Guillain-Barré syndrome following SARS-CoV-2 vaccination in the UK: a prospective surveillance study

Abstract

Objective: To investigate features of Guillain-Barré syndrome (GBS) following SARS-CoV-2 vaccines and evaluate for a causal link between the two.

Methods: We captured cases of GBS after SARS-CoV-2 vaccination through a national, open-access, online surveillance system. For each case, the certainty of GBS was graded using the Brighton criteria, and the relationship to the vaccine was examined using modified WHO Causality Assessment criteria. We compared age distribution of cases with that of prepandemic GBS cases and clinical features with the International GBS Outcome Study (IGOS).

Results: Between 1 January and 30 June 2021, we received 67 reports of GBS following the ChAdOx1 vaccine (65 first doses) and three reports following the BNT162b2 vaccine (all first doses). The causal association with the vaccine was classified as probable for 56 (80%, all ChAdOx1), possible for 12 (17%, 10 ChAdOx1) and unlikely for two (3%, 1 ChAdOx1). A greater proportion of cases occurred in the 50-59 age group in comparison with prepandemic GBS. Most common clinical variants were sensorimotor GBS (n=55; 79%) and facial diplegia with paraesthesias (n=10; 14%). 10% (n=7/69) of patients reported an antecedent infection, compared with 77% (n=502/652) of the IGOS cohort (p<0.00001). Facial weakness (63% (n=44/70) vs 36% (n=220/620); p<0.00001) and sensory dysfunction (93% (n=63/68) vs 69% (n=408/588); p=0.00005) were more common but disease severity and outcomes were similar to the IGOS study.

Interpretation: Most reports of GBS followed the first dose of ChAdOx1 vaccine. While our study cannot confirm or refute causation, this observation, together with the absence of alternative aetiologies, different than expected age distribution and the presence of unusual clinical features support a causal link. Clinicians and surveillance bodies should remain vigilant to the possibility of this very rare adverse event and its atypical variants.

Keywords: COVID-19; clinical neurology; guillain-barre syndrome.

Figure 1

Study flow chart showing clinical variants of Guillain-Barré syndrome (GBS) and levels of certainty of a link to the vaccine, as determined by the modified WHO Causality Assessment. *Levels of certainty of a link to the vaccine, as determined by the modified WHO Causality Assessment. †The five excluded cases comprised one with insufficient data, two with alternative diagnosis (neurosarcoidois and CIDP) made subsequently by the treating clinicians and two rapidly fatal cases that had features inconsistent with GBS and were excluded following discussions with the independent assessors. One of these two cases had upgoing plantars, normal CSF protein and no imaging or nerve conduction studies performed prior to death. The second case had normal CSF protein but raised white cell count and widespread demyelination on brain and spinal MRI. ‡Reasons for categorisation as ‘possible’ (n=12) included: antecedent infection without a recognised microbiological trigger for GBS ((n=5): URTI (n=2), IECOPD (n=1), Klebsiella urinary tract infection (n=1), gastroenteritis with no suspicion of Campylobacter and in unlikely temporal association with GBS (n=1)), raised C reactive protein without infective symptoms (n=1), use of small molecule inhibitors anecdotally associated with GBS (n=1), presence of systemic disease that might cause GBS-mimicking neuropathy ((n=3): CLL with acute axonal neuropathy (n=1) and MGUS with AIDP (n=1), suspected endocrinopathy and functional neurological overlay (n=1)), overlay with subacute demyelinating neuropathy (n=1), event occurring between 6 and 12 weeks from vaccination (n=1). ~Reasons for categorisation as ‘unlikely’ included microbiological evidence or clinical suspicion of Campylobacter jejuni infection (n=2). AIDP, acute inflammatory demyelinating polyradiculoneuropathy; CIDP, chronic inflammatory demyelinating polyneuropathy; CLL, chronic lymphocytic leukaemia; CSF, cerebrospinal fluid; IECOPD, infective exacerbation of chronic obstructive pulmonary disease; MGUS, monoclonal gammopathy of undetermined significance; URTI, upper respiratory tract infection.

Figure 2

Time from SARS-CoV-2 vaccination to the onset of Guillain-Barré syndrome. a Median time from vaccination to symptom onset was 15 days (IQR 10–19). fTwo out of seventy subjects developed symptoms after more than 6 weeks (46 and 55 days).

Figure 3

Population (left-hand axis) and background Guillain-Barré syndrome (GBS) incidence rate (right-hand axis) -among adult men (A) and women (B) in England, 2015–2019, per age group.

Figure 4

Age distribution of GBS cases reported after ChAdOx1 vaccination (n=67) compared with background GBS cases in adults in England 2015–2019 (n=8423)*. *Background incident cases of GBS were identified from Hospital Episode Statistics Admitted Patient Care data, as described previously, and the age-specific incidence rates were calculated using Office for National Statistics midyear population estimates from 2020. The proportion of postvaccination GBS cases occurring at ages 50–59 years was higher than among baseline cases (29.9%, 95% CI 18.9 to 40.8 vs baseline 17.4%, 95% CI 16.6 to 18.3), while the proportion of postvaccination cases was lower than baseline for ages 20–29 years (1.5, 0 to 4.4 vs 7.4, 6.8 to 7.9), 70–79 years (11.9, 4.2 to 19.7 vs 20.8, 20.0 to 21.7) ≥80 years (3.0, 0 to 7.1 vs 11.9, 11.2 to 12.6). GBS, Guillain-Barré syndrome.