LAUSR

Significance Decisions surrounding how to safely reopen universities directly impact 7% of the US population (students, staff) and indirectly impact tens of millions more (families, communities). After witnessing large COVID-19 outbreaks among students from August 2020 to the present, universities want to provide safety while minimizing social and financial costs, despite uncertainty about vaccine hesitancy, vaccine efficacy, more transmissible variants with the potential for immune escape, and community prevalence. When the Delta variant is dominant, we find substantial risk reduction in moving student populations from mostly (75%) to fully (100%) vaccinated, in testing vaccinated students once per week even when all students are vaccinated, and in more frequent testing targeted to the most social groups of students. We consider epidemiological modeling for the design of COVID-19 interventions in university populations, which have seen significant outbreaks during the pandemic. A central challenge is sensitivity of predictions to input parameters coupled with uncertainty about these parameters. Nearly 2 y into the pandemic, parameter uncertainty remains because of changes in vaccination efficacy, viral variants, and mask mandates, and because universities’ unique characteristics hinder translation from the general population: a high fraction of young people, who have higher rates of asymptomatic infection and social contact, as well as an enhanced ability to implement behavioral and testing interventions. We describe an epidemiological model that formed the basis for Cornell University’s decision to reopen for in-person instruction in fall 2020 and supported the design of an asymptomatic screening program instituted concurrently to prevent viral spread. We demonstrate how the structure of these decisions allowed risk to be minimized despite parameter uncertainty leading to an inability to make accurate point estimates and how this generalizes to other university settings. We find that once-per-week asymptomatic screening of vaccinated undergraduate students provides substantial value against the Delta variant, even if all students are vaccinated, and that more targeted testing of the most social vaccinated students provides further value.