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

Stoddard, Madison; Novokhodko, Alexander; Sarkar, Sharanya; Egeren, Debra Van; White, Laura F.; Hochberg, Natasha S.; Rogers, Michael S.; Zetter, Bruce R.; Joseph‐McCarthy, Diane; Chakravarty, Arijit

doi:10.3390/covid2120121

Cited by 3 publications

(4 citation statements)

References 106 publications

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“…The findings presented here are broadly consistent with previously published work by us 83 , where we showed that even small changes in the IFR under endemic conditions could lead to large death tolls. Here, we have extended that work by demonstrating behavior under excursions from endemicity.…”

Section: Discussionsupporting

confidence: 93%

The gray swan: model-based assessment of the risk of sudden failure of hybrid immunity to SARS-CoV-2

Stoddard¹,

Yuan²,

Sarkar

et al. 2023

Preprint

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In the fourth year of the COVID-19 pandemic, public health authorities worldwide have adopted a strategy of learning to live with SARS-CoV-2. This has involved the removal of measures for limiting viral spread, resulting in a large burden of recurrent SARS-CoV-2 infections. Crucial for managing this burden is the concept of the so-called wall of hybrid immunity, through repeated reinfections and vaccine boosters, to reduce the risk of severe disease and death. Protection against both infection and severe disease is provided by the induction of neutralizing antibodies (nAbs) against SARS-CoV-2. However, pharmacokinetic (PK) waning and rapid viral evolution both degrade nAb binding titers. The recent emergence of variants with strongly immune evasive potential against both the vaccinal and natural immune responses raises the question of whether the wall of population-level immunity can be maintained in the face of large jumps in nAb binding potency. Here we use an agent-based simulation to address this question. Our findings suggest large jumps in viral evolution may cause failure of population immunity resulting in sudden increases in mortality. As a rise in mortality will only become apparent in the weeks following a wave of disease, reactive public health strategies will not be able to provide meaningful risk mitigation. Learning to live with the virus could thus lead to large death tolls with very little warning. Our work points to the importance of proactive management strategies for the ongoing pandemic, and to the need for multifactorial approaches to COVID-19 disease control.

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Section: Discussionsupporting

confidence: 93%

The gray swan: model-based assessment of the risk of sudden failure of hybrid immunity to SARS-CoV-2

Stoddard¹,

Yuan²,

Sarkar

et al. 2023

Preprint

Self Cite

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“…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 [60–62]), 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).…”

Section: Resultsmentioning

confidence: 99%

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

Stoddard¹,

Yuan²,

Sarkar

et al. 2023

Preprint

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While the rapid deployment of SARS-CoV-2 vaccines had a significant impact on the ongoing COVID-19 pandemic, rapid viral immune evasion and waning neutralizing antibody titers have degraded vaccine efficacy. Nevertheless, vaccine manufacturers and public health authorities have a number of levers at their disposal to maximize the benefits of vaccination. Here, we use an agent-based modeling framework coupled with the outputs of a population pharmacokinetic model to examine the impact of boosting frequency and durability of vaccinal response on vaccine efficacy. Our work suggests that repeated dosing at frequent intervals (multiple times a year) may offset the degradation of vaccine efficacy, preserving their utility in managing the ongoing pandemic. Our work relies on assumptions about antibody accumulation and the tolerability of repeated vaccine doses. Given the practical significance of potential improvements in vaccinal utility, clinical research to better understand the effects of repeated vaccination would be highly impactful. These findings are particularly relevant as public health authorities worldwide seek to reduce the frequency of boosters to once a year or less. Our work suggests practical recommendations for vaccine manufacturers and public health authorities and draws attention to the possibility that better outcomes for SARS-CoV-2 public health remain within reach.

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“…Another commonly held perception has been that the virus will attenuate over time to become less virulent [48,54]. This is also 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 [55]. Another common misconception is that T-cell activation by vaccines should provide stable protection against infection or severe disease.…”

Section: Discussionmentioning

confidence: 99%

“…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-the transmissibility, the degree of immune evasion, the 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 strategies, as has been observed already for previous waves of the pandemic [25,26].…”

Section: Introductionmentioning

confidence: 99%

Vaccines Alone Cannot Slow the Evolution of SARS-CoV-2

Egeren

Stoddard²,

White

et al. 2023

Vaccines

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The rapid emergence of immune-evading viral variants of SARS-CoV-2 calls into question the practicality of a vaccine-only public-health strategy for managing the ongoing COVID-19 pandemic. It has been suggested that widespread vaccination is necessary to prevent the emergence of future immune-evading mutants. Here, we examined that proposition using stochastic computational models of viral transmission and mutation. Specifically, we looked at the likelihood of emergence of immune escape variants requiring multiple mutations and the impact of vaccination on this process. Our results suggest that the transmission rate of intermediate SARS-CoV-2 mutants will impact the rate at which novel immune-evading variants appear. While vaccination can lower the rate at which new variants appear, other interventions that reduce transmission can also have the same effect. Crucially, relying solely on widespread and repeated vaccination (vaccinating the entire population multiple times a year) is not sufficient to prevent the emergence of novel immune-evading strains, if transmission rates remain high within the population. Thus, vaccines alone are incapable of slowing the pace of evolution of immune evasion, and vaccinal protection against severe and fatal outcomes for COVID-19 patients is therefore not assured.

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

Cited by 3 publications

References 106 publications

The gray swan: model-based assessment of the risk of sudden failure of hybrid immunity to SARS-CoV-2

The gray swan: model-based assessment of the risk of sudden failure of hybrid immunity to SARS-CoV-2

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

Vaccines Alone Cannot Slow the Evolution of SARS-CoV-2

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