Pandemics require quick decisions about how to distribute a limited number of vaccines, even when the disease is not fully understood and vaccine delivery is limited. We create a disease model that divides the population into groups based on how likely they are to be hospitalized and how likely they are to get infected, so we can test different group-based vaccination strategies. We compare vaccinating only one group, simple step-by-step priority policies that vaccinate groups for set time periods, and a sensitivity analysis to see which model factors most affect outcomes.

We find that vaccinating people who are both high-risk for hospitalization and highly likely to become infected leads to the biggest reductions in total hospitalized time and deaths, while vaccinating lower-risk groups gives little improvement in severe outcomes. A short step-by-step policy that quickly prioritizes high-risk groups can reduce infections and deaths within about 20 days. The sensitivity analysis shows that the death rate and the rate at which infected people move into hospitalization have the strongest influence on severe outcomes, showing that hospital and clinical processes matter a lot in addition to vaccination. Overall, these results support clear, practical, and easy-to-apply prioritization rules for reducing severe disease when vaccine supply is limited.

Graphene quantum dots (GQDs) have emerged in nanobiotechnology as useful tools for numerous biomedical applications, including non-invasive cellular imaging, drug delivery, and gene targeting. Several studies have shown the successful uptake of GQDs in healthy and cancerous cells. While some in vitro and in vivo studies highlight mechanisms underlying GQD internalization in cells, there is a gap in our understanding of GQD interactions with complex biological media, such as blood serum. Proteins in biofluid environments adsorb to the surface of nanoparticles such as carbon nanotubes, forming the “protein corona.” Graphene quantum dots have an abundance of charged surface functional groups, which are likely to interact with complementary charged regions in proteins. Herein, we investigate the interactions of individual proteins with negatively charged sodium citrate and reduced graphene oxide-derived GQDs, as well as positively charged nitrogen-doped GQDs. This study will advance our understanding of protein-GQD interactions in physiological environments, ultimately guiding the optimization of GQDs for biomedical applications.

Influenza can cause severe respiratory illness and spreads quickly, making prevention especially important for people at higher risk of complications. Because vaccines are not always fully protective, effective antivirals can provide an added layer of defense before infection begins. CD388 is a new antiviral being tested as a preventive treatment for influenza. In this project, we used a mathematical model to better understand how the drug changes the course of infection inside the body. Viral load data from a human challenge study were fit to a target-cell model with an eclipse phase, allowing us to estimate key infection parameters. Compared to placebo, CD388 lowered peak viral load and reduced overall viral burden by about 22%, largely by suppressing viral production. Bootstrap analysis was used to assess uncertainty in the parameter estimates. These results help explain how CD388 limits viral spread and supports its potential as a prophylactic therapy.

Favipiravir, an antiviral that inhibits viral RNA-dependent RNA polymerase, has demonstrated promise as a therapeutic for RNA viral infections such as SARS-CoV-2. Mathematical modeling of viral kinetics provides a tool for analyzing the progression of viral infections and the action of antiviral drugs. In the present investigation, the viral kinetics of SARS-CoV-2 infection in cynomolgus macaques treated with the antiviral drug favipiravir were analyzed using a target cell-limited mathematical model of viral infection. Parameters of the model representing the dynamics of viral infection and replication were estimated by fitting the model to the viral kinetics data. Statistical resampling techniques were applied to analyze the uncertainty of the parameter estimates and to compare viral kinetics between the different treatment regimens. The results demonstrate that antiviral treatment induces measurable effects on viral kinetic parameters, reflecting dose-response effects on viral infection dynamics.

About one quarter of patients hospitalized with influenza-like illnesses are infected with more than one respiratory virus. Coinfections can lead to more serious outcomes for patients and are more complex to treat than infections with single viruses. Mathematical models can be used to help us understand the dynamics of viral coinfections and optimize treatment. Previous mathematical models of viral coinfections assume a cell-free transmission pathway with virus leaving one cell and traveling to nearby uninfected cells. However, viruses can also tunnel directly from one cell to another, which can affect how coinfecting viruses interact. This project analyzes a system of coupled ordinary differential equations that includes both cell-free and cell-to-cell transmission to better replicate actual viral spread. We measure coinfection duration for combinations of five common respiratory viruses as a function of the amount of cell-to-cell transmission. We find that coinfection duration depends nonlinearly on the cell-to-cell transmission rates, with differing patterns for different coinfecting viruses. This study highlights the importance of considering different transmission modes when modeling viral dynamics.