Endemicity is not a victory: the unmitigated downside risks of widespread SARS-CoV-2 transmission

Abstract

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.

Pathways to altered virulence of SARS-CoV-2

“…Our work suggests a lack of selective pressure on SARS-CoV-2 to evolve to be less virulent, as the peak of risk of transmission during an infection is temporally separated from the peak of mortality risk by multiple weeks (22)(23)(24). Thus, it can be expected that SARS-CoV-2 variants showing an increased mortality rate are unlikely to experience a loss of transmissibility, as measured by 𝑅𝑅 0 (22).…”

“…Our work suggests a lack of selective pressure on SARS-CoV-2 to evolve to be less virulent, as the peak of risk of transmission during an infection is temporally separated from the peak of mortality risk by multiple weeks (22)(23)(24). Thus, it can be expected that SARS-CoV-2 variants showing an increased mortality rate are unlikely to experience a loss of transmissibility, as measured by 𝑅𝑅 0 (22). Significantly, this suggests that virulence of SARS-CoV-2 variants is likely to be under drift and not natural selection, being free to increase or decrease randomly with ongoing viral evolution.…”

Vaccines alone cannot slow the evolution of SARS-CoV-2

“…Another commonly held perception has been that the virus will attenuate over time to become less virulent [44,50]. This, too, is demonstrably false-variants such as Alpha, Beta, Gamma and Delta all had higher infection fatality rates (IFRs) than the ancestral strain (see Table S3 in [24]), and we have demonstrated in an earlier work that the IFR is not likely to be under strong selection pressure at this point [24],a point made by others as well [51].…”

“…At this point in time, a case can be made that a crucial determinant of the eventual resolution of the crisis phase of the pandemic will hinge on the ongoing rate of viral evolution. Each new variant brings with it a set of unknowns in terms of key viral properties-transmissibility, degree of immune evasion, superspreading, and infection fatality rate (see Table S3 in [24]). A scenario involving repeated waves of infection driven by the emergence of new variants thus poses tremendous challenges for formulating and communicating public health strategy, as has been observed already for previous waves of the pandemic [25,26].…”

The impact of vaccination frequency on COVID-19 public health outcomes: A model-based analysis

“…Frequent boosting coupled with high compliance is predicted to substantially reduce the impact of COVID-19 at the population level. Despite the high transmissibility of omicron (R 0 = 8.2 [60][61][62]), complete suppression of spread is possible with a high degree of compliance and frequent boosting (i.e. approximately 90% compliance with boosters every three months, or perfect compliance with boosters every four months) (Figure 4A).…”