaction test results and an absence of clinical features suggestive of COVID-19. Forty-three patients with COVID-19 and 11 patients with diseases other than COVID-19 were included. Skeletal muscle samples from the patients who died with COVID-19 showed a higher overall pathology score (mean [SD], 3.4 [1.8] vs 1.5 [1.0]; 95%CI, 0-3; P < .001) and a higher inflammation score (mean [SD], 3.5 [2.1] vs 1.0 [0.6]; 95%CI, 0-4; P < .001). Relevant expression of MHC class I antigens on the sarcolemma was present in 23 of 42 specimens from patients with COVID-19 (55%) and upregulation of MHC class II antigens in 7 of 42 specimens from patients with COVID-19 (17%), but neither were found in any of the controls. Increased numbers of natural killer cells (median [interquartile range], 8  vs 3  cells per 10 high-power fields; 95%CI, 1-10 cells per 10 high-power fields; P < .001) were found. Skeletal muscles showed more inflammatory features than cardiac muscles, and inflammation was most pronounced in patients with COVID-19 with chronic courses.
Overall, this Covid-19 paper of the month showed that most individuals with severe COVID-19 showed signs of myositis ranging from mild to severe. Inflammation of skeletal muscles was associated with the duration of illness and was more pronounced than cardiac inflammation.
The authors did not identify a significant viral load in most skeletal and cardiac muscles and the low viral load is very likely attributable to circulating viral RNA rather than genuine infection of myocytes.
These results suggested that SARS-CoV-2 may be associated with a post-infectious, immune-mediated myopathy.
Complementary to the above study, Suh et al explored the spectrum of skeletal muscle and nerve pathology of patients who died following SARS-CoV-2 infection and assessed the direct viral invasion of these tissues.
The authors examined psoas muscle and femoral nerve sampled from 35 consecutive autopsies of patients who died following SARS-CoV-2 infection and 10 SARS-CoV-2-negative controls.
The SARS-CoV-2-positive patients had a mean age at death of 67.8 years and the
duration of symptom onset to death ranged from 1-49 days. Four patients had neuromuscular symptoms. Peak creatine kinase was elevated in 74%. Muscle examination showed type 2 atrophy in 32 patients, necrotizing myopathy in 9, and myositis in 7. Neuritis was seen in 9. Major histocompatibility complex-1 (MHC-1) expression was observed in all cases of necrotizing myopathy and myositis and 8 additional patients. Abnormal expression of myxovirus resistance protein A (MxA) was present on capillaries in muscle in 9 patients and in nerve in 7.
SARS-CoV-2 immunohistochemistry was negative in muscle and nerve in all patients.
In the 10 controls, muscle examination showed type 2 atrophy in all patients, necrotic muscle fibers in 1, MHC-1 expression in non-necrotic/non-regenerating fibers in 3, MxA expression on capillaries in 2. Inflammatory cells were no present and nerves showed no inflammatory cells or MxA expression.
Suh et al. demonstrated inflammatory/immune-mediated damage of muscles and nerves likely related to release of cytokines in patients who died following SARS-CoV-2 infection. However, in line with Ashman et al, they did not find any evidence of direct SARS-CoV-2 invasion of these tissues.
Further studies are necessary to explore how to prevent these pathological changes of muscle and nerve triggered by the SARS-CoV2 infection to improve the prognosis of these patients.