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Young Females Had Higher Risk of Cardiac Death After Non-mRNA COVID Vaccine

There was no evidence of a significant change in the number of cardiac-related deaths or death occurring from any cause in the 3 months after a COVID-19 vaccination in young people in England, statisticians found.

Overall, deaths were not significantly higher in the first 12 weeks following vaccination among people aged 12-29 years compared with mortality rates in the general population of this age more than 12 weeks after receiving any vaccine dose, the Office for National Statistics (ONS) reported.

However, an increase in cardiac deaths in young women after a first dose of a non-mRNA vaccine was identified, with the risk being three-and-a-half times higher in the 12 weeks following vaccination, compared with the long-term risk, it said. 

Previous Studies Identified Possible Health Associations

Several studies have reported an increase in the risk of myocarditis and myopericarditis associated with mRNA vaccines, including Pfizer-BioNTech and Moderna, and an increased risk of thrombotic and other rare cardiovascular events after vaccination with the Oxford-AstraZeneca vaccine, especially in young people.

However, any impact on mortality from COVID vaccines remained unclear.

The latest investigation, published in the journal Nature Communications, used electronic health data for England to examine any association between COVID vaccination and mortality. According to the study, there was no strong evidence of an increase in risk of cardiac or all-cause death after vaccination for males aged 12-29 years for either vaccine type. But statistical modelling demonstrated a raised risk of cardiac death in females following a first dose of a non-mRNA vaccine (IRR 3.52, 1.71 to 7.26), and for all doses combined (IRR 3.02, 1.65, to 5.53).

The increased risk corresponded to one additional cardiac death for every 16,486 (95% CI 13,688 to 28,426) females aged 12-29 who received a first dose of a non-mRNA vaccine. The ONS also found that a positive SARS-CoV-2 test was associated with increased cardiac and all-cause mortality among people who were either vaccinated or unvaccinated at the time of testing.

Commenting on the findings, Vahé Nafilyan, a senior statistician at the ONS, said: "We find no evidence that the risk of cardiac or all cause death is increased in the weeks following vaccination with mRNA vaccines. However, receiving a first dose of a non-mRNA vaccine was associated with an increased risk of cardiac death in young women."

Vaccination with the principal non-mRNA vaccine used in the UK, the Oxford-AstraZeneca vaccine, was stopped for young people under age 30 years in April 2021 following safety concerns.

"Most of the young people who received it would have been prioritised due to clinical vulnerability or being healthcare workers. Therefore, these results cannot be generalised to the population as a whole," Mr Nafilyan said.

"Whilst vaccination carries some risks, these need to be assessed in light of its benefits. Our analysis also shows that the risk of death is greatly increased following a positive test for COVID-19, even in young people, and many studies show that vaccines are highly effective at preventing hospitalisation or death following COVID-19 infection."

Findings Were 'Unexpected'

Commenting on the findings for the Science Media Centre, Adam Finn, professor of paediatrics at the University of Bristol, found the results "interesting" but said that they generated as many questions as answers. "The findings are somewhat unexpected, as concerns about rare cardiac side-effects – specifically myocarditis and pericarditis – have hitherto been particularly associated with mRNA vaccine second doses in males, especially when the dose interval was short, whereas the signal reported here is primarily in non-mRNA first doses in females."

He added: "The presence of a signal in association with a positive SARS CoV2 infection test raises the question whether the spike protein – which is expressed both during infection and following vaccination – is the cause."

Stephen Evans, emeritus professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said: "This study does not estimate vaccine effectiveness and it is difficult to assess the exact balance of benefit and harm in this age group for the time when Omicron was (is) prevalent, but it is clear that infection with this virus can rarely lead to death in this age group, and death following vaccination is even rarer."