With interest we read the article by Needham et al. about a retrospective observational study of 69 patients with severe COVID-19 requiring mechanical ventilation during 16-73 days [1]. Eleven of these patients developed mononeuritis multiplex, diagnosed upon the clinical presentation and results of nerve conduction studies. We have the following comments and concerns.

The main shortcoming of the study is that the cause of mononeuritis multiplex was not identified in any patient [1]. Though the authors speculate that the distribution of sensory or motor deficits suggested vasculitis, none of the 11 patients had undergone nerve biopsy. To diagnose vasculitic neuropathy, it is a prerequisite that nerve biopsy is carried out.

There is increasing evidence that SARS-CoV-2 can trigger the development of Guillain-Barre syndrome (GBS) [2]. GBS is particularly difficult to diagnose in intubated, mechanically ventilated, and sedated patients. To exclude GBS as the cause of motor or sensory deficits in the 11 patients it is crucial to investigate the cerebrospinal fluid (CSF) and demonstrate the dissociation cyto-albuminique. However, none of the 11 patients had undergone a spinal tap why GBS was not excluded as cause of neuropathy in any patient. Though nerve conduction studies (NCSs) did not reveal demyelinating features, this does not exclude the presence of the GBS subtypes acute motor axonal neuropathy (AMAN) or acute motor and sensory axonal neuropathy (AMSAN).     

Four of the 11 patients with mononeuritis multiplex had diabetes [1]. We should be told how diabetic neuropathy was excluded in these four cases. Particularly, we should know the HbA1c values and if any of the four patients had symptoms or signs prior to the infection with SARS-CoV-2 suggesting diabetic neuropathy. 

A further shortcoming is that the individual history was not carefully taken.  It is crucial to know if any of the 11 patients had been diagnosed with neuropathy already prior to the acquisition of the viral infection. Particularly, we should know how many were alcoholics, how may had renal insufficiency, vitamin deficiency, a history of malignancy, or a history of chemotherapy prior to the viral infection. 

It is also unreported which drugs the eleven patients were receiving prior to the admission to the ICU. From a number of drugs it is known that they may cause neuropathy. Drugs known to trigger the development of neuropathy include platins, disulfiram, phenytoin, vincristine, amiodarone, hydralazine, perhexiline, metronidazole, fluoroquinolones, nitrofurantoin, thalidomide, isoniazid, or dapsone. Drugs given specifically for COVID-19, which can be made responsible for neuropathy include chloroquine [3], lopinavir [4], and tocilizumab [5]. Thus, we should be told how many of the 11 patients were under a therapy with any of these drugs.

We should also know how the authors explain symmetrical weakness, in the absence of critical ill myopathy, and critical ill neuropathy only in a single patient. Which was the cause of symmetrical weakness in the remaining ten patients?

Overall, this study has a number of shortcomings which should be met before drawing final conclusions. It is crucial to know the history and medication prior to the viral infection, the medication during the ICU treatment, to intensify the search for the underlying cause of multiplex neuropathy, and the CSF findings. Though the authors request detailed neurological assessment of patients with post-COVID-19 neuropathy and symmetric weakness, they did not apply this approach to their patients.