Importance: The COVID-19 pandemic poses an existential threat to many US residential colleges: either they open their doors to students in September or they risk serious financial consequences.

Objective: To define SARS-CoV-2 screening performance standards that would permit the safe return of students to campus for the Fall 2020 semester.

Design: Decision and cost-effectiveness analysis linked to a compartmental epidemic model to evaluate campus screening using tests of varying frequency (daily-weekly), sensitivity (70%-99%), specificity (98%-99.7%), and cost ($10-$50/test). Reproductive numbers Rt = {1.5, 2.5, 3.5} defined three epidemic scenarios, with additional infections imported via exogenous shocks. We generally adhered to US government guidance for parameterization data.

Participants: A hypothetical cohort of 5000 college-age, uninfected students. Main Outcome(s) and Measure(s): Cumulative tests, infections, and costs; daily isolation dormitory census; incremental cost-effectiveness; and budget impact. All measured over an 80-day, abbreviated semester. Results: With Rt = 2.5, daily screening with a 70% sensitive, 98% specific test produces 85 cumulative student infections and isolation dormitory daily census averaging 108 (88% false positives). Screening every 2 (7) days nets 135 (3662) cumulative infections and daily isolation census 66 (252) with 73% (4%) false positives. Across all scenarios, test frequency exerts more influence on outcomes than test sensitivity. Cost-effectiveness analysis selects screening every {2, 1, 7} days with a 70% sensitive test as the preferred strategy for Rt = {2.5, 3.5, 1.5}, implying a screening cost of {$470, $920, $120} per student per semester.

Conclusions & Relevance: Rapid, inexpensive and frequently conducted screening (even if only 70% sensitive) would be cost-effective and produce a modest number of COVID-19 infections. While the optimal screening frequency hinges on the success of behavioral interventions to reduce the base severity of transmission (Rt), this could permit the safe return of student to campus.