Association of Cerebral Venous Thrombosis with mRNA COVID-19 Vaccines: A Disproportionality Analysis of the World Health Organization Pharmacovigilance Database

Abstract

Cerebral venous thrombosis (CVT), a rare thrombotic event that can cause serious neurologic deficits, has been reported after some ChAdOx1 nCoV-19 vaccinations against coronavirus disease 2019 (COVID-19). However, there are few reports of associations between COVID-19 mRNA vaccination and CVT. We retrospectively analyzed CVT occurrence, time of onset after vaccination, outcomes (recovered/not recovered), and death after COVID-19 vaccination from adverse drug reactions (ADR) reports in VigiBase. A disproportionality analysis was performed regarding COVID-19 mRNA vaccines (BNT162b2 and mRNA-1273) and the ChAdOx1 nCoV-19 vaccine. We identified 756 (0.07%) CVT cases (620 (0.05%) after BNT162b2 and 136 (0.01%) after mRNA-1273) of 1,154,023 mRNA vaccine-related ADRs. Significant positive safety signals were noted for COVID-19 mRNA vaccines (95% lower end of information component = 1.56; reporting odds ratio with 95% confidence interval (CI) = 3.27). The median days to CVT onset differed significantly between the BNT162b2 and ChAdOx1 nCoV-19 vaccines (12 (interquartile range, 3–22) and 11 (interquartile range, 7–16), respectively; p = 0.02). Fewer CVT patients died after receiving mRNA vaccines than after receiving the ChAdOx1 nCoV-19 vaccine (odds ratio, 0.32; 95% CI, 0.22–0.45; p < 0.001). We noted a potential safety signal for CVT occurrence after COVID-19 mRNA vaccination. Therefore, awareness about the risk of CVT, even after COVID-19 mRNA vaccination, is necessary.

Associations of Guillain‐Barré syndrome with coronavirus disease 2019 vaccination: Disproportionality analysis using the World Health Organization pharmacovigilance database

“…Our study was conducted in the format of an observation case control study. We extracted all cases of GBS reported as ADR resulting from BNT162b2, mRNA‐1273, or ChAdOx1 nCoV‐19 vaccination by October 15, 2021, in VigiBase using the following Medical Dictionary for Drug Regulatory Activities (MedDRA) preferred terms (PTs) 21‐23 . We defined the GBS as narrow definitions: “Guillain‐Barre syndrome” and as broad definitions: “ Guillain‐Barre syndrome ,” “ Miller‐Fisher syndrome ,” “ Acute motor‐sensory axonal neuropathy ,” “ Acute motor axonal neuropathy ,” “ Bickerstaff's encephalitis .” Data on sex, age group, type of vaccination, reporting nation, time to onset of GBS, outcomes (seriousness and final) were acquired.…”

“…The IC is a logarithmic measure of the strength of the association between drug administration and ADRs. Detailed methods to calculate the IC value have been described in previous reports 21,22,26‐28 . To obtain IC values, the entire VigiBase database or all drugs in the category should be defined as the denominator, and data comparisons between drugs or between vaccines cannot be completed 26‐28 .…”

“…Disproportionality analyses of adverse drug reactions (ADRs) resulting from BNT162b2, mRNA-1273, or ChAdOx1 nCoV-19 vaccination was conducted using personal case safety reports from VigiBase, the WHO's global deduplicated database, which includes reports in more than 130 nations. [20][21][22] VigiBase is operated by the Uppsala Monitoring Centre (UMC) and has gathered the details of suspected medication-related ADRs from the national pharmacovigilance centers of each participating country since 1967. This information originates from many different sources, including patients, physicians, pharmaceutical companies, healthcare professionals, and post-marketing surveillance studies.…”

“…Detailed methods to calculate the IC value have been described in previous reports. 21,22,[26][27][28] To obtain IC values, the entire VigiBase database or all drugs in the category should be defined as the denominator, and data comparisons between drugs or between vaccines cannot be completed. [26][27][28] We used Bayesian confidence propagation neural network, which was validated by UMC, to calculate IC.…”

A Disproportionality Analysis for Association of Systemic Capillary Leak Syndrome with COVID-19 Vaccination Using the World Health Organization Pharmacovigilance Database

“…Disproportionality analysis of adverse drug reactions (ADR) with BNT162b2, mRNA-1273, and ChAdOx1 nCoV-19 vaccines was performed using individual case safety reports from VigiBase, the WHO's global deduplicated database, which includes reports from more than 130 countries [21,22]. VigiBase is managed by the Uppsala Monitoring Center (UMC) and collects information on suspected medication-related ADRs from national pharmacovigilance centers in each contributing country since 1967.…”