No excess risk of death or multimorbidity following hemorrhagic stroke after mRNA vaccination compared with historical cases: a population-based cohort study

Abstract

Introduction While the association between hemorrhagic stroke and prior COVID-19 mRNA vaccination remains inconclusive, an examination of its prognosis may generate evidence on the potential causality of this relationship. If a causal link does exist, transient vaccine-related mechanisms (e.g., thrombocytopenia) might lead to a more favorable prognosis than naturally acquired cases. Aims This study aimed to compare the prognosis of postvaccination hemorrhagic stroke and historical conventional cases with the same clinical diagnoses. Methods A retrospective cohort study was conducted using a territory-wide electronic public healthcare database in Hong Kong, linked with population-based vaccination records. Since the roll-out of mRNA Vaccines (BNT162b2), patients aged 18 years or older hospitalized with hemorrhagic stroke within 28 days after mRNA vaccination were compared with conventional hemorrhagic stroke recorded between 2016 and 2017. The two-year follow-up period began from the diagnosis of hemorrhagic stroke. All-cause mortality and multimorbidity were examined using Cox proportional hazards models, with 95% confidence intervals (95%CIs) derived from bootstrap resampling (1000 iterations). Results A total of 2578 patients were included for analysis: 110 in the postvaccination group and 2468 in the conventional group. Over the two-year follow-up period, all-cause death occurred in 27.27% (30/110) of the postvaccination group versus 29.78% (735/2468) in the conventional group. Multimorbidity was observed in 63.64% (70/110) of postvaccination cases and 73.14% (1805/2468) of conventional cases, respectively. Adjusted analyses showed no significant differences in all-cause mortality (adjusted Hazard Ratio [aHR] = 0.93, 95%CI:0.64-1.28) or multimorbidity risk (aHR = 0.85, 95%CI:0.66-1.05) between the two groups. Conclusion Hemorrhagic stroke following mRNA vaccination had a similar long-term prognosis with conventional cases. These findings may suggest that most post-vaccination hemorrhagic strokes are coincidental rather than vaccine-induced and do not confer a different prognosis.