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Risk of neurologic complications was higher after SARS-CoV-2 infection than after COVID-19 vaccination, an analysis of 32 million people in England showed.

Observed neurologic events associated with the Oxford-AstraZeneca and Pfizer-BioNTech (Comirnaty) vaccines were rare and risks after COVID infection was much greater, reported Julia Hippisley-Cox, MBChB, MD, of the University of Oxford, and colleagues in .

Within 28 days of a positive SARS-CoV-2 test, there was a substantially higher risk of seven neurologic outcomes studied, including encephalitis, meningitis, or myelitis, myasthenic disorders, and Guillain-Barré syndrome (GBS), totaling 123, 163, and 145 excess cases per 10 million people, respectively.

There was an increased risk of GBS in the 28 days after people received the AstraZeneca vaccine, an estimated 38 excess cases per 10 million people vaccinated. Bell's palsy showed an increased risk 15 to 21 days after AstraZeneca vaccination, but this was not significant over 28 days. Within 28 days of the first dose of the Pfizer vaccine, an increased risk of hemorrhagic stroke of 60 extra cases per 10 million people emerged.

"This study, for the first time, provides strong support for the associations between several neurological complications and COVID-19 vaccines as well as COVID-19 infection," Hippisley-Cox told 麻豆传媒.

"All vaccines have side effects," she added. "It is important to track safety before, during, and after vaccine approval to support risk-benefit evaluations in the population."

Earlier research suggested a relationship between GBS and adenovirus vector COVID-19 vaccines, including the AstraZeneca and the Johnson & Johnson shot. In the U.S., the FDA has warned that, in a small number of people, the Johnson & Johnson vaccine may trigger GBS. Other studies have shown that people with COVID-19 were nearly seven times more likely to have a Bell's palsy diagnosis than those who were vaccinated.

"A nagging question in the era of COVID-19 vaccination has been the risk of neurological complications following vaccination compared to following SARS CoV-2 infection," noted Lyell Jones Jr., MD, of the Mayo Clinic in Rochester, Minnesota, who wasn't involved with the research.

"Studies looking at complications of one or the other may miss important context," Jones told 麻豆传媒. "By simultaneously reviewing outcomes in both groups, the authors offer a first good look at comparing those neurological risks."

Overall, SARS CoV-2 infection was associated with substantial and occasionally very large increased risks for all neurologic complications examined in this analysis, Jones pointed out.

"The upshot of this study is that in terms of risks of neurological complications, the risks associated with vaccination are consistently much lower than with SARS CoV-2 infection," he said. "For example, patients were about 61 times more likely to be hospitalized for myasthenic exacerbations after SARS CoV-2 infection than baseline, with no increased risk following vaccination."

Hippisley-Cox and colleagues investigated hospital admissions from neurologic complications in 28 days after a first dose of the AstraZeneca (20,417,752 people) or Pfizer (12,134,782 people) vaccine, linking the English National Immunisation Management System (NIMS) database to national hospital records. Participants were vaccinated in England from December 2020 through May 2021. The researchers also looked at 28-day outcomes for 2,005,280 people in the same population who had a positive SARS-CoV-2 test.

Incidence rate ratios (IRRs) -- 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 a self-controlled case series method. Outcomes included acute central nervous system demyelinating events; encephalitis, meningitis, and myelitis; GBS; Bell's palsy; myasthenic disorder; hemorrhagic stroke; and subarachnoid hemorrhage.

Overall, there was a substantially higher risk of all neurological outcomes in the 28 days after a positive COVID test (IRR 5.25, 95% CI 3.00-9.18).

At 15-21 days after the first Pfizer shot, there was an increased risk of hemorrhagic stroke (IRR 1.38, 95% CI 1.12-1.71). "For presumed immune-mediated complications, there were no elevated incidence rate ratios for the Pfizer-BioNTech vaccine," Jones observed.

At 15-21 days after AstraZeneca vaccination, there was an increased risk of GBS (IRR 2.90, 95% CI 2.15–3.92) and Bell's palsy (IRR 1.29, 95% CI 1.08–1.56). Data from an independent cohort of more than 3 million people in Scotland supported the link between the AstraZeneca vaccine and GBS (IRR 2.32 at 1-28 days, 95% CI 1.08-5.02).

"While there were higher incidence rate ratios for the Oxford-AstraZeneca vaccine for Guillain-Barré syndrome and Bell's palsy -- up to 2.90 and 1.29 respectively -- the corresponding risks for those conditions was much higher for SARS CoV-2 patients, with incidence rate ratios of about 33, or more than 10 times higher than with the vaccine," Jones noted.

A self-controlled case series design avoids some of the major challenges of conventional case-control studies in terms of patient matching, Jones pointed out. It eliminates time invariant confounding, but there are "some intrinsic generalizability limitations with this design, in that all patients have at least one exposure and a subset have two," he said.

"Coding was used for case ascertainment, which may not always be accurate in uncommon conditions," Jones noted. In addition, neurologic complications were identified when patients were hospitalized, and milder cases may have been missed.

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