Post-marketing active surveillance of Guillain Barré Syndrome following COVID-19 vaccination in persons aged ≥12 years in Italy: A multi-database self-controlled case series study.

BackgroundRecently published studies have reported association of COVID-19 vaccine ChAdOx1-S (Vaxzevria) with Guillain Barré Syndrome (GBS). Less is known about the safety of other COVID-19 vaccines with respect to GBS outcome. This study investigated the association of COVID-19 vaccines with GBS in more than 15 million persons aged ≥12 years in Italy.MethodsStudy population was all individuals aged ≥12 years who received at least one dose of COVID-19 vaccines, admitted to emergency care/hospital for GBS from 27 December 2020-30 September 2021 in Italy. Identification of GBS cases and receipt of at least one dose of mRNA-1273 (Elasomeran), BNT162b2 (Tozinameran), ChAdOx1-S (Vaxzevria) and Ad26.COV2.S (Janssen) through record linkage between regional health care and vaccination registries. Relative Incidence (RI) was estimated Self-controlled case series method adapted to event-dependent exposure using in the 42-day exposure risk period after each dose compared with other observation periods.ResultsIncreased risk of GBS was found after first (RI = 6.83; 95% CI 2.14-21.85) and second dose (RI = 7.41; 2.35-23.38) of mRNA-1273 and first dose of ChAdOx1-S (RI = 6.52; 2.88-14.77). Analysis by age found an increased risk among those aged≥60 years after first (RI = 8.03; 2.08-31.03) and second dose (RI = 7.71; 2.38-24.97) of mRNA-1273. The first dose of ChAdOx1-S was associated with GBS in those aged 40-59 (RI = 4.50; 1.37-14.79) and in those aged ≥ 60 years (RI = 6.84; 2.56-18.28).ConclusionsmRNA-1273 and ChAdOx1-S vaccines were associated with an increased risk of GBS however this risk resulted in a small number of excess cases. Limitations were loss of GBS outpatient cases and imprecision of the estimates in the subgroup analysis due to a low number of events

Characteristics of GBS cases by vaccine brand, n. 287 (27 December 2020–30 September 2021).

Characteristics of GBS cases by vaccine brand, n. 287 (27 December 2020–30 September 2021).</p

Characteristics of vaccinated population aged ≥12 years by age group (27 December 2020–30 September 2021).

Characteristics of vaccinated population aged ≥12 years by age group (27 December 2020–30 September 2021).</p

Excess of cases estimates with 95% CIs for GBS cases corresponding to exposures with RIs estimated in the 42 days risk period with p<0.05.

Excess of cases estimates with 95% CIs for GBS cases corresponding to exposures with RIs estimated in the 42 days risk period with p<0.05.</p

Flow chart of selection of the study population (27 December 2020–30 September 2021).

Flow chart of selection of the study population (27 December 2020–30 September 2021).</p

Sensitivity analyses: Relative Incidences estimated by Self-Controlled Case Series model by vaccine brand and dose: 287 Guillain Barré Syndrome events in the anti-COVID-19 vaccinated population (27 December 2020–30 September 2021).

Sensitivity analyses: Relative Incidences estimated by Self-Controlled Case Series model by vaccine brand and dose: 287 Guillain Barré Syndrome events in the anti-COVID-19 vaccinated population (27 December 2020–30 September 2021).</p

Distribution of first and second dose vaccine administrations by calendar week (27 December 2020–30 September 2021).

Distribution of first and second dose vaccine administrations by calendar week (27 December 2020–30 September 2021).</p

RECORD PE checklist of items.

BackgroundRecently published studies have reported association of COVID-19 vaccine ChAdOx1-S (Vaxzevria) with Guillain Barré Syndrome (GBS). Less is known about the safety of other COVID-19 vaccines with respect to GBS outcome. This study investigated the association of COVID-19 vaccines with GBS in more than 15 million persons aged ≥12 years in Italy.MethodsStudy population was all individuals aged ≥12 years who received at least one dose of COVID-19 vaccines, admitted to emergency care/hospital for GBS from 27 December 2020–30 September 2021 in Italy. Identification of GBS cases and receipt of at least one dose of mRNA-1273 (Elasomeran), BNT162b2 (Tozinameran), ChAdOx1-S (Vaxzevria) and Ad26.COV2.S (Janssen) through record linkage between regional health care and vaccination registries. Relative Incidence (RI) was estimated Self-controlled case series method adapted to event-dependent exposure using in the 42-day exposure risk period after each dose compared with other observation periods.ResultsIncreased risk of GBS was found after first (RI = 6.83; 95% CI 2.14–21.85) and second dose (RI = 7.41; 2.35–23.38) of mRNA-1273 and first dose of ChAdOx1-S (RI = 6.52; 2.88–14.77). Analysis by age found an increased risk among those aged≥60 years after first (RI = 8.03; 2.08–31.03) and second dose (RI = 7.71; 2.38–24.97) of mRNA-1273. The first dose of ChAdOx1-S was associated with GBS in those aged 40–59 (RI = 4.50; 1.37–14.79) and in those aged ≥ 60 years (RI = 6.84; 2.56–18.28).ConclusionsmRNA-1273 and ChAdOx1-S vaccines were associated with an increased risk of GBS however this risk resulted in a small number of excess cases. Limitations were loss of GBS outpatient cases and imprecision of the estimates in the subgroup analysis due to a low number of events.</div

Relative Incidences estimated by Self-Controlled Case Series model by vaccine brand and dose: 287 Guillain Barré Syndrome events in the anti-COVID-19 vaccinated population (27 December 2020–30 September 2021).

Relative Incidences estimated by Self-Controlled Case Series model by vaccine brand and dose: 287 Guillain Barré Syndrome events in the anti-COVID-19 vaccinated population (27 December 2020–30 September 2021).</p

Characteristics of vaccinated population by anti-COVID-19 vaccine brand (27 December 2020–30 September 2021).

Characteristics of vaccinated population by anti-COVID-19 vaccine brand (27 December 2020–30 September 2021).</p