AbstractObjectivesTo estimate population health outcomes under delayedsecond dose versus standard schedule SARS-CoV-2 mRNA vaccination.DesignAgent-based modeling on a simulated population of 100,000 based on a real-world US county. The simulation runs were replicated 10 times. To test the robustness of these findings, simulations were performed under different estimates for single-dose efficacy and vaccine administration rates, and under the possibility that a vaccine prevents only symptoms but not asymptomatic spread.Settingpopulation level simulation.Participants100,000 agents are included in the simulation, with a representative distribution of demographics and occupations. Networks of contacts are established to simulate potentially infectious interactions though occupation, household, and random interactionsInterventionswe simulate standard Covid-19 vaccination, versus delayed-second-dose vaccination prioritizing first dose. Sensitivity analyses include first-dose vaccine efficacy of 70%, 80% and 90% after day 12 post-vaccination; vaccination rate of 0.1%, 0.3%, and 1% of population per day; assuming the vaccine prevents only symptoms but not asymptomatic spread; and an alternative vaccination strategy that implements delayed-second-dose only for those under 65 years of age.Main outcome measurescumulative Covid-19 mortality over 180 days, cumulative infections and hospitalizations.ResultsOver all simulation replications, the median cumulative mortality per 100,000 for standard versus delayed second dose was 226 vs 179; 233 vs 207; and 235 vs 236; for 90%, 80% and 70% first-dose efficacy, respectively. The delayed-second-dose strategy was optimal for vaccine efficacies at or above 80%, and vaccination rates at or below 0.3% population per day, both under sterilizing and non-sterilizing vaccine assumptions, resulting in absolute cumulative mortality reductions between 26 and 47 per 100,000. The delayed-second-dose for those under 65 performed consistently well under all vaccination rates tested.ConclusionsA delayed-second-dose vaccination strategy, at least for those under 65, could result in reduced cumulative mortality under certain conditions.