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BACKGROUND The Centers for Disease Control and Prevention (CDC) is a national public health protection agency in the US. With the escalating impact of COVID-19 pandemic on society in the United States and around the world, the CDC has become one of the focal points of public discussion. OBJECTIVE This study aims to identify the topics and the overarching themes of the topics emerging from the public COVID-19-related discussion on Twitter about the CDC, and to further provide insight into public\'s concerns, focus of attention, perception of the CDC\'s current performance, and expectations from the CDC. METHODS Tweets were downloaded from a large-scale COVID-19 Twitter chatter dataset from March 11, 2020, when the WHO declared COVID-19 a pandemic, to August 14, 2020. We used R to clean the tweets and retain the tweets that contain any of the following keywords (\'cdc\', \'CDC\', \'centers for disease control and prevention\', \'CDCgov\', \'cdcgov\'), while eliminating all 91 tweets by CDC itself. The final data included in the analysis consists of 290,764 unique tweets from 152,314 different users. We used R to perform the Latent Dirichlet Allocation (LDA) algorithm for topic modeling. RESULTS The Twitter data generated sixteen topics that the public linked to the CDC when they talked about COVID-19. Among the topics, the most discussed was COVID-19 death counts, accounting for 12.16% of the total 290,764 tweets in the analysis, followed by general opinions about credibility of the CDC and other authorities, and the CDC\'s COVID-19 guidelines, with over 20,000 tweets for each. The sixteen topics fall into four overarching themes: knowing the virus and the situation, policy and government actions, response guidelines, and general opinion about credibility. CONCLUSIONS Social media such as Twitter provide a valuable database for public opinion. In a protracted pandemic such as COVID-19, quickly and efficiently identifying the topics within the public discussion on Twitter would help public health agencies understand the public\'s concerns, focus of attention, and expectation from them and further provide insight for the next-round communication with the public. CLINICALTRIAL
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