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Background A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak affecting 52 people from a large school community in Santiago, Chile, was identified (12 March) 9 days after the first case in the country. We assessed the magnitude of the outbreak and the role students and staff played using self-administered antibody detection tests and a self-administered survey. Methods The school was closed on 13 March, and the entire community was placed under quarantine. We implemented a home-delivery, self-administered, immunoglobin (Ig) G/IgM antibody test and survey to a classroom-stratified sample of students and all staff from 4–19 May. We aimed to determine the overall seroprevalence rates by age group, reported symptoms, and contact exposure, and to explore the dynamics of transmission. Results The antibody positivity rates were 9.9% (95% confidence interval [CI], 8.2–11.8) for 1009 students and 16.6% (95% CI, 12.1–21.9) for 235 staff. Among students, positivity was associated with a younger age (P  = .01), a lower grade level (P  = .05), prior real-time polymerase chain reaction (RT-PCR) positivity (P  = .03), and a history of contact with a confirmed case (P  < .001). Among staff, positivity was higher in teachers (P  = .01) and in those previously RT-PCR positive (P  < .001). Excluding RT-PCR–positive individuals, antibody positivity was associated with fever in adults and children (P  = .02 and P  = .002, respectively), abdominal pain in children (P  = .001), and chest pain in adults (P  = .02). Within antibody-positive individuals, 40% of students and 18% of staff reported no symptoms (P  = .01). Conclusions Teachers were more affected during the outbreak and younger children were at a higher risk for infection, likely because index case(s) were teachers and/or parents from the preschool. Self-administered antibody testing, supervised remotely, proved to be a suitable and rapid tool. Our study provides useful information for school reopenings. [ABSTRACT FROM AUTHOR]