Editors' Note: Skeletal Muscle and Peripheral Nerve Histopathology in COVID-19

Dr. Suh et al. microscopically examined psoas muscle and femoral nerve samples from 35 consecutive autopsies of patients who died after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease-2019 (COVID-19), compared with 10 SARS-CoV-2–negative controls. They found that both muscle and nerve tissue demonstrated inflammatory or immune-mediated damage, attributing these changes to cytokine release, but found no evidence of direct SARS-CoV-2 invasion of these tissues. In response, Dr. Machado et al. noted that the authors did not perform histopathologic examination in symptomatic patients, positing that viral RNA may have been cleared from muscle and nerve tissue before cell death. Although they agree that overactivated immune responses is an indirect mechanism of COVID-19-induced musculoskeletal and nerve manifestations, they also point to the angiotensin-converting enzyme 2 (ACE2) receptor as a potential means for direct invasion of these tissues by the virus. Responding to these comments, the authors caution that direct invasion of skeletal muscles and nerves by SARS-CoV-2 is yet to be proven, pointing to similar results from another large autopsy series. With respect to not sampling symptomatic patients, they note that their patients were too weak or ill to give a reliable history. In addition, they found SARS-CoV-2 in the lungs of all their autopsy cases, suggesting that the clearance of the virus from the tissues was unlikely to be a major confounding factor. This exchange highlights the large disconnect between hypothesized mechanisms of direct invasion by SARS-CoV-2 and the lack of convincing pathologic evidence of such invasion in neurologic disease.

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