Endemicity Is Not a Victory: The Unmitigated Downside Risks of Widespread SARS-CoV-2 Transmission

We have entered a new phase of the ongoing COVID-19 pandemic, as the strategy of relying solely on the current SARS-CoV-2 vaccines to bring the pandemic to an end has become infeasible. In response, public-health authorities in many countries have advocated for a strategy of using the vaccines to limit morbidity and mortality while permitting unchecked SARS-CoV-2 spread (“learning to live with the disease”). The feasibility of this strategy is critically dependent on the infection fatality rate (IFR) of COVID-19. An expectation exists, both in the lay public and in the scientific community, that future waves of the virus will exhibit decreased IFR, either due to viral attenuation or the progressive buildup of immunity. In this work, we examine the basis for that expectation, assessing the impact of virulence on transmission. Our findings suggest that large increases in virulence for SARS-CoV-2 would result in minimal loss of transmission, implying that the IFR may be free to increase or decrease under neutral evolutionary drift. We further examine the effect of changes in the IFR on the steady-state death toll under conditions of endemic COVID-19. Our modeling suggests that endemic SARS-CoV-2 implies vast transmission resulting in yearly US COVID-19 death tolls numbering in the hundreds of thousands under many plausible scenarios, with even modest increases in the IFR leading to an unsustainable mortality burden. Our findings thus highlight the critical importance of enacting a concerted strategy (involving for example global access to vaccines, therapeutics, prophylactics and nonpharmaceutical interventions) to suppress SARS-CoV-2 transmission, thereby reducing the risk of catastrophic outcomes. Our findings also highlight the importance of continued investment in novel biomedical interventions to prevent viral transmission.