BackgroundShortly after Pfizer and Moderna received emergency use authorizations from the Food and Drug Administration, there were increased reports of COVID-19 vaccine-related deaths in the Vaccine Adverse Event Reporting System (VAERS). In January 2021, Major League Baseball legend and Hall of Famer, Hank Aaron, passed away at the age of 86 years from natural causes, just 2 weeks after he received the COVID-19 vaccine. Antivaccination groups attempted to link his death to the Moderna vaccine, similar to other attempts misrepresenting data from the VAERS to spread COVID-19 misinformation.ObjectiveThis study assessed the spread of misinformation linked to erroneous claims about Hank Aaron’s death on Twitter and then characterized different vaccine misinformation and hesitancy themes generated from users who interacted with this misinformation discourse.MethodsAn initial sample of tweets from January 31, 2021, to February 6, 2021, was queried from the Twitter Search Application Programming Interface using the keywords “Hank Aaron” and “vaccine.” The sample was manually annotated for misinformation, reporting or news media, and public reaction. Nonmedia user accounts were also classified if they were verified by Twitter. A second sample of tweets, representing direct comments or retweets to misinformation-labeled content, was also collected. User sentiment toward misinformation, positive (agree) or negative (disagree), was recorded. The Strategic Advisory Group of Experts Vaccine Hesitancy Matrix from the World Health Organization was used to code the second sample of tweets for factors influencing vaccine confidence.ResultsA total of 436 tweets were initially sampled from the Twitter Search Application Programming Interface. Misinformation was the most prominent content type (n=244, 56%) detected, followed by public reaction (n=122, 28%) and media reporting (n=69, 16%). No misinformation-related content reviewed was labeled as misleading by Twitter at the time of the study. An additional 1243 comments on misinformation-labeled tweets from 973 unique users were also collected, with 779 comments deemed relevant to study aims. Most of these comments expressed positive sentiment (n=612, 78.6%) to misinformation and did not refute it. Based on the World Health Organization Strategic Advisory Group of Experts framework, the most common vaccine hesitancy theme was individual or group influences (n=508, 65%), followed by vaccine or vaccination-specific influences (n=110, 14%) and contextual influences (n=93, 12%). Common misinformation themes observed included linking the death of Hank Aaron to “suspicious” elderly deaths following vaccination, claims about vaccines being used for depopulation, death panels, federal officials targeting Black Americans, and misinterpretation of VAERS reports. Four users engaging with or posting misinformation were verified on Twitter at the time of data collection.ConclusionsOur study found that the death of a high-profile ethnic minority celebrity led to the spread of misinformation on Twitter. This misinformation directly challenged the safety and effectiveness of COVID-19 vaccines at a time when ensuring vaccine coverage among minority populations was paramount. Misinformation targeted at minority groups and echoed by other verified Twitter users has the potential to generate unwarranted vaccine hesitancy at the expense of people such as Hank Aaron who sought to promote public health and community immunity.