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November 01, 2021
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Although ‘rare,’ more data link J&J COVID-19 shot to cerebral venous sinus thrombosis

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In a recent population-based cohort study, researchers observed an increased risk for cerebral venous sinus thrombosis after administration of the Johnson & Johnson COVID-19 vaccine.

However, they reported that “this rare adverse effect must be considered in the context of the effectiveness of the vaccine in preventing COVID-19.”

Infographic that reads: The incidence of cerebral venous sinus thrombosis per 100,000 person-years was 2.34 in the pre-pandemic cohor and 8.65 in the Johnson & Johnson vaccine cohort.
Reference:  Ashrani AA, et al. JAMA Intern Med. 2021;doi:10.1001/jamainternmed.2021.6352.

According to Johns Hopkins, cerebral venous sinus thrombosis, or CVST, affects about five in every 1 million individuals annually.

In April, the CDC and FDA recommended pausing the rollout of Johnson & Johnson’s COVID-19 vaccine after several cases of CVST were identified among people who received the vaccine. Days later, the Advisory Committee on Immunization Practices recommended resuming use of the vaccine, saying the benefits outweigh the risks. To date, the CDC estimates that more than 15 million people in the United States have received the Johnson & Johnson vaccine.

In the new study, Aneel A. Ashrani, MD, MS, an internist, hematologist and oncologist at Mayo Clinic, and colleagues identified all CVST cases that were reported from Jan. 1, 2001, through Dec. 31, 2015, in Olmsted County, Minnesota, which houses multiple Mayo Clinic facilities. The researchers compared that data with information gleaned from the CDC’s Vaccine Adverse Event Reporting System (VAERS) from Feb. 28 — the date the Johnson & Johnson vaccine was authorized — to May 7. According to the researchers, previous studies making similar comparisons have yielded mixed results.

Aneel A. Ashrani

Ashrani and colleagues reported that 39 individuals in the pre-pandemic cohort (median age at diagnosis, 41 years; 56.4% women) experienced CVST, 29 of whom had a “predisposing thromboembolism risk factor.” This led to an incidence rate of 2.34 per 100,000 person-years (PY; 95% CI, 1.6-3.08). The age-adjusted CVST rate was 2.46 per 100,000 PY (95% CI, 1.43-3.49) in women and 2.34 per 100,000 PY (95% CI, 1.22-3.46) in men. The highest rate of CVST occurred in men aged 65 years and older (6.22 per 100,000 PY; 95% CI, 2.5-12.82), then women aged 18 to 29 years (4.71 per 100,000 PY; 2.26-8.66).

In the VAERS database, the researchers identified 46 possible cases of CVST (median age at possible occurrence, 45 years; 71.1% women) among Johnson & Johnson COVID-19 vaccine recipients, which occurred within 92 days of vaccine administration. Eight possible CVST cases were not included due to possible duplication or the CVST not being “objectively diagnosed,” the researchers wrote. The median time from vaccination to CVST in the 38 studied cases was 9 days (interquartile range [IQR] = 6-13; range, 1-51). In addition, 81.6% of the possible CVST cases occurred within 15 days of vaccination and 94.7% occurred within 30 days. The overall CVST incidence rate after Johnson & Johnson COVID-19 vaccination was 8.65 per 100,000 PY (95% CI, 5.88-12.28) at 15 days; 5.02 per 100,000 PY (95% CI, 3.52-6.95) at 30 days; and 1.73 per 100,000 PY (95% CI, 1.22-2.37) at 92 days.

After further analysis, the researchers found that the 15-day post-vaccination CVST incidence rate was 13.01 per 100,000 PY (95% CI, 8.24-19.52) in women and 4.41 per 100,000 PY (95% CI, 1.9-8.68) in men.

The CVST rate among women was 5.1-fold higher in the post-vaccination cohort than the pre-pandemic cohort (13.01 vs. 2.53 per 100,000 PY), according to the researchers. Also, among women in the post-vaccination cohort, the risk for CVST was highest in those aged 40 to 49 years (29.5 per 100,000 PY; 95% CI, 13.5-55.95), then in women aged 30 to 39 years (26.5 per 100,000 PY, 95% CI, 10.65-54.63), “but the absolute CVST risk was still low,” Ashrani and colleagues wrote.

“It was surprising that it is predominantly women (especially 30- to 49-year-old women) who are at a higher risk for CVST in the first 15 days after the administration of Johnson & Johnson COVID-19 vaccine,” Ashrani told Healio Primary Care. “We do not have a good explanation for it but speculate that they may have additional/concomitant CVST risk factors, (eg, oral contraceptive pill use) or may have a predisposition to autoantibody production that may have led to vaccine-associated thrombocytopenia with thrombosis.”

When considering boosters, Ashrani said “there are no good data regarding the risk of administering a booster shot in individuals who had thrombotic complications following the Johnson & Johnson vaccine.”

He cited a recent correspondence in The New England Journal of Medicine that showed all five individuals who were taking anticoagulation therapy for a thrombotic complication stemming from the Johnson & Johnson or AstraZeneca COVID-19 vaccine and then received the Pfizer-BioNTech vaccine 10 to 18 weeks later did not experience a recurrent thromboembolic complication.

“In individuals who had thrombotic complications after the administration of an adenovirus vector-based COVID-19 vaccine (eg, the J&J vaccine), my bias would be to consider one of the mRNA-based vaccines (ie, one manufactured by Pfizer-BioNTech or Moderna) for their booster shot,” Ashrani said.

References

Ashrani AA, et al. JAMA Intern Med. 2021;doi:10.1001/jamainternmed.2021.6352.

CDC. COVID-19 data tracker weekly review. https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html. Accessed Nov. 1, 2021.

CDC. COVID-19 vaccinations in the United States. https://covid.cdc.gov/covid-data-tracker/#vaccinations_vacc-total-admin-rate-total. Accessed Nov. 1, 2021.

Johns Hopkins Medicine. Cerebral venous sinus thrombosis. https://www.hopkinsmedicine.org/health/conditions-and-diseases/cerebral-venous-sinus-thrombosis. Accessed Nov. 1, 2021.

Schönborn L, et al. N Engl J Med. 2021;doi:10.1056/NEJMc2112760.