Analysis of Thromboembolic and Thrombocytopenic Events After the AZD1222, BNT162b2, and MRNA-1273 COVID-19 Vaccines in 3 Nordic Countries.

Importance: Vaccinations are paramount to halt the COVID-19 pandemic, and safety data are essential to determine the risk-benefit ratio of each COVID-19 vaccine. Objective: To evaluate the association between the AZD1222, BNT162b2, and mRNA-1273 vaccines and subsequent thromboembolic and thrombocytopenic events. Design, Setting, and Participants: This self-controlled case series used individual-level data from national registries in Norway, Finland, and Denmark. Participants included individuals with hospital contacts because of coronary artery disease, coagulation disorders, or cerebrovascular disease between January 1, 2020, and May 16, 2021. Exposures: AZD1222, BNT162b2, or mRNA-1273 vaccine. Main Outcomes and Measure: Relative rate (RR) of hospital contacts for coronary artery disease, coagulation disorders, or cerebrovascular disease in a 28-day period following vaccination compared with the control period prior to vaccination. Results: We found 265 339 hospital contacts, of whom 112 984 [43%] were for female patients, 246 092 [93%] were for patients born in 1971 or earlier, 116 931 [44%] were for coronary artery disease, 55 445 [21%] were for coagulation disorders, and 92 963 [35%] were for cerebrovascular disease. In the 28-day period following vaccination, there was an increased rate of coronary artery disease following mRNA-1273 vaccination (RR, 1.13 [95% CI, 1.02-1.25]), but not following AZD1222 vaccination (RR, 0.92 [95% CI, 0.82-1.03]) or BNT162b2 vaccination (RR, 0.96 [95% CI, 0.92-0.99]). There was an observed increased rate of coagulation disorders following all 3 vaccines (AZD1222: RR, 2.01 [95% CI, 1.75-2.31]; BNT162b2: RR, 1.12 [95% CI, 1.07-1.19]; and mRNA-1273: RR, 1.26 [95% CI, 1.07-1.47]). There was also an observed increased rate of cerebrovascular disease following all 3 vaccines (AZD1222: RR, 1.32 [95% CI, 1.16-1.52]; BNT162b2: RR, 1.09 [95% CI, 1.05-1.13]; and mRNA-1273: RR, 1.21 [95% CI, 1.09-1.35]). For individual diseases within the main outcomes, 2 notably high rates were observed: 12.04 (95% CI, 5.37-26.99) for cerebral venous thrombosis and 4.29 (95% CI, 2.96-6.20) for thrombocytopenia, corresponding to 1.6 (95% CI, 0.6-2.6) and 4.9 (95% CI, 2.9-6.9) excess events per 100 000 doses, respectively, following AZD1222 vaccination. Conclusions and Relevance: In this self-controlled case series, there was an increased rate of hospital contacts because of coagulation disorders and cerebrovascular disease, especially for thrombocytopenia and cerebral venous thrombosis, following vaccination with AZD1222. Although increased rates of several thromboembolic and thrombocytopenic outcomes following BNT162b2 and mRNA-1273 vaccination were observed, these increases were less than the rates observed after AZD1222, and sensitivity analyses were not consistent. Confirmatory analysis on the 2 mRNA vaccines by other methods are warranted.

Association Between Human Papillomavirus Vaccination and Primary Ovarian Insufficiency in a Nationwide Cohort.

Importance: Anecdotal case reports have suggested an association between human papillomavirus (HPV) vaccination and primary ovarian insufficiency, but observational studies of HPV and primary ovarian insufficiency are rare, and their findings do not support an association. However, available studies have been limited by statistical power, and concerns about infertility after vaccination are associated with lower levels of uptake of the cancer-preventing vaccine in many countries. Objective: To evaluate the risk of primary ovarian insufficiency after quadrivalent human papillomavirus (4HPV) vaccination. Design, Setting, and Participants: This retrospective cohort study with follow-up from 2007 to 2016 used nationwide data for 996 300 Danish-born girls and women aged 11 to 34 years. Cox proportional hazards regression was used to estimate hazard ratios (HRs) of primary ovarian insufficiency diagnoses by 4HPV vaccination status with adjustment for age, calendar period, and a propensity score summarizing health care use. Data were analyzed from October 2020 to January 2021. Exposures: Receiving 4HPV vaccination compared with receiving no vaccination. Main Outcomes and Measures: The main outcome was hospital contacts for primary ovarian insufficiency, and the main outcome measures were HRs comparing rates of primary ovarian insufficiency among vaccinated and unvaccinated individuals. Results: During 6 781 166 person-years of follow-up among 996 300 girls and women aged 11 to 34 years (505 829 vaccinated individuals [50.8%] and 490 471 unvaccinated individuals [49.2%]), 144 individuals were diagnosed with primary ovarian insufficiency, including 54 individuals diagnosed after 4HPV vaccination. The median (interquartile range) age of primary ovarian insufficiency diagnosis was 26.94 (12.68) years. The adjusted HR of primary ovarian insufficiency comparing 4HPV vaccination to no vaccination was 0.96 (95% CI, 0.55-1.68). Conclusions and Relevance: This study found no association between HPV vaccination and primary ovarian insufficiency. However, given the rarity of the outcome in this study, the presence of a clinically relevant increase in rate of diagnosis cannot be excluded.