We read with interest the article by Diaz et al. [1] about three patients with SARS-CoV-2 related Guillain-Barre Syndrome (GBS) [1]. Patient-1 was a 53yo male, patient-2 a 68yo female and patient-3 a 78yo female [1]. GBS was treated with Intravenous Immunoglobulins (IVIG) in all three patients [1]. Despite prolonged Intensive Care Unit (ICU) and hospital stay of all three patients their outcome was favourable [1]. The study is appealing but raises concerns that need to be discussed.

The algorithm should be extended. In patients who cannot report symptoms of GBS because of sedation, GBS can be suspected not only upon the clinical exam, unsuccessful weaning in the absence of an obvious cause, electrophysiological studies, Cerebrospinal Fluid (CSF) investigations, but also upon the presence of autonomic disturbances and a beneficial effect of ex juvantibus intravenous immunoglobulins (IVIG). Furthermore, the cytokine and chemokine profiles in the CSF can suggest an immune mediated neurological disease. In GBS patients particularly interleukin-6 (IL-6), IL-8, IL-1a and TNF-alpha are upregulated [2]. 

Missing in the article is the duration of intubation and sedation in all three patients. We should be told when each single patient awaked to reports symptoms. 

It should be explained why it took 22 respectively 18 days to diagnose GBS in patient-2 and patient-3. Which was the rationale to consider GBS in these two patients? 

Patient-2 had normal CSF protein but was staying on the ICU during 41 days [1]. We should be told how critical ill neuropathy was excluded as a differential in this particular patient.

Patient-2 had received hydroxy-chloroquine, azithromycin, atazanavir and ritonavir [1]. We should be told how toxic neuropathy was excluded in patient-2 as the cause of neuropathy.

Missing is the search for SARS-CoV-2 in the CSF in all three patients. Though only rarely reported, the virus may be present in single cases with SARS-CoV-2 associated GBS [3].

Missing is the information if the three patients were vaccinated with an anti-SARS-CoV-2 vaccine after availability of vaccines. In patients with a history of GBS, relapses of GBS after anti-SARS-CoV-2 vaccinations have been reported [4]. Assuming that the three patients were vaccinated, did they tolerate the vaccines without side effects? 

Since GBS may be accompanied by autonomic fiber involvement and since autonomic involvement in GBS greatly affects the outcome of these patients, we should be informed how many of the three patients had autonomic involvement and what autonomic abnormalities were found.

According to table patient-2 had not only Acute Inflammatory Demyelinating Polyneuropathy (AIDP) but also involvement of the cranial nerves, at least the 7^th cranial nerve (facial diplegia) [1]. The frequent affection of cranial nerves in SARs-CoV-2 associated GBS should be discussed [5]. 

The term “differential diagnoses” should be replaced by “triggers of GBS”. Infectious agents listed under this header do not constitute differential diagnoses of GBS but rather causative agents.

Overall, the interesting study has several limitations and inconsistencies that call the results and their interpretation into question. Clarifying these weaknesses would strengthen the conclusions and could improve the status of the study.

Conflict of Interest

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

No funding was received.

Ethical Approval

Was in accordance with ethical guidelines. The study was approved by the institutional review board.

Author Contribution 

Josef Finsterer: Design, literature search, discussion, first draft, critical comments, final approval:

• Consent to Participate: Was obtained from the patient

• Consent for Publication: Was obtained from the patient

• Availability of Data: All data are available from the corresponding author

• Code Availability: Not applicable

1. Diaz, P. et al. "The Challenge of Diagnosing Guillain-Barré Syndrome in Patients with COVID-19 in the Intensive Care Unit." Journal of Neuroimmunology, vol. 366, 15 May 2022, p. 577842. https://doi.org/10.1016/j.jneuroim.2022.577842.

2. Gigli, G.L. et al. "HLA and Immunological Features of SARS-CoV-2-Induced Guillain-Barré Syndrome." Neurological Sciences, vol. 41, no. 12, Dec. 2020, pp. 3391–3394. https://doi.org/10.1007/s10072-020-04787-7.

3. Khan, F. et al. "COVID-19-Associated Guillain-Barré Syndrome: Postinfectious Alone or Neuroinvasive Too?" Journal of Medical Virology, vol. 93, no. 10, Oct. 2021, pp. 6045–6049. https://doi.org/10.1002/jmv.27159.

4. Finsterer, J. "Exacerbating Guillain-Barré Syndrome Eight Days after Vector-Based COVID-19 Vaccination." Case Reports in Infectious Diseases, 8 May 2021, article ID 3619131. https://doi.org/10.1155/2021/3619131.

5. Finsterer, J. et al. "COVID-19 Associated Cranial Nerve Neuropathy: A Systematic Review." Bosnian Journal of Basic Medical Sciences, vol. 22, no. 1, 1 Feb. 2022, pp. 39–45. https://doi.org/10.17305/bjbms.2021.6341.