Cerebral Venous Sinus Thrombosis following COVID-19 Vaccination: Analysis of 552 Worldwide Cases

Abstract

To date, billions of vaccine doses have been administered to restrain the current COVID-19 pandemic worldwide. Rare side effects, including intravascular blood clots, were reported in the general population after vaccination. Among these, cerebral venous sinus thrombosis (CVST) has been considered the most serious one. To shed further light on such an event, we conducted a literature search for case descriptions of CVST in vaccinated people. Findings were analyzed with emphasis on demographic characteristics, type of vaccine, site of thrombosis, clinical and histopathological findings. From 258 potential articles published till September 2021, 41 studies were retrieved for a total of 552 patients. Of these, 492 patients (89.1%) had received AZD1222/Vaxzevria, 45 (8.2%) BNT162b2/CX-024414 Spikevax, 15 (2.7%) JNJ-78436735, and 2 (0.3%) Covishield vaccine. CVST occurred in 382 women and 170 men (mean aged 44 years), and the median timing from the shot was 9 days (range 2–45). Thrombi were predominantly seen in transverse (84%), sigmoid (66%), and/or superior sagittal (56%) sinuses. Brain injury (chiefly intracranial bleeding) occurred in 32% of cases. Of 426 patients with detailed clinical course, 63% were discharged in good clinical conditions, at times with variable neurological sequelae, whereas 37% deceased, largely due to brain injury. This narrative review confirmed CVST as a rare event after (adenoviral vector) COVID-19 vaccination, with a women/men rate ratio of 2.25. Though the pathogenesis of thrombosis is still under discussion, currently available histopathological findings likely indicate an underlying immune vasculitis.

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

“…In agreement with the well-known relationship between the ChAdOx1 nCoV-19 vaccine and CVT [ 32 , 33 ], our results showed a potential safety signal of the ChAdOx1 nCoV-19 vaccine for CVT. Additionally, in one recent study, about 90% of CVT cases following COVID-19 vaccination occurred after the administration of the ChAdOx1 nCoV-19 vaccine [ 15 ]. The ChAdOx1 nCoV-19 vaccine can cause systemic thromboembolism due to thrombosis with thrombocytopenia syndrome [ 34 ].…”

“…Hematologic disorders, inflammatory diseases, pregnancy, malignancy, hormonal abnormality, and meningitis are the main associative or risk factors for the development of CVT [ 14 ]. The risk factors of CVT after COVID-19 vaccination were similar, with the exception that allergic reactions to the vaccine components and platelet abnormalities were additional factors [ 15 ]. Since the initiation of COVID-19 vaccination, cases of CVT associated with COVID-19 vaccines have been reported, with some being fatal [ 16 , 17 , 18 , 19 , 20 ].…”

Cerebral venous thrombosis after COVID-19 vaccines: Do we know the mechanism?

“…Several pathological issues were discussed in our study ( Figure ), such as vaccine-induced immune thrombotic thrombocytopenia, prothrombotic conditions, age, sex, anatomical and dysfunctional variants of the venous system, allergic reactions to vaccine components and impaired protein-homeostasis-systems, 2 , 5 but we as yet have no certain proof of the precise mechanism(s) of vascular thrombogenicity. Therefore, additional efforts should be directed towards redefining the COVID-19 vaccine-related thrombogenic settings and preparing clinicians to be aware of such unexpected, often devastating, outcomes.…”

“…Interestingly, these findings support ours from a recent review of 552 worldwide-published cases of CVST after Covid-19 vaccination. 2 In both studies, CVST occurred after the first dose of ChAdOx1nCoV-19 vaccination, and coexisting thrombocytopenia was established in some patients. Andrews et al.…”

“…Regrettably, most patients experiencing poor outcomes after vaccine administration were apparently healthy subjects (approximately one third of cases in our review died due to severe intracranial bleeding and brain injury, with multiorgan thrombosis present in >90% of these), and available histopathological findings demonstrated an underlying immune macro- and micro-vasculitis. 2 …”