No Arabic abstract
How to strategically allocate the available vaccines is a crucial issue for pandemic control. In this work, we propose a mathematical framework for optimal stabilizing vaccine allocation, where our goal is to send the infections to zero as soon as possible with a fixed number of vaccine doses. This framework allows us to efficiently compute the optimal vaccine allocation policy for general epidemic spread models including SIS/SIR/SEIR and a new model of COVID-19 transmissions. By fitting the real data in New York State to our framework, we found that the optimal stabilizing vaccine allocation policy suggests offering vaccines priority to locations where there are more susceptible people and where the residents spend longer time outside the home. Besides, we found that offering vaccines priority to young adults (20-29) and middle-age adults (20-44) can minimize the cumulative infected cases and the death cases. Moreover, we compared our method with five age-stratified strategies in cite{bubar2021model} based on their epidemics model. We also found its better to offer vaccine priorities to young people to curb the disease and minimize the deaths when the basic reproduction number $R_0$ is moderately above one, which describes the most world during COVID-19. Such phenomenon has been ignored in cite{bubar2021model}.
As a common strategy of contagious disease containment, lockdown will inevitably weaken the economy. The ongoing COVID-19 pandemic underscores the trade-off arising from public health and economic cost. An optimal lockdown policy to resolve this trade-off is highly desired. Here we propose a mathematical framework of pandemic control through an optimal non-uniform lockdown, where our goal is to reduce the economic activity as little as possible while decreasing the number of infected individuals at a prescribed rate. This framework allows us to efficiently compute the optimal lockdown policy for general epidemic spread models, including both the classical SIS/SIR/SEIR models and a new model of COVID-19 transmissions. We demonstrate the power of this framework by analyzing publicly available data of inter-county travel frequencies to analyze a model of COVID-19 spread in the 62 counties of New York State. We find that an optimal lockdown based on epidemic status in April 2020 would have reduced economic activity more stringently outside of New York City compared to within it, even though the epidemic was much more prevalent in New York City at that point. Such a counterintuitive result highlights the intricacies of pandemic control and sheds light on future lockdown policy design.
We apply optimal control theory to a generalized SEIR-type model. The proposed system has three controls, representing social distancing, preventive means, and treatment measures to combat the spread of the COVID-19 pandemic. We analyze such optimal control problem with respect to real data transmission in Italy. Our results show the appropriateness of the model, in particular with respect to the number of quarantined/hospitalized (confirmed and infected) and recovered individuals. Considering the Pontryagin controls, we show how in a perfect world one could have drastically diminish the number of susceptible, exposed, infected, quarantined/hospitalized, and death individuals, by increasing the population of insusceptible/protected.
The recent global surge in COVID-19 infections has been fueled by new SARS-CoV-2 variants, namely Alpha, Beta, Gamma, Delta, etc. The molecular mechanism underlying such surge is elusive due to 4,653 non-degenerate mutations on the spike protein, which is the target of most COVID-19 vaccines. The understanding of the molecular mechanism of transmission and evolution is a prerequisite to foresee the trend of emerging vaccine-breakthrough variants and the design of mutation-proof vaccines and monoclonal antibodies. We integrate the genotyping of 1,489,884 SARS-CoV-2 genomes isolates, 130 human antibodies, tens of thousands of mutational data points, topological data analysis, and deep learning to reveal SARS-CoV-2 evolution mechanism and forecast emerging vaccine-escape variants. We show that infectivity-strengthening and antibody-disruptive co-mutations on the S protein RBD can quantitatively explain the infectivity and virulence of all prevailing variants. We demonstrate that Lambda is as infectious as Delta but is more vaccine-resistant. We analyze emerging vaccine-breakthrough co-mutations in 20 countries, including the United Kingdom, the United States, Denmark, Brazil, and Germany, etc. We envision that natural selection through infectivity will continue to be the main mechanism for viral evolution among unvaccinated populations, while antibody disruptive co-mutations will fuel the future growth of vaccine-breakthrough variants among fully vaccinated populations. Finally, we have identified the co-mutations that have the great likelihood of becoming dominant: [A411S, L452R, T478K], [L452R, T478K, N501Y], [V401L, L452R, T478K], [K417N, L452R, T478K], [L452R, T478K, E484K, N501Y], and [P384L, K417N, E484K, N501Y]. We predict they, particularly the last four, will break through existing vaccines. We foresee an urgent need to develop new vaccines that target these co-mutations.
We propose and study a new mathematical model of the human immunodeficiency virus (HIV). The main novelty is to consider that the antibody growth depends not only on the virus and on the antibodies concentration but also on the uninfected cells concentration. The model consists of five nonlinear differential equations describing the evolution of the uninfected cells, the infected ones, the free viruses, and the adaptive immunity. The adaptive immune response is represented by the cytotoxic T-lymphocytes (CTL) cells and the antibodies with the growth function supposed to be trilinear. The model includes two kinds of treatments. The objective of the first one is to reduce the number of infected cells, while the aim of the second is to block free viruses. Firstly, the positivity and the boundedness of solutions are established. After that, the local stability of the disease free steady state and the infection steady states are characterized. Next, an optimal control problem is posed and investigated. Finally, numerical simulations are performed in order to show the behavior of solutions and the effectiveness of the two incorporated treatments via an efficient optimal control strategy.
The pandemic of COVID-19 has caused severe public health consequences around the world. Many interventions of COVID-19 have been implemented. It is of great public health and societal importance to evaluate the effects of interventions in the pandemic of COVID-19. In this paper, with help of synthetic control method, regression discontinuity and a Susceptible-Infected and infectious without isolation-Hospitalized in isolation-Removed (SIHR) model, we evaluate the horizontal and longitudinal effects of stringent interventions implemented in Wenzhou, a representative urban city of China, where stringent interventions were enforced to curb its own epidemic situation with rapidly increasing newly confirmed cases. We found that there were statistically significant treatment effects of those stringent interventions which reduced the cumulative confirmed cases of COVID-19. Those reduction effects would increase over time. Also, if the stringent interventions were delayed by 2 days or mild interventions were implemented instead, the expected number of cumulative confirmed cases would have been nearly 2 times or 5 times of the actual number. The effects of stringent interventions are significant in mitigating the epidemic situation of COVID-19. The slower the interventions were implemented, the more severe the epidemic would have been, and the stronger the interventions would have been required.