The BNT162b2 mRNA vaccine (Pfizer-BioNTech) was the first SARS-CoV-2 vaccine authorized and most widely used in older persons in France. Although no increases in cardiovascular events were reported in the phase 3 trials, 1 questions emerged once the vaccine was used on a large scale because older people were underrepresented in the trials. We evaluated the short-term risk of severe cardiovascular events among French people aged 75 years or older after the administration of the BNT162b2 mRNA vaccine.Methods | This population-based study used the French National Health Data System linked to the national COVID-19 vaccination database. Eligible participants were all persons unvaccinated or vaccinated with the BNT162b2 vaccine, aged 75 years or older, admitted to the hospital between December 15, 2020, and April 30, 2021, for acute myocardial infarction, hemorrhagic stroke, ischemic stroke, or pulmonary embolism (diagnoses identified using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes) (Table 1 and eTable in the Supplement).We undertook within-person comparisons using a selfcontrolled case series method adapted to cardiovascular event-dependent exposures and high-event-related mortality that can cancel or defer subsequent vaccination or increase short-term mortality 2 (eMethods in the Supplement). Only exposures preceding the event were considered. Exposure risk intervals were the 1 through 14 days following each of the 2 vaccine doses. The exposure risk interval was further subdivided into days 1 through 7 and 8 through 14. Except for the vaccination day, the remaining periods were regarded as nonrisk periods. Unvaccinated persons were

We propose a modified self-controlled case series (SCCS) method to handle both event-dependent exposures and high event-related mortality. This development is motivated by an epidemiological study undertaken in France to quantify potential risks of cardiovascular events associated with COVID-19 vaccines.Event-dependence of vaccinations, and high event-related mortality, are likely to arise in other SCCS studies of COVID-19 vaccine safety. Using this case study and simulations to broaden its scope, we explore these features and the biases they may generate, implement the modified SCCS model, illustrate some of the properties of this model, and develop a new test for presence of a dose effect. The model we propose has wider application, notably when the event of interest is death.

Cases of myocarditis and pericarditis have been reported following the receipt of Covid-19 mRNA vaccines. As vaccination campaigns are still to be extended, we aimed to provide a comprehensive assessment of the association, by vaccine and across sex and age groups. Using nationwide hospital discharge and vaccine data, we analysed all 1612 cases of myocarditis and 1613 cases of pericarditis that occurred in France in the period from May 12, 2021 to October 31, 2021. We perform matched case-control studies and find increased risks of myocarditis and pericarditis during the first week following vaccination, and particularly after the second dose, with adjusted odds ratios of myocarditis of 8.1 (95% confidence interval [CI], 6.7 to 9.9) for the BNT162b2 and 30 (95% CI, 21 to 43) for the mRNA-1273 vaccine. The largest associations are observed for myocarditis following mRNA-1273 vaccination in persons aged 18 to 24 years. Estimates of excess cases attributable to vaccination also reveal a substantial burden of both myocarditis and pericarditis across other age groups and in both males and females.

Severe cardiovascular events (myocardial infarction [MI], pulmonary embolism [PE], and stroke) have been reported after COVID-19 vaccination. In this French registry-based analysis of adults younger than 75 years, administration of the Pfizer–BioNTech or Moderna mRNA vaccine was not associated with increased risk for MI, PE, or stroke. However, recipients of the Oxford–AstraZeneca vaccine had greater risk for MI and PE in the second week after vaccination. A similar association for the Janssen adenoviral-based vaccine could not be ruled out.