Guillain-Barré syndrome (GBS) post vaccination

Rare adverse event temporally associated with vaccination

Aug 11, 2022

Guillain-Barré syndrome (GBS) is a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. GBS post vaccination can occur with causality difficult to assess with occurrence frequency close to background frequency.

Hypothesis: Vaccinations can cause GBS onset in some vaccinees (rare frequency).

Literature evidence: GBS has been associated with influenza[1] and COVID-19 vaccinations[2]. GBS has been reported following Moderna[3–7], Pfizer BioNTech BNT162b2[8–16], Oxford AstraZeneca ChAdOx1 day[12,17–31], Johnson & Johnson/Janssen Ad26.CoV2.S[7,32–36], Sinopharm[30,31], and Sputnik V[31,37] COVID-19 vaccines. It has been suggested that many GBS patients are expected as sporadic cases and should not be considered causal[38]. For Pfizer BioNTech BNT162b2 mRNA vaccine, no increased incidence of GBS in a cohort of 3.9 million recipients was detected[39]. A review of GBS incidence in Vaccine Safety Datalink found an increased incidence following Ad.26.COV.2 but not BNT172b2 or mRNA-1273 vaccines[40]. An excess of GBS cases following AstraZeneca-Oxford ChAdOx1-S vaccination has also been identified[41]. An increased risk for GBS after first dose but not second dose of ChAdOx1 nCov-19 vaccination has been reported[42]. Warnings that rare GBS cases may link to Johnson & Johnson/Janssen and AstraZeneca vaccines have been issued[43]. One etiology model for GBS following COVID-19 vaccination is autoimmune autoantibodies[2]; but, no serum anti-ganglioside antibodies were found in 15 of 17 patients tested[44]. Nearly all GBS patients after COVID-19 vaccinations also had facial weakness or paralysis[40].

Vaccine Adverse Event Reporting System (VAERS) evidence: VAERS was data mined for reports of GBS post vaccination. The day of onset for seven vaccines are illustrated in Figure 1. The VAERS data indicate a non-random pattern with the highest number of reports within 24 hours of vaccination for multiple vaccines. Reporting bias is unlikely to account for this non-random pattern.

Figure 1. Guillain-Barré syndrome days to onset in VAERS[45]. Vaccines plotted include COVID-19 (Pfizer-BioNTech, Moderna, and Janssen), Influenza, Shingles Zoster (SHINGRIX), Human papillomavirus HPV (GARDASIL), and Pneumococcal PNEUMO (PREVNAR13).

This onset pattern is too rapid for molecular mimicry, epitope sharing, and autoimmune antibodies to be causative prior to day 7. Similar patterns shared by COVID-19, Influenza, Shingles Zoster, human papillomavirus, and Pneumococcal vaccines support innate immune responses as a major component of disease early etiology. Clinically, most GBS patients following COVID-19 vaccination showed typical demyelination neuropathy with albumin-cytological dissociation[46]; the timing suggests that demyelination neuropathy and albumin-cytological dissociation might be subsequent events in the disease etiology for patients with immediate onset adverse events. The immediate onset pattern of GBS following vaccination is different from the observed pattern for Zoster vaccines[47]; their reported Zoster vaccine onset pattern is consistent with the development of autoimmune antibodies in contrast to the immediate onset Zoster vaccine records in VAERS (Figure 1). Note that autoantibodies are detected for some GBS patients post COVID-19 vaccination[11,48]; onset of GBS for multiple patients is consistent with the development of autoantibodies[6,10–12,16,19–28]. Of these nine patients, four tested positive with with ganglioside antibody panel (2: anti-GM1, antig-GD1a, and anti-sulfatide)[37].

Innate Immune Responses & Peripheral Nervous System:

Consistent with the observed immediate onset of reported pain associated adverse events, innate immune response molecules are known to be associated with pain. These innate immune responses include the release of inflammatory molecules, including histamine, interleukin 1β (IL-1β), interleukin 6 (IL-6), monocyte chemoattractant protein (MCP-1), prostaglandin E2 (PGE2), tumor necrosis factor (TNF; formerly TNFα), etc.; these innate immune cells include macrophages, granulocytes including mast cells, T helper cells, and other immune cells[49–52]. PGE2 is a well-known lipid mediator that contributes to inflammatory, neuropathic, and visceral pain, see[52]. IL-1β, IL-6, and TNF are involved in the process of pathological pain[49]. Histamine is known to be algesic (cause pain) to peripheral nervous system[53].

Proposed GBS post vaccination etiology (ordered events):

• Vaccination: 1+ vaccines

• Innate immune system responds to vaccine

• Innate immune cells responses trigger GBS in some vaccinees with a low frequency

• Immune cells infiltration at blood-never barrier during inflammation (albumin-cytological dissociation)

• Some individuals with GBS develop autoantibodies post immune cells infiltration of peripheral nervous system

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