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The SARS-CoV-2 pandemic has generated a considerable number of infections and associated morbidity and mortality across the world. Recovery from these infections, combined with the onset of large-scale vaccination, have led to rapidly-changing population-level immunological landscapes. In turn, these complexities have highlighted a number of important unknowns related to the breadth and strength of immunity following recovery or vaccination. Using simple mathematical models, we investigate the medium-term impacts of waning immunity against severe disease on immuno-epidemiological dynamics. We find that uncertainties in the duration of severity-blocking immunity (imparted by either infection or vaccination) can lead to a large range of medium-term population-level outcomes (i.e. infection characteristics and immune landscapes). Furthermore, we show that epidemiological dynamics are sensitive to the strength and duration of underlying host immune responses; this implies that determining infection levels from hospitalizations requires accurate estimates of these immune parameters. More durable vaccines both reduce these uncertainties and alleviate the burden of SARS-CoV-2 in pessimistic outcomes. However, heterogeneity in vaccine uptake drastically changes immune landscapes toward larger fractions of individuals with waned severity-blocking immunity. In particular, if hesitancy is substantial, more robust vaccines have almost no effects on population-level immuno-epidemiology, even if vaccination rates are compensatorily high among vaccine-adopters. This pessimistic scenario for vaccination heterogeneity arises because those few individuals that are vaccine-adopters are so readily re-vaccinated that the duration of vaccinal immunity has no appreciable consequences on their immune status. Furthermore, we find that this effect is heightened if vaccine-hesitants have increased transmissibility (e.g. due to riskier behavior). Overall, our results illustrate the necessity to characterize both transmission-blocking and severity-blocking immune time scales. Our findings also underline the importance of developing robust next-generation vaccines with equitable mass vaccine deployment. 

Abstract Objective:To evaluate the economic costs of reducing the University of Virginia Hospital’s present “3-negative” policy, which continues methicillin-resistantStaphylococcus aureus(MRSA) contact precautions until patients receive 3 consecutive negative test results, to either 2 or 1 negative. Design:Cost-effective analysis. Settings:The University of Virginia Hospital. Patients:The study included data from 41,216 patients from 2015 to 2019. Methods:We developed a model for MRSA transmission in the University of Virginia Hospital, accounting for both environmental contamination and interactions between patients and providers, which were derived from electronic health record (EHR) data. The model was fit to MRSA incidence over the study period under the current 3-negative clearance policy. A counterfactual simulation was used to estimate outcomes and costs for 2- and 1-negative policies compared with the current 3-negative policy. Results:Our findings suggest that 2-negative and 1-negative policies would have led to 6 (95% CI, −30 to 44;P< .001) and 17 (95% CI, −23 to 59; −10.1% to 25.8%;P< .001) more MRSA cases, respectively, at the hospital over the study period. Overall, the 1-negative policy has statistically significantly lower costs ($628,452; 95% CI, $513,592–$752,148) annually (P< .001) in US dollars, inflation-adjusted for 2023) than the 2-negative policy ($687,946; 95% CI, $562,522–$812,662) and 3-negative ($702,823; 95% CI, $577,277–$846,605). Conclusions:A single negative MRSA nares PCR test may provide sufficient evidence to discontinue MRSA contact precautions, and it may be the most cost-effective option. 

Large-scale population displacements arising from conflict-induced forced migration generate uncertainty and introduce several policy challenges. Addressing these concerns requires an interdisciplinary approach that integrates knowledge from both computational modeling and social sciences. We propose a generalized computational agent-based modeling framework grounded by Theory of Planned Behavior to model conflict-induced migration outflows within Ukraine during the start of that conflict in 2022. Existing migration modeling frameworks that attempt to address policy implications primarily focus on destination while leaving absent a generalized computational framework grounded by social theory focused on the conflict-induced region. We propose an agent-based framework utilizing a spatiotemporal gravity model and a Bi-threshold model over a Graph Dynamical System to update migration status of agents in conflict-induced regions at fine temporal and spatial granularity. This approach significantly outperforms previous work when examining the case of Russian invasion in Ukraine. Policy implications of the proposed framework are demonstrated by modeling the migration behavior of Ukrainian civilians attempting to flee from regions encircled by Russian forces. We also showcase the generalizability of the model by simulating a past conflict in Burundi, an alternative conflict setting. Results demonstrate the utility of the framework for assessing conflict-induced migration in varied settings as well as identifying vulnerable civilian populations. 

Despite hundreds of methods published in the literature, forecasting epidemic dynamics remains challenging yet important. The challenges stem from multiple sources, including: the need for timely data, co-evolution of epidemic dynamics with behavioral and immunological adaptations, and the evolution of new pathogen strains. The ongoing COVID-19 pandemic highlighted these challenges; in an important article, Reich et al. did a comprehensive analysis highlighting many of these challenges.In this paper, we take another step in critically evaluating existing epidemic forecasting methods. Our methods are based on a simple yet crucial observation - epidemic dynamics go through a number of phases (waves). Armed with this understanding, we propose a modification to our deployed Bayesian ensembling case time series forecasting framework. We show that ensembling methods employing the phase information and using different weighting schemes for each phase can produce improved forecasts. We evaluate our proposed method with both the currently deployed model and the COVID-19 forecasthub models. The overall performance of the proposed model is consistent across the pandemic but more importantly, it is ranked third and first during two critical rapid growth phases in cases, regimes where the performance of most models from the CDC forecasting hub dropped significantly. 

Disease surveillance systems provide early warnings of disease outbreaks before they become public health emergencies. However, pandemics containment would be challenging due to the complex immunity landscape created by multiple variants. Genomic surveillance is critical for detecting novel variants with diverse characteristics and importation/emergence times. Yet, a systematic study incorporating genomic monitoring, situation assessment, and intervention strategies is lacking in the literature. We formulate an integrated computational modeling framework to study a realistic course of action based on sequencing, analysis, and response. We study the effects of the second variant’s importation time, its infectiousness advantage and, its cross-infection on the novel variant’s detection time, and the resulting intervention scenarios to contain epidemics driven by two-variants dynamics. Our results illustrate the limitation in the intervention’s effectiveness due to the variants’ competing dynamics and provide the following insights: i) There is a set of importation times that yields the worst detection time for the second variant, which depends on the first variant’s basic reproductive number; ii) When the second variant is imported relatively early with respect to the first variant, the cross-infection level does not impact the detection time of the second variant. We found that depending on the target metric, the best outcomes are attained under different interventions’ regimes. Our results emphasize the importance of sustained enforcement of Non-Pharmaceutical Interventions on preventing epidemic resurgence due to importation/emergence of novel variants. We also discuss how our methods can be used to study when a novel variant emerges within a population. 

Real-time forecasting of non-stationary time series is a challenging problem, especially when the time series evolves rapidly. For such cases, it has been observed that ensemble models consisting of a diverse set of model classes can perform consistently better than individual models. In order to account for the nonstationarity of the data and the lack of availability of training examples, the models are retrained in real-time using the most recent observed data samples. Motivated by the robust performance properties of ensemble models, we developed a Bayesian model averaging ensemble technique consisting of statistical, deep learning, and compartmental models for fore-casting epidemiological signals, specifically, COVID-19 signals. We observed the epidemic dynamics go through several phases (waves). In our ensemble model, we observed that different model classes performed differently during the various phases. Armed with this understanding, in this paper, we propose a modification to the ensembling method to employ this phase information and use different weighting schemes for each phase to produce improved forecasts. However, predicting the phases of such time series is a significant challenge, especially when behavioral and immunological adaptations govern the evolution of the time series. We explore multiple datasets that can serve as leading indicators of trend changes and employ transfer entropy techniques to capture the relevant indicator. We propose a phase prediction algorithm to estimate the phases using the leading indicators. Using the knowledge of the estimated phase, we selectively sample the training data from similar phases. We evaluate our proposed methodology on our currently deployed COVID-19 forecasting model and the COVID-19 ForecastHub models. The overall performance of the proposed model is consistent across the pandemic. More importantly, it is ranked second during two critical rapid growth phases in cases, regimes where the performance of most models from the ForecastHub dropped significantly.