Review of 'Manifestation of Guillain-Barre Syndrome After Infection with SARS-CoV-2 versus Other Prior Infections : a Meta-Analysis and Severity Assessment'

Review of ‘Manifestation of Guillain-Barre Syndrome After Infection with SARS-CoV-2 versus Other Prior Infections: a Meta-Analysis and Severity Assessment’ by Sarah Betts, Katherine Bockholt and Barbara Calhoun

Thanks for inviting me to review this article though I am not a medical doctor.  I have an interest in studies of COVID-19 and furnishing some of my comments:

It is an interesting article that discusses a very rare disease like Guillain-Barre Syndrome (GBS) that affects 1 in 100,000 people. Hence collecting those samples of studies are very difficult and due to the lesser sampling size, arriving at any conclusion is very hard too. The sample size here is 109 and it is a Meta-analysis. The authors did not find a significant difference between the severity of GBS patients who are associated with or without COVID-19. Knowing the nature of severity of the GBS disease, the evolution of the disease in the COVID-19 era is an interesting area to explore. However, the manuscript can be improved and I indicated a few directions for improvements and recommended a major revision.

Main points:

1.  The last line of the abstract ‘results from this analysis show there is no significant difference between the severity of GBS for patients with GBS associated with COVID-19 and GBS without COVID-19 association.’ It is quite an expected result as it is an autoimmune disease mainly affecting the nervous system, triggered by viral or bacterial infection. Hence once the system is affected and disease sets in, the severity is expected not to follow on what virus or bacteria was the initial trigger. Hence what additional insight you can add to that would be of major interest.   
2.  In line 8 of Abstract you mentioned ‘the rise of COVID-19 caused an increase in patients who developed GBS after infection with SARS-CoV-2’. Since during the COVID-19 era, the numbers of GBS patients are anomalously high or not you need to give the anomaly counts of patients. Whether that count is significant or not over that period, that would be a good outcome. If normal count per year is not available, results of two years before COVID-19 can be compared. Otherwise, if you have any data or reference to support that mention in the text with few lines of discussion.
3. You may calculate the anomaly count (from the normal average year) since COVID-19 started and also since vaccination started. 
4. Further focus could be after the period of the start of vaccination. Whether that anomaly count varies among vaccinated and unvaccinated groups will be a very useful result. If that result varies, then within how many days range after the vaccination, such diseases are more frequent.  As your work is a meta analysis based on published records, there may not be any record of vaccinated vs. unvaccinated. If records are there you may incorporate some analyses; otherwise, you may include some discussions as mentioned, including this reference (CDC). Some adverse effects like GBS were reported for COVID-19 vaccination by CDC, US Government:

Ref: CDC, section: Guillain-Barré Syndrome (GBS) after COVID-19 Vaccination

CDC: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events.html accessed on 06/01/2024

5. Whether within two weeks of vaccination, people are more susceptible to developing COVID-19 or not (even asymptotic) and afterwards affected by GBS is an interesting area to explore. If people with more vaccine doses (boosters) were more likely to develop GBS or not is another area. You may simply focus on the period when the booster dose was started and consider specific countries to test the anomaly count of GBS disease. If based on your available data some analyses are not possible, at least mention a few lines so that it could lead directions to an improved understanding of a severe, rare disease like GBS.

In the first line of the abstract, you mentioned ‘Guillain-Barré Syndrome (GBS) is a rare, autoimmune disease …………’.  I would like to mention two useful references in this regard. Those discussed with scientific basis on how COVID-19 vaccines can affect autoimmune response:

Ref:

a) Seneff S,  Nigh G, Kyriakopoulos AM et al. 2022, Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs, Food and Chemical Toxicology, Volume 164, 113008, ISSN 0278-6915, https://doi.org/10.1016/j.fct.2022.113008

b) Seneff, S., and Nigh, G. (2021). Worse Than the Disease? Reviewing Some Possible Unintended Consequences of the mRNA Vaccines Against COVID-19. International Journal of Vaccine Theory, Practice, and Research, 2(1), 38–79. https://doi.org/10.56098/ijvtpr.v2i1.23