Cerebral venous sinus thrombosis (CVST) is not significantly linked to COVID-19 vaccines or non-COVID vaccines in a large multi-state US health system

Abstract

Cerebral venous sinus thrombosis (CVST) has been reported in a small number of individuals who have received the mRNA vaccines1 or the adenoviral vector vaccines for COVID-19 in the US2 and Europe3. Continued pharmacovigilance is integral to mitigating the risk of rare adverse events that clinical trials are underpowered to detect, however, these anecdotal reports have led to the pause or withdrawal of some vaccines in many jurisdictions and exacerbated vaccine hesitancy at a critical moment in the fight against the COVID-19 pandemic. We investigated the frequencies of CVST seen among individuals who received FDA-authorized COVID-19 vaccines from Pfizer-BioNTech (n = 94,818 doses), Moderna (n = 36,350 doses) and Johnson & Johnson - J&J (n = 1,745 doses), and among individuals receiving one of 10 FDA-approved non-COVID-19 vaccines (n = 771,805 doses). Comparing the incidence rates of CVST in 30-day time windows before and after vaccination, we found no statistically significant differences for the COVID-19 vaccines or any other vaccines studied in this population. In total, we observed 3 cases of CVST within the 30 days following Pfizer-BioNTech vaccination (2 females, 1 male; Ages (years): [79, 80, 84]), including one individual with a prior history of thrombosis and another individual with recent trauma in the past 30 days. We did not observe any cases of CVST among the patients receiving Moderna or J&J vaccines in this study population. We further found the baseline CVST incidence in the study population between 2017 and 2021 to be 45 to 98 per million patient years. Overall, this real-world evidence-based study highlights that CVST is rare and is not significantly associated with COVID-19 vaccination. In addition, there is a need for a concerted international effort to monitor EHR data across diverse patient populations and to investigate the underlying biological mechanisms leading to these rare clotting events.

Real-time analysis of a mass vaccination effort confirms the safety of FDA-authorized mRNA COVID-19 vaccines

“…We have also previously shown that the rate of CVST is similar in the 15 and 30 days prior to and after BNT162b2 or mRNA-1273 vaccination in a large cohort at the Mayo Clinic. 26 Taken together with the absence of an increase in emergent clinical visits following each dose, these data suggest favorable tolerability of both vaccines. We show the numbers and percent of individuals in each group who had at least one phenotype-containing EHR note within 7, 14, or 21 days of the actual or assigned first vaccination date.…”

Real-world effectiveness of Ad26.COV2.S adenoviral vector vaccine for COVID-19

“…We have previously leveraged recent advances in deep neural networks to perform high throughput machine-augmented curation of electronic health record (EHR) systems 5,6 . This has enabled the rapid assessment of real world effectiveness and safety of the mRNA vaccines mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech), as well as a targeted investigation of cerebral venous sinus thrombosis (CVST) incidence among patients receiving COVID-19 vaccines (including Ad26.COV2.S) within the Mayo Clinic Health System [7][8][9] . We believe such approaches are essential for vaccine development, deployment, and most importantly to build trust and transparency for the public.…”

Untangling the Intricacies of Infection, Thrombosis, Vaccination, and Antiphospholipid Antibodies for COVID-19

“…Despite previous large-scale studies of similar vaccine efficacy, the number of patients required to find such uncommon post-vaccination events is greater [136]. Data from a large group of US vaccines, in which most were given RNA vaccines, did not find an association with cerebral thrombosis [137]. One of the latter vaccines was temporally associated with a relapse of thrombotic thrombocytopenic purpura in a case report [138].…”