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1. Synergistic interventions to control COVID-19: Mass testing and isolation mitigates reliance on distancing

   https://doi.org/10.1371/journal.pcbi.1009518  

   Howerton, Emily ; Ferrari, Matthew J. ; Bjørnstad, Ottar N. ; Bogich, Tiffany L. ; Borchering, Rebecca K. ; Jewell, Chris P. ; Nichols, James D. ; Probert, William J. ; Runge, Michael C. ; Tildesley, Michael J. ; et al ( October 2021 , PLOS Computational Biology)

   Flegg, Jennifer A. (Ed.)

   Stay-at-home orders and shutdowns of non-essential businesses are powerful, but socially costly, tools to control the pandemic spread of SARS-CoV-2. Mass testing strategies, which rely on widely administered frequent and rapid diagnostics to identify and isolate infected individuals, could be a potentially less disruptive management strategy, particularly where vaccine access is limited. In this paper, we assess the extent to which mass testing and isolation strategies can reduce reliance on socially costly non-pharmaceutical interventions, such as distancing and shutdowns. We develop a multi-compartmental model of SARS-CoV-2 transmission incorporating both preventative non-pharmaceutical interventions (NPIs) and testing and isolation to evaluate their combined effect on public health outcomes. Our model is designed to be a policy-guiding tool that captures important realities of the testing system, including constraints on test administration and non-random testing allocation. We show how strategic changes in the characteristics of the testing system, including test administration, test delays, and test sensitivity, can reduce reliance on preventative NPIs without compromising public health outcomes in the future. The lowest NPI levels are possible only when many tests are administered and test delays are short, given limited immunity in the population. Reducing reliance on NPIs is highly dependent on the ability of a testing program to identify and isolate unreported, asymptomatic infections. Changes in NPIs, including the intensity of lockdowns and stay at home orders, should be coordinated with increases in testing to ensure epidemic control; otherwise small additional lifting of these NPIs can lead to dramatic increases in infections, hospitalizations and deaths. Importantly, our results can be used to guide ramp-up of testing capacity in outbreak settings, allow for the flexible design of combined interventions based on social context, and inform future cost-benefit analyses to identify efficient pandemic management strategies. 

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2. Evaluation of COVID-19 vaccination strategies with a delayed second dose

   https://doi.org/10.1371/journal.pbio.3001211  

   Moghadas, Seyed M. ; Vilches, Thomas N. ; Zhang, Kevin ; Nourbakhsh, Shokoofeh ; Sah, Pratha ; Fitzpatrick, Meagan C. ; Galvani, Alison P. ( April 2021 , PLOS Biology)

   Read, Andrew Fraser (Ed.)

   Two of the Coronavirus Disease 2019 (COVID-19) vaccines currently approved in the United States require 2 doses, administered 3 to 4 weeks apart. Constraints in vaccine supply and distribution capacity, together with a deadly wave of COVID-19 from November 2020 to January 2021 and the emergence of highly contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants, sparked a policy debate on whether to vaccinate more individuals with the first dose of available vaccines and delay the second dose or to continue with the recommended 2-dose series as tested in clinical trials. We developed an agent-based model of COVID-19 transmission to compare the impact of these 2 vaccination strategies, while varying the temporal waning of vaccine efficacy following the first dose and the level of preexisting immunity in the population. Our results show that for Moderna vaccines, a delay of at least 9 weeks could maximize vaccination program effectiveness and avert at least an additional 17.3 (95% credible interval [CrI]: 7.8–29.7) infections, 0.69 (95% CrI: 0.52–0.97) hospitalizations, and 0.34 (95% CrI: 0.25–0.44) deaths per 10,000 population compared to the recommended 4-week interval between the 2 doses. Pfizer-BioNTech vaccines also averted an additional 0.60 (95% CrI: 0.37–0.89) hospitalizations and 0.32 (95% CrI: 0.23–0.45) deaths per 10,000 population in a 9-week delayed second dose (DSD) strategy compared to the 3-week recommended schedule between doses. However, there was no clear advantage of delaying the second dose with Pfizer-BioNTech vaccines in reducing infections, unless the efficacy of the first dose did not wane over time. Our findings underscore the importance of quantifying the characteristics and durability of vaccine-induced protection after the first dose in order to determine the optimal time interval between the 2 doses. 

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3. Deep reinforcement learning framework for controlling infectious disease outbreaks in the context of multi-jurisdictions

   https://doi.org/10.3934/mbe.2023640  

   Khatami, Seyedeh N. ; Gopalappa, Chaitra ( June 2023 , Mathematical Biosciences and Engineering)

   In the absence of pharmaceutical interventions, social distancing and lockdown have been key options for controlling new or reemerging respiratory infectious disease outbreaks. The timely implementation of these interventions is vital for effectively controlling and safeguarding the economy.Motivated by the COVID-19 pandemic, we evaluated whether, when, and to what level lockdowns are necessary to minimize epidemic and economic burdens of new disease outbreaks. We formulated the question as a sequential decision-making Markov Decision Process and solved it using deep Q-network algorithm. We evaluated the question under two objective functions: a 2-objective function to minimize economic burden and hospital capacity violations, suitable for diseases with severe health risks but with minimal death, and a 3-objective function that additionally minimizes the number of deaths, suitable for diseases that have high risk of mortality.A key feature of the model is that we evaluated the above questions in the context of two-geographical jurisdictions that interact through travel but make autonomous and independent decisions, evaluating under cross-jurisdictional cooperation and non-cooperation. In the 2-objective function under cross-jurisdictional cooperation, the optimal policy was to aim for shutdowns at 50 and 25% per day. Though this policy avoided hospital capacity violations, the shutdowns extended until a large proportion of the population reached herd immunity. Delays in initiating this optimal policy or non-cooperation from an outside jurisdiction required shutdowns at a higher level of 75% per day, thus adding to economic burdens. In the 3-objective function, the optimal policy under cross-jurisdictional cooperation was to aim for shutdowns of up to 75% per day to prevent deaths by reducing infected cases. This optimal policy continued for the entire duration of the simulation, suggesting that, until pharmaceutical interventions such as treatment or vaccines become available, contact reductions through physical distancing would be necessary to minimize deaths. Deviating from this policy increased the number of shutdowns and led to several deaths.In summary, we present a decision-analytic methodology for identifying optimal lockdown strategy under the context of interactions between jurisdictions that make autonomous and independent decisions. The numerical analysis outcomes are intuitive and, as expected, serve as proof of the feasibility of such a model. Our sensitivity analysis demonstrates that the optimal policy exhibits robustness to minor alterations in the transmission rate, yet shows sensitivity to more substantial deviations. This finding underscores the dynamic nature of epidemic parameters, thereby emphasizing the necessity for models trained across a diverse range of values to ensure effective policy-making. 

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4. Impact of Vaccination and Nonpharmaceutical Interventions With Possible COVID-19 Viral Evolutions Using an Agent-Based Simulation

   https://doi.org/10.1016/j.focus.2023.100155  

   Lee, Serin ; Zabinsky, Zelda B. ; Wasserheit, Judith N. ; Ross, Jennifer M. ; Chen, Shi ; Liu, Shan ( February 2024 , AJPM Focus)

   The objective is to understand the role of emerging variants, vaccination, and NPI policies on COVID-19 infections and deaths. We aim to identify scenarios in which COVID-19 can be managed such that the death rate from COVID-19 becomes comparable with the combined annual mortality rate from influenza and pneumonia. As a case study for a large urban area, we simulate COVID-19 transmission in King County, Washington, (greater Seattle) using an agent- based simulation model. Calibrated to local epidemiological data, our study uses detailed synthetic population data and includes interactions between vaccination and specific NPIs while considering waning immunity and emergence of variants. Virus mutation scenarios include 12 combinations of infectivity, disease severity, and immune evasiveness. A highly effective pancoronavirus vaccine that works against all strains is considered an optimistic scenario. Our findings highlight the potential benefits of pancoronavirus vaccines that offer enhanced and longer-lasting immunity. We emphasize the crucial role of nonpharmaceutical interventions in reducing COVID-19 deaths regardless of virus mutation scenarios. Owing to highly immune evasive and contagious SARS-CoV-2 variants, most scenarios in this study fail to reduce the mortality of COVID-19 to the level of influenza and pneumonia. However, our findings indicate that periodic vaccinations and a threshold nonpharmaceutical intervention policy may succeed in achieving this goal. This indicates the need for caution and vigilance in managing a continuing COVID-19 epidemic. 

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5. A pre-registered short-term forecasting study of COVID-19 in Germany and Poland during the second wave

   https://doi.org/10.1038/s41467-021-25207-0  

   Bracher, J. ; Wolffram, D. ; Deuschel, J. ; Görgen, K. ; Ketterer, J. L. ; Ullrich, A. ; Abbott, S. ; Barbarossa, M. V. ; Bertsimas, D. ; Bhatia, S. ; et al ( December 2021 , Nature Communications)

   Abstract Disease modelling has had considerable policy impact during the ongoing COVID-19 pandemic, and it is increasingly acknowledged that combining multiple models can improve the reliability of outputs. Here we report insights from ten weeks of collaborative short-term forecasting of COVID-19 in Germany and Poland (12 October–19 December 2020). The study period covers the onset of the second wave in both countries, with tightening non-pharmaceutical interventions (NPIs) and subsequently a decay (Poland) or plateau and renewed increase (Germany) in reported cases. Thirteen independent teams provided probabilistic real-time forecasts of COVID-19 cases and deaths. These were reported for lead times of one to four weeks, with evaluation focused on one- and two-week horizons, which are less affected by changing NPIs. Heterogeneity between forecasts was considerable both in terms of point predictions and forecast spread. Ensemble forecasts showed good relative performance, in particular in terms of coverage, but did not clearly dominate single-model predictions. The study was preregistered and will be followed up in future phases of the pandemic. 

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