Age-Stratified Risk of Cerebral Venous Sinus Thrombosis After SARS-CoV-2 Vaccination

Abstract

Background and ObjectivesCerebral Venous Sinus Thrombosis (CVST) as a part of the thrombosis and thrombocytopenia syndrome is a rare adverse drug reaction of SARS-CoV-2 vaccination. Estimated background rate of CVST with thrombocytopenia is 0.1 per million per month. We assessed the age-stratified risk of CVST with and without thrombocytopenia after SARS-CoV-2 vaccination.MethodsWe estimated the absolute risk of CVST with and without thrombocytopenia within 28 days of first dose of four SARS-CoV-2 vaccinations, using data from the European Medicines Agency’s EudraVigilance database (until 13 June 2021). As a denominator, we used data on vaccine delivery from 31 European countries. For 22.8 million adults from 25 countries, we estimated the absolute risk of CVST after the first dose of ChAdOx1 nCov-19 per age category.ResultsThe absolute risk of CVST within 28 days of first dose vaccination was 7.5 (95%CI 6.9-8.3), 0.7 (95%CI 0.2-2.4), 0.6 (95%CI 0.5-0.7) and 0.6 (95%CI 0.3-1.1) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2 and mRNA-1273, respectively. The absolute risk of CVST with thrombocytopenia within 28 days of first dose vaccination was 4.4 (95%CI 3.9-4.9), 0.7 (95%CI 0.2-2.4), 0.0 (95%CI 0.0-0.1) and 0.0 (95%CI 0.0-0.2) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2 and mRNA-1273, respectively. In recipients of ChAdOx1 nCov-19, the absolute risk of CVST, both with and without thrombocytopenia, was the highest in the 18-24 years age group (7.3 per million, 95%CI 2.8-18.8 and 3.7 per million, 95%CI 1.0-13.3, respectively). The risk of CVST with thrombocytopenia in ChAdOx1 nCov-19 recipients was the lowest in the age group≥70 years (0.2, 95%CI 0.0-1.3). Age <60 compared to ≥60 was a predictor for CVST with thrombocytopenia (incidence rate ratio 5.79; 95%CI 2.98-11.24, p<0.001).DiscussionThe risk of CVST with thrombocytopenia within 28 days of first dose vaccination with ChAdOx1 nCov-19 was higher in younger age groups. The risk of CVST with thrombocytopenia was slightly increased in patients receiving Ad26.COV2.S, compared with the estimated background risk. The risk of CVST with thrombocytopenia was not increased in recipients of SARS-CoV-2 mRNA vaccines.

High Incidence and Unique Features of Cerebral Venous Sinus Thrombosis in Hospitalized Patients With COVID-19 Infection

“…1 Two adenovirus-based COVID-19 vaccinations have been associated with a rare risk of simultaneous acute thrombosis-usually cerebral venous sinus thrombosis (CVST)-and thrombocytopenia in an entity called vaccine-induced thrombotic thrombocytopenia. 2,3 CVST is rare in the non-COVID general population. Risk factors for CVST include pregnancy, malignancy, hormone use, and thrombophilia.…”

“…Two adenovirus-based COVID-19 vaccinations have been associated with a rare risk of simultaneous acute thrombosis—usually cerebral venous sinus thrombosis (CVST)—and thrombocytopenia in an entity called vaccine-induced thrombotic thrombocytopenia. 2,3…”

“…CVST incidence associated with adenovirus-based COVID-19 vaccination is extremely low and ranges between 7.5 per million after the AstraZeneca vaccine (99% CI, 2.7–4.7) 3 to 0.9 per million (99% CI, 0.2–2.3) after the Janssen vaccine. 7 The incidence of CVST in unvaccinated COVID-19–infected patients has not been widely reported.…”

Cerebral venous thrombosis due to vaccine-induced immune thrombotic thrombocytopenia after a second ChAdOx1 nCoV-19 dose

“…[1][2][3][4] The absolute risk of VITT and VITTrelated CVT is estimated at 20 and 8 per million first doses of ChAdOx1 nCoV-19, respectively. 5,6 So far, no definite VITT cases occurring after a second ChAdOx1 nCoV-19 vaccine dose have been reported, raising the question if VITT only occurs after a first dose. Two pharmacovigilance studies reported cases of thrombosis with thrombocytopenia after a second ChAdOx1 nCoV-19 dose, but because of lack of clinical data, none of these could be classified as VITT.…”

Management of Cerebral Venous Thrombosis Due to Adenoviral COVID‐19 Vaccination

“…Nevertheless, it is still one of the largest studies on this extremely rare disease, for which power calculations and an interventional randomized study is not feasible. 24 Although true consecutiveness of cases in all countries participating in the registry remains a challenge, we attempted to minimize this bias ensuring inclusion of consecutive patients from the participating centers. Furthermore, complex patterns of management of patients with VITT‐CVT led to the presence of confounders which were difficult to account for and make the results vulnerable to confounding by indication.…”