Assessing the best time interval between doses in a two-dose vaccination regimen to reduce the number of deaths in an ongoing epidemic of SARS-CoV-2
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Abstract
The SARS-CoV-2 pandemic is a major concern all over the world and, as vaccines became available at the end of 2020, optimal vaccination strategies were subjected to intense investigation. Considering their critical role in reducing disease burden, the increasing demand outpacing production, and that most currently approved vaccines follow a two-dose regimen, the cost-effectiveness of delaying the second dose to increment the coverage of the population receiving the first dose is often debated. Finding the best solution is complex due to the trade-off between vaccinating more people with lower level of protection and guaranteeing higher protection to a fewer number of individuals. Here we present a novel extended age-structured SEIR mathematical model that includes a two-dose vaccination schedule with a between-doses delay modelled through delay differential equations and linear optimization of vaccination rates. By maintaining the minimum stock of vaccines under a given production rate, we evaluate the dose interval that minimizes the number of deaths. We found that the best strategy depends on an interplay between the vaccine production rate and the relative efficacy of the first dose. In the scenario of low first-dose efficacy, it is always better to vaccinate the second dose as soon as possible, while for high first-dose efficacy, the best strategy of time window depends on the production rate and also on second-dose efficacy provided by each type of vaccine. We also found that the rate of spread of the infection does not affect significantly the thresholds of the best window, but is an important factor in the absolute number of total deaths. These conclusions point to the need to carefully take into account both vaccine characteristics and roll-out speed to optimize the outcome of vaccination strategies.
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SciScore for 10.1101/2021.07.28.21261200: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
No key resources detected.
Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Their results agree with ours but it has the limitation of not guaranteeing that the mean period with single-dose protection is preserved in a varying vaccination rate, which is only possible using a more complex formulation, such as delay differential equations as used here. They also argue that, while the “release” strategy enables better allocation of vaccines, in a real-world situation the implementation of such strategy is too complicated …
SciScore for 10.1101/2021.07.28.21261200: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
No key resources detected.
Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Their results agree with ours but it has the limitation of not guaranteeing that the mean period with single-dose protection is preserved in a varying vaccination rate, which is only possible using a more complex formulation, such as delay differential equations as used here. They also argue that, while the “release” strategy enables better allocation of vaccines, in a real-world situation the implementation of such strategy is too complicated to manage. While we agree that this strategy adds a complication factor, we also believe that stock optimization models such as the one developed in this study could be linked to vaccination databases and, as the vaccination roll-outs to tackle the SARS-CoV-2 pandemic were centralized by the national health systems, thus allowing more efficient allocation of vaccines. Throughout this study, we assumed that post second-dose efficacies do not depend on the time-window between doses, although evidence suggests that this is not the case for AZD1222 vaccine [36]. This simplifying assumption probably leads to a slight underestimation of the benefits of increasing the lag between doses for this vaccine. We have also assumed that first dose efficacy is constant over time, when in reality it builds up over approximately 2 weeks and wanes later on [27, 33]. This can be addressed using agent-based models [22], or age-of-infection models in a differential equations formulation, but that would greatly increase the complexity of the algorithm. This d...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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