key: cord-0918464-dm6bp7pc
authors: García-Grimshaw, Miguel; Michel-Chávez, Anaclara; Vera-Zertuche, Juan Mauricio; Galnares-Olalde, Javier Andrés; Hernández-Vanegas, Laura E.; Figueroa-Cucurachi, Melissa; Paredes-Ceballos, Orlando; Reyes-Terán, Gustavo; Carbajal-Sandoval, Guillermo; Ceballos-Liceaga, Santa Elizabeth; Arauz, Antonio; Valdés-Ferrer, Sergio Iván
title: Guillain-Barré syndrome is infrequent among recipients of the BNT162b2 mRNA COVID-19 vaccine
date: 2021-08-04
journal: Clin Immunol
DOI: 10.1016/j.clim.2021.108818
sha: ac962ea27ecab88fe33d2653108c9e7e1721f211
doc_id: 918464
cord_uid: dm6bp7pc

Vaccines are the most effective strategy to mitigate the global impact of COVID-19. However, vaccine hesitancy is common, particularly among minorities. Guillain-Barré syndrome (GBS) is the most common autoimmune illness of the peripheral nervous system, occurring at an incidence of 1.1/100,000 worldwide. A causal link between mRNA vaccines and GBS has not been previously evaluated. We analyzed a cohort of 3,890,250 Hispanic/Latinx recipients of the BNT162b2 mRNA vaccine (613,780 of whom had already received both doses) for incident GBS occurring within 30 days from vaccine administration. Seven cases of GBS were detected among first-dose recipients, for an observed incidence of 0.18/100,000 administered doses during the prespecified timeframe of 30 days. No cases were reported after second-dose administration. Our data suggest that, among recipients of the BNT162b2 mRNA vaccine, GBS may occur at the expected community-based rate; however, this should be taken with caution as the current incidence of GBS among the unvaccinated population against COVID-19 is still undetermined. We hope that this preliminary data will increase the public perception of safety toward mRNA-based vaccines and reduce vaccine hesitancy.

Vaccines are the most effective strategy to mitigate the global impact of COVID-19. However, vaccine hesitancy is common, particularly among minorities. Guillain-Barré syndrome (GBS) is the most common autoimmune illness of the peripheral nervous system, occurring at an incidence of 1.1/100,000 worldwide. A causal link between mRNA vaccines and GBS has not been previously evaluated. We analyzed a cohort of 3,890,250 Hispanic/Latinx recipients of the BNT162b2 mRNA vaccine (613,780 of whom had already received both doses) for incident GBS occurring within 30 days from vaccine administration. Seven cases of GBS were detected among first-dose recipients, for an observed incidence of 0.18/100,000 administered doses during the prespecified timeframe of 30 days. No cases were reported after second-dose administration. Our data suggest that, among recipients of the BNT162b2 mRNA vaccine, GBS may occur at the expected community-based rate; however, this should be taken with caution as the current incidence of GBS among the unvaccinated population against COVID-19 is still undetermined. We hope that this preliminary data will increase the public perception of safety toward mRNA-based vaccines and reduce vaccine hesitancy.

J o u r n a l P r e -p r o o f

Within months after the first case of SARS-CoV-2 infection was detected, two mRNA vaccines, BNT162b2 (Pfizer-BioNTech) [1] and mRNA-1273 (Moderna) [2] have demonstrated to reduce COVID-19 incidence and severity effectively [3] . Despite the magnitude of the pandemic or the availability of effective vaccines, hesitancy towards vaccines is not uncommon, particularly, but not exclusively among minorities [4] [5] [6] . Hypothetically, vaccines may lead to the loss of selftolerance and autoimmune disease and cause neural tissue damage, although, with current vaccines, the association is neither supported by empirical nor epidemiological [7, 8] .

Guillain-Barré syndrome (GBS) is the most common autoimmune disorder of the peripheral nervous system, resulting in flaccid paralysis and areflexia [9] . GBS may occur spontaneously after bacterial or viral infections, and it has been historically linked to several vaccines, but epidemiological studies have not found a direct association between current vaccines and GBS [10, 11] . Globally, the annual estimated incidence rate of GBS in adults ranges from 0.84-1.91/100,000 persons/year [9, 12] . In Mexico, the reported incidence ranges from 4-71./1,000,000 persons/year [13] ; in a preliminary report, we observed an incidence of 0.43/100,000 administered doses among 704,003 recipients of the first dose of BNT162b2 vaccine [14] . Here, we report an update on the incidence of GBS among recipients of the BNT162b2 mRNA COVID-19 vaccine in Mexico in a larger nationwide cohort of ~3.9 million recipients, including recipients of one or both doses of the vaccine.

We conducted a nationwide, retrospective, observational cohort study evaluating GBS incidence among recipients of the BNT162b2 mRNA COVID-19 vaccine in Mexico. Cases were also classified according to the Brighton Collaboration Diagnostic Criteria for GBS presenting as an AEFI [15] . 

During the study period, a total of 3,890,250 persons had received at least one dose of the BNT162b2 mRNA COVID-19 vaccine, and 613,780 had received both doses in Mexico [16] ; among them, seven cases of GBS following immunization were reported nationwide, all after the first dose of the vaccine, for an observed incidence of 0.18/100,000 administered doses.

Demographic information, pre-existing medical conditions, clinical presentation, treatment, and outcome data are summarized in Table 1 . In four cases, a gastrointestinal or systemic infection preceded the appearance of neurologic symptoms; in two of those, infections were still present at GBS onset. In three cases, viral infections were confirmed; one patient (case two) had selflimited diarrhea of infectious characteristics shortly before GBS onset, but an infectious agent J o u r n a l P r e -p r o o f Journal Pre-proof could not be identified by stool culture or molecular methods during the in-hospital stay. In two cases (cases five and six), an associated trigger could not be determined, and case number seven had previously received an influenza vaccine 40 days before GBS symptoms onset. As of the day of this report, there has been only one death (case six), which was related to ventilatorassociated pneumonia complicated with septic shock, and the remaining six patients had been discharged home.

In this large (~3.9 million) and diverse cohort reflective of a population-wide immunization program, we observed that the BNT162b2 mRNA COVID-19 vaccine did might increase the risk of GBS when compared to the expected community-based incidence in Mexico [13] ; however, this should be taken with caution as the current incidences of GBS among the unvaccinated population against COVID-19 are currently unknown. Also, a reduction of other infections due to public health mitigation strategies may have reduced the observed incidence in the nonimmunized population [17] .

Interestingly, in most cases, concurrent infectious triggers were detected, suggesting that gastrointestinal infections -and not vaccines-may be responsible for most cases. Among several infections that may increase the risk of GBS, Campylobacter jejuni is the most common, particularly in the acute motor axonal neuropathy (AMAN) form. None of the four cases evaluated for Campylobacter jejuni tested positive; however, in three cases, acute enteric viral infections known to induce GBS (hepatitis A in two cases, norovirus in one) were confirmed.

One patient (case seven) had been immunized against influenza 40 days before GBS onset;

while both vaccines may have synergistically triggered an autoimmune response, this observed association seems to be coincidental, as millions of healthy people have received both vaccines in short succession without a subsequent outbreak of GBS. Our study has limitations, including that we relied on a passive surveillance system for this report. While cases of GBS may have occurred and not been reported, due to the paralytic nature of GBS we think that is unlikely. However, milder cases may have not been reported by the patient or may have been misdiagnosed, hence misclassified.

Our data show that GBS is infrequent among recipients of the BNT162b2 vaccine. The presence of a concomitant trigger in most of our cases suggests a lack of mechanistic connection between mRNA vaccines and GBS. This data from a large and diverse cohort indicates that at least considering GBS, mRNA vaccines are safe. Vaccines are our fastest and safest public health strategy to counter the pandemic. We hope that this data will strengthen the public perception of vaccine safety, helping to reduce vaccine hesitancy. 

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