Intermediate levels of asymptomatic transmission can lead to the highest levels of epidemic fatalities

Abstract Asymptomatic infections have hampered the ability to characterize and prevent the transmission of SARS-CoV-2 throughout the ongoing pandemic. Even though asymptomatic infections reduce severity at the individual level, they can make population-level outcomes worse if asymptomatic individuals—unaware they are infected—transmit more than symptomatic individuals. Using an epidemic model, we show that intermediate levels of asymptomatic infection lead to the highest levels of epidemic fatalities when the increase in asymptomatic transmission, due either to individual behavior or mitigation efforts, is strong. We generalize this result to include presymptomatic transmission, showing how intermediate levels of non-symptomatic transmission can lead to the highest levels of fatalities. Finally, we extend our framework to illustrate how the intersection of asymptomatic spread and immunity profiles determine epidemic trajectories, including population-level severity, of future variants.