This study draws on corpus methodology to investigate people’s reactions to COVID-19 vaccination using the data of Macau netizens’ comments on a YouTube channel. Four main topics under discussion were identified based on the word lists. Meanwhile, people were concerned about the activity of vaccines and were also engaged in heated debates on both domestic and foreign vaccines according to the collocation of “疫苗” yìmiáo (vaccine). The discussion topics and concerns varied along with time, evidenced by the results of word lists and collocates of each month. It is also noticeable that some misinformation on vaccines burgeoned and faded before and after the mass vaccination of Macau residents. The supportive voices for the (Chinese) vaccines were building up their momentum over time. This phenomenon lends support to the effective persuasion of gain-framed messages in advocating safe behaviour based on Prospect Theory. Our research has revealed that the corpus-based study of online comments can be leveraged to uncover people’s social behaviour in the pandemic context.