Ashrani AA, Crusan DJ, Petterson T, et al. - Among individuals who received Ad26.COV2.S COVID-19 vaccination, a significantly higher cerebral venous sinus thrombosis (CVST) incidence rate was observed at 15 days post vaccination vs the prepandemic rate. It is necessary to consider the higher rate of this rare adverse effect in the context of the effectiveness of the vaccine in preventing COVID-19 (absolute reduction of severe or critical COVID-19 of 940 per 100 000 person-years).

• A possible link between Ad26.COV2.S (Johnson & Johnson/Janssen) COVID-19 vaccination and CVST has been suggested in recent reports.

• A population-based cohort study of all incident cases of CVST in Olmsted County, Minnesota from January 1, 2001, through December 31, 2015, to compare the age- and gender-specific CVST rates following Ad26.COV2.S vaccination vs the prepandemic CVST rate.

• Overall CVST incidence, adjusted by age and gender, was 2.34 per 100,000 person-years (PY).

• For females and males, age-adjusted CVST rates were 2.46 per 100,000 PY and 2.34 per 100,000 PY, respectively.

• In US, 8,727,851 Ad26.COV2.S vaccine doses were administered (as of May 7, 2021); 38 objectively diagnosed cases of CVST existed post- Ad26.COV2.S vaccination.

• At 15-, 30-, and 92 days, the overall incidence rate of post–Ad26.COV2.S vaccination CVST was 8.65 per 100,000 PY, 5.02 per 100,000 PY, and 1.73 per 100,000 PY, respectively.

• CVST incidence rates for females and males, at 15-days postvaccination, were 13.01 per 100,000 PY and 4.41 per 100,000 PY, respectively.

• A 5.1-fold higher postvaccination CVST rate was observed in females vs the pre-COVID-19 pandemic rate (13.01 vs 2.53 per 100,000 PY).

• A slightly higher overall prepandemic CVST incidence rate in this study vs other studies (0.22-1.57 per 100,000 PY) is possibly due to capturing all objectively diagnosed incident CVST cases in a well-defined population, including those identified at autopsy.