We read with interest the review article by Galnares-Olalde et al., about the Mexican Guillain-Barré syndrome (GBS) and related to SARS-CoV-2 and anti-SARS-CoV-2 vaccines¹. It was concluded that a clear link between SARS-CoV-2, anti-SARS-CoV-2 vaccines, and GBS has yet to be established¹. The study is appealing but raises the following concerns that need to be discussed.

We do not agree with the statement in the introduction that GBS is generally associated with axonal damage¹. In Europe and North America, GBS is a demyelinating disorder, and the most common subtype is acute, inflammatory, and demyelinating polyneuropathy².

We also do not agree with the statement in the abstract that there is no causal relation between SARS-CoV-2 and GBS¹. There are several arguments for a causal relation between SARS-CoV-2 and GBS. First, most of the >400 reported cases, as per the end of June 2021, of SARS-CoV-2-associated GBS developed time-linked to the infection, usually within 4 weeks after onset of the infection. Second, there is an upregulation of cytokines and chemokines in the cerebrospinal fluid resulting in a pattern of elevated interleukin-6 (IL-6), IL-8, and TNF-alpha³. Third, there are several other immunological disorders triggered by SARS-CoV-2 (e.g., immune encephalitis, multiple sclerosis, neuromyelitis optica, and MIS-C). Fourth, SARS-CoV-2 infection can cause reversible conduction block⁴. Missing in Figure 1 is the pure dysautonomic type of GBS, which has been recently reported in a 79-year-old male who developed autonomic dysfunction 10d after onset of COVID-19⁵.

Dear Editor,

We greatly appreciate the comments and observations on our review article by Dr. Finsterer¹. Concerning the epidemiological differences in electrophysiological variants of Guillain-Barré syndrome (GBS), we are aware that in Caucasians (persons from Europe and North America), acute inflammatory demyelinating neuropathy is the predominant variant, an epidemiological observation mentioned in our article¹. Nonetheless, as we stated in the title of our article, we aimed to discuss mainly GBS epidemiology in Mexico, where acute motor axonal neuropathy is the prevailing electrophysiological variant².

The cited case report regarding cytokine elevation in cerebrospinal fluid is quite interesting³. We acknowledge the information of GBS cases occurring within close temporality to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Moreover, potential connection with plausible mechanistic associations has been made throughout the ongoing coronavirus disease 2019 (COVID-19) pandemic. However, despite these possible links, large-scale studies have failed to demonstrate a causal association between SARS-CoV-2 and GBS. We base this statement on the results of the largest epidemiological study on GBS and COVID-19 conducted to date by Lunn and colleagues in 2021, where they found no relationship between GBS and SARS-CoV-2 infections across the United Kingdom during the pandemic’s first wave⁴. The aforementioned is supported by the fact that as the number of COVID-19 cases increased, the number of GBS cases did not, compared to pre-pandemic reports, a finding that reinforces the need for further population-based studies to establish a potential causal link⁴.

It is important to note that the worldwide incidence of GBS decreased during the pandemic, possibly related to a reduction in the number of non-SARS-CoV-2 respiratory infections promoted by the widespread use of facemasks, suggesting that sporadic cases of GBS may occur even with close temporality to SARS-CoV-2 infection. Furthermore, regarding the inclusion of the pure dysautonomic clinical variant in our figure, we decided not to include it since the recognition of this variant is still in debate, as most of these patients during their disease course usually develop motor or sensory symptoms⁵. Moreover, the case report cited by Dr. Finsterer also states that this variant is still under debate⁶. Finally, it is well-known that case reports represent the lowest level of evidence; hence, we cannot establish a causal relationship without large-scale or population-based epidemiological studies.