Integrating dynamical modeling and phylogeographic inference to characterize global influenza circulation.

Global seasonal influenza circulation involves a complex interplay between local (seasonality, demography, host immunity) and global factors (international mobility) shaping recurrent epidemic patterns. No studies so far have reconciled the two spatial levels, evaluating the coupling between national epidemics, considering heterogeneous coverage of epidemiological and virological data, integrating different data sources. We propose a novel combined approach based on a dynamical model of global influenza spread (GLEAM), integrating high-resolution demographic and mobility data, and a generalized linear model of phylogeographic diffusion that accounts for time-varying migration rates. Seasonal migration fluxes across global macro-regions simulated with GLEAM are tested as phylogeographic predictors to provide model validation and calibration based on genetic data. Seasonal fluxes obtained with a specific transmissibility peak time and recurrent travel outperformed the raw air-transportation predictor, previously considered as optimal indicator of global influenza migration. Influenza A subtypes supported autumn-winter reproductive number as high as 2.25 and an average immunity duration of 2 years. Similar dynamics were preferred by influenza B lineages, with a lower autumn-winter reproductive number. Comparing simulated epidemic profiles against FluNet data offered comparatively limited resolution power. The multiscale approach enables model selection yielding a novel computational framework for describing global influenza dynamics at different scales - local transmission and national epidemics vs. international coupling through mobility and imported cases. Our findings have important implications to improve preparedness against seasonal influenza epidemics. The approach can be generalized to other epidemic contexts, such as emerging disease outbreaks to improve the flexibility and predictive power of modeling.

Redefining pandemic preparedness: Multidisciplinary insights from the CERP modelling workshop in infectious diseases, workshop report.

In July 2023, the Center of Excellence in Respiratory Pathogens organized a two-day workshop on infectious diseases modelling and the lessons learnt from the Covid-19 pandemic. This report summarizes the rich discussions that occurred during the workshop. The workshop participants discussed multisource data integration and highlighted the benefits of combining traditional surveillance with more novel data sources like mobility data, social media, and wastewater monitoring. Significant advancements were noted in the development of predictive models, with examples from various countries showcasing the use of machine learning and artificial intelligence in detecting and monitoring disease trends. The role of open collaboration between various stakeholders in modelling was stressed, advocating for the continuation of such partnerships beyond the pandemic. A major gap identified was the absence of a common international framework for data sharing, which is crucial for global pandemic preparedness. Overall, the workshop underscored the need for robust, adaptable modelling frameworks and the integration of different data sources and collaboration across sectors, as key elements in enhancing future pandemic response and preparedness.

Dynamic planning of a two-dose vaccination campaign with uncertain supplies.

The ongoing COVID-19 pandemic has led public health authorities to face the unprecedented challenge of planning a global vaccination campaign, which for most protocols entails the administration of two doses, separated by a bounded but flexible time interval. The partial immunity already offered by the first dose and the high levels of uncertainty in the vaccine supplies have been characteristic of most of the vaccination campaigns implemented worldwide and made the planning of such interventions extremely complex. Motivated by this compelling challenge, we propose a stochastic optimization framework for optimally scheduling a two-dose vaccination campaign in the presence of uncertain supplies, taking into account constraints on the interval between the two doses and on the capacity of the healthcare system. The proposed framework seeks to maximize the vaccination coverage, considering the different levels of immunization obtained with partial (one dose only) and complete vaccination (two doses). We cast the optimization problem as a convex second-order cone program, which can be efficiently solved through numerical techniques. We demonstrate the potential of our framework on a case study calibrated on the COVID-19 vaccination campaign in Italy. The proposed method shows good performance when unrolled in a sliding-horizon fashion, thereby offering a powerful tool to help public health authorities calibrate the vaccination campaign, pursuing a trade-off between efficacy and the risk associated with shortages in supply.

A model predictive control approach to optimally devise a two-dose vaccination rollout: A case study on COVID-19 in Italy.

The COVID-19 pandemic has led to the unprecedented challenge of devising massive vaccination rollouts, toward slowing down and eventually extinguishing the diffusion of the virus. The two-dose vaccination procedure, speed requirements, and the scarcity of doses, suitable spaces, and personnel, make the optimal design of such rollouts a complex problem. Mathematical modeling, which has already proved to be determinant in the early phases of the pandemic, can again be a powerful tool to assist public health authorities in optimally planning the vaccination rollout. Here, we propose a novel epidemic model tailored to COVID-19, which includes the effect of nonpharmaceutical interventions and a concurrent two-dose vaccination campaign. Then, we leverage nonlinear model predictive control to devise optimal scheduling of first and second doses, accounting both for the healthcare needs and for the socio-economic costs associated with the epidemics. We calibrate our model to the 2021 COVID-19 vaccination campaign in Italy. Specifically, once identified the epidemic parameters from officially reported data, we numerically assess the effectiveness of the obtained optimal vaccination rollouts for the two most used vaccines. Determining the optimal vaccination strategy is nontrivial, as it depends on the efficacy and duration of the first-dose partial immunization, whereby the prioritization of first doses and the delay of second doses may be effective for vaccines with sufficiently strong first-dose immunization. Our model and optimization approach provide a flexible tool that can be adopted to help devise the current COVID-19 vaccination campaign, and increase preparedness for future epidemics.

Modelling and predicting the effect of social distancing and travel restrictions on COVID-19 spreading.

To date, the only effective means to respond to the spreading of the COVID-19 pandemic are non-pharmaceutical interventions (NPIs), which entail policies to reduce social activity and mobility restrictions. Quantifying their effect is difficult, but it is key to reducing their social and economic consequences. Here, we introduce a meta-population model based on temporal networks, calibrated on the COVID-19 outbreak data in Italy and applied to evaluate the outcomes of these two types of NPIs. Our approach combines the advantages of granular spatial modelling of meta-population models with the ability to realistically describe social contacts via activity-driven networks. We focus on disentangling the impact of these two different types of NPIs: those aiming at reducing individuals' social activity, for instance through lockdowns, and those that enforce mobility restrictions. We provide a valuable framework to assess the effectiveness of different NPIs, varying with respect to their timing and severity. Results suggest that the effects of mobility restrictions largely depend on the possibility of implementing timely NPIs in the early phases of the outbreak, whereas activity reduction policies should be prioritized afterwards.