Shielding under endemic SARS-CoV-2 conditions is easier said than done: a model-based analysis

Stoddard, Madison; Yuan, Lin; Sarkar, Sharanya; Mazewski, Matthew; Egeren, Debra Van; Mangalaganesh, Shruthi; Nolan, Ryan P.; Rogers, Michael S.; Hather, Greg; White, Laura F.; Chakravarty, Arijit

doi:10.1101/2023.01.22.23284884

Cited by 5 publications

(11 citation statements)

References 60 publications

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“…Outcomes for invasion scenarios in which the novel strain induces less durable immunity than the original strain. The duration of immunity against wild-type SARS-CoV-2 infection is estimated to be 550 days [42]. …”

Section: Resultsmentioning

confidence: 99%

“…As we have explored in other analyses using agent-based models, the immunity landscape is more complex than this SIRS model can capture. This complexity arises due to heterogeneity in individual exposure to infection and vaccination, interindividual variability in antibody durability, and neutralizing antibody build-up over successive infections and vaccinations [42,57]. In particular, we surmise that the build-up of neutralizing potency over successive infections may cause the apparent cross-immunities between strains to not be fixed over time.…”

Section: Discussionmentioning

confidence: 99%

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Antibody escape, the risk of serotype formation, and rapid immune waning: modeling the implications of SARS-CoV-2 immune evasion

Albright

Egeren

Thakur

et al. 2023

Preprint

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As the COVID-19 pandemic progresses, widespread community transmission of SARS-CoV-2 has ushered in a volatile era of viral immune evasion rather than the much-heralded stability of "endemicity" or "herd immunity." At this point, an array of viral variants has rendered essentially all monoclonal antibody therapeutics obsolete and strongly undermined the impact of vaccinal immunity on SARS-CoV-2 transmission. In this work, we demonstrate that antigenic drift resulting in evasion of pre-existing immunity is highly evolutionarily favored and likely to cause waves of short-term transmission. In the long-term, invading variants that induce weak cross-immunity against pre-existing strains may co-circulate with those pre-existing strains. This would result in the formation of serotypes that increase disease burden, complicate SARS-CoV-2 control and raise the potential for increases in viral virulence. Less durable immunity does not drive positive selection as a trait, but such strains may transmit at high levels if they establish. Overall, our results draw attention to the importance of inter-strain cross-immunity as a driver of transmission trends and the importance of early immune evasion data to predict the trajectory of the pandemic.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Antibody escape, the risk of serotype formation, and rapid immune waning: modeling the implications of SARS-CoV-2 immune evasion

Albright

Egeren

Thakur

et al. 2023

Preprint

Self Cite

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show abstract

“…Thus, this model accounts for inter-individual heterogeneity in nAb waning rates after vaccination [51] and infection [54], a steady rate of nAb potency loss due to immune evasion, variability in contact behavior between individuals, and variation in severe disease susceptibility due to age. For the heterogeneity in outcomes simulations, we assumed that 50% of the population is vaccinated, which is in rough agreement with the fraction of the eligible population that has received a first booster in the US [59].…”

Section: Agent-based Simulation Of Infection and Mortality Burdenmentioning

confidence: 99%

“…Lastly, as the pandemic has progressed, it has become clear that the delayed post-acute sequelae of COVID-19 ("Long COVID") also represent an important component of the morbidity burden of SARS-CoV-2 infections [52,53], with the potential for substantial impact on population-level health and economic outcomes [54][55][56]. The risk of long COVID upon infection has also been shown to be only modestly reduced by vaccination [53,57,58].…”

Section: Introductionmentioning

confidence: 99%

“…In our prior work, we applied mixed-effects modeling to published SARS-CoV-2 nAb titers post-vaccination [51] and found a wide range of half-lives, with a 95% confidence interval ranging from 33-320 days. Lastly, as the pandemic has progressed, it has become clear that the delayed post-acute sequelae of COVID-19 (“Long COVID”) also represent an important component of the morbidity burden of SARS-CoV-2 infections [52,53], with the potential for substantial impact on population-level health and economic outcomes [54–56]. The risk of long COVID upon infection has also been shown to be only modestly reduced by vaccination [53,57,58].…”

Section: Introductionmentioning

confidence: 99%

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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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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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Shielding under endemic SARS-CoV-2 conditions is easier said than done: a model-based analysis

Cited by 5 publications

References 60 publications

Antibody escape, the risk of serotype formation, and rapid immune waning: modeling the implications of SARS-CoV-2 immune evasion

Antibody escape, the risk of serotype formation, and rapid immune waning: modeling the implications of SARS-CoV-2 immune evasion

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

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

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