Intracranial aneurysm rupture within three days after receiving mRNA anti-COVID-19 vaccination: Three case reports

BACKGROUND: Although neurological adverse events have been reported after receiving coronavirus disease 2019 (COVID-19) vaccines, associations between COVID-19 vaccination and aneurysmal subarachnoid hemorrhage (SAH) have rarely been discussed. We report here the incidence and details of three patients who presented with intracranial aneurysm rupture shortly after receiving messenger ribonucleic acid (mRNA) COVID-19 vaccines. CASE DESCRIPTION: We retrospectively reviewed the medical records of individuals who received a first and/ or second dose of mRNA COVID-19 vaccine between March 6, 2021, and June 14, 2021, in a rural district in Japan, and identified the occurrences of aneurysmal SAH within 3 days after mRNA vaccination. We assessed incidence rates (IRs) for aneurysmal SAH within 3 days after vaccination and spontaneous SAH for March 6–June 14, 2021, and for the March 6–June 14 intervals of a 5-year reference period of 2013–2017. We assessed the incidence rate ratio (IRR) of aneurysmal SAH within 3 days after vaccination and spontaneous SAH compared to the crude incidence in the reference period (2013–2017). Among 34,475 individuals vaccinated during the study period, three women presented with aneurysmal SAH (IR: 1058.7/100,000 person-years), compared with 83 SAHs during the reference period (IR: 20.7/100,000 persons-years). IRR was 0.026 (95% confidence interval [CI] 0.0087–0.12; P < 0.001). A total of 28 spontaneous SAHs were verified from the Iwate Stroke Registry database during the same period in 2021 (IR: 34.9/100,000 person-years), and comparison with the reference period showed an IRR of 0.78 (95%CI 0.53–1.18; P = 0.204). All three cases developed SAH within 3 days (range, 0–3 days) of the first or second dose of BNT162b2 mRNA COVID-19 vaccine by Pfizer/BioNTech. The median age at the time of SAH onset was 63.7 years (range, 44– 75 years). Observed locations of ruptured aneurysms in patients were the bifurcations of the middle cerebral artery, internal carotid-posterior communicating artery, and anterior communicating artery, respectively. Favorable outcomes (modified Rankin scale scores, 0–2) were obtained following microsurgical clipping or intra-aneurysm coiling. CONCLUSION: Although the advantages of COVID-19 vaccination appear to outweigh the risks, pharmacovigilance must be maintained to monitor potentially fatal adverse events and identify possible associations.