COVID-19 vaccine-associated cerebral venous thrombosis in Germany: a descriptive study

Schulz, J. B.; Berlit, P.; Diener, H.-C.; Gerloff, C.; Greinacher, A.; Klein, C.; Petzold, G.; Poli, S.; Piccininni, M.; Kurth, T.; Roehrig, R.; Steinmetz, H.; Thiele, T.

Objective: Reports of cerebral venous thrombosis (CVT) after ChAdOx1 vaccination against SARS-CoV-2 have raised safety concerns and an emerging mechanism termed vaccine induced immune thrombotic thrombocytopenia (VITT) was identified. We aimed to estimate the frequency of CVT and other cerebrovascular events after vaccination with BNT162b2, ChAdOx1, and mRNA-1273, 114 German Departments of Neurology participated in a systematic survey. Design: descriptive study. Setting: Germany. Population: Patients with reported cerebrovascular events within the first month after a COVID-19 vaccine administration. Methods: We designed web-based questionnaire, which was e-mailed to all Departments of Neurology of University and non-university hospitals in Germany on April 6, 2021. Data collection was closed at midnight on April 14, 2021. We asked to report cases of cerebral sinus-venous thrombosis, cerebral venous thrombosis, ischemic stroke and haemorrhage within one month of a COVID-19 vaccination. Incidence rates of cerebral events and CVT within one month from first vaccine shot administration was calculated by using official statistics of 9 German States. Results: A total of 62 cases were detected, of whom 45 had CVT, 9 primary ischemic stroke, 4 primary intracerebral hemorrhage (ICH), and 4 other events. Eleven patients of 60 (18.3%) had a fatal outcome. Mean age was 46.7 years (48 patients <60 years, 77.4%), 75.8% of patients were female. Fifty-three events were observed after vaccination with ChAdOx1 (85.5%), 9 after BNT162b2 (14.5%). No events were reported after mRNA-1273 vaccination. The overall incidence rate of CVT within one month from first dose administration was 6.5 (95% CI, 4.4 to 9.2) per 100,000 person-years and 8.8 (95% CI, 6.4 to 11.9) for any included cerebrovascular event. The one-month incidence rate of CVT was higher among ChAdOx1 vaccinated persons (17.9, 95% CI, 11.8 to 26.1). The incidence rate ratio was 9.68 (3.46 to 34.98) for ChAdOx1 compared to mRNA-based vaccines and 3.14 (1.22 to 10.65) for women compared to non-women after adjusting for age group. In 26/45 patients with CVT (57.8%), VITT was graded highly probable, in 19/45 patients (42.2%) the association was less likely. A high-grade probability was not confined to CVT but also occurred in 5/9 patients (55.6%) with primary ischemic stroke and 2/4 patients (50%) with ICH following vaccination. Conclusions: Given an incidence of CVT in the general population of 0.22 to 1.75 per 100,000 person-years, these findings point towards and higher risk for CVT after ChAdOx1 vaccination, especially for women.