Rare Type of Stroke More Common After SARS-CoV-2 Infection Than After mRNA Vax

The risk of cerebral venous thrombosis (CVT) is much higher among patients infected with SARS-CoV-2 than among people who have received an mRNA-based COVID-19 vaccine, affirms a study out of Singapore.

The estimated incidence of this rare type of stroke within 6 weeks was 32.1 times higher among infected patients than among those who received at least one dose of mRNA vaccine, and 28.4 times higher compared with those who received two doses of vaccine, Tu Tian Ming, MBBS (National Neuroscience Institute, Singapore), and colleagues report in a study published online this week in JAMA Network Open.

The data suggest that CVT risk is not increased much—if at all—with the mRNA-based vaccines from Pfizer/BioNTech and Moderna compared with the background rate in the general population.

“CVT remains rare after mRNA-based SARS-CoV-2 vaccines, reinforcing [their] safety profile,” Tu et al write.

Prior studies have demonstrated an elevated risk of CVT among patients with COVID-19. But the complication has also been tied to use of COVID-19 vaccines, primarily the adenovirus vector-based COVID-19 vaccines from Oxford/AstraZeneca and Johnson & Johnson, with CVT often occurring in the context of a condition dubbed vaccine-induced immune thrombotic thrombocytopenia (VITT). CVT has not been as frequently linked to use of the mRNA-based vaccines.

“Reports of CVT with adenovirus vector-based vaccines may have potentially affected vaccine acceptance,” Tu et al write. “Therefore, by directly comparing CVT rates after mRNA-based SARS-CoV-2 vaccination to after SARS-CoV-2 infection, the perception of CVT after vaccination may be more appropriately contextualized, and vaccination rates may be potentially improved.”

I personally think, and I’m very reassured by the data, that there is no increased risk by the mRNA vaccinations. Jörg Schulz

For the current study, the investigators examined data from all public acute hospitals in Singapore on 62,447 people with SARS-CoV-2 infection (median age 34 years; 94% men) and more than 3 million people who received an mRNA-based vaccine (median age 50 years; 54% men) between January 23, 2020, and August 3, 2021. About three-quarters of vaccinees received shots from Pfizer/BioNTech.

CVT requiring hospitalization, confirmed with either CT or magnetic resonance venogram, was identified in six patients (median age 33.5 years; all men) with confirmed SARS-CoV-2 infection. None had thrombocytopenia, and one died.

In the vaccinated group, there were nine CVT cases (median age 60 years; 78% men), six after receipt of the Pfizer/BioNTech shot and three after receipt of the Moderna vaccine. Most occurred in people who had received two doses; the median interval between vaccination and symptom onset was 28 days after a first dose and 7 after a second dose. Thrombocytopenia wasn’t seen in any of these patients.

The crude incidence rate of CVT was much higher among patients with SARS-CoV-2 infection than among those who received at least one dose of mRNA vaccine (83.3 vs 2.6 per 100,000 person-years).

The researchers note that the large number of asymptomatic infections occurring during the pandemic means, on one hand, that many CVT cases linked to the virus could have been missed and, on the other hand, the incidence of the complication could have been overestimated. Moreover, they say, the crude incidence rates and incidence rate ratios weren’t adjusted for differences between groups and “must be interpreted with caution.”

The data indicate a greater risk of CVT among recipients of the mRNA vaccines—with incidence rate ratios of 2.28 and 3.59 per 100,000 person-years for those who received the Pfizer/BioNTech and Moderna shots, respectively—but no difference between those two vaccines (P = 0.75).

Still, Tu et al point out that the confidence intervals around the estimated incidence rates with the mRNA vaccines fall within rates observed in the general populations of Australia and the United States, “suggesting the association of CVT with mRNA-based SARS-CoV-2 vaccine may be similar to background risk. However, due 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.”

For Jörg Schulz, MD (Rheinisch-Westfälische Technische Hochschule Aachen University, Germany), whose group has studied CVT risk associated with COVID-19 vaccination, the findings from Singapore align with those from prior studies and “are very much reassuring” because of the large size of the data set.

Risk of CVT “is probably not increased at all” after mRNA vaccination, Schulz told TCTMD, “at least not comparable to the risk that adenovirus vector-based vaccination has with the newly identified mechanism of VITT that does not exist with mRNA vaccinations.”

Indications that the mRNA vaccines are also associated with CVT could be related to the increased attention to CVT driven by the link seen with the adenovirus vector-based vaccines, he proposed. “I personally think, and I’m very reassured by the data, that there is no increased risk by the mRNA vaccinations.”