Nationwide Cohort observational study on the safety and efficacy of COVID-19 vaccination in patients with Moyamoya disease

www.nature.com/scientificreports OPEN Nationwide Cohort observational study on the safety and efficacy of COVID-19 vaccination in patients with Moyamoya disease Hyoung Soo Byoun1, Si Un Lee2,4, Yu Deok Won3,4, Tae Won Choi2, Sang Hyo Lee2, Young-Deok Kim2, Seung Pil Ban2, Jae Seung Bang2, O-Ki Kwon2 & Chang Wan Oh2 The safety and efficacy of coronavirus disease 2019 (COVID-19) vaccination in patients diagnosed with Moyamoya disease (MMD) have not been established. Using National Health Insurance Service data, this study analyzed the occurrence of stroke-related events and mortality following COVID-19 vaccination among patients diagnosed with MMD from 2008 to 2020. Among 10,297 MMD patients, 296 (2.9%) experienced events and 175 (1.7%) died in 2021. Significant risk factors for events included ages 50–59 (Odds Ratio [OR] 3.29; P = 0.022) and 60 or above (OR 5.20; P = 0.001) (reference group: age in 20s), low BMI (OR 2.00; P = 0.011), previous stroke (OR 1.96; P < 0.001), and COVID-19 infection (OR 2.28; P = 0.034). Female (OR 0.64 [95% CI 0.50–0.82]; p = 0.011), revascularization surgery (RS) (OR 0.38 [95% CI 0.21–0.70]; p < 0.001), and vaccination (OR 0.17 [95% CI 0.13–0.22]; p < 0.001) were associated with reduced odds of stroke-related events. For mortality, significant risks were age over 60 (OR 7.09; P = 0.008), low BMI (OR 3.87; P = 0.001), and prior stroke (OR 1.74; p = 0.004), while being female, RS (OR 0.41; P = 0.022), and vaccination (OR 0.12; P < 0.001) were associated with a lower frequency of mortality. mRNA vaccines were associated with a significantly lower incidence of events, mortality, and COVID-19 infections compared to vector vaccines. COVID-19 vaccination is linked to reduced stroke-related events and mortality in MMD patients, with mRNA vaccines showing a significantly lower incidence compared to vector vaccines. COVID-19 infection raises the risk of events, underscoring the benefit of vaccination. Keywords Coronavirus disease, Moyamoya disease, Stroke, Vaccination Numerous studies have underscored cerebral venous sinus thrombosis (CVST) due to vaccine-induced thrombotic thrombocytopenia (VITT) as a critical, albeit rare, adverse effect of coronavirus disease 2019 (COVID-19) vaccination. It is reported that nearly half of the patients who experience strokes related to CVST endure severe outcomes1,2. Despite these concerns, the literature suggests that the benefits of proceeding with COVID-19 vaccination outweigh the risks associated with complications from a COVID-19 infection3–6. However, there remains a pronounced scarcity of data concerning the risks tied to the adverse effects of COVID-19 vaccination in patients with moyamoya disease (MMD) despite isolated case reports documenting cerebral hemorrhages post-vaccination in individuals with pre-existing vascular conditions7. MMD, a rare condition with a notably high prevalence in Korea, Japan, Taiwan, and China8–11, features bilateral constriction or closure at the bifurcation of the distal internal carotid artery, along with the emergence of compensatory arterial collateral formations at the base of the brain12. Initial manifestations of hemorrhagic and ischemic strokes in MMD cohorts are quantified at 17% and 33%, respectively. Longitudinal observations further elucidate that recurrent events escalate to 30–60% for hemorrhagic strokes and 65–82% for ischemic strokes. Notably, even in a hemodynamically compensated state, patients with symptomatic MMD encounter substantial risks for subsequent cerebrovascular accidents, with a 5-year and 10-year stroke risk of 15% and 40%, respectively13–17. There have been reports of instances where patients diagnosed with MMD suffered cerebral 1Department of Neurosurgery, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju-si, Korea. 2Department of Neurosurgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Korea. 3Department of Neurosurgery, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri-si, Korea. 4Si Un Lee and Yu Deok Won contributed equally to this work as corresponding authors. email: ; Scientific Reports | (2024) 14:24400 | https://doi.org/10.1038/s41598-024-73940-5 1 www.nature.com/scientificreports/ hemorrhages subsequent to COVID-19 vaccination, resulting in either fatality or significant disability18,19. These incidents have highlighted the urgent need for research into the impact of vaccination on patients with MMD. The rarity of MMD introduces challenges in the precise evaluation of stroke incidence and risk subsequent to COVID-19 vaccination. However, the National Health Insurance Service (NHIS) in Korea, through its comprehensive compilation of medical records covering 98% of the population and the classification of MMD as a specially noted condition, provides a distinct and valuable dataset. This resource enables the undertaking of extensive observational studies, thereby significantly improving the robustness and reliability of the resultant data. Therefore, this study is designed to examine the effects of COVID-19 vaccination on the incidence of stroke in patients with MMD, utilizing data sourced from the NHIS and focusing on vaccinations administered during the year 2021. Methods Data source This study utilized data sourced from the NHIS, comprising medical insurance billing records. Notably, approximately 97% of the Korean population is registered with the NHIS, enabling comprehensive documentation of all insurance-based medical interventions. The NHIS database encompasses a wide array of records, including hospital admissions, outpatient visits, pharmaceutical prescriptions, and national health examination outcomes. Korean adults are mandated to partake in biannual health screenings conducted by the NHIS, which assess vital statistics such as height, weight, and blood pressure (BP), in addition to conducting urine and blood laboratory tests. Participants are also required to complete questionnaires detailing their medical history, familial health background, and lifestyle habits. Significantly, the registration of serious or rare diseases within the NHIS registry adheres to stringent criteria, rendering the database an invaluable resource for conducting epidemiological research on large cohorts with respect to grave or uncommon ailments. The reliability of the NHIS data has been corroborated through numerous studies, affirming its utility in the field of medical research20–24. Using the International Classification of Diseases, 10th Revision (ICD-10) diagnostic codes, we collected data from patients with primary outcomes or medical histories. Statement of ethics The current study was approved by the Institutional Review Board and Ethical Committee of Seoul National University Bundang Hospital (X-1910-572-903), and the requirement for obtaining individual patient consent was waived owing t (...truncated)