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

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.

Modelling optimal vaccination strategies against COVID-19 in a context of Gamma variant predominance in Brazil

“…However, we see in the other results that, as soon as one increases the number of doses available, one strategy begins to be significantly more beneficial than others. These results are supported by the findings in [17] .…”

“…Ferreira et al [17] also demonstrated that first dose efficacy and availability are essential parameters when considering the optimal interval between doses, whereas varying values of infection transmission (effective reproduction number) did not impact estimates. This was also observed in our study, supporting our choice of using various scenarios with fixed probabilities of infection over the time horizon of the study.…”

“…Infection transmission dynamics are encoded in a transition matrix that provides the proportion of individuals moving through model compartments daily [15] . Model structure is an extended SEIR compartmental model [16] , accounting also for asymptomatic, hospitalized, and deceased individuals, thus described as SEAIRHD [17] . The model is structured in 10-year age sub-groups.…”

“…To estimate the number of vaccine doses that should be allocated for the first or second dose, we use a modified version of the dose optimization model developed previously and described in further detail elsewhere [17] , that accounts for varying vaccine production and deployment rates, as well as individuals vaccinated with only one dose (see further details on the SM). This optimization model calculates the number of first or second doses administered by day, given a pre-specified production rate and dose interval, minimizing the number of doses that should be kept in stock while guaranteeing that individuals receive the second dose in a timely manner.…”

Vaccination reduces viral load and accelerates viral clearance in SARS-CoV-2 Delta variant-infected patients

“…However, we need to pay attention to the possibility that some risk factors, such as obesity, diabetes and cancer, may still affect the clinical outcomes of patients [ 36 , 37 ]. In addition, vaccines may differ in protective efficacy, but two-dose vaccination could still significantly reduce the risk of new SARS-CoV-2 infection [ 38 , 39 ]. With the evolution of the SARS-CoV-2 virus, the protective effect of existing vaccines may be reduced, specific vaccine design for different mutant strains may be the focus in the future [ 31 ].…”