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As the availability of COVID-19 vaccines, it is badly needed to develop vaccination guidelines to prioritize the vaccination delivery in order to effectively stop COVID-19 epidemic and minimize the loss. We evaluated the effect of age-specific vaccination strategies on the number of infections and deaths using an SEIR model, considering the age structure and social contact patterns for different age groups for each of different countries. In general, the vaccination priority should be given to those younger people who are active in social contacts to minimize the number of infections, while the vaccination priority should be given to the elderly to minimize the number of deaths. But this principle may not always apply when the interaction of age structure and age-specific social contact patterns is complicated. Partially reopening schools, workplaces or households, the vaccination priority may need to be adjusted accordingly. Prematurely reopening social contacts could initiate a new outbreak or even a new pandemic out of control if the vaccination rate and the detection rate are not high enough. Our result suggests that it requires at least nine months of vaccination (with a high vaccination rate > 0.1%) for Italy and India before fully reopening social contacts in order to avoid a new pandemic. [ABSTRACT FROM AUTHOR]

Poor drug adherence is considered one of major barriers to achieving the clinical and public health benefits of many pharmacotherapies. In the current paper, we aim to investigate the impact of dose omission on the plasma concentrations of two-compartment pharmacokinetic models with two typical routes of drug administration, namely the intravenous bolus and extravascular first-order absorption. First, we reformulate the classical two-compartment pharmacokinetic models with a new stochastic feature, where a binomial random model of dose intake is integrated. Then, we formalize the explicit expressions of expectation and variance for trough concentrations and limit concentrations, with the latter proved of the existence and uniqueness for steady-state distribution. Moreover, we mathematically demonstrate the strict stationarity and ergodicity of trough concentrations as a Markov chain. In addition, we numerically simulate the impact of drug non-adherence to different extents on the variability and regularity of drug concentration and compare the drug pharmacokinetic preference between one and two compartment pharmacokinetic models. The results of sensitivity analysis also suggest the drug non-adherence as one of the most sensitive model parameters to the expectation of limit concentration. Our modelling and analytical approach can be integrated into the chronic disease models to estimate or quantitatively predict the therapy efficacy with drug pharmacokinetics presumably affected by random dose omissions. [ABSTRACT FROM AUTHOR]

Most models of COVID-19 are implemented at a single micro or macro scale, ignoring the interplay between immune response, viral dynamics, individual infectiousness and epidemiological contact networks. Here we develop a data-driven model linking the within-host viral dynamics to the between-host transmission dynamics on a multilayer contact network to investigate the potential factors driving transmission dynamics and to inform how school closures and antiviral treatment can influence the epidemic. Using multi-source data, we initially determine the viral dynamics and estimate the relationship between viral load and infectiousness. Then, we embed the viral dynamics model into a four-layer contact network and formulate an agent-based model to simulate between-host transmission. The results illustrate that the heterogeneity of immune response between children and adults and between vaccinated and unvaccinated infections can produce different transmission patterns. We find that school closures play a significant effect on mitigating the pandemic as more adults get vaccinated and the virus mutates. If enough infected individuals are diagnosed by testing before symptom onset and then treated quickly, the transmission can be effectively curbed. Our multiscale model reveals the critical role played by younger individuals and antiviral treatment with testing in controlling the epidemic. [ABSTRACT FROM AUTHOR]