Evaluating vaccine allocation strategies using simulation-assisted causal modeling.

We develop a model to retrospectively evaluate age-dependent counterfactual vaccine allocation strategies against the coronavirus disease 2019 (COVID-19) pandemic. To estimate the effect of allocation on the expected severe-case incidence, we employ a simulation-assisted causal modeling approach that combines a compartmental infection-dynamics simulation, a coarse-grained causal model, and literature estimates for immunity waning. We compare Israel's strategy, implemented in 2021, with counterfactual strategies such as no prioritization, prioritization of younger age groups, or a strict risk-ranked approach; we find that Israel's implemented strategy was indeed highly effective. We also study the impact of increasing vaccine uptake for given age groups. Because of its modular structure, our model can easily be adapted to study future pandemics. We demonstrate this by simulating a pandemic with characteristics of the Spanish flu. Our approach helps evaluate vaccination strategies under the complex interplay of core epidemic factors, including age-dependent risk profiles, immunity waning, vaccine availability, and spreading rates.

Proactive Contact Tracing.

The COVID-19 pandemic has spurred an unprecedented demand for interventions that can reduce disease spread without excessively restricting daily activity, given negative impacts on mental health and economic outcomes. Digital contact tracing (DCT) apps have emerged as a component of the epidemic management toolkit. Existing DCT apps typically recommend quarantine to all digitally-recorded contacts of test-confirmed cases. Over-reliance on testing may, however, impede the effectiveness of such apps, since by the time cases are confirmed through testing, onward transmissions are likely to have occurred. Furthermore, most cases are infectious over a short period; only a subset of their contacts are likely to become infected. These apps do not fully utilize data sources to base their predictions of transmission risk during an encounter, leading to recommendations of quarantine to many uninfected people and associated slowdowns in economic activity. This phenomenon, commonly termed as "pingdemic," may additionally contribute to reduced compliance to public health measures. In this work, we propose a novel DCT framework, Proactive Contact Tracing (PCT), which uses multiple sources of information (e.g. self-reported symptoms, received messages from contacts) to estimate app users' infectiousness histories and provide behavioral recommendations. PCT methods are by design proactive, predicting spread before it occurs. We present an interpretable instance of this framework, the Rule-based PCT algorithm, designed via a multi-disciplinary collaboration among epidemiologists, computer scientists, and behavior experts. Finally, we develop an agent-based model that allows us to compare different DCT methods and evaluate their performance in negotiating the trade-off between epidemic control and restricting population mobility. Performing extensive sensitivity analysis across user behavior, public health policy, and virological parameters, we compare Rule-based PCT to i) binary contact tracing (BCT), which exclusively relies on test results and recommends a fixed-duration quarantine, and ii) household quarantine (HQ). Our results suggest that both BCT and Rule-based PCT improve upon HQ, however, Rule-based PCT is more efficient at controlling spread of disease than BCT across a range of scenarios. In terms of cost-effectiveness, we show that Rule-based PCT pareto-dominates BCT, as demonstrated by a decrease in Disability Adjusted Life Years, as well as Temporary Productivity Loss. Overall, we find that Rule-based PCT outperforms existing approaches across a varying range of parameters. By leveraging anonymized infectiousness estimates received from digitally-recorded contacts, PCT is able to notify potentially infected users earlier than BCT methods and prevent onward transmissions. Our results suggest that PCT-based applications could be a useful tool in managing future epidemics.

Pyfectious: An individual-level simulator to discover optimal containment policies for epidemic diseases.

Simulating the spread of infectious diseases in human communities is critical for predicting the trajectory of an epidemic and verifying various policies to control the devastating impacts of the outbreak. Many existing simulators are based on compartment models that divide people into a few subsets and simulate the dynamics among those subsets using hypothesized differential equations. However, these models lack the requisite granularity to study the effect of intelligent policies that influence every individual in a particular way. In this work, we introduce a simulator software capable of modeling a population structure and controlling the disease's propagation at an individualistic level. In order to estimate the confidence of the conclusions drawn from the simulator, we employ a comprehensive probabilistic approach where the entire population is constructed as a hierarchical random variable. This approach makes the inferred conclusions more robust against sampling artifacts and gives confidence bounds for decisions based on the simulation results. To showcase potential applications, the simulator parameters are set based on the formal statistics of the COVID-19 pandemic, and the outcome of a wide range of control measures is investigated. Furthermore, the simulator is used as the environment of a reinforcement learning problem to find the optimal policies to control the pandemic. The obtained experimental results indicate the simulator's adaptability and capacity in making sound predictions and a successful policy derivation example based on real-world data. As an exemplary application, our results show that the proposed policy discovery method can lead to control measures that produce significantly fewer infected individuals in the population and protect the health system against saturation.

Listening to bluetooth beacons for epidemic risk mitigation.

The ongoing COVID-19 pandemic let to efforts to develop and deploy digital contact tracing systems to expedite contact tracing and risk notification. Unfortunately, the success of these systems has been limited, partly owing to poor interoperability with manual contact tracing, low adoption rates, and a societally sensitive trade-off between utility and privacy. In this work, we introduce a new privacy-preserving and inclusive system for epidemic risk assessment and notification that aims to address these limitations. Rather than capturing pairwise encounters between user devices as done by existing systems, our system captures encounters between user devices and beacons placed in strategic locations where infection clusters may originate. Epidemiological simulations using an agent-based model demonstrate that, by utilizing location and environmental information and interoperating with manual contact tracing, our system can increase the accuracy of contact tracing actions and may help reduce epidemic spread already at low adoption.

Simpson's Paradox in COVID-19 Case Fatality Rates: A Mediation Analysis of Age-Related Causal Effects.

We point out an instantiation of Simpson's paradox in COVID-19 case fatality rates (cfrs): comparing a large-scale study from China (February 17) with early reports from Italy (March 9), we find that cfrs are lower in Italy for every age group, but higher overall. This phenomenon is explained by a stark difference in case demographic between the two countries. Using this as a motivating example, we introduce basic concepts from mediation analysis and show how these can be used to quantify different direct and indirect effects when assuming a coarse-grained causal graph involving country, age, and case fatality. We curate an age-stratified cfr dataset with [Formula: see text]750 k cases and conduct a case study, investigating total, direct, and indirect (age-mediated) causal effects between different countries and at different points in time. This allows us to separate age-related effects from others unrelated to age and facilitates a more transparent comparison of cfrs across countries at different stages of the COVID-19 pandemic. Using longitudinal data from Italy, we discover a sign reversal of the direct causal effect in mid-March, which temporally aligns with the reported collapse of the healthcare system in parts of the country. Moreover, we find that direct and indirect effects across 132 pairs of countries are only weakly correlated, suggesting that a country's policy and case demographic may be largely unrelated. We point out limitations and extensions for future work, and finally, discuss the role of causal reasoning in the broader context of using AI to combat the COVID-19 pandemic. Impact Statement-During a global pandemic, understanding the causal effects of risk factors such as age on COVID-19 fatality is an important scientific question. Since randomised controlled trials are typically infeasible or unethical in this context, causal investigations based on observational data-such as the one carried out in this article-will, therefore, be crucial in guiding our understanding of the available data. Causal inference, in particular mediation analysis, can be used to resolve apparent statistical paradoxes; help educate the public and decision-makers alike; avoid unsound comparisons; and answer a range of causal questions pertaining to the pandemic, subject to transparently stated assumptions. Our exposition helps clarify how mediation analysis can be used to investigate direct and indirect effects along different causal paths and thus serves as a stepping stone for future studies of other important risk factors for COVID-19 besides age.

Real-time prediction of COVID-19 related mortality using electronic health records.

Coronavirus disease 2019 (COVID-19) is a respiratory disease with rapid human-to-human transmission caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the exponential growth of infections, identifying patients with the highest mortality risk early is critical to enable effective intervention and prioritisation of care. Here, we present the COVID-19 early warning system (CovEWS), a risk scoring system for assessing COVID-19 related mortality risk that we developed using data amounting to a total of over 2863 years of observation time from a cohort of 66 430 patients seen at over 69 healthcare institutions. On an external cohort of 5005 patients, CovEWS predicts mortality from 78.8% (95% confidence interval [CI]: 76.0, 84.7%) to 69.4% (95% CI: 57.6, 75.2%) specificity at sensitivities greater than 95% between, respectively, 1 and 192 h prior to mortality events. CovEWS could enable earlier intervention, and may therefore help in preventing or mitigating COVID-19 related mortality.