Variability of symptoms in neuralgic amyotrophy following infection with SARS-CoV-2.

The report of Cacciavillani and colleagues contributes to the discussion of the possibility of peripheral nerve involvement in coronavirus disease 2019 (COVID‐19) and adds to our observation of neuralgic amyotrophy following infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2).1, 2 Their case viewed in conjunction with a growing body of evidence underscores a relevant pathophysiological problem of the disease. The mechanisms whereby SARS‐CoV‐2 targets the human organism might extend beyond the known pathway of binding to the angiotensin‐converting enzyme 2 receptor, which is expressed in the epithelium of the respiratory tract, the endothelium, the gastrointestinal system, and other organs. In fact, a direct neuroinvasive potential has been suggested by several authors. Supporting this hypothesis is a recent investigation that detected SARS‐CoV‐2 RNA in 36.4% (8/22) of brain biopsies obtained from fatal COVID‐19 cases, but the route whereby the virus invades the nervous system is unclear. Interestingly, research prior to the COVID‐19 pandemic showed that earlier coronaviruses, such as hemagglutinating encephalomyelitis virus, may first enter peripheral nerve terminals before traveling to the central nervous system (CNS) via synapse‐connected routes.5, 6 Whether this mechanism also applies to SARS‐CoV‐2 remains to be answered. However, our patient as well the patient reported by Cacciavillani and colleagues presented with symptoms of peripheral nerve involvement without any signs of CNS damage. In fact, peripheral nerve damage might occur in almost 10% of patients hospitalized for SARS‐CoV‐2 infection. Whether peripheral nervous system complications following COVID‐19, such as neuralgic amyotrophy, result from direct neuroinvasion or from an auto‐immune post‐infectious mechanism needs to be elucidated. Understanding the sequence of events leading to neural damage in patients with COVID‐19 might help identify diagnostic and therapeutic targets, highlighting the need for prospective research on patterns of peripheral and central nervous system involvement in patients with COVID‐19.

The report of Cacciavillani includes an important observation that differed from our report. Their patient developed neuralgic amyotrophy possibly related to infection with SARS‐CoV‐2 without any clinical or electrophysiological signs of motor nerve involvement. This observation highlights the possible variability of symptoms in patients with peripheral nervous system involvement of SARS‐CoV‐2 infection and the importance of detailed assessment of patients with COVID‐19 for neurological deficits. Pure sensory involvement in neuralgic amyotrophy not associated with COVID‐19 is rather uncommon. However, the reason for sensory nerve fiber sparing in patients with neuralgic amyotrophy is poorly understood, and the neurotropic pathways of SARS‐CoV‐2 even more so.

Taken together, the first detailed reports of acute involvement of the peripheral nervous system following infection with SARS‐CoV‐2, viewed in conjunction with hypothesized mechanisms of neurotropism and high frequencies of neurological symptoms in observational studies of COVID‐19, substantiate a need for mechanistic and prospective research on the invasion of the nervous system by SARS‐CoV‐2.

CONFLICTS OF INTEREST

None of the authors has any conflict of interest to disclose.

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