key: cord-0786820-cifb4q9w
authors: Hameed, Sajid; Khan, Sara
title: Reply to “Digging deeper on the neurophysiological assessment in COVID-19 patients”
date: 2021-12-07
journal: Clin Neurophysiol
DOI: 10.1016/j.clinph.2021.11.003
sha: 4057d035f8b5d1c8df2a4de92ff133be70dee3df
doc_id: 786820
cord_uid: cifb4q9w

nan

We appreciate the comments provided to us in the Letter "Digging deeper on the neurophysiological assessment in COVID-19 patients" by Bocci et al. (2022) , and we thank the editors for the opportunity to respond to the observations offered and to expand the discussion of our work (Hameed et al., 2021) . Isolated reports of myopathy and acute neuropathy (i.e., Guillain-Barre syndrome) were initially reported (Tankisi et al., 2020; Ghosh et al., 2020; Sedaghat and Karimi, 2020) . With time, larger case series were published (Cabañes-Martínez et al., 2020; Bax et al., 2021; Bocci et al., 2021; Frithiof et al., 2021) .

We reported myopathic EMG changes in 39% of our cases, neuropathic changes in 6%, and mixed myopathic-neuropathic changes in 28%. A higher percentage of myopathy in COVID-19 patients has been reported by Cabañes-Martínez et al. (2020) , while other studies have reported a higher incidence of neuropathy (Bax et al., 2021; Bocci et al., 2021; Frithiof et al., 2021) . We believe some of the reasons for this discrepancy are small sample sizes, patient selection, duration of hospitalization, different therapeutic regimens, and different electrodiagnostic techniques used.

We included all COVID-19 inpatients that underwent electromyographic and nerve conduction studies (EMG/NCS) in our hospital irrespective of their disease severity, intensive care unit (ICU) admission, or need of mechanical ventilation, while some of the published studies only included COVID-19 ICU patients (Cabañes-Martínez et al., 2020; Bax et al., 2021; Bocci et al., 2021; Frithiof et al., 2021) . We also included only those patients that were referred by the primary physician or consulting neurologists. Therefore, we may have missed some of the cases who were either having mild neuromuscular manifestations or were critically ill with multiple issues. Further, different SARS-COV-2 variants in different parts of the world may also lead to different neuromuscular manifestations.

Rightly stated, some of our patients with myopathy had normal creatine phosphokinase (CPK) levels, especially those who did not require mechanical ventilation or ICU admission. Due to 3 certain limitations, such as the lack of muscle biopsy ordered by the primary physician and unavailability of second-level electrophysiological tests, including the direct muscle stimulation (DMS) technique, we were unable differentiate whether our patients developed myopathy secondary to the direct viral attack or had critical illness myopathy (CIM). The myopathic EMG changes in these patients may be due to other reasons, such as steroid use, which may present with normal CPK levels. Further, two patients in our study had long time intervals of 120 and 180 days, respectively, between COVID-19 infection and EMG/NCS testing. Both patients had multiple hospital admissions for worsening respiratory function post-COVID-19. At that time, we were no longer able to establish a causal relationship of their neuromuscular manifestations with COVID-19. It is, in fact, always difficult to establish a causal relationship in observational studies with small sample sizes with multiple risk factors. On the other hand, we cannot simply refute a causal relationship only on the basis of the delay since COVID-19 onset, as the long-term effects of COVID-19 on the nervous system are still largely elusive. If the respiratory systems may worsen as a long-term post-COVID-19 sequelae (Ojo et al., 2020) , the same may occur with the nervous/neuromuscular system. Many COVID-19 patients presenting with non-specific symptoms of chronic myalgias and fatigue were reported to have myopathic changes on EMG (Agergaard et al., 2021) , suggesting a post-infectious pathophysiology.

At present, we can safely presume that the number of unanswered questions is greater than the answered ones for COVID-19-related neuromuscular manifestations. With time and large-scale studies, we may be able to unravel some of the present mysteries. Our paper is an effort to add another piece to the puzzle of COVID-19-related neuromuscular manifestations.

Myopathic changes in patients with long-term fatigue after COVID-19

Clinical and neurophysiological characterization of muscular weakness in severe COVID-19

Critical illness neuropathy in severe COVID-19: a case series

Digging deeper on the neurophysiological assessment in COVID-19 patients

Neuromuscular involvement in COVID-19 critically ill patients

Critical illness polyneuropathy, myopathy and neuronal biomarkers in COVID-19 patients: A prospective study

Autonomic dysfunction heralding acute motor axonal neuropathy in COVID-19

Electrodiagnostic findings in COVID-19 patients: A single center experience

Pulmonary fibrosis in COVID-19 survivors: predictive factors and risk reduction strategies

Guillain Barre syndrome associated with COVID-19 infection: a case report

Critical illness myopathy as a consequence of Covid-19 infection

None of the authors have potential conflicts of interest to be disclosed.