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Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-22271905


BackgroundSARS-CoV-2 vaccination of persons aged 12 years and older has reduced disease burden in the United States. The COVID-19 Scenario Modeling Hub convened multiple modeling teams in September 2021 to project the impact of expanding vaccine administration to children 5-11 years old on anticipated COVID-19 burden and resilience against variant strains. MethodsNine modeling teams contributed state- and national-level projections for weekly counts of cases, hospitalizations, and deaths in the United States for the period September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of: 1) presence vs. absence of vaccination of children ages 5-11 years starting on November 1, 2021; and 2) continued dominance of the Delta variant vs. emergence of a hypothetical more transmissible variant on November 15, 2021. Individual team projections were combined using linear pooling. The effect of childhood vaccination on overall and age-specific outcomes was estimated by meta-analysis approaches. FindingsAbsent a new variant, COVID-19 cases, hospitalizations, and deaths among all ages were projected to decrease nationally through mid-March 2022. Under a set of specific assumptions, models projected that vaccination of children 5-11 years old was associated with reductions in all-age cumulative cases (7.2%, mean incidence ratio [IR] 0.928, 95% confidence interval [CI] 0.880-0.977), hospitalizations (8.7%, mean IR 0.913, 95% CI 0.834-0.992), and deaths (9.2%, mean IR 0.908, 95% CI 0.797-1.020) compared with scenarios where children were not vaccinated. This projected effect of vaccinating children 5-11 years old increased in the presence of a more transmissible variant, assuming no change in vaccine effectiveness by variant. Larger relative reductions in cumulative cases, hospitalizations, and deaths were observed for children than for the entire U.S. population. Substantial state-level variation was projected in epidemic trajectories, vaccine benefits, and variant impacts. ConclusionsResults from this multi-model aggregation study suggest that, under a specific set of scenario assumptions, expanding vaccination to children 5-11 years old would provide measurable direct benefits to this age group and indirect benefits to the all-age U.S. population, including resilience to more transmissible variants.

Estee Y Cramer; Evan L Ray; Velma K Lopez; Johannes Bracher; Andrea Brennen; Alvaro J Castro Rivadeneira; Aaron Gerding; Tilmann Gneiting; Katie H House; Yuxin Huang; Dasuni Jayawardena; Abdul H Kanji; Ayush Khandelwal; Khoa Le; Anja Muehlemann; Jarad Niemi; Apurv Shah; Ariane Stark; Yijin Wang; Nutcha Wattanachit; Martha W Zorn; Youyang Gu; Sansiddh Jain; Nayana Bannur; Ayush Deva; Mihir Kulkarni; Srujana Merugu; Alpan Raval; Siddhant Shingi; Avtansh Tiwari; Jerome White; Neil F Abernethy; Spencer Woody; Maytal Dahan; Spencer Fox; Kelly Gaither; Michael Lachmann; Lauren Ancel Meyers; James G Scott; Mauricio Tec; Ajitesh Srivastava; Glover E George; Jeffrey C Cegan; Ian D Dettwiller; William P England; Matthew W Farthing; Robert H Hunter; Brandon Lafferty; Igor Linkov; Michael L Mayo; Matthew D Parno; Michael A Rowland; Benjamin D Trump; Yanli Zhang-James; Samuel Chen; Stephen V Faraone; Jonathan Hess; Christopher P Morley; Asif Salekin; Dongliang Wang; Sabrina M Corsetti; Thomas M Baer; Marisa C Eisenberg; Karl Falb; Yitao Huang; Emily T Martin; Ella McCauley; Robert L Myers; Tom Schwarz; Daniel Sheldon; Graham Casey Gibson; Rose Yu; Liyao Gao; Yian Ma; Dongxia Wu; Xifeng Yan; Xiaoyong Jin; Yu-Xiang Wang; YangQuan Chen; Lihong Guo; Yanting Zhao; Quanquan Gu; Jinghui Chen; Lingxiao Wang; Pan Xu; Weitong Zhang; Difan Zou; Hannah Biegel; Joceline Lega; Steve McConnell; VP Nagraj; Stephanie L Guertin; Christopher Hulme-Lowe; Stephen D Turner; Yunfeng Shi; Xuegang Ban; Robert Walraven; Qi-Jun Hong; Stanley Kong; Axel van de Walle; James A Turtle; Michal Ben-Nun; Steven Riley; Pete Riley; Ugur Koyluoglu; David DesRoches; Pedro Forli; Bruce Hamory; Christina Kyriakides; Helen Leis; John Milliken; Michael Moloney; James Morgan; Ninad Nirgudkar; Gokce Ozcan; Noah Piwonka; Matt Ravi; Chris Schrader; Elizabeth Shakhnovich; Daniel Siegel; Ryan Spatz; Chris Stiefeling; Barrie Wilkinson; Alexander Wong; Sean Cavany; Guido Espana; Sean Moore; Rachel Oidtman; Alex Perkins; David Kraus; Andrea Kraus; Zhifeng Gao; Jiang Bian; Wei Cao; Juan Lavista Ferres; Chaozhuo Li; Tie-Yan Liu; Xing Xie; Shun Zhang; Shun Zheng; Alessandro Vespignani; Matteo Chinazzi; Jessica T Davis; Kunpeng Mu; Ana Pastore y Piontti; Xinyue Xiong; Andrew Zheng; Jackie Baek; Vivek Farias; Andreea Georgescu; Retsef Levi; Deeksha Sinha; Joshua Wilde; Georgia Perakis; Mohammed Amine Bennouna; David Nze-Ndong; Divya Singhvi; Ioannis Spantidakis; Leann Thayaparan; Asterios Tsiourvas; Arnab Sarker; Ali Jadbabaie; Devavrat Shah; Nicolas Della Penna; Leo A Celi; Saketh Sundar; Russ Wolfinger; Dave Osthus; Lauren Castro; Geoffrey Fairchild; Isaac Michaud; Dean Karlen; Matt Kinsey; Luke C. Mullany; Kaitlin Rainwater-Lovett; Lauren Shin; Katharine Tallaksen; Shelby Wilson; Elizabeth C Lee; Juan Dent; Kyra H Grantz; Alison L Hill; Joshua Kaminsky; Kathryn Kaminsky; Lindsay T Keegan; Stephen A Lauer; Joseph C Lemaitre; Justin Lessler; Hannah R Meredith; Javier Perez-Saez; Sam Shah; Claire P Smith; Shaun A Truelove; Josh Wills; Maximilian Marshall; Lauren Gardner; Kristen Nixon; John C. Burant; Lily Wang; Lei Gao; Zhiling Gu; Myungjin Kim; Xinyi Li; Guannan Wang; Yueying Wang; Shan Yu; Robert C Reiner; Ryan Barber; Emmanuela Gaikedu; Simon Hay; Steve Lim; Chris Murray; David Pigott; Heidi L Gurung; Prasith Baccam; Steven A Stage; Bradley T Suchoski; B. Aditya Prakash; Bijaya Adhikari; Jiaming Cui; Alexander Rodriguez; Anika Tabassum; Jiajia Xie; Pinar Keskinocak; John Asplund; Arden Baxter; Buse Eylul Oruc; Nicoleta Serban; Sercan O Arik; Mike Dusenberry; Arkady Epshteyn; Elli Kanal; Long T Le; Chun-Liang Li; Tomas Pfister; Dario Sava; Rajarishi Sinha; Thomas Tsai; Nate Yoder; Jinsung Yoon; Leyou Zhang; Sam Abbott; Nikos I Bosse; Sebastian Funk; Joel Hellewell; Sophie R Meakin; Katharine Sherratt; Mingyuan Zhou; Rahi Kalantari; Teresa K Yamana; Sen Pei; Jeffrey Shaman; Michael L Li; Dimitris Bertsimas; Omar Skali Lami; Saksham Soni; Hamza Tazi Bouardi; Turgay Ayer; Madeline Adee; Jagpreet Chhatwal; Ozden O Dalgic; Mary A Ladd; Benjamin P Linas; Peter Mueller; Jade Xiao; Yuanjia Wang; Qinxia Wang; Shanghong Xie; Donglin Zeng; Alden Green; Jacob Bien; Logan Brooks; Addison J Hu; Maria Jahja; Daniel McDonald; Balasubramanian Narasimhan; Collin Politsch; Samyak Rajanala; Aaron Rumack; Noah Simon; Ryan J Tibshirani; Rob Tibshirani; Valerie Ventura; Larry Wasserman; Eamon B O'Dea; John M Drake; Robert Pagano; Quoc T Tran; Lam Si Tung Ho; Huong Huynh; Jo W Walker; Rachel B Slayton; Michael A Johansson; Matthew Biggerstaff; Nicholas G Reich.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21250974


Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub ( collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multi-model ensemble forecast that combined predictions from dozens of different research groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naive baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-week horizon 3-5 times larger than when predicting at a 1-week horizon. This project underscores the role that collaboration and active coordination between governmental public health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks. Significance StatementThis paper compares the probabilistic accuracy of short-term forecasts of reported deaths due to COVID-19 during the first year and a half of the pandemic in the US. Results show high variation in accuracy between and within stand-alone models, and more consistent accuracy from an ensemble model that combined forecasts from all eligible models. This demonstrates that an ensemble model provided a reliable and comparatively accurate means of forecasting deaths during the COVID-19 pandemic that exceeded the performance of all of the models that contributed to it. This work strengthens the evidence base for synthesizing multiple models to support public health action.

Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20225409


Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid-sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes.

Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20179960


In the United States, schools closed in March 2020 due to COVID-19 and began reopening in August 2020, despite continuing transmission of SARS-CoV-2. In states where in-person instruction resumed at that time, two major unknowns were the capacity at which schools would operate, which depended on the proportion of families opting for remote instruction, and adherence to face-mask requirements in schools, which depended on cooperation from students and enforcement by schools. To determine the impact of these conditions on the statewide burden of COVID-19 in Indiana, we used an agent-based model calibrated to and validated against multiple data types. Using this model, we quantified the burden of COVID-19 on K-12 students, teachers, their families, and the general population under alternative scenarios spanning three levels of school operating capacity (50%, 75%, and 100%) and three levels of face-mask adherence in schools (50%, 75%, and 100%). Under a scenario in which schools operated remotely, we projected 45,579 (95% CrI: 14,109-132,546) infections and 790 (95% CrI: 176-1680) deaths statewide between August 24 and December 31. Reopening at 100% capacity with 50% face-mask adherence in schools resulted in a proportional increase of 42.9 (95% CrI: 41.3-44.3) and 9.2 (95% CrI: 8.9-9.5) times that number of infections and deaths, respectively. In contrast, our results showed that at 50% capacity with 100% face-mask adherence, the number of infections and deaths were 22% (95% CrI: 16%-28%) and 11% (95% CrI: 5%-18%) higher than the scenario in which schools operated remotely. Within this range of possibilities, we found that high levels of school operating capacity (80-95%) and intermediate levels of face-mask adherence (40-70%) resulted in model behavior most consistent with observed data. Together, these results underscore the importance of precautions taken in schools for the benefit of their communities.

Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20177493


BackgroundThe COVID-19 pandemic has driven demand for forecasts to guide policy and planning. Previous research has suggested that combining forecasts from multiple models into a single "ensemble" forecast can increase the robustness of forecasts. Here we evaluate the real-time application of an open, collaborative ensemble to forecast deaths attributable to COVID-19 in the U.S. MethodsBeginning on April 13, 2020, we collected and combined one- to four-week ahead forecasts of cumulative deaths for U.S. jurisdictions in standardized, probabilistic formats to generate real-time, publicly available ensemble forecasts. We evaluated the point prediction accuracy and calibration of these forecasts compared to reported deaths. ResultsAnalysis of 2,512 ensemble forecasts made April 27 to July 20 with outcomes observed in the weeks ending May 23 through July 25, 2020 revealed precise short-term forecasts, with accuracy deteriorating at longer prediction horizons of up to four weeks. At all prediction horizons, the prediction intervals were well calibrated with 92-96% of observations falling within the rounded 95% prediction intervals. ConclusionsThis analysis demonstrates that real-time, publicly available ensemble forecasts issued in April-July 2020 provided robust short-term predictions of reported COVID-19 deaths in the United States. With the ongoing need for forecasts of impacts and resource needs for the COVID-19 response, the results underscore the importance of combining multiple probabilistic models and assessing forecast skill at different prediction horizons. Careful development, assessment, and communication of ensemble forecasts can provide reliable insight to public health decision makers.

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