On Oct. 25, 2021, researchers from across the UK, led by the University of Oxford, have reported on the risks of developing neurological complications following a positive COVID-19 PCR test, or a first dose of either the Oxford-AstraZeneca or Pfizer-BioNTech COVID-19 vaccinations. Two cases of such complications led to pauses in Oxford-AstraZeneca trials for investigation, and in some countries to limit use of the Oxford-AstraZeneca vaccine to people considered at low risk of severe outcomes from COVID-19 infection (i.e., to young people).

Writing in Nature Medicine, the researchers detail the findings from an analysis of anonymised healthcare records of over 32 million people across England. They assessed the risk of developing neurological complications within 28 days of a first dose of either the ChAdOx1 nCov-19 or BNT162b2 mRNA vaccines, or within 28 days of a positive COVID-19 PCR test. They found that both vaccines result in an increase of certain types of neurological ‘adverse’ events for a short time after administration, but that infection with COVID-19 led to a greater risk than receiving either vaccine.

The researchers also carried out an additional analysis limited to people who had a positive COVID-19 test before vaccination. This did not change their results, showing a greater risk of all neurological complications following SARS-CoV-2 infection before vaccination. However, the number of people infected after vaccination was too small for a separate analysis.

Initial vaccine clinical trials were not large enough to be able to detect very rare adverse neurological events – those that happen in less than 1 person out of 10,000. This study was able to achieve this by looking at the real-world data from over 32 million healthcare records in England.

The study used what is known as a ‘self-controlled case series (SCCS)’ design. An SCSS compares how often ‘adverse events’ – in this case neurological complications – happen in different set windows of time within the same person; before, in a short period after, and in a later period after an exposure. In this case, the ‘exposure’ was either of the two common COVID vaccines in the UK or a positive test for COVID-19.

In an SCCS a separate control group is not needed as each patient is used as their own control, since the trail compares the rates of adverse events before the exposure (i.e., the control time) to after exposure. Combining and analysing the data for millions of individuals then allows the rates of adverse events before and after a vaccine or positive COVID-19 test to be determined and compared.

‘This study demonstrates the very considerable power of UK data to investigate very rare safety concerns at pace and at scale. As far as we’re aware, no other country has this capability to do this and independently replicate findings.’