Background: The Omicron outbreak is characterized by breakthrough infection and reinfection. If no strategic solution can be found, vaccination-rate-based risk compensation may prolong the COVID-19 crisis. Infection control in university students may have an indirect impact on the COVID-19 burden for other age groups Methods: To reveal the association between related factors and a symptomatic episode of COVID-19, a school-wide web-based questionnaire survey was conducted among university students as a part of the annual health check-up in April, 2023. The positive outcome was confined to the first symptomatic onset during the Omicron variant outbreak. Results: In this self-administered and non-observational survey, risk or protective associations were merely estimated statistically in university students (n = 5,406). In measured factors, karaoke and club/group activities could maintain the statistical significance in adjusted odds ratios (ORs) as (relative) risk factors, and science course, measles/rubella (MR) vaccination, and COVID-19 vaccination remained as (relative) protective factors in adjusted OR analyses. Club/group activities (with member gathering) and karaoke sing-along sessions in university students may frequently have WHO’s three Cs. These risk factors are still important topics for the infection control of COVID-19 in university students. Together with some recent reports from other researchers, the significant protective role of MR vaccine in our survey warrants further clinical investigation. Conclusions: If the breakthrough infection continuously constitutes the majority of infection, real data in test-negative case-control or web-based questionnaire design continue to be important for statistical analysis to determine the minimal requirement of our strategies which may replace COVID-19 vaccines.