Could monitoring headaches after COVID-19 vaccination help identify rare cases of cerebral venous thrombosis?

Shortly after the mass vaccination program against coronavirus disease 2019 (COVID-19) began in the UK, news outlets began to report severe side effects in a minority of those vaccinated. One of the more serious conditions that occurred is known as cerebral venous thrombosis (CVT) – a blood clot in the brain's venous sinuses that can lead to swelling, hemorrhage and death.

Even more worrying, CVT in those who had recently been vaccinated showed a much higher mortality rate than CVT that had been triggered by alternate sources. Headache is the most common symptom following vaccination, and is also one of the most frequent symptoms of CVT.

Researchers from the Akershus University Hospital in Norway investigated 77 cases of CVT in vaccinated subjects to identify risks and warning signs to better predict these severe side effects. The group's findings can be found in the Journal of Headache and Pain.

It is worth noting that these symptoms only occurred in a very small minority of individuals, and authorities recommend that everyone eligible to become vaccinated does so.

The researchers searched through PubMed for all case studies and reported cases of CVT, as well as examining reports from the United States Centers for Disease Control and Prevention and the European Medicines Data. They evaluated these gathered cases based on certain variables, including age, sex, use of contraceptives, use of hormone replacement therapy, presence of a headache, presence of additional symptoms, the interval between headache and first symptom, intracranial hemorrhage and death.

For a control group, they used reports of headaches following the vaccines from the United States Vaccine Adverse Event Reporting System. A search of 'headache' against coronavirus vaccines returns over 100,000 results.

To analyze the cases, univariate logistic regression was used, with a standard 0.05% confidence limit. In total, 4.2% of patients suffering CVT were between 60 and 69, 95.8% of patients were below sixty, and 46.5% were below 40. This is supported by previous studies from CVT in non-vaccinated patients, showing that individuals ~30 years old are at most risk. Women were more affected than men, and made up 89.7% of cases. Five patients used contraceptives, and one was receiving estrogen therapy.

It normally took over a week following the vaccination for the first symptom to present – in 50% of cases, this was a headache, with various systemic or neurological symptoms in the other 50%. In ~25% of cases, multiple location thrombosis was recorded. In 24.7% of cases, the patient died. The statistical analysis clearly showed that In patients with CVT, the presence of headache was associated with increased risk of hemorrhage — but not with increased risk of death.

While headache is a very common side effect, in the vast majority of cases, it is resolved harmlessly and quickly. In almost all of the cases of CVT in which the headache was described, the onset was delayed for a week or longer – a rarity in patients that did not suffer CVT. The headaches were also severe, became progressively more so, and did not respond well to treatment.

The authors highlight the value this early warning sign could provide, especially as most cases of CVT are not immediately diagnosed, and delayed treatment reduces patient prognosis significantly. They urge that physicians be informed of this warning sign. Informing recently vaccinated individuals could also increase survival rates – although it may easily increase vaccine hesitancy as well. CVT can be detected with computed tomography, which will could show warning signs such as hyperdense veins or sinus, venous infarcts, edema or intracranial hemorrhage. World Health Organization recommended treatment includes immunoglobulins and non-heparin-based anticoagulants.

Journal reference:
Sam Hancock

Written by

Sam Hancock

Sam completed his MSci in Genetics at the University of Nottingham in 2019, fuelled initially by an interest in genetic ageing. As part of his degree, he also investigated the role of rnh genes in originless replication in archaea.

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