Study: COVID much more likely than vaccines to cause blood clots

COVID-19—the actual disease—poses 8 to 10 times the threat of blood clots in the brain than do coronavirus vaccines, a large, non–peer-reviewed study led by University of Oxford researchers finds.

The study, published today on the preprint server OSF, involved an electronic health records network of 81 million patients at 59 healthcare systems, mainly in the United States.

The researchers tallied patients diagnosed as having cerebral venous thrombosis (CVT) in the 2 weeks after they received either their COVID-19 diagnosis or their first dose of the Pfizer/BioNTech or Moderna vaccine from Jan 20, 2020, to Mar 25, 2021. The researchers then compared those with rates of CVT in an unmatched cohort who had the flu and in the general population over the same period.

Only 2 cases in vaccinees

The risk of CVT was 8 to 10 times higher in the 513,284 patients with a COVID-19 diagnosis than in the 489,871 vaccinees and 100 times greater than in the general population. There were only two cases of CVT in the vaccine population, one after vaccination with the Pfizer vaccine and one after receipt of an undetermined mRNA vaccine. Patients younger than 30 years accounted for 30% of coronavirus-related CVT. The rate in the 172,742 flu patients was 0 per 1 million.

CVT in all patient groups was rare, at 39 per 1 million COVID-19 patients and 4 in 1 million vaccine recipients. The risk of CVT after COVID-19 was about 10 times higher than those from a single dose of the Pfizer or Moderna vaccines and, according to the European Medicines Agency (EMA), about eight times higher than after the AstraZeneca/Oxford vaccine. (The researchers couldn't ascertain this in the study population because this vaccine is not in use in the United States.)

The death rate among COVID-19 patients was 20% for those who had CVT and 18.8% for portal vein (liver) thrombosis (PVT), which was assessed in the same populations.

The incidence of PVT was 436.4 per 1 million people with COVID-19, 98.4 per 1 million among flu patients, and 44.9 per 1 million after vaccination with the Pfizer or Moderna vaccine. Twenty-two cases of PVT were diagnosed among vaccinees, 11 after the Pfizer vaccine, 2 after the Moderna vaccine, and 9 after a vaccine of an undetermined brand (either Pfizer or Moderna).

Cautions and context

Recent reports of blood clots after receipt of the AstraZeneca and Johnson & Johnson COVID-19 vaccines in young women have led to pauses in the rollouts of the two adenovirus vaccines in Europe (AstraZeneca) and the United States (Johnson & Johnson).

For example, yesterday, the New England Journal of Medicine published a letter to the editor from physicians at the University of Nebraska Medical Center in Omaha detailing the case of an otherwise healthy 48-year-old woman who became critically ill with splanchnic-vein thrombosis, or the formation of blood clots at unusual sites in the body, 2 weeks after receiving the Johnson & Johnson vaccine.

Study coauthor Paul Harrison, MD said in University of Oxford news release that their study shows the dramatic increase in risk of CVT from COVID-19. "The COVID-19 risk is higher than we see with the current vaccines, even for those under 30; something that should be taken into account when considering the balances between risks and benefits for vaccination," he said.

In the release, lead author Maxime Taquet, PhD, said that the study data should be interpreted cautiously because the AstraZeneca vaccine data were from the European Medicines Agency monitoring, while data on the other vaccines were from the TriNetX electronic health records network. "However, the signals that COVID-19 is linked to CVT, as well as portal vein thrombosis—a clotting disorder of the liver—is clear, and one we should take note of," he said.

Among expert reactions today on the Science Media Centre website, David Werring, PhD, of University College London, said the study had methodological limitations. "In particular, the authors could not verify the accuracy of the diagnosis of CVST [cerebral venous sinus thrombosis], which we know can be challenging, requiring appropriate clinical expertise and timely scanning of the veins in the brain," he said.

"Furthermore, they were not able to look at the risks of CVST associated with the AstraZeneca vaccine in the same population.”

Kevin McConway, PhD, of the Open University, United Kingdom, said the results should reassure the public that the risk of CVT from vaccines is low.

"The researchers are not claiming that vaccines do not increase the risk at all compared to the risk in people who have not been vaccinated and have also not had COVID-19—but they say the CVT risk in people who have had COVID-19 is about 100 times the risk in the general population," he said. "I do think this puts things into context."

The authors called for future research into whether coronavirus-related CVT occurs under the same or a different mechanism as in the vaccine-related complication.

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