Abstract
Background: The start of 2021 was marked by the initiation of a global vaccination campaign against the novel coronavirus SARS-CoV-2. Formulating an optimal distribution strategy under social and economic constraints is challenging. Optimal distribution is additionally constrained by the potential emergence of vaccine resistance. Analogous to chronic low-dose antibiotic exposure, recently inoculated individuals who are not yet immune play an outsized role in the emergence of resistance. Classical epidemiological modelling is well suited to explore how the behavior of the inoculated population impacts the total number of infections over the entirety of an epidemic. Methods: A deterministic model of epidemic evolution is analyzed, with seven compartments defined by their relationship to the emergence of vaccine-resistant mutants and representing three susceptible populations, three infected populations, and one recovered population. This minimally computationally intensive design enables simulation of epidemics across a broad parameter space. The results are used to identify conditions minimizing the cumulative number of infections. Results: When an escape variant is only modestly less infectious than the originating strain within a naïve population, the cumulative number of infections does not monotonically decrease with the rate of vaccine distribution. Analysis of the model also demonstrates that inoculated individuals play a major role in the mitigation or exacerbation of vaccine-resistant outbreaks. Modulating the rate of host-host contact for the inoculated population by less than an order of magnitude can alter the cumulative number of infections by more than 20%. Conclusions: Mathematical modeling shows that limiting post-vaccination contacts can perceptibly affect the course of an epidemic. The consideration of limitations on post-vaccination contacts remains relevant for the entire duration of any vaccination campaign including the current status of SARS-CoV-2 vaccination.
Highlights
The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the COVID-19 pandemic motivated dramatic public health intervention including recommendations for isolation and quarantine throughout most of 2020 and early 2021.1 The beginning of 2021 was marked by widespread vaccine distribution which continues at an accelerating pace at the time of this writing
Varying q within an order of magnitude alters the cumulative number of infections added or subtracted by more than 20% of the cumulative number of infections in the absence of vaccination, RNull, again demonstrating the critical role played by inoculated hosts with respect to vaccine escape
Contact rates for recently vaccinated and not yet fully immune hosts can have a substantial impact on the outcomes of vaccination campaigns
Summary
The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the COVID-19 pandemic motivated dramatic public health intervention including recommendations for isolation and quarantine throughout most of 2020 and early 2021.1 The beginning of 2021 was marked by widespread vaccine distribution which continues at an accelerating pace at the time of this writing. Vaccinated, inoculated, hosts that are not yet immune are a key population to consider This population remains highly susceptible to infection with the originating strain, and in these hosts, mutations conferring resistance are more likely to provide a selective advantage. A substantial fraction or even most of the virus shed by such hosts will be resistant mutants This situation is analogous to the administration of a low-dose antibiotic regime.[14,15] In both cases, the pathogen is introduced to a susceptible host and is subject to elevated selective pressure towards the emergence of resistant (escape) variants. Results: When an escape variant is only modestly less infectious than the originating strain within a naïve population, the cumulative number of infections does not monotonically decrease with the rate of vaccine distribution. The consideration of limitations on post-vaccination contacts remains relevant for the entire duration of any vaccination campaign including version 2
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