Bayesian uncertainty quantification to identify population level vaccine hesitancy behaviours (preprint)

When effective vaccines are available, vaccination programs are typically one of the best defences against the spread of an infectious disease. Unfortunately, vaccination rates may be suboptimal for a prolonged duration as a result of slow uptake of vaccines by the public. Key factors driving slow vaccination uptake can be a complex interaction of vaccine roll-out policies and logistics, and vaccine hesitancy behaviours potentially caused by an inflated sense of risk in adverse reactions in some populations or community complacency in communities that have not yet experienced a large outbreak. In the recent COVID-19 pandemic, public health responses around the world began to include vaccination programs from late 2020 to early 2021 with an aim of relaxing non-pharmaceutical interventions such as lockdowns and travel restrictions. For many jurisdictions there have been challenges in getting vaccination rates high enough to enable the relaxation of restrictions based on non-pharmaceutical interventions. A key concern during this time was vaccine hestitancy behaviours potentially caused by vaccine safety concerns fuelled by misinformation and community complacency in jurisdictions that had seen very low COVID-19 case numbers throughout 2020, such as Australia and New Zealand. We develop a novel stochastic epidemiological model of COVID-19 transmission that incorporates changes in population behaviour relating to responses based on non-pharmaceutical interventions and community vaccine uptake as functions of the reported COVID-19 cases, deaths, and vaccination rates. Through a simulation study, we develop a Bayesian analysis approach to demonstrate that different factors inhibiting the uptake of vaccines by the population can be isolated despite key model parameters being subject to substantial uncertainty. In particular, we are able to identify the presence of vaccine hesitancy in a population using reported case, death and vaccination count data alone. Furthermore, our approach provides insight as to whether the dominant concerns driving hesitancy are related to vaccine safety or complacency. While our simulation study is inspired by the COVID-19 pandemic, our tools and techniques are general and could be enable vaccination programs of various infectious diseases to be adapted rapidly in response to community behaviours moving forward into the future.

Rapid community-driven development of a SARS-CoV-2 tissue simulator (preprint)

The 2019 novel coronavirus, SARS-CoV-2, is an emerging pathogen of critical significance to international public health. Knowledge of the interplay between molecular-scale virus-receptor interactions, single-cell viral replication, intracellular-scale viral transport, and emergent tissue-scale viral propagation is limited. Moreover, little is known about immune system-virus-tissue interactions and how these can result in low-level (asymptomatic) infections in some cases and acute respiratory distress syndrome (ARDS) in others, particularly with respect to presentation in different age groups or pre-existing inflammatory risk factors like diabetes. Given the nonlinear interactions within and among each of these processes, multiscale simulation models can shed light on the emergent dynamics that lead to divergent outcomes, identify actionable "choke points" for pharmacologic interventions, screen potential therapies, and identify potential biomarkers that differentiate patient outcomes. Given the complexity of the problem and the acute need for an actionable model to guide therapy discovery and optimization, we introduce and iteratively refine a prototype of a multiscale model of SARS-CoV-2 dynamics in lung tissue. The first prototype model was built and shared internationally as open source code and an online interactive model in under 12 hours, and community domain expertise is driving rapid refinements with a two-to-four week release cycle. In a sustained community effort, this consortium is integrating data and expertise across virology, immunology, mathematical biology, quantitative systems physiology, cloud and high performance computing, and other domains to accelerate our response to this critical threat to international health.