Digging deeper on the neurophysiological assessment in COVID-19 patients.

We read with interest the paper entitled “Electrodiagnostic findings in COVID-19 patients: a single centre experience”, by Hameed and Colleagues, recently published in this Journal, presenting a case series of neurological complications in COVID-19 patients (Hameed et al., 2021). Even in the era of a global vaccination campaign, this topic still remains a challenge for clinicians. As the pandemics emerged at a global scale, many neurological manifestations have been increasingly reported worldwide, involving both the Peripheral (PNS) and the Central Nervous System (CNS) (Priori et al., 2020). A recent work also classified the causal relationship between SARS-CoV-2 infection and neurological complications as possible, probable or definite, basing on clinical, laboratory and neuroradiological findings (Ellul et al., 2020). Moreover, a growing body of evidence has strengthened the hypothesis of a neurogenic component underlying the respiratory failure in severe COVID-19 patients (Bocci et al., 2021, Matschke et al., 2020).

Although the paper by Hameed describes a large cohort of COVID-19 patients, along with a point-to-point correlation between neurophysiological and clinical/laboratory findings, we would like to raise some concerns about the clinical and neurophysiological data as described in this work. In particular, a higher percentage of myopathies (CIM) were described compared to Critical Illness Neuropathy (CIP), while the existing literature reports opposite findings (Bax et al., 2021, Bocci et al., 2021, Frithiof et al., 2021). Also creatin-phospho-kinase levels seem to suggest a neuropathic rather than a myopathic disorder and the time interval between the hospitalization and the electrodiagnostic (EDX) assessment appears too long for establishing a final diagnosis between these conditions. More important, from a neurophysiological perspective, second-level electrophysiological tests were not included; in particular, the Direct Muscle Stimulation technique is now considered the most reliable and accurate approach to differentiate CIP from CIM (Lefaucheur et al., 2006). All papers describing CIP or CIM in COVID-19 have used non-conventional EDX approaches, even in some pioneering studies reporting a slight predominance of myopathic rather than neuropathic changes (Bagnato et al., 2020). The possibility of a predominant neuropathic involvement is further supported by the recent histopathological demonstration of a “viral trafficking” between the brainstem and lungs, along the vagus nerve (Bulfamante et al., 2021).

This point is of key importance because CIP/CIM differently impact on the recovery and rehabilitation strategies, possibly delaying the discharge from Intensive Care Units.

Finally, regarding non-length dependent neuropathies, the authors reported two confirmed cases of axonal Guillain-Barré Syndrome (GBS), including one patient with Acute Motor Axonal Neuropathy and one with Acute Motor Sensory Axonal Neuropathy. To date, demyelinating GBS (Acute Inflammatory Demyelinating Polyneuropathy) is considered more common than axonal variants in COVID-19 patients (Filosto et al., 2021). GBS following SARS-CoV-2 infection usually shares same clinical and electrodiagnostic findings with non-COVID-19 related polyradiculoneuropathies, despite a very short delay from the primary infection, with neurological signs just emerging few days after respiratory symptoms. Also in these cases, a non-conventional EDX approach may be helpful including, for instance, the evaluation of sensory sparing patterns, as described in axonal as well as in demyelinating forms of GBS (Umapathi et al., 2015).

Overall, it is conceivable that clinical and neurophysiological findings reported by Hameed and co-workers may ultimately be explained by different SARS-CoV-2 variants in Pakistan and Middle East compared to European and American countries. Viral variants may differently affect the Central and the Peripheral Nervous System, thus resulting in different neurological phenotypes.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.