Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection

Abstract

Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive test (n = 2,005,280). There was an increased risk of Guillain-Barré syndrome (incidence rate ratio (IRR), 2.90; 95% confidence interval (CI): 2.15-3.92 at 15-21 days after vaccination) and Bell's palsy (IRR, 1.29; 95% CI: 1.08-1.56 at 15-21 days) with ChAdOx1nCoV-19. There was an increased risk of hemorrhagic stroke (IRR, 1.38; 95% CI: 1.12-1.71 at 15-21 days) with BNT162b2. An independent Scottish cohort provided further support for the association between ChAdOx1nCoV and Guillain-Barré syndrome (IRR, 2.32; 95% CI: 1.08-5.02 at 1-28 days). There was a substantially higher risk of all neurological outcomes in the 28 days after a positive SARS-CoV-2 test including Guillain-Barré syndrome (IRR, 5.25; 95% CI: 3.00-9.18). Overall, we estimated 38 excess cases of Guillain-Barré syndrome per 10 million people receiving ChAdOx1nCoV-19 and 145 excess cases per 10 million people after a positive SARS-CoV-2 test. In summary, although we find an increased risk of neurological complications in those who received COVID-19 vaccines, the risk of these complications is greater following a positive SARS-CoV-2 test.

Fig. 1. IRRs and 95% CIs for neurological outcomes following ChAdOx1nCoV-19 vaccination, BNT162b2 vaccination and positive SARS-CoV-2 test.

The IRRs are presented for pre-defined risk periods (0, 1–7, 8–14, 15–21 and 22–28 days) after each exposure and for the pre-risk period (28 days prior to exposure) and computed using a population of n = 32,553,534 vaccinated individuals. The horizontal bold line indicates an IRR of 1.

Fig. 2. Schematic presentation of the SCCS study design.

Each patient is followed from the index date to the study end date and is censored if death occurred or if they had a second dose of vaccine. Risk intervals (0, 1–7, 8–14, 15–21 and 22–28 days after exposure), the pre-risk interval (the 28 days prior to exposure) and the baseline periods (from study start to 29 days before exposure, and from 29 days after exposure to study end) are shown.

Extended Data Fig. 1. Incidence rate ratios (IRR 95% CI) for single outcomes in pre-defined risk periods immediately before and after exposure to ChAdOx1nCoV-19 vaccine.

Incidence rate ratios (IRR 95% CI) for single outcomes in pre-defined risk periods immediately before and after exposure to ChAdOx1nCoV-19 vaccine, adjusted for calendar time from 1 December 2020 to 31 May 2021 computed using a population of size n = 32,553,534 vaccinated individuals. Comparisons between different sensitivity analyses (cells with < 5 are suppressed). Horizontal bold line indicates 1.

Extended Data Fig. 2. Incidence rate ratios (IRR 95% CI) for single outcomes in pre-defined risk periods immediately before and after exposure to BNT162b2 mRNA vaccine.

Incidence rate ratios (IRR 95% CI) for single outcomes in pre-defined risk periods immediately before and after exposure to BNT162b2 mRNA vaccine, adjusted for calendar time from 1 December 2020 to 31 May 2021 computed using a population of size n = 32,553,534 vaccinated individuals. Comparisons between different sensitivity analyses (cells with < 5 are suppressed). Horizontal bold line indicates 1.

Extended Data Fig. 3. Data flow chart.

Flowchart of data used in this study showing how data from National Immunisation Management System (NIMS), Second Generation Surveillance System (SGSS), Hospital Episode Statistics (HES) and Office of National Statistic (ONS) were used to obtain information about vaccinations, SARS-CoV-2 test results, and hospital admissions for neurological outcomes and deaths, respectively.

Extended Data Fig. 4. Number of hospital admissions or deaths for each outcome in the baseline and in the exposed set by week.

Number of hospital admissions or deaths for each outcome in the baseline and in the exposed set by week from 1 December 2020 to 31 May 2021 (n = 32,553,534).

Extended Data Fig. 5. Number of hospital admissions or deaths for each outcome prior and post each vaccine.

Number of hospital admissions or deaths for each outcome prior and post each vaccine from 1 December 2020 to 31 May 2021 (n = 32,553,534). Red line: vaccine date; green line: 28 days prior vaccine; black line: 28 days post vaccine.

Extended Data Fig. 6. Time between end of study or censored date and date of hospital admission or deaths for each outcome.

Time between end of study or censored date and date of hospital admission or deaths for each outcome from 1 December 2020 to 31 May 2021 (n = 32,553,534).