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COVID vaccine hesitancy among patients with sickle cell disease (SCD) was prevalent during the pandemic. This subset of vaccine hesitancy within the SCD population is of particular concern due to the elevated risk of severe illness associated with COVID-19 in individuals with SCD. Numerous factors contribute to vaccine hesitancy in this context, including concerns specific to SCD, such as potential interactions with disease-modifying therapies, uncertainty regarding vaccine efficacy in this population, mistrust in healthcare systems, and historical disparities in healthcare access and delivery. Underlying psychological factors, such as fear and anxiety, may also influence vaccine hesitancy in patients with SCD.