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Background  In 2019, with the COVID-19 pandemic sweeping across the globe, public health systems worldwide faced severe challenges. Amid the pandemic, one simulation game,  Plague Inc.,  has received substantial attention. This game has indirectly drawn greater public attention to public health issues by simulating pathogen transmission and disease symptoms.    Objective  Against this backdrop, this research investigates whether the gameful experience of  Plague Inc.  has indirectly affected public knowledge, attitudes, and practices (KAP) regarding COVID-19.    Methods  An online survey was conducted through social networking services in Taiwan from May 6-28, 2020.    Results  A total of 486 subjects participated in this study, of which 276 (56.8%) had played  Plague Inc.  This study had several findings. First, participants who had played  Plague Inc.  demonstrated higher levels of knowledge ( P =.03, median 7, IQR 7-8) and attitudes ( P =.007, median 8, IQR 7-8) than participants who had not played  Plague Inc.  (knowledge: median 7, IQR 6-8; attitude: median 7, IQR 6-8). Second, there was a significant correlation between creative thinking (ρ=.127,  P =.04) and dominance (ρ=.122,  P =.04) in attitude. Finally, there was a significant correlation between creative thinking (ρ=.126,  P <.001) and dominance (ρ=.119,  P =.049) in practice.    Conclusions  Serious games highlighting the theme of pathogen transmission may enhance public knowledge and attitudes regarding COVID-19. Furthermore, the creative thinking and dominance involved in gameful experiences may act as critical factors in public attitudes and practices regarding COVID-19. These findings should be further verified through experimental research in the future.

How Gameful Experience Affects Public Knowledge, Attitudes, and Practices Regarding COVID-19 Among the Taiwanese Public: Cross-sectional Study