CVT risk higher after COVID-19 than COVID-19 mRNA vaccine

An observational study from Singapore has shown that the incidence of cerebral venous thrombosis (CVT) following SARS-CoV-2 infection is greater than that following receipt of an mRNA-based SARS-CoV-2 vaccine.

“[T]he incidence rate ratio (IRR) of CVT requiring hospitalization within 6 weeks of SARS-CoV-2 infection was 32 times higher compared with after mRNA-based SARS-CoV-2 vaccination,” the authors pointed out.

The study, conducted at all public acute hospitals in Singapore between January 23, 2020, and August 3, 2021, included individuals who had received mRNA SARS-CoV-2 vaccination and who were hospitalized for symptomatic CVT (confirmed with brain CT or MRI) within 6 weeks of the last vaccine dose or a SARS-CoV-2 diagnosis. The population comprised 62,447 individuals who had been diagnosed with SARS-CoV-2 (median age 34 years, 94.5 percent male) and 3,006,662 individuals who had received ≥1 dose of an mRNA SARS-CoV-2 vaccination (median age 50 years, 54.1 percent male). About 69 percent had received two vaccine doses and 75.9 percent received the BNT162b2 vaccine. The total observation periods for CVT incidence following SARS-CoV-2 diagnosis or mRNA vaccine receipt were 18 months and 31 weeks, respectively.

Six CVT cases were diagnosed after a SARS-CoV-2 infection (median age 33.5 years, 100 percent male), while nine CVT cases were diagnosed after receipt of an mRNA SARS-CoV-2 vaccine (median age 60 years, 77.8 percent male [n=7]).

The crude incidence rate (IR) of CVT was higher following a SARS-CoV-2 infection compared with receipt of ≥1 dose of the mRNA SARS-CoV-2 vaccine (83.3 vs 2.59 per 100,000 person-years). [JAMA Network Open 2022;5:e222940]

The crude IRR for hospitalization for CVT was significantly higher after a SARS-CoV-2 infection than after receiving an mRNA SARS-CoV-2 vaccine, regardless of whether it was following receipt of ≥1 dose (32.1, 95 percent confidence interval [CI], 9.40–101.0; p<0.001) or two doses (28.4, 95 percent CI, 7.9–98.6; p<0.001) of the vaccine.

There was no significant difference in the risk for CVT hospitalization between recipients of the mRNA-1273 and BNT162b2 vaccines (1.57, 95 percent CI, 0.26–7.39; p=0.75), though comparison was difficult due to the low number of events.

The IR of CVT post–SARS-CoV-2 infection of 83.3 per 100,000 person-years was also higher than that of the general US population (1.3–2.0 per 100,000 person-years). [Neurology 2020;95:e2200-e2213] According to the authors, this finding highlights the association between CVT and SARS-CoV-2, though they acknowledged that other factors may be at play that could not be discerned in this observational study.

“[D]ue to the rarity of CVT events, and the lack of direct comparison to baseline risk in our population, true association of CVT due to the vaccines could not be definitively concluded,” the authors added.

Five of the six cases of post–SARS-CoV-2 CVT occurred in the absence of respiratory symptoms, suggesting that the mechanism of CVT development post-infection may differ from that of respiratory disease.

Eighty-three percent of individuals with SARS-CoV-2–related CVT had normal prothrombotic evaluation, which indicated a lack of other risk factors for thrombosis. Conversely, 33 percent of individuals with CVT after vaccination had abnormal prothrombotic evaluation, suggesting the presence of risk factors.

The incidence of CVT following adenoviral vector-based SARS-CoV-2 vaccines has been tied to thrombocytopenia. However, in this study, none of the patients with post-mRNA vaccine CVT had thrombocytopenia.

The authors acknowledged several limitations such as the lack of a comparator group (eg, CVT rates in the general local population), limiting CVT incidence to hospitalized cases which may have excluded milder cases or asymptomatic SARS-CoV-2, and excluding patients in private hospitals. Furthermore, only 35 percent of the local population, primarily older individuals, had received vaccination at data cut-off.

“CVT remains rare after mRNA-based SARS-CoV-2 vaccines, reinforcing its safety profile,” they concluded.