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Current models of COVID-19 transmission predict infection from reported or assumed interactions. Here we leverage high-resolution observations of interaction to simulate infectious processes. Ultra-Wide Radio Frequency Identification (RFID) systems were employed to track the real-time physical movements and directional orientation of children and their teachers in 4 preschool classes over a total of 34 observations. An agent-based transmission model combined observed interaction patterns (individual distance and orientation) with CDC-published risk guidelines to estimate the transmission impact of an infected patient zero attending class on the proportion of overall infections, the average transmission rate, and the time lag to the appearance of symptomatic individuals. These metrics highlighted the prophylactic role of decreased classroom density and teacher vaccinations. Reduction of classroom density to half capacity was associated with an 18.2% drop in overall infection proportion while teacher vaccination receipt was associated with a 25.3% drop. Simulation results of classroom transmission dynamics may inform public policy in the face of COVID-19 and similar infectious threats.