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We devised a model to interpret discordant SARS-CoV-2 test results. We estimate that, during March 2020-May 2022, a patient in the United States who received a positive rapid antigen test result followed by a negative nucleic acid test result had only a 15.4% (95% CI 0.6%-56.7%) chance of being infected. [ABSTRACT FROM AUTHOR]

We evaluated the population-level benefits of expanding treatment with the antiviral drug Paxlovid (nirmatrelvir/ritonavir) in the United States for SARS-CoV-2 Omicron variant infections. Using a multiscale mathematical model, we found that treating 20% of symptomatic case-patients with Paxlovid over a period of 300 days beginning in January 2022 resulted in life and cost savings. In a low-transmission scenario (effective reproduction number of 1.2), this approach could avert 0.28 million (95% CI 0.03-0.59 million) hospitalizations and save US $56.95 billion (95% CI US $2.62-$122.63 billion). In a higher transmission scenario (effective reproduction number of 3), the benefits increase, potentially preventing 0.85 million (95% CI 0.36-1.38 million) hospitalizations and saving US $170.17 billion (95% CI US $60.49-$286.14 billion). Our findings suggest that timely and widespread use of Paxlovid could be an effective and economical approach to mitigate the effects of COVID-19. [ABSTRACT FROM AUTHOR]

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission continues to evolve, understanding the contribution of location-specific variations in nonpharmaceutical interventions and behaviors to disease transmission during the initial epidemic wave will be key for future control strategies. We offer a rigorous statistical analysis of the relative effectiveness of the timing of both official stay-at-home orders and population mobility reductions during the initial stage of the US coronavirus disease 2019 (COVID-19) epidemic. We used a Bayesian hierarchical regression to fit county-level mortality data from the first case on January 21, 2020, through April 20, 2020, and quantify associations between the timing of stay-at-home orders and population mobility with epidemic control. We found that among 882 counties with an early local epidemic, a 10-day delay in the enactment of stay-at-home orders would have been associated with 14,700 additional deaths by April 20 (95% credible interval: 9,100, 21,500), whereas shifting orders 10 days earlier would have been associated with nearly 15,700 fewer lives lost (95% credible interval: 11,350, 18,950). Analogous estimates are available for reductions in mobility—which typically occurred before stay-at-home orders—and are also stratified by county urbanicity, showing significant heterogeneity. Results underscore the importance of timely policy and behavioral action for early-stage epidemic control. [ABSTRACT FROM AUTHOR]

Background Global vaccine development efforts have been accelerated in response to the devastating coronavirus disease 2019 (COVID-19) pandemic. We evaluated the impact of a 2-dose COVID-19 vaccination campaign on reducing incidence, hospitalizations, and deaths in the United States. Methods We developed an agent-based model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and parameterized it with US demographics and age-specific COVID-19 outcomes. Healthcare workers and high-risk individuals were prioritized for vaccination, whereas children under 18 years of age were not vaccinated. We considered a vaccine efficacy of 95% against disease following 2 doses administered 21 days apart achieving 40% vaccine coverage of the overall population within 284 days. We varied vaccine efficacy against infection and specified 10% preexisting population immunity for the base-case scenario. The model was calibrated to an effective reproduction number of 1.2, accounting for current nonpharmaceutical interventions in the United States. Results Vaccination reduced the overall attack rate to 4.6% (95% credible interval [CrI]: 4.3%–5.0%) from 9.0% (95% CrI: 8.4%–9.4%) without vaccination, over 300 days. The highest relative reduction (54%–62%) was observed among individuals aged 65 and older. Vaccination markedly reduced adverse outcomes, with non-intensive care unit (ICU) hospitalizations, ICU hospitalizations, and deaths decreasing by 63.5% (95% CrI: 60.3%–66.7%), 65.6% (95% CrI: 62.2%–68.6%), and 69.3% (95% CrI: 65.5%–73.1%), respectively, across the same period. Conclusions Our results indicate that vaccination can have a substantial impact on mitigating COVID-19 outbreaks, even with limited protection against infection. However, continued compliance with nonpharmaceutical interventions is essential to achieve this impact. [ABSTRACT FROM AUTHOR]

Background: As of 28 July 2021, 60% of adults in the United States had been fully vaccinated against COVID-19, and more than 34 million cases had been reported. Given the uncertainty regarding undocumented infections, the population level of immunity against COVID-19 in the United States remains undetermined.Objective: To estimate the population immunity, defined as the proportion of the population that is protected against SARS-CoV-2 infection due to prior infection or vaccination.Design: Statistical and simulation modeling to estimate overall and age-specific population immunity.Setting: United States.Participants: Simulated age-stratified population representing U.S. demographic characteristics.Measurements: The true number of SARS-CoV-2 infections in the United States was inferred from data on reported deaths using age-specific infection-fatality rates (IFRs). Taking into account the estimates for vaccine effectiveness and protection against reinfection, the overall population immunity was determined as the sum of protection levels in vaccinated persons and those who were previously infected but not vaccinated.Results: Using age-specific IFR estimates from the Centers for Disease Control and Prevention, it was estimated that as of 15 July 2021, 114.9 (95% credible interval [CrI], 103.2 to 127.4) million persons had been infected with SARS-CoV-2 in the United States. The mean overall population immunity was 62.0% (CrI, 58.4% to 66.4%). Adults aged 65 years or older were estimated to have the highest immunity level (77.2% [CrI, 76.2% to 78.6%]), and children younger than 12 years had the lowest immunity level (17.9% [CrI, 14.4% to 21.9%]).Limitation: Publicly reported deaths may underrepresent actual deaths.Conclusion: As of 15 July 2021, the U.S. population immunity against COVID-19 may still have been insufficient to contain the outbreaks and safely revert to prepandemic social behavior.Primary Funding Source: National Science Foundation, National Institutes of Health, Notsew Orm Sands Foundation, Canadian Institutes of Health Research, and Natural Sciences and Engineering Research Council of Canada. [ABSTRACT FROM AUTHOR]

During rollout of coronavirus disease vaccination, policymakers have faced critical trade-offs. Using a mathematical model of transmission, we found that timing of vaccination rollout would be expected to have a substantially greater effect on mortality rate than risk-based prioritization and uptake and that prioritizing first doses over second doses may be lifesaving. [ABSTRACT FROM AUTHOR]

As COVID-19 spreads across the United States, people experiencing homelessness (PEH) are among the most vulnerable to the virus. To mitigate transmission, municipal governments are procuring isolation facilities for PEH to utilize following possible exposure to the virus. Here we describe the framework for anticipating isolation bed demand in PEH communities that we developed to support public health planning in Austin, Texas during March 2020. Using a mathematical model of COVID-19 transmission, we projected that, under no social distancing orders, a maximum of 299 (95% Confidence Interval: 223, 321) PEH may require isolation rooms in the same week. Based on these analyses, Austin Public Health finalized a lease agreement for 205 isolation rooms on March 27th 2020. As of October 7th 2020, a maximum of 130 rooms have been used on a single day, and a total of 602 PEH have used the facility. As a general rule of thumb, we expect the peak proportion of the PEH population that will require isolation to be roughly triple the projected peak daily incidence in the city. This framework can guide the provisioning of COVID-19 isolation and post-acute care facilities for high risk communities throughout the United States. [ABSTRACT FROM AUTHOR]

Individuals in low socioeconomic brackets are considered at-risk for developing influenza-related complications and often exhibit higher than average influenza-related hospitalization rates. This disparity has been attributed to various factors, including restricted access to preventative and therapeutic health care, limited sick leave, and household structure. Adequate influenza surveillance in these at-risk populations is a critical precursor to accurate risk assessments and effective intervention. However, the United States of America's primary national influenza surveillance system (ILINet) monitors outpatient healthcare providers, which may be largely inaccessible to lower socioeconomic populations. Recent initiatives to incorporate Internet-source and hospital electronic medical records data into surveillance systems seek to improve the timeliness, coverage, and accuracy of outbreak detection and situational awareness. Here, we use a flexible statistical framework for integrating multiple surveillance data sources to evaluate the adequacy of traditional (ILINet) and next generation (BioSense 2.0 and Google Flu Trends) data for situational awareness of influenza across poverty levels. We find that ZIP Codes in the highest poverty quartile are a critical vulnerability for ILINet that the integration of next generation data fails to ameliorate. Author summary: Public health agencies maintain increasingly sophisticated surveillance systems, which integrate diverse data streams within limited budgets. Here we develop a method to design robust and efficient forecasting systems for influenza hospitalizations. With these forecasting models, we find support for a key data gap namely that the USA's public health surveillance data sets are much more representative of higher socioeconomic sub-populations and perform poorly for the most at-risk communities. Thus, our study highlights another related socioeconomic inequity—a reduced capability to monitor outbreaks in at-risk populations—which impedes effective public health interventions. [ABSTRACT FROM AUTHOR]

As emerging and re-emerging infectious arboviruses like dengue, chikungunya, and Zika threaten new populations worldwide, officials scramble to assess local severity and transmissibility, with little to no epidemiological history to draw upon. Indirect estimates of risk from vector habitat suitability maps are prone to great uncertainty, while direct estimates from epidemiological data are only possible after cases accumulate and, given environmental constraints on arbovirus transmission, cannot be widely generalized beyond the focal region. Combining these complementary methods, we use disease importation and transmission data to improve the accuracy and precision of a priori ecological risk estimates. We demonstrate this approach by estimating the spatiotemporal risks of Zika virus transmission throughout Texas, a high-risk region in the southern United States. Our estimates are, on average, 80% lower than published ecological estimates—with only six of 254 Texas counties deemed capable of sustaining a Zika epidemic—and they are consistent with the number of autochthonous cases detected in 2017. Importantly our method provides a framework for model comparison, as our mechanistic understanding of arbovirus transmission continues to improve. Real-time updating of prior risk estimates as importations and outbreaks arise can thereby provide critical, early insight into local transmission risks as emerging arboviruses expand their global reach. [ABSTRACT FROM AUTHOR]

The maximum entropy model, a commonly used species distribution model (SDM) normally combines observations of the species occurrence with environmental information to predict the geographic distributions of animal or plant species. However, it only produces point estimates for the probability of species existence. To understand the uncertainty of the point estimates, we analytically derived the variance of the outputs of the maximum entropy model from the variance of the input. We applied the analytic method to obtain the standard deviation of dengue importation probability and Aedes aegypti suitability. Dengue occurrence data and Aedes aegypti mosquito abundance data, combined with demographic and environmental data, were applied to obtain point estimates and the corresponding variance. To address the issue of not having the true distributions for comparison, we compared and contrasted the performance of the analytical expression with the bootstrap method and Poisson point process model which proved of equivalence of maximum entropy model with the assumption of independent point locations. Both Dengue importation probability and Aedes aegypti mosquito suitability examples show that the methods generate comparatively the same results and the analytic method we introduced is dramatically faster than the bootstrap method and directly apply to maximum entropy model. [ABSTRACT FROM AUTHOR]

Background: Confirmed local transmission of Zika Virus (ZIKV) in Texas and Florida have heightened the need for early and accurate indicators of self-sustaining transmission in high risk areas across the southern United States. Given ZIKV's low reporting rates and the geographic variability in suitable conditions, a cluster of reported cases may reflect diverse scenarios, ranging from independent introductions to a self-sustaining local epidemic.Methods: We present a quantitative framework for real-time ZIKV risk assessment that captures uncertainty in case reporting, importations, and vector-human transmission dynamics.Results: We assessed county-level risk throughout Texas, as of summer 2016, and found that importation risk was concentrated in large metropolitan regions, while sustained ZIKV transmission risk is concentrated in the southeastern counties including the Houston metropolitan region and the Texas-Mexico border (where the sole autochthonous cases have occurred in 2016). We found that counties most likely to detect cases are not necessarily the most likely to experience epidemics, and used our framework to identify triggers to signal the start of an epidemic based on a policymakers propensity for risk.Conclusions: This framework can inform the strategic timing and spatial allocation of public health resources to combat ZIKV throughout the US, and highlights the need to develop methods to obtain reliable estimates of key epidemiological parameters. [ABSTRACT FROM AUTHOR]

Background: Influenza vaccination is vital for reducing H1N1 infection-mediated morbidity and mortality. To reduce transmission and achieve herd immunity during the initial 2009-2010 pandemic season, the US Centers for Disease Control and Prevention (CDC) recommended that initial priority for H1N1 vaccines be given to individuals under age 25, as these individuals are more likely to spread influenza than older adults. However, due to significant delay in vaccine delivery for the H1N1 influenza pandemic, a large fraction of population was exposed to the H1N1 virus and thereby obtained immunity prior to the wide availability of vaccines. This exposure affects the spread of the disease and needs to be considered when prioritizing vaccine distribution. Methods: To determine optimal H1N1 vaccine distributions based on individual self-interest versus population interest, we constructed a game theoretical age-structured model of influenza transmission and considered the impact of delayed vaccination. Results: Our results indicate that if individuals decide to vaccinate according to self-interest, the resulting optimal vaccination strategy would prioritize adults of age 25 to 49 followed by either preschool-age children before the pandemic peak or older adults (age 50-64) at the pandemic peak. In contrast, the vaccine allocation strategy that is optimal for the population as a whole would prioritize individuals of ages 5 to 64 to curb a growing pandemic regardless of the timing of the vaccination program. Conclusions: Our results indicate that for a delayed vaccine distribution, the priorities that are optimal at a population level do not align with those that are optimal according to individual self-interest. Moreover, the discordance between the optimal vaccine distributions based on individual self-interest and those based on population interest is even more pronounced when vaccine availability is delayed. To determine optimal vaccine allocation for pandemic influenza, public health agencies need to consider both the changes in infection risks among age groups and expected patterns of adherence. [ABSTRACT FROM AUTHOR]

In 2009, public health agencies across the globe worked to mitigate the impact of the swine-origin influenza A (pH1N1) virus. These efforts included intensified surveillance, social distancing, hygiene measures, and the targeted use of antiviral medications to prevent infection (prophylaxis). In addition, aggressive antiviral treatment was recommended for certain patient subgroups to reduce the severity and duration of symptoms. To assist States and other localities meet these needs, the U.S. Government distributed a quarter of the antiviral medications in the Strategic National Stockpile within weeks of the pandemic's start. However, there are no quantitative models guiding the geo-temporal distribution of the remainder of the Stockpile in relation to pandemic spread or severity. We present a tactical optimization model for distributing this stockpile for treatment of infected cases during the early stages of a pandemic like 2009 pH1N1, prior to the wide availability of a strain-specific vaccine. Our optimization method efficiently searches large sets of intervention strategies applied to a stochastic network model of pandemic influenza transmission within and among U.S. cities. The resulting optimized strategies depend on the transmissability of the virus and postulated rates of antiviral uptake and wastage (through misallocation or loss). Our results suggest that an aggressive community-based antiviral treatment strategy involving early, widespread, pro-rata distribution of antivirals to States can contribute to slowing the transmission of mildly transmissible strains, like pH1N1. For more highly transmissible strains, outcomes of antiviral use are more heavily impacted by choice of distribution intervals, quantities per shipment, and timing of shipments in relation to pandemic spread. This study supports previous modeling results suggesting that appropriate antiviral treatment may be an effective mitigation strategy during the early stages of future influenza pandemics, increasing the need for systematic efforts to optimize distribution strategies and provide tactical guidance for public health policy-makers. [ABSTRACT FROM AUTHOR]

Background The threat of avian influenza and the 2004-2005 influenza vaccine supply shortage in the United States have sparked a debate about optimal vaccination strategies to reduce the burden of morbidity and mortality caused by the influenza virus. Methods and Findings We present a comparative analysis of two classes of suggested vaccination strategies: mortality-based strategies that target high-risk populations and morbidity-based strategies that target high-prevalence populations. Applying the methods of contact network epidemiology to a model of disease transmission in a large urban population, we assume that vaccine supplies are limited and then evaluate the efficacy of these strategies across a wide range of viral transmission rates and for two different age-specific mortality distributions. We find that the optimal strategy depends critically on the viral transmission level (reproductive rate) of the virus: morbidity-based strategies outperform mortality-based strategies for moderately transmissible strains, while the reverse is true for highly transmissible strains. These results hold for a range of mortality rates reported for prior influenza epidemics and pandemics. Furthermore, we show that vaccination delays and multiple introductions of disease into the community have a more detrimental impact on morbidity-based strategies than mortality-based strategies. Conclusions If public health officials have reasonable estimates of the viral transmission rate and the frequency of new introductions into the community prior to an outbreak, then these methods can guide the design of optimal vaccination priorities. When such information is unreliable or not available, as is often the case, this study recommends mortality-based vaccination priorities. [ABSTRACT FROM AUTHOR]

Highlights: [•] We develop a mathematical model of seasonal influenza in the United States. [•] We identify optimal vaccination allocation strategies under parameter uncertainty. [•] Strategies targeting schoolchildren and young adults are robust to uncertainty. [•] Parameter uncertainty is vital to the evaluation of public health interventions. [ABSTRACT FROM AUTHOR]

School reopenings in 2021 and 2022 coincided with the rapid emergence of new SARS-CoV-2 variants in the United States. In-school mitigation efforts varied, depending on local COVID-19 mandates and resources. Using a stochastic age-stratified agent-based model of SARS-CoV-2 transmission, we estimate the impacts of multiple in-school strategies on both infection rates and absenteeism, relative to a baseline scenario in which only symptomatic cases are tested and positive tests trigger a 10-day isolation of the case and 10-day quarantine of their household and classroom. We find that monthly asymptomatic screening coupled with the 10-day isolation and quarantine period is expected to avert 55.4% of infections while increasing absenteeism by 104.3%. Replacing quarantine with test-to-stay would reduce absenteeism by 66.3% (while hardly impacting infection rates), but would require roughly 10-fold more testing resources. Alternatively, vaccination or mask wearing by 50% of the student body is expected to avert 54.1% or 43.1% of infections while decreasing absenteeism by 34.1% or 27.4%, respectively. Separating students into classrooms based on mask usage is expected to reduce infection risks among those who wear masks (by 23.1%), exacerbate risks among those who do not (by 27.8%), but have little impact on overall risk. A combined strategy of monthly screening, household and classroom quarantine, a 50% vaccination rate, and a 50% masking rate (in mixed classrooms) is expected to avert 81.7% of infections while increasing absenteeism by 90.6%. During future public health emergencies, such analyses can inform the rapid design of resource-constrained strategies that mitigate both public health and educational risks., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Coronavirus Disease 2019 (COVID-19) continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval)., Methods and Findings: The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023 and April 15, 2025 under 6 scenarios representing the intersection of considered levels of immune escape and vaccination. Annually reformulated vaccines are assumed to be 65% effective against symptomatic infection with strains circulating on June 15 of each year and to become available on September 1. Age- and state-specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. State and national projections from 8 modeling teams were ensembled to produce projections for each scenario and expected reductions in disease outcomes due to vaccination over the projection period. From April 15, 2023 to April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November to January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% projection interval (PI) [1,438,000, 4,270,000]) hospitalizations and 209,000 (90% PI [139,000, 461,000]) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% confidence interval (CI) [104,000, 355,000]) fewer hospitalizations and 33,000 (95% CI [12,000, 54,000]) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000-598,000) fewer hospitalizations and 49,000 (95% CI [29,000, 69,000]) fewer deaths., Conclusions: COVID-19 is projected to be a significant public health threat over the coming 2 years. Broad vaccination has the potential to substantially reduce the burden of this disease, saving tens of thousands of lives each year., Competing Interests: JE is president of General Biodefense LLC, a private consulting group for public health informatics, and has interest in READE.ai, a medical artificial intelligence solutions company. MR reports stock ownership in Becton Dickinson & Co., which manufactures medical equipment used in COVID-19 testing, vaccination, and treatment. JL has served as an expert witness on cases where the likely length of the pandemic was of issue. The remaining authors declare no competing interests., (Copyright: © 2024 Jung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We evaluated the population-level benefits of expanding treatment with the antiviral drug Paxlovid (nirmatrelvir/ritonavir) in the United States for SARS-CoV-2 Omicron variant infections. Using a multiscale mathematical model, we found that treating 20% of symptomatic case-patients with Paxlovid over a period of 300 days beginning in January 2022 resulted in life and cost savings. In a low-transmission scenario (effective reproduction number of 1.2), this approach could avert 0.28 million (95% CI 0.03-0.59 million) hospitalizations and save US $56.95 billion (95% CI US $2.62-$122.63 billion). In a higher transmission scenario (effective reproduction number of 3), the benefits increase, potentially preventing 0.85 million (95% CI 0.36-1.38 million) hospitalizations and saving US $170.17 billion (95% CI US $60.49-$286.14 billion). Our findings suggest that timely and widespread use of Paxlovid could be an effective and economical approach to mitigate the effects of COVID-19.

As SARS-CoV-2 emerged as a global threat in early 2020, China enacted rapid and strict lockdown orders to prevent introductions and suppress transmission. In contrast, the United States federal government did not enact national orders. State and local authorities were left to make rapid decisions based on limited case data and scientific information to protect their communities. To support local decision making in early 2020, we developed a model for estimating the probability of an undetected COVID-19 epidemic (epidemic risk) in each US county based on the epidemiological characteristics of the virus and the number of confirmed and suspected cases. As a retrospective analysis we included county-specific reproduction numbers and found that counties with only a single reported case by March 16, 2020 had a mean epidemic risk of 71% (95% CI: 52-83%), implying COVID-19 was already spreading widely by the first detected case. By that date, 15% of US counties covering 63% of the population had reported at least one case and had epidemic risk greater than 50%. We find that a 10% increase in model estimated epidemic risk for March 16 yields a 0.53 (95% CI: 0.49-0.58) increase in the log odds that the county reported at least two additional cases in the following week. The original epidemic risk estimates made on March 16, 2020 that assumed all counties had an effective reproduction number of 3.0 are highly correlated with our retrospective estimates (r = 0.99; p<0.001) but are less predictive of subsequent case increases (AIC difference of 93.3 and 100% weight in favor of the retrospective risk estimates). Given the low rates of testing and reporting early in the pandemic, taking action upon the detection of just one or a few cases may be prudent., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Javan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In response to COVID-19, schools across the United States closed in early 2020; many did not fully reopen until late 2021. Although regular testing of asymptomatic students, teachers, and staff can reduce transmission risks, few school systems consistently used proactive testing to safeguard return to classrooms. Socioeconomically diverse public school districts might vary testing levels across campuses to ensure fair, effective use of limited resources. We describe a test allocation approach to reduce overall infections and disparities across school districts. Using a model of SARS-CoV-2 transmission in schools fit to data from a large metropolitan school district in Texas, we reduced incidence between the highest and lowest risk schools from a 5.6-fold difference under proportional test allocation to 1.8-fold difference under our optimized test allocation. This approach provides a roadmap to help school districts deploy proactive testing and mitigate risks of future SARS-CoV-2 variants and other pathogen threats.

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 (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of 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 naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk 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.

Forecasting the burden of COVID-19 has been impeded by limitations in data, with case reporting biased by testing practices, death counts lagging far behind infections, and hospital census reflecting time-varying patient access, admission criteria, and demographics. Here, we show that hospital admissions coupled with mobility data can reliably predict severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission rates and healthcare demand. Using a forecasting model that has guided mitigation policies in Austin, TX, we estimate that the local reproduction number had an initial 7-d average of 5.8 (95% credible interval [CrI]: 3.6 to 7.9) and reached a low of 0.65 (95% CrI: 0.52 to 0.77) after the summer 2020 surge. Estimated case detection rates ranged from 17.2% (95% CrI: 11.8 to 22.1%) at the outset to a high of 70% (95% CrI: 64 to 80%) in January 2021, and infection prevalence remained above 0.1% between April 2020 and March 1, 2021, peaking at 0.8% (0.7-0.9%) in early January 2021. As precautionary behaviors increased safety in public spaces, the relationship between mobility and transmission weakened. We estimate that mobility-associated transmission was 62% (95% CrI: 52 to 68%) lower in February 2021 compared to March 2020. In a retrospective comparison, the 95% CrIs of our 1, 2, and 3 wk ahead forecasts contained 93.6%, 89.9%, and 87.7% of reported data, respectively. Developed by a task force including scientists, public health officials, policy makers, and hospital executives, this model can reliably project COVID-19 healthcare needs in US cities., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

Background: Global vaccine development efforts have been accelerated in response to the devastating coronavirus disease 2019 (COVID-19) pandemic. We evaluated the impact of a 2-dose COVID-19 vaccination campaign on reducing incidence, hospitalizations, and deaths in the United States., Methods: We developed an agent-based model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and parameterized it with US demographics and age-specific COVID-19 outcomes. Healthcare workers and high-risk individuals were prioritized for vaccination, whereas children under 18 years of age were not vaccinated. We considered a vaccine efficacy of 95% against disease following 2 doses administered 21 days apart achieving 40% vaccine coverage of the overall population within 284 days. We varied vaccine efficacy against infection and specified 10% preexisting population immunity for the base-case scenario. The model was calibrated to an effective reproduction number of 1.2, accounting for current nonpharmaceutical interventions in the United States., Results: Vaccination reduced the overall attack rate to 4.6% (95% credible interval [CrI]: 4.3%-5.0%) from 9.0% (95% CrI: 8.4%-9.4%) without vaccination, over 300 days. The highest relative reduction (54%-62%) was observed among individuals aged 65 and older. Vaccination markedly reduced adverse outcomes, with non-intensive care unit (ICU) hospitalizations, ICU hospitalizations, and deaths decreasing by 63.5% (95% CrI: 60.3%-66.7%), 65.6% (95% CrI: 62.2%-68.6%), and 69.3% (95% CrI: 65.5%-73.1%), respectively, across the same period., Conclusions: Our results indicate that vaccination can have a substantial impact on mitigating COVID-19 outbreaks, even with limited protection against infection. However, continued compliance with nonpharmaceutical interventions is essential to achieve this impact., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

During rollout of coronavirus disease vaccination, policymakers have faced critical trade-offs. Using a mathematical model of transmission, we found that timing of vaccination rollout would be expected to have a substantially greater effect on mortality rate than risk-based prioritization and uptake and that prioritizing first doses over second doses may be lifesaving.

Rapid diagnostic testing for COVID-19 is key to guiding social distancing orders and containing emerging disease clusters by contact tracing and isolation. However, communities throughout the US do not yet have adequate access to tests. Pharmacies are already engaged in testing, but there is capacity to greatly increase coverage. Using a facility location optimization model and willingness-to-travel estimates from US National Household Travel Survey data, we find that if COVID-19 testing became available in all US pharmacies, an estimated 94% of the US population would be willing to travel to obtain a test, if warranted. Whereas the largest chain provides high coverage in densely populated states, like Massachusetts, Rhode Island, New Jersey, and Connecticut, independent pharmacies would be required for sufficient coverage in Montana, South Dakota, and Wyoming. If only 1,000 ZIP code areas for pharmacies in the US are selected to provide testing, judicious selection, using our optimization model, provides estimated access to 29 million more people than selecting pharmacies simply based on population density.

Background: To mitigate the COVID-19 pandemic, countries worldwide have enacted unprecedented movement restrictions, physical distancing measures, and face mask requirements. Until safe and efficacious vaccines or antiviral drugs become widely available, viral testing remains the primary mitigation measure for rapid identification and isolation of infected individuals. We aimed to assess the economic trade-offs of expanding and accelerating testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across the USA in different transmission scenarios., Methods: We used a multiscale model that incorporates SARS-CoV-2 transmission at the population level and daily viral load dynamics at the individual level to assess eight surveillance testing strategies that varied by testing frequency (from daily to monthly testing) and isolation period (1 or 2 weeks), compared with the status-quo strategy of symptom-based testing and isolation. For each testing strategy, we first estimated the costs (incorporating costs of diagnostic testing and admissions to hospital, and salary lost while in isolation) and years of life lost (YLLs) prevented under rapid and low transmission scenarios. We then assessed the testing strategies across a range of scenarios, each defined by effective reproduction number (R e ), willingness to pay per YLL averted, and cost of a test, to estimate the probability that a particular strategy had the greatest net benefit. Additionally, for a range of transmission scenarios (R e from 1·1 to 3), we estimated a threshold test price at which the status-quo strategy outperforms all testing strategies considered., Findings: Our modelling showed that daily testing combined with a 2-week isolation period was the most costly strategy considered, reflecting increased costs with greater test frequency and length of isolation period. Assuming a societal willingness to pay of US$100 000 per YLL averted and a price of $5 per test, the strategy most likely to be cost-effective under a rapid transmission scenario (R e of 2·2) is weekly testing followed by a 2-week isolation period subsequent to a positive test result. Under low transmission scenarios (R e of 1·2), monthly testing of the population followed by 1-week isolation rather than 2-week isolation is likely to be most cost-effective. Expanded surveillance testing is more likely to be cost-effective than the status-quo testing strategy if the price per test is less than $75 across all transmission rates considered., Interpretation: Extensive expansion of SARS-CoV-2 testing programmes with more frequent and rapid tests across communities coupled with isolation of individuals with confirmed infection is essential for mitigating the COVID-19 pandemic. Furthermore, resources recouped from shortened isolation duration could be cost-effectively allocated to more frequent testing., Funding: US National Institutes of Health, US Centers for Disease Control and Prevention, and Love, Tito's., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Widespread, convenient access to COVID-19 testing has been challenging in the United States. We make a case for provisioning COVID-19 tests through the United States Postal Service (USPS) facilities and demonstrate a simple method for selecting locations to improve access. We provide quantitative evidence that even a subset of USPS facilities could provide broad access, particularly in remote and at-risk communities with limited access to health care. Based on daily travel surveys, census data, locations of USPS facilities, and an established care-seeking model, we estimate that more than 94% of the US population would be willing to travel to an existing USPS facility if warranted. For half of the US population, this would require traveling less than 2.5 miles from home; for 90%, the distance would be less than 7 miles. In Georgia, Illinois, and Minnesota, we estimate that testing at USPS facilities would provide access to an additional 4.1, 3.1, and 1.3 million people and reduce the median travel distance by 3.0, 0.8, and 1.2 miles, respectively, compared with existing testing sites per 28 July 2020. We also discuss the option of distributing test-at-home kits via USPS instead of private carriers. Finally, our proposal provides USPS an opportunity to increase revenues and expand its mission, thus improving its future prospects and relevance.

Forecasting the emergence and spread of influenza viruses is an important public health challenge. Timely and accurate estimates of influenza prevalence, particularly of severe cases requiring hospitalization, can improve control measures to reduce transmission and mortality. Here, we extend a previously published machine learning method for influenza forecasting to integrate multiple diverse data sources, including traditional surveillance data, electronic health records, internet search traffic, and social media activity. Our hierarchical framework uses multi-linear regression to combine forecasts from multiple data sources and greedy optimization with forward selection to sequentially choose the most predictive combinations of data sources. We show that the systematic integration of complementary data sources can substantially improve forecast accuracy over single data sources. When forecasting the Center for Disease Control and Prevention (CDC) influenza-like-illness reports (ILINet) from week 48 through week 20, the optimal combination of predictors includes public health surveillance data and commercially available electronic medical records, but neither search engine nor social media data., Competing Interests: The authors have declared that no competing interests exist.

Mathematical models incorporate various data sources and advanced computational techniques to portray real-world disease transmission and translate the basic science of infectious diseases into decision-support tools for public health. Unlike standard epidemiologic methods that rely on complete data, modeling is needed when there are gaps in data. By combining diverse data sources, models can fill gaps when critical decisions must be made using incomplete or limited information. They can be used to assess the effect and feasibility of different scenarios and provide insight into the emergence, spread, and control of disease. During the past decade, models have been used to predict the likelihood and magnitude of infectious disease outbreaks, inform emergency response activities in real time (1), and develop plans and preparedness strategies for future events, the latter of which proved invaluable during outbreaks such as severe acute respiratory syndrome and pandemic influenza (2-6). Ideally, modeling is a multistep process that involves communication between modelers and decision-makers, allowing them to gain a mutual understanding of the problem to be addressed, the type of estimates that can be reliably generated, and the limitations of the data. As models become more detailed and relevant to real-time threats, the importance of modeling in public health decision-making continues to grow.

Importance: Infection with the respiratory syncytial virus (RSV) is the leading cause of hospitalizations in children, accounting for more than 90,000 hospitalizations every year in the United States. For children who are at risk for severe RSV infections, the American Academy of Pediatrics recommends immunoprophylaxis with a series of up to 5 injections of the antibody palivizumab administered monthly, beginning on November 1 of each year. However, many practitioners initiate injections at the onset of RSV season as indicated by local surveillance., Objectives: To evaluate the effectiveness of current regimens for palivizumab injections across different cities and to design an optimized regimen., Design, Setting, and Participants: We performed a mathematical modeling study of the risk for hospitalization due to RSV infection. The model accounted for the pharmacokinetics of the antibody, the timing of the injections, and seasonal patterns of RSV, including geographic and year-to-year variability. We used the model to estimate the efficacy of current regimens, including the American Academy of Pediatrics recommendation, and to design a more effective injection regimen, the optimized fixed start (OFS), which uses city-specific initiation dates. Participants were the approximately 700,000 individuals who had specimens tested for RSV by National Respiratory and Enteric Virus Surveillance System laboratories in 18 US cities from July 1, 1994, through June 30, 2011 (a total of 725,741 tests)., Interventions: Different palivizumab injection regimens., Main Outcomes and Measures: The primary outcome measure was reduction in hospitalizations due to RSV infections. The secondary measures were cost (number of palivizumab doses) and duration of protection (in days)., Results: The American Academy of Pediatrics-recommended 5-injection regimen is expected to reduce hospitalization risk by a median of 2.7% (range, -2.2% to 6.1%) compared with the conventional regimen based on RSV surveillance. The 5-injection OFS regimen is expected to further reduce risk by a median of 6.8% (range, 4.9% to 14.8%), and the 4-injection OFS regimen is expected to achieve efficacy comparable to that of the conventional 5-injection regimen while reducing costs by 20%., Conclusions and Relevance: Modified palivizumab regimens can improve protection for children at risk for severe outcomes of RSV infection and thereby lower rates of hospitalization due to RSV.

Mathematical modeling of disease transmission has provided quantitative predictions for health policy, facilitating the evaluation of epidemiological outcomes and the cost-effectiveness of interventions. However, typical sensitivity analyses of deterministic dynamic infectious disease models focus on model architecture and the relative importance of parameters but neglect parameter uncertainty when reporting model predictions. Consequently, model results that identify point estimates of intervention levels necessary to terminate transmission yield limited insight into the probability of success. We apply probabilistic uncertainty analysis to a dynamic model of influenza transmission and assess global uncertainty in outcome. We illustrate that when parameter uncertainty is not incorporated into outcome estimates, levels of vaccination and treatment predicted to prevent an influenza epidemic will only have an approximately 50% chance of terminating transmission and that sensitivity analysis alone is not sufficient to obtain this information. We demonstrate that accounting for parameter uncertainty yields probabilities of epidemiological outcomes based on the degree to which data support the range of model predictions. Unlike typical sensitivity analyses of dynamic models that only address variation in parameters, the probabilistic uncertainty analysis described here enables modelers to convey the robustness of their predictions to policy makers, extending the power of epidemiological modeling to improve public health., (Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: As Pandemic (H1N1) 2009 influenza spreads around the globe, it strikes school-age children more often than adults. Although there is some evidence of pre-existing immunity among older adults, this alone may not explain the significant gap in age-specific infection rates., Methods and Findings: Based on a retrospective analysis of pandemic strains of influenza from the last century, we show that school-age children typically experience the highest attack rates in primarily naive populations, with the burden shifting to adults during the subsequent season. Using a parsimonious network-based mathematical model which incorporates the changing distribution of contacts in the susceptible population, we demonstrate that new pandemic strains of influenza are expected to shift the epidemiological landscape in exactly this way., Conclusions: Our analysis provides a simple demographic explanation for the age bias observed for H1N1/09 attack rates, and suggests that this bias may shift in coming months. These results have significant implications for the allocation of public health resources for H1N1/09 and future influenza pandemics.