key: cord-0838701-chs73swx
authors: Sessa, Maurizio; Kragholm, Kristian; Hviid, Anders; Andersen, Morten
title: Thromboembolic events in younger women exposed to Pfizer-BioNTech or Moderna COVID-19 vaccines
date: 2021-07-26
journal: Expert opinion on drug safety
DOI: 10.1080/14740338.2021.1955101
sha: 0b8ec807e0d879b2180fa23769dbe81688931572
doc_id: 838701
cord_uid: chs73swx

Introduction: Concerns about the increased risk of blood clots associated with the VAXZEVRIA (previously named Oxford-AstraZeneca COVID-19 vaccine) and Johnson & Johnson (Janssen) COVID-19 vaccines raises the question of the thrombotic safety of other COVID-19 vaccines such as Pfizer-BioNTech or Moderna, especially in younger women, who at the early stage of the pandemic was a priority group for vaccination. Methods: Using the US-based Vaccine Adverse Event Reporting System (VAERS) and the FDA Event Reporting System (FAERS), we retrieved cases of thrombosis following vaccinations or hormonal contraceptive use in women aged ≤ 50 years. We used the reporting odds ratio (ROR) as a disproportionality measure. Results: On 19 March 2021, out of 13.6 million women aged ≤ 50 exposed to at least one dose of Pfizer-BioNTech or Moderna COVID-19 vaccines in the US, only 61 cases were reported with a total of 68 thromboembolic events (1 case per 222,951 vaccinated). None of the thromboembolic events included in our analysis were disproportionally reported for the two COVID-19 vaccines. Conclusion: Our results do support that, when compared to hormonal contraceptive use, the mRNA vaccines do not show disproportional reporting of thromboembolic events in younger women.

The European Medicines Agency (EMA) recently concluded that blood clots in combination with thrombocytopenia can occur in less than 1 in 10,000 people exposed to VAXZEVRIA (previously named Oxford-AstraZeneca COVID-19 vaccine) [1] . Analogously, concerns about the increased risk of blood clots associated with the Johnson & Johnson (Janssen) COVID-19 vaccine also emerged. This raises the question of the thrombotic safety of other COVID-19 vaccines such as Pfizer-BioNTech or Moderna, especially in younger women working as frontline personnel, who in the early stage of the pandemic was a priority group for vaccination. Of note, these rare events are now well established also in older people and men.

We conducted an analysis of the reporting of thromboembolic events following vaccination with the Pfizer-BioNTech or Moderna COVID-19 vaccines compared to hormonal contraceptive use, which is known to be associated with an increased but acceptable risk of thromboembolic events. Using the US-based Vaccine Adverse Event Reporting System (VAERS) [2] and the Food and Drug Administration Adverse Event Reporting System (FAERS) [3] , we retrieved all cases of thrombosis reports following Pfizer-BioNTech/Moderna COVID-19 vaccinations or hormonal contraceptive use in women aged ≤ 50 years. We used the reporting odds ratio (ROR) to investigate disproportional reporting of thrombotic events between the mRNA vaccines and widely used hormonal contraceptives (gestodene, levonorgestrel, levonorgestrel/ ethinyl estradiol, and progesterone). Thromboembolic events under investigation were thrombosis, cerebrovascular accident, myocardial infarction, and pulmonary embolism. Analyses were conducted using state-of-the-art methodological standards for disproportionality analysis [4] . Underreporting for thrombotic events associated with hormonal contraceptives in spontaneous reporting databases has been previously reported (reporting rate of 5.1/ 100,000 women-years versus 61/100,000 women-years observed in large phase-3 clinical trials) [5] . Therefore, we conducted a sensitivity analysis correcting the reporting odds ratio (ROR) for underreporting by multiplying the number of events by 1.932, which has been obtained as follows: 1 + (61-5.1)/61.

On 19 March 2021, out of 13.6 million women aged ≤ 50 exposed to at least one dose of Pfizer-BioNTech or Moderna COVID-19 vaccines in the US, only 61 cases were reported with a total of 68 thromboembolic events (1 case per 222,951 vaccinated). The median time-to-event was 3 days (interquartile range, IQR 1-6 days) and the median age of the cases was 42 years [IQR, 35-46]. Twenty-five out of 61 cases (41%) reported risk factors for thromboembolic events such as COVID-19 infection (4), hypertension (4), medical history of venous thrombosis (3), cancer (2), atrial fibrillation (1), diabetes mellitus (2), obesity (1), IgG deficiency requiring IgG infusion (1), protein-c-deficiency (1), systemic lupus (1), or exposure to hormonal contraceptive (3), ibuprofen (1), or phentermine (1). None of the thromboembolic events included in our analysis were disproportionally reported following the Pfizer-BioNTech or Moderna COVID-19 vaccines ( Table 1 ). The results from the sensitivity analysis were in line with the results of the main analysis (Table 2 ). Based on the results of the main analysis, for hormonal contraceptives, the proportions of thrombotic events over the total number of adverse events reported during the study period were 0.07%, 0.07%, 0.04%, and 0.10% for thrombosis, cerebrovascular accident, myocardial infarction, and pulmonary embolism, respectively.

In conclusion, while it is well known, that underreporting of adverse events is significant in pharmacovigilance, our results do support that, when compared to hormonal contraceptive use, the mRNA vaccines do not show disproportional reporting of thromboembolic events in younger women.

Dr Sessa had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Sessa, Hviid, Andersen, Kragholm. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: All authors. Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Sessa.

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

This paper was not funded.

Maurizio Sessa http://orcid.org/0000-0003-0874-4744 

European public assessment report

Updated information regarding the safety profile of Vaxzevria

The vaccine adverse event reporting system (VAERS)

Food and drug administration adverse event reporting system (FAERS)

Screening for adverse reactions in EudraVigilance

Safety of a new oral contraceptive containing drospirenone