We read with interest the article by Khan et al. about five patients with SARS-CoV-2 associated Guillain-Barré syndrome (GBS), of whom one was positive for SARS-CoV-2 in the cerebro-spinal fluid (CSF) upon a polymerase-chain reaction (PCR) test [1]. It was concluded that SARS-CoV-2 associated GBS is immune-mediated in most cases but the remainder of patients experience infectious polyradiculitis [1]. The study is appealing but raises comments.

We do not agree with the statement that “the para-infectious nature of SARS-CoV-2 associated GBS is exemplified by the presence of the virus in the CSF”. GBS is an immunological but not infectious disorder. In this respect we should be informed about the reference limits for cycle threshold (CT) value of the PCR test. According to the reference limits of our laboratory a CT value >30 is not infectious. Assuming that the CT value of 31 in patient-5 was non-infectious either, a direct attack of the radices by the virus is rather unlikely. Documentation of virus RNA the CSF not necessarily means that the dosage of the RNA is high enough to induce an infection.

We should be told if respiratory dysfunction in patient-3 was due to COVID-10, due to GBS, or due to both. Since the patient presented with bulbar involvement in GBS it is quite likely that also respiratory muscles were affected Knowing if respiratory dysfunction was exclusively or additionally due to GBS is crucial as the degree and type of therapy may vary if respiratory muscles are additionally affected or not in GBS. Particularly with patient-3 it should be discussed why only one cycle of immunoglobulins (IVIGs) and methyl-prednisolone were administered without considering a second cycle of immunoglobulins (IVIG) or plasmapheresis. 

Missing with all patients is their previous history. Since the severity of GBS may depend on previous affection of the peripheral nervous system, it is crucial to know how many of the five patients had chronic affection of the peripheral nervous system at onset of GBS. Missing in this respect is also the drug history of the five included patients. Since various drugs are neurotoxic and may influence the severity of GBS, it is crucial to know not only the medication on admission but also the drugs that were applied during hospitalisation. Additionally, it is crucial to know how many required mechanical ventilation and if bedding  or critically ill neuropathy could be an additional pathophysiological factor of neuropathy [2] Concerning patient-4 we should be informed if constrictive pericarditis was due to the SARs-CoV-2 infection or just a feature of her previous history.

Tachypnoea and tachycardia in patient-5 is no reason to exclude autonomic involvement. On the contrary, tachycardia and tachypnoea can be an indication for sympathetic overactivity. We should be told if the patient presented with manifestations of autonomic dysfunction other than tachycardia, such as pupillary dysfunction, sicca syndrome, gastro-intestinal dysmotility, bladder or bowel dysfunction, or impotence. 

A further limitation is that in patient-5 no CSF cytokine profile was provided. Recent data indicate that cytokines such as interleukin (IL)-6, IL-8, IL1b, or TNF-alpha are frequently elevated in the CSF of patients with SARS-CoV-2 associated GBS [3]. 

Overall, the study has some limitations which challenge the results and their interpretation.  Even if virus   RNA    can    be   found   in the CSF, that does not exclude the suspected immunological nature of GBS in the five presented patients.