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Neurological complications after first dose of Pfizer and AstraZeneca vaccines

Increased but low risk of Guillain–Barré syndrome and Bell’s palsy after first dose of the Oxford–AstraZeneca  vaccine, as well as of haemorrhagic stroke after first dose of the Pfizer–BioNTech vaccine, writes MedicalBrief. However, there is substantially higher risk of seven neurological conditions following COVID-19 diagnosis, an analysis of 32m adults in the United Kingdom found.

The authors of the study, published in Nature Medicine, emphasise that the observed neurological complications associated with the Oxford–AstraZeneca (ChAdOx1nCoV-19) and Pfizer–BioNTech (BNT162b2) vaccines are rare, and the risk of neurological disorders as a result of SARS-CoV-2 infection is much greater.

Several vaccines, including the Oxford–AstraZeneca and Pfizer–BioNTech vaccines, are approved for use in multiple countries and have been shown to reduce SARS-CoV-2 infections, transmissions, hospitalisations and deaths. However, there have been reports of rare neurological complications associated with SARS-CoV-2 infection and vaccines.

To investigate the possibility of an association between vaccinations and SARS-CoV-2 infection and the development of neurological disorders, Julia Hippisley-Cox and colleagues from the University of Oxford conducted a self-controlled case study series that examined hospital admissions for neurological complications in the 28 days after a first dose of the Oxford–AstraZeneca or Pfizer–BioNTech vaccine, or a positive test for SARS-CoV-2.

They found an increased risk of Guillain–Barré syndrome in the 28 days following vaccination with the Oxford–AstraZeneca vaccine — an estimated 38 excess cases per 10m people vaccinated. An increased risk of Bell’s palsy was also noted 15–21 days after vaccination; however, this risk was not significant over the whole 28-day study period. There was also an increased risk of haemorrhagic stroke within 28 days of the Pfizer-BioNTech vaccine — namely, an estimated 60 extra cases per 10m people.

Within this same time period after a positive SARS-CoV-2 test, there was a substantially higher risk of all seven neurological outcomes studied, including encephalitis meningitis and myelitis, myasthenic disorders, and Guillain–Barré syndrome — amounting to 123, 163, and 145 excess cases per 10m people, respectively. The authors replicated their findings in an independent national cohort of more than 3m people from Scotland, which provided support for the association between the Oxford–AstraZeneca vaccine and Guillain–Barré syndrome.

The authors anticipate that these results will inform risk–benefit evaluations for vaccine programmes as well as clinical decision making and resource allocation for these rare neurological complications. They conclude that these findings are likely to be of relevance to other countries; however, it would be useful to replicate the findings in similarly large datasets, internationally.

Study details

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

Martina Patone, Lahiru Handunnetthi, Defne Saatci, Jiafeng Pan, Srinivasa Vittal Katikireddi, Saif Razvi, David Hunt, Xue W. Mei, Sharon Dixon, Francesco Zaccardi, Kamlesh Khunti, Peter Watkinson, Carol A. C. Coupland, James Doidge, David A. Harrison, Rommel Ravanan, Aziz Sheikh, Chris Robertson & Julia Hippisley-Cox

Published in Nature Medicine on 25 October 2021


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 haemorrhagic 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 10m  people receiving ChAdOx1nCoV-19 and 145 excess cases per 10m  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.

The coronavirus disease 19 (COVID-19) pandemic has seen the development and deployment of vaccines at an unprecedented speed and scale. Several vaccines including ChAdOx1nCoV-19 and BNT162b2 are approved for use in multiple countries and these have been shown to reduce COVID-19 infections, transmissions, hospitalisations and deaths in randomised controlled trials and real-world effectiveness studies. However, the clinical trials were underpowered to detect rare adverse events that are important for ongoing risk–benefit evaluations of these vaccines and for informing post-vaccination clinical practice. Therefore, the identification of such rare adverse events is now a global scientific priority.

The increased risk of cerebral venous sinus thrombosis following the ChAdOx1nCoV-19 vaccine is an example of a rare adverse neurological event. These findings have prompted the United Kingdom, several European countries and two Canadian provinces to limit the use of the ChAdOx1nCoV-19 vaccine or restrict its use pending further risk–benefit analysis in those at low risk of severe outcomes from infection. Furthermore, two cases of transverse myelitis were identified in the treatment arm during ChAdOx1nCoV-19 clinical trials3. These cases triggered two temporary study pauses, including careful regulatory review by the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA). One case of transverse myelitis was considered to be possibly causally related to the vaccine, and an association of rare neuroinflammatory side-effects with ChAdOx1nCoV-19 could not be ruled out.

Since the start of large-scale vaccine programs across the world, additional case reports have linked other neurological adverse events to COVID-19 vaccination, including Guillain–Barré syndrome. Furthermore, surveillance studies have found a possible link between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and neurological events, including Guillain–Barré syndrome and myelitis. However, case reports and surveillance studies are limited by small numbers, as well as potential selection and recording biases. Therefore, detailed assessments of potential neurological adverse events associated with COVID-19 vaccines and infection are urgently needed.

The English National Immunisation (NIMS) Database of COVID-19 vaccination includes data on vaccine type, date and doses for all people vaccinated in England. We linked NIMS, at the individual patient level, to national data for mortality, hospital admissions and SARS-CoV-2 infection data to examine the associations between the first dose of ChAdOx1nCoV-19 or BNT162b2 vaccines and neurological complications: acute central nervous system (CNS) demyelinating events, encephalitis meningitis and myelitis, Guillain–Barré syndrome, Bell’s palsy, myasthenic disorders, haemorrhagic stroke and subarachnoid hemorrhage. We use the same population to investigate the associations between a positive SARS-CoV-2 test as a secondary exposure and the same neurological conditions. Incidence rate ratios (IRRs), that is, the rates of hospital admission or death from each neurological outcome in the risk period after vaccination or after a positive test relative to the baseline period, were estimated using the self-controlled case series (SCCS) methodology. A relative incidence greater than one indicates an increased risk after vaccination or a SARS-CoV-2-positive test. We also carried out an independent replication of the risk of neurological outcomes in a national cohort from Scotland using the SCCS design.

Overall, 32,552,534 people received their first dose of COVID19 vaccine (ChAdOx1nCoV-19, n = 20,417,752; BNT162b2, n = 12,134,782) in England between 1 December 2020 and 31 May 2021. In the population of vaccinated people, 2,005,280 (~6%) had a SARS-CoV-2-positive test. Of those with a positive test, 1,838,628 (~91%) had their SARS-CoV-2 test prior to vaccination.


Nature Medicine article – Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection (Open access)


See more from MedicalBrief archives:


Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination


Pfizer vaccination linked to 3x high risk of myocarditis — Israel study


COVID-19, not Pfizer vaccine, tied to Bell’s palsy — 2 studies


AstraZeneca shoots itself in the foot, again



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