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Background: Safe and effective vaccines could help to end the ongoing Ebola virus disease epidemic in parts of west Africa, and mitigate future outbreaks of the virus. We assess the statistical validity and power of randomised controlled trial (RCT) and stepped-wedge cluster trial (SWCT) designs in Sierra Leone, where the incidence of Ebola virus disease is spatiotemporally heterogeneous, and is decreasing rapidly. Methods: We projected district-level Ebola virus disease incidence for the next 6 months, using a stochastic model fitted to data from Sierra Leone. We then simulated RCT and SWCT designs in trial populations comprising geographically distinct clusters at high risk, taking into account realistic logistical constraints, and both individual-level and cluster-level variations in risk. We assessed false-positive rates and power for parametric and non-parametric analyses of simulated trial data, across a range of vaccine efficacies and trial start dates. Findings: For an SWCT, regional variation in Ebola virus disease incidence trends produced increased false-positive rates (up to 0·15 at α=0·05) under standard statistical models, but not when analysed by a permutation test, whereas analyses of RCTs remained statistically valid under all models. With the assumption of a 6-month trial starting on Feb 18, 2015, we estimate the power to detect a 90% effective vaccine to be between 49% and 89% for an RCT, and between 6% and 26% for an SWCT, depending on the Ebola virus disease incidence within the trial population. We estimate that a 1-month delay in trial initiation will reduce the power of the RCT by 20% and that of the SWCT by 49%. Interpretation: Spatiotemporal variation in infection risk undermines the statistical power of the SWCT. This variation also undercuts the SWCT's expected ethical advantages over the RCT, because an RCT, but not an SWCT, can prioritise vaccination of high-risk clusters. Funding: US National Institutes of Health, US National Science Foundation, and Canadian Institutes of Health Research.

Background: Over-prescribing of antibiotics is considered to result in increased morbidity and mortality from drug-resistant organisms. A resulting common wisdom is that it would be better for society if physicians would restrain their prescription of anti

Severe acute respiratory syndrome (SARS) has been transmitted extensively within hospitals, and healthcare workers (HCWs) have comprised a large proportion of SARS cases worldwide. We present a stochastic model of a SARS outbreak in a community and its hospital. For a range of basic reproductive numbers (R0) corresponding to conditions in different cities (but with emphasis on R0∼ 3 as reported for Hong Kong and Singapore), we evaluate contact precautions and case management (quarantine and isolation) as containment measures. Hospital-based contact precautions emerge as the most potent measures, with hospital-wide measures being particularly important if screening of HCWs is inadequate. For R0= 3, case isolation alone can control a SARS outbreak only if isolation reduces transmission by at least a factor of four and the mean symptom-onset-to-isolation time is less than 3 days. Delays of a few days in contact tracing and case identification severely degrade the utility of quarantine and isolation, particularly in high-transmission settings. Still more detrimental are delays between the onset of an outbreak and the implementation of control measures; for given control scenarios, our model identifies windows of opportunity beyond which the efficacy of containment efforts is reduced greatly. By considering pathways of transmission in our system, we show that if hospital-based transmission is not halted, measures that reduce community-HCW contact are vital to preventing a widespread epidemic. The implications of our results for future emerging pathogens are discussed.

Extensively drug-resistant tuberculosis (XDR TB) has emerged as a threat to TB control efforts in several high-burden areas, generating international concern. XDR TB is now found in every region of the world, but appears most worrisome in the context of HIV and in resource-limited settings with congregate hospital wards. Here, we examine the emergence and transmission dynamics of the disease, incorporating the mathematical modelling literature related to airborne infection and epidemiological studies related to the operations of TB control programmes in resource-limited settings. We find that while XDR TB may present many challenges in the setting of resource constraints, the central problems highlighted by the emergence of XDR TB are those that have plagued TB programmes for years. These include a slow rate of case detection that permits prolonged infectiousness, the threat of airborne infection in enclosed spaces, the problem of inadequate treatment delivery and treatment completion, and the need to develop health systems that can address the combination of TB and poverty. Mathematical models of TB transmission shed light on the idea that community-based therapy and rapid detection systems may be beneficial in resource-limited settings, while congregate hospital wards are sites for major structural reform. [ABSTRACT FROM AUTHOR]

Background: Extensively drug-resistant (XDR) tuberculosis has spread among hospitalised patients in South Africa, but the epidemic-level effect of hospital-based infection control strategies remains unknown. We modelled the plausible effect of rapidly available infection control strategies on the overall course of the XDR tuberculosis epidemic in a rural area of South Africa.Methods: We investigated the effect of administrative, environmental, and personal infection control measures on the epidemic trajectory of XDR tuberculosis in the rural community of Tugela Ferry. Assessments were done with a mathematical model incorporating over 2 years of longitudinal inpatient and community-based data. The model simulated inpatient airborne tuberculosis transmission, community tuberculosis transmission, and the effect of HIV and antiretroviral therapy.Findings: If no new interventions are introduced, about 1300 cases of XDR tuberculosis are predicted to occur in the area of Tugela Ferry by the end of 2012, more than half of which are likely to be nosocomially transmitted. Mask use alone would avert fewer than 10% of cases in the overall epidemic, but could prevent a large proportion of cases of XDR tuberculosis in hospital staff. The combination of mask use with reduced hospitalisation time and a shift to outpatient therapy could prevent nearly a third of XDR tuberculosis cases. Supplementing this approach with improved ventilation, rapid drug resistance testing, HIV treatment, and tuberculosis isolation facilities could avert 48% of XDR tuberculosis cases (range 34-50%) by the end of 2012. However, involuntary detention could result in an unexpected rise in incidence due to restricted isolation capacity.Interpretation: A synergistic combination of available nosocomial infection control strategies could prevent nearly half of XDR tuberculosis cases, even in a resource-limited setting. XDR tuberculosis transmission will probably continue in the community, indicating the need to develop and implement parallel community-based programmes. [ABSTRACT FROM AUTHOR]

Background: Two prefusion F protein-based vaccines, Arexvy and Abrysvo, have been authorized by the US Food and Drug Administration for protecting older adults against respiratory syncytial virus (RSV)-associated lower respiratory tract illness. We evaluated the health benefits and cost-effectiveness of these vaccines., Methods: We developed a discrete-event simulation model, parameterized with the burden of RSV disease including outpatient care, hospitalization, and death for adults aged 60 years or older in the United States. Taking into account the costs associated with these RSV-related outcomes, we calculated the net monetary benefit using quality-adjusted life-year (QALY) gained as a measure of effectiveness and determined the range of price-per-dose (PPD) for Arexvy and Abrysvo vaccination programs to be cost-effective from a societal perspective., Results: Using a willingness-to-pay of $95 000 per QALY gained, we found that vaccination programs could be cost-effective for a PPD up to $127 with Arexvy and $118 with Abrysvo over the first RSV season. Achieving an influenza-like vaccination coverage of 66% for the population of older adults in the United States, the budget impact of these programs at the maximum PPD ranged from $6.48 to $6.78 billion. If the benefits of vaccination extend to a second RSV season as reported in clinical trials, we estimated a maximum PPD of $235 for Arexvy and $245 for Abrysvo, with 2-year budget impacts of $11.78 and $12.25 billion, respectively., Conclusions: Vaccination of older adults would provide substantial direct health benefits by reducing outcomes associated with RSV-related illness in this population., Competing Interests: Potential conflicts of interest. S. M. M. previously had advisory roles for Janssen Canada and Sanofi for cost-effectiveness of their products. M. C. F. has received consultation fees from Sanofi Pasteur regarding vaccine products, outside the work reported here. J. M. L.’s institution, Dalhousie University, has received funds for clinical trials conducted by the Canadian Center for Vaccinology from GSK, Janssen, Sanofi, Immunovaccine, Inventprise, Merck, Pfizer, VIDO, VBI, and Entos. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The U.S. Food and Drug Administration has proposed administering annual SARS-CoV-2 vaccines., Objective: To evaluate the effectiveness of an annual SARS-CoV-2 vaccination campaign, quantify the health and economic benefits of a second dose provided to children younger than 2 years and adults aged 50 years or older, and optimize the timing of a second dose., Design: An age-structured dynamic transmission model., Setting: United States., Participants: A synthetic population reflecting demographics and contact patterns in the United States., Intervention: Vaccination against SARS-CoV-2 with age-specific uptake similar to that of influenza vaccination., Measurements: Incidence, hospitalizations, deaths, and direct health care cost., Results: The optimal timing between the first and second dose delivered to children younger than 2 years and adults aged 50 years or older in an annual vaccination campaign was estimated to be 5 months. In direct comparison with a single-dose campaign, a second booster dose results in 123 869 fewer hospitalizations (95% uncertainty interval [UI], 121 994 to 125 742 fewer hospitalizations) and 5524 fewer deaths (95% UI, 5434 to 5613 fewer deaths), averting $3.63 billion (95% UI, $3.57 billion to $3.69 billion) in costs over a single year., Limitations: Population immunity is subject to degrees of immune evasion for emerging SARS-CoV-2 variants. The model was implemented in the absence of nonpharmaceutical interventions and preexisting vaccine-acquired immunity., Conclusion: The direct health care costs of SARS-CoV-2, particularly among adults aged 50 years or older, would be substantially reduced by administering a second dose 5 months after the initial dose., Primary Funding Source: Natural Sciences and Engineering Research Council of Canada, Notsew Orm Sands Foundation, National Institutes of Health, Centers for Disease Control and Prevention, and National Science Foundation., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-2451.

In the absence of universal healthcare in the United States, federal programs of Medicaid and Medicare are vital to providing healthcare coverage for low-income households and elderly individuals, respectively. However, both programs are under threat, with either enacted or proposed retractions. Specifically, raising Medicare age eligibility and the addition of work requirements for Medicaid qualification have been proposed, while termination of continuous enrollment for Medicaid was recently effectuated. Here, we assess the potential impact on mortality and morbidity resulting from these policy changes. Our findings indicate that the policy change to Medicare would lead to over 17,000 additional deaths among individuals aged 65 to 67 and those to Medicaid would lead to more than 8,000 deaths among those under the age of 65. To illustrate the implications for morbidity, we further consider a case study among those people with diabetes who would be likely to lose their health insurance under the policy changes. We project that these insurance retractions would lead to the loss of coverage for over 700,000 individuals with diabetes, including more than 200,000 who rely on insulin., Competing Interests: Competing interests statement:The authors declare no competing interest.

Paxlovid, a SARS-CoV-2 antiviral, not only prevents severe illness but also curtails viral shedding, lowering transmission risks from treated patients. By fitting a mathematical model of within-host Omicron viral dynamics to electronic health records data from 208 hospitalized patients in Hong Kong, we estimate that Paxlovid can inhibit over 90% of viral replication. However, its effectiveness critically depends on the timing of treatment. If treatment is initiated three days after symptoms first appear, we estimate a 17% chance of a post-treatment viral rebound and a 12% (95% CI: 0-16%) reduction in overall infectiousness for non-rebound cases. Earlier treatment significantly elevates the risk of rebound without further reducing infectiousness, whereas starting beyond five days reduces its efficacy in curbing peak viral shedding. Among the 104 patients who received Paxlovid, 62% began treatment within an optimal three-to-five-day day window after symptoms appeared. Our findings indicate that broader global access to Paxlovid, coupled with appropriately timed treatment, can mitigate the severity and transmission of SARS-Cov-2., Competing Interests: ZD, YB, EL employee of Laboratory of Data Discovery for Health Limited, LW, YL, AG, RK, LM No competing interests declared, BC reports honoraria from AstraZeneca, Fosun Pharma, GlaxoSmithKline, Moderna, Pfizer,Sanofi Pasteur, and Roche; employee of Laboratory of Data Discovery for Health Limited; the authors report no other potential conflicts of interest, (© 2024, Du, Wang, Bai et al.)

The ongoing Russian aggression against Ukraine has forced over eight million people to migrate out of Ukraine. Understanding the dynamics of forced migration is essential for policy-making and for delivering humanitarian assistance. Existing work is hindered by a reliance on observational data which is only available well after the fact. In this work, we study the efficacy of a data-driven agent-based framework motivated by social and behavioral theory in predicting outflow of migrants as a result of conflict events during the initial phase of the Ukraine war. We discuss policy use cases for the proposed framework by demonstrating how it can leverage refugee demographic details to answer pressing policy questions. We also show how to incorporate conflict forecast scenarios to predict future conflict-induced migration flows. Detailed future migration estimates across various conflict scenarios can both help to reduce policymaker uncertainty and improve allocation and staging of limited humanitarian resources in crisis settings., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Background: Two prefusion F protein-based vaccines, Arexvy and Abrysvo, have been approved by Health Canada for protecting older adults against respiratory syncytial virus (RSV)-associated lower respiratory tract disease. We estimated the health benefits and cost-effectiveness of these vaccines under a publicly funded single-dose vaccination program in Ontario that targets residents of long-term care homes (LTCHs). Additionally, we evaluated an extended program that broadens vaccination to include community-dwelling older adults., Methods: A discrete-event simulation model was parameterised with the burden of RSV disease including outpatient care, hospitalisation, and death among adults aged 60 years or older in Ontario, Canada. Accounting for direct and indirect costs (in 2023 Canadian dollars) associated with RSV-related outcomes, we calculated the net monetary benefit using quality-adjusted life-year (QALY) gained, and determined the range of price-per-dose (PPD) for vaccination programs to be cost-effective from both healthcare and societal perspectives over two RSV seasons. The incremental cost-effectiveness ratio (ICER) was calculated to estimate the additional costs required to gain one QALY., Results: Using a willingness-to-pay of $50,000 per QALY gained, we found that vaccinating 90% of residents in LTCHs with Arexvy would be cost-effective from a societal perspective for a PPD up to $163, producing a mean ICER value of $49,984 (95% CI: $47,539 to $52,704) per QALY gained with a two-year budget impact of $463,468 per 100,000 older adults. The reduction of hospitalizations was estimated at 7.0% compared to the no-vaccination scenario. Extending the program to include community-dwelling older adults with a 74% coverage akin to influenza vaccination, Arexvy remains cost-effective for a PPD up to $139, with a mean ICER value of $49,698 (95% CI: 48,022 to 51,388) per QALY gained and a two-year budget impact of $8.63 million. Compared to the no-vaccination scenario, the extended program resulted in a 57.3% reduction in RSV-related hospitalisations., Conclusions: Vaccinating residents of LTCHs against RSV disease would be cost-effective depending on PPD; extending the program to community-dwelling older adults would provide substantial health benefits, averting significant direct healthcare costs and productivity losses., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A Shoukat, is employed at BlueDot. GSK is a client of BlueDot. The contractual relationship between GSK and BlueDot began after the work in this study was completed, and is unrelated to this study. JM Langley’s institution, Dalhousie University, has received funds for clinical trials conducted by the Canadian Center for Vaccinology from GSK, Janssen, Sanofi, Immunovaccine, Inventprise, Merck, Pfizer, VIDO, VBI and Entos. JJ LeBlanc reports advisory roles to Pfizer, Merck, Janssen, and Sanofi, outside the work presented here. SM Moghadas previously had advisory roles for Janssen Canada and Sanofi unrelated to this study. Other authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.

Importance: The seasonality of COVID-19 is important for effective healthcare and public health decision-making. Previous waves of SARS-CoV-2 infections have indicated that the virus will likely persist as an endemic pathogen with distinct surges. However, the timing and patterns of potentially seasonal surges remain uncertain, rendering effective public health policies uninformed and in danger of poorly anticipating opportunities for intervention, such as well-timed booster vaccination drives. Applying an evolutionary approach to long-term data on closely related circulating coronaviruses, our research provides projections of seasonal surges that should be expected at major temperate population centers. These projections enable local public health efforts that are tailored to expected surges at specific locales or regions. This knowledge is crucial for enhancing medical preparedness and facilitating the implementation of targeted public health interventions., Competing Interests: The authors declare no conflict of interest.

Background: The cost-effectiveness of immunisation strategies with a long-acting monoclonal antibody (nirsevimab) and/or a protein-based maternal vaccine (RSVpreF) for protecting infants from Respiratory Syncytial Virus (RSV)-associated illness has not been previously determined for Canada. We estimated the health benefits and cost-effectiveness of nirsevimab for immunising the entire birth cohort, regardless of gestational age or other risk factors. Additionally, we evaluated the health benefits and cost-effectiveness of a combined strategy of year-round vaccination of pregnant women with RSVpreF and immunisation of infants at high risk, including those born preterm or with chronic conditions, with nirsevimab during the RSV season., Methods: We developed a discrete-event simulation model, parameterized with the data on medically-attended RSV infections among infants under one year of age from 2010 to 2019, including outpatient care, hospitalisations, and deaths. Intervention scenarios targeting twelve monthly birth cohorts and pregnant women, reflecting the 2021 census data for Ontario, Canada were evaluated over a follow-up time horizon of one year from birth. Taking into account the costs (in 2023 Canadian dollars) associated with RSV-related outcomes, we calculated the net monetary benefit using the quality-adjusted life-year (QALY) gained. Further, we determined the range of price-per-dose (PPD) for nirsevimab and RSVpreF within which the program was cost-effective. Cost-effectiveness analyses were conducted from both healthcare and societal perspectives., Findings: Using a willingness-to-pay of CAD$50,000 per QALY gained, we found that immunising the entire birth cohort with nirsevimab would be cost-effective from a societal perspective for a PPD of up to $290, with an annual budget impact of $83,978 for 1113 infants per 100,000 population. An alternative, combined strategy of vaccinating pregnant women and immunising only infants at high risk of severe disease would lead to a lower budget impact of $49,473 per 100,000 population with a PPD of $290 and $195 for nirsevimab and RSVpreF vaccine, respectively. This combined strategy would reduce infant mortality by 76%-85%, comparable to a 78% reduction achieved through a nirsevimab-only program of the entire birth cohort. The PPD for cost-effective programs with nirsevimab was sensitive to the target population among infants., Interpretation: Passive immunisation of infants under 6 months of age with nirsevimab and vaccination of pregnant women with RSVpreF could be a cost-effective strategy for protecting infants during their first RSV season., Funding: This study was supported by the Canadian Immunisation Research Network (CIRN) and the Canadian Institutes of Health Research (CIHR). Seyed M. Moghadas acknowledges support from the Natural Sciences and Engineering Research Council of Canada (MfPH and Discovery grants). Alison P. Galvani acknowledges support from the The Notsew Orm Sands Foundation., Competing Interests: JM Langley's institution, Dalhousie University, has received funds for clinical trials conducted by the Canadian Center for Vaccinology from GSK, Janssen, Sanofi, Immunovaccine, Inventprise, Merck, Pfizer, VIDO, VBI and Entos. SM Moghadas previously had advisory roles for Janssen Canada and Sanofi for cost-effectiveness of their products. Other authors declare that they have no competing interests., (© 2023 The Author(s).)

Background: Uptake of the COVID-19 bivalent booster vaccine (targeting the original SARS-CoV-2 strain and subvariants BA.4 and BA.5 of the Omicron variant) among eligible residents of New York City (NYC) has been modest and declining. Assessing the impact of improved population-level booster coverage with bivalent vaccines in NYC can help inform investment towards vaccination and potential cost-savings., Methods: We calibrated an agent-based model of disease transmission to confirmed and probable cases of COVID-19 in NYC and simulated it to project outcomes under two scenarios. In the base case scenario, we assumed that vaccination continued with the average daily rate of 92 vaccine doses per 100,000 administered during December 2022. In the counterfactual scenario, we modeled a high-uptake scenario between January 1, 2023 and March 31, 2023, with an average daily rate of 296 vaccine doses per 100,000 population that increased bivalent coverage in NYC to match the age-specific influenza vaccine coverage of the 2020-2021 season. Vaccination rate outside the campaign duration remained the same as the base case scenario., Findings: Compared to the base case, the high-uptake scenario averted 88,274 (95% Confidence Interval [CI]: 77,097-100,342) cases, and prevented 2,917 (95% CI: 2,557-3,267) hospitalizations between January 1 through the end of June 2023. Averted outcomes resulted in net savings of $217.2 (95% CI: 190.0-242.2) million in direct healthcare costs. We estimated that the high-uptake scenario would avert 72,879 (95% CI: 63,894-82,228) days of student absenteeism from schools due to COVID-19 illness., Interpretation: Our results illustrate the continued benefits of COVID-19 vaccines in preventing severe health outcomes, averting healthcare costs, and maintaining educational continuity in NYC., Funding: The Canadian Institutes of Health Research, The Natural Sciences and Engineering Research Council of Canada, NIH, Centers for Disease Control and Prevention (CDC), NSF, The Commonwealth Fund, and The Notsew Orm Sands Foundation., Competing Interests: Authors declare that they have no competing interests., (© 2023 Published by Elsevier Ltd.)

Respiratory syncytial virus (RSV) is the most common cause of early childhood lower respiratory tract infection (LRTI) in low- and middle-income countries (LMICs). Maternal vaccines, birth-dose extended half-life monoclonal antibodies (mAbs), and pediatric vaccines are under development for prevention of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in young children. We analyzed the health and economic impact of RSV interventions used alone or in combinations in Mali. We modeled age-specific and season-specific risks of RSV LRTI in children through three years, using WHO Preferred Product Characteristics and data generated in Mali. Health outcomes included RSV LRTI cases, hospitalizations, deaths, and disability-adjusted life-years (DALYs). We identified the optimal combination of products across a range of scenarios. We found that mAb delivered at birth could avert 878 DALYs per birth cohort at an incremental cost-effectiveness ratio (ICER) of $597 per DALY averted compared to no intervention if the product were available at $1 per dose. Combining mAb with pediatric vaccine administered at 10/14 weeks, 1947 DALYs would be prevented. The ICER of this combination strategy is $1514 per DALY averted compared to mAb alone. Incorporating parameter uncertainty, mAb alone is likely to be optimal from the societal perspective at efficacy against RSV LRTI above 66%. The optimal strategy was sensitive to economic considerations, including product prices and willingness-to-pay for DALYs. For example, the combination of mAb and pediatric vaccine would be optimal from the government perspective at a willingness-to-pay above $775 per DALY. Maternal vaccine alone or in combination with other interventions was never the optimal strategy, even for high vaccine efficacy. The same was true for pediatric vaccine administered at 6/7 months. At prices comparable to existing vaccine products, extended half-life RSV mAbs would be impactful and efficient components of prevention strategies in LMICs such as Mali., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: • Rachel S. Laufer reports no interests. • Ranju Baral reports that her institution has received research grants from the Bill and Melinda Gates Foundation. • Andrea G. Buchwald reports no interests. • James D. Campbell reports that his institution has received research grants from GlaxoSmithKline and Pfizer. • Flanon Coulibaly reports no interests. • Fatoumata Diallo reports no interests. • Moussa Doumbia reports no interests. • Amanda J. Driscoll reports no interests. • Alison P. Galvani reports no interests. • Adama M. Keita reports no interests. • Kathleen M. Neuzil reports that her institution has received research grants from GlaxoSmithKline, Pfizer, PATH, and National Institutes of Health for vaccine research. She is a member of SAGE. • Clint Pecenka reports that his institution has received research grants from the Bill and Melinda Gates Foundation. • Samba Sow reports no interests. • Justin R. Ortiz reports grants to his institution from National Science Foundation, Bill & Melinda Gates Foundation, Pfizer, National Institutes of Health, and World Health Organization outside the submitted work. • Meagan C. Fitzpatrick reports personal fees from Sanofi Pasteur, outside the submitted work., (Copyright: © 2023 Laufer 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.)

Importance: Adverse outcomes of COVID-19 in the pediatric population include disease and hospitalization, leading to school absenteeism. Booster vaccination for eligible individuals across all ages may promote health and school attendance., Objective: To assess whether accelerating COVID-19 bivalent booster vaccination uptake across the general population would be associated with reduced pediatric hospitalizations and school absenteeism., Design, Setting, and Participants: In this decision analytical model, a simulation model of COVID-19 transmission was fitted to reported incidence data from October 1, 2020, to September 30, 2022, with outcomes simulated from October 1, 2022, to March 31, 2023. The transmission model included the entire age-stratified US population, and the outcome model included children younger than 18 years., Interventions: Simulated scenarios of accelerated bivalent COVID-19 booster campaigns to achieve uptake that was either one-half of or similar to the age-specific uptake observed for 2020 to 2021 seasonal influenza vaccination in the eligible population across all age groups., Main Outcomes and Measures: The main outcomes were estimated hospitalizations, intensive care unit admissions, and isolation days of symptomatic infection averted among children aged 0 to 17 years and estimated days of school absenteeism averted among children aged 5 to 17 years under the accelerated bivalent booster campaign simulated scenarios., Results: Among children aged 5 to 17 years, a COVID-19 bivalent booster campaign achieving age-specific coverage similar to influenza vaccination could have averted an estimated 5 448 694 (95% credible interval [CrI], 4 936 933-5 957 507) days of school absenteeism due to COVID-19 illness. In addition, the booster campaign could have prevented an estimated 10 019 (95% CrI, 8756-11 278) hospitalizations among the pediatric population aged 0 to 17 years, of which 2645 (95% CrI, 2152-3147) were estimated to require intensive care. A less ambitious booster campaign with only 50% of the age-specific uptake of influenza vaccination among eligible individuals could have averted an estimated 2 875 926 (95% CrI, 2 524 351-3 332 783) days of school absenteeism among children aged 5 to 17 years and an estimated 5791 (95% CrI, 4391-6932) hospitalizations among children aged 0 to 17 years, of which 1397 (95% CrI, 846-1948) were estimated to require intensive care., Conclusions and Relevance: In this decision analytical model, increased uptake of bivalent booster vaccination among eligible age groups was associated with decreased hospitalizations and school absenteeism in the pediatric population. These findings suggest that although COVID-19 prevention strategies often focus on older populations, the benefits of booster campaigns for children may be substantial.

Competing Interests: We declare no competing interests.

Competing Interests: We declare no competing interests.

Competing Interests: Declaration of interests The Lancet Commission on Vaccine Refusal, Acceptance, and Demand in the USA is cohosted by the Yale Institute for Global Health and the Baylor College of Medicine. All authors are Commissioners. PJH is a developer of a COVID-19 vaccine construct, which was licensed by Baylor College of Medicine to Biological E, a commercial vaccine manufacturer for scale-up, production, testing, and licensure. NTB reports personal fees from WHO, Centers for Disease Control and Prevention, Sanofi, and Merck outside of the submitted work. RMC reports receiving research grant funding from Novo Nordisk Foundation (Denmark), outside of the submitted work. RL reports grants from Pfizer, GlaxoSmithKline, Sanofi Pasteur, and Merck, and personal fees from BIO, outside of the submitted work. YAM is a member of a Data Safety Monitoring Board for Pfizer and is a site Principal Investigator for a Pfizer vaccine trial, outside the submitted work. MMM reports personal fees from law firms representing retail pharmacies, generic drug companies, and a health insurer that have sued branded drug companies for marketing and antitrust law violations, outside of the submitted work, and serves as an adviser to Verily Life Sciences on a mobile app designed to facilitate safe return to work and school during COVID-19. DJO reports grants from the US National Institutes of Health, outside the submitted work. DAS reports personal fees from Pfizer, Janssen, and Moderna, is on advisory boards and receives compensation from these companies for time attending meetings, and reports grants from Merck, outside of the submitted work. All other authors declare no competing interests.

The Russian invasion of Ukraine on February 24, 2022, has displaced more than a quarter of the population. Assessing disease burdens among displaced people is instrumental in informing global public health and humanitarian aid efforts. We estimated the disease burden in Ukrainians displaced both within Ukraine and to other countries by combining a spatiotemporal model of forcible displacement with age- and gender-specific estimates of cardiovascular disease (CVD), diabetes, cancer, HIV, and tuberculosis (TB) in each of Ukraine's 629 raions (i.e., districts). Among displaced Ukrainians as of May 13, we estimated that more than 2.63 million have CVDs, at least 615,000 have diabetes, and over 98,500 have cancer. In addition, more than 86,000 forcibly displaced individuals are living with HIV, and approximately 13,500 have TB. We estimated that the disease prevalence among refugees was lower than the national disease prevalence before the invasion. Accounting for internal displacement and healthcare facilities impacted by the conflict, we estimated that the number of people per hospital has increased by more than two-fold in some areas. As regional healthcare systems come under increasing strain, these estimates can inform the allocation of critical resources under shifting disease burdens.

Competing Interests: Declaration of interests PJH is a developer of a COVID-19 vaccine construct, which was licensed by Baylor College of Medicine to Biological E, a commercial vaccine manufacturer for scale-up, production, testing, and licensure. NTB reports personal fees from WHO, CDC, and Merck, outside the submitted work. RMC reports receiving research grant funding from Novo Nordisk Foundation (Denmark), outside the submitted work. RL reports grants from Pfizer, GlaxoSmithKline, Sanofi Pasteur, and Merck, and personal fees from BIO, outside the submitted work. YAM is a member of a data safety monitoring board for Pfizer and a site principal investigator for a Pfizer vaccine trial, outside the submitted work. MMM reports personal fees from law firms representing retail pharmacies and generic drug companies that have sued other drug companies for antitrust law violations, outside the submitted work, and serves as an adviser to Verily Life Sciences on an app designed to facilitate safe return to work and school during the COVID-19 pandemic. DJO reports grants from the US National Institutes of Health, outside the submitted work. DAS reports grants from Merck and personal fees from Pfizer and Janssen, outside the submitted work. All other authors declare no competing interests.

Background: Diagnostic testing has been pivotal in detecting SARS-CoV-2 infections and reducing transmission through the isolation of positive cases. We quantified the value of implementing frequent, rapid antigen (RA) testing in the workplace to identify screening programs that are cost-effective., Methods: To project the number of cases, hospitalizations, and deaths under alternative screening programs, we adapted an agent-based model of COVID-19 transmission and parameterized it with the demographics of Ontario, Canada, incorporating vaccination and waning of immunity. Taking into account healthcare costs and productivity losses associated with each program, we calculated the incremental cost-effectiveness ratio (ICER) with quality-adjusted life year (QALY) as the measure of effect. Considering RT-PCR testing of only severe cases as the baseline scenario, we estimated the incremental net monetary benefits (iNMB) of the screening programs with varying durations and initiation times, as well as different booster coverages of working adults., Results: Assuming a willingness-to-pay threshold of CDN$30,000 per QALY loss averted, twice weekly workplace screening was cost-effective only if the program started early during a surge. In most scenarios, the iNMB of RA screening without a confirmatory RT-PCR or RA test was comparable or higher than the iNMB for programs with a confirmatory test for RA-positive cases. When the program started early with a duration of at least 16 weeks and no confirmatory testing, the iNMB exceeded CDN$1.1 million per 100,000 population. Increasing booster coverage of working adults improved the iNMB of RA screening., Conclusions: Our findings indicate that frequent RA testing starting very early in a surge, without a confirmatory test, is a preferred screening program for the detection of asymptomatic infections in workplaces., (© 2022. The Author(s).)

Importance: New York City, an early epicenter of the pandemic, invested heavily in its COVID-19 vaccination campaign to mitigate the burden of disease outbreaks. Understanding the return on investment (ROI) of this campaign would provide insights into vaccination programs to curb future COVID-19 outbreaks., Objective: To estimate the ROI of the New York City COVID-19 vaccination campaign by estimating the tangible direct and indirect costs from a societal perspective., Design, Setting, and Participants: This decision analytical model of disease transmission was calibrated to confirmed and probable cases of COVID-19 in New York City between December 14, 2020, and January 31, 2022. This simulation model was validated with observed patterns of reported hospitalizations and deaths during the same period., Exposures: An agent-based counterfactual scenario without vaccination was simulated using the calibrated model., Main Outcomes and Measures: Costs of health care and deaths were estimated in the actual pandemic trajectory with vaccination and in the counterfactual scenario without vaccination. The savings achieved by vaccination, which were associated with fewer outpatient visits, emergency department visits, emergency medical services, hospitalizations, and intensive care unit admissions, were also estimated. The value of a statistical life (VSL) lost due to COVID-19 death and the productivity loss from illness were accounted for in calculating the ROI., Results: During the study period, the vaccination campaign averted an estimated $27.96 (95% credible interval [CrI], $26.19-$29.84) billion in health care expenditures and 315 724 (95% CrI, 292 143-340 420) potential years of life lost, averting VSL loss of $26.27 (95% CrI, $24.39-$28.21) billion. The estimated net savings attributable to vaccination were $51.77 (95% CrI, $48.50-$55.85) billion. Every $1 invested in vaccination yielded estimated savings of $10.19 (95% CrI, $9.39-$10.87) in direct and indirect costs of health outcomes that would have been incurred without vaccination., Conclusions and Relevance: Results of this modeling study showed an association of the New York City COVID-19 vaccination campaign with reduction in severe outcomes and avoidance of substantial economic losses. This significant ROI supports continued investment in improving vaccine uptake during the ongoing pandemic.

Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests.

Competing Interests: We declare no competing interests.

Competing Interests: Declaration of interests PJH is a developer of a COVID-19 vaccine construct, which was licensed by Baylor College of Medicine to Biological E, a commercial vaccine manufacturer for scale-up, production, testing, and licensure. NTB reports personal fees from WHO, US national Centers for Disease Control and Prevention, and Merck outside the submitted work. RMC received research grant funding from Novo Nordisk Foundation, outside the submitted work. RL reports grants from Pfizer, GlaxoSmithKline, Sanofi Pasteur, and Merck, and personal fees from BIO and the Infectious Disease Prevention Network, outside the submitted work. YAM is a member of a data safety monitoring board for Pfizer and a site Principal Investigator for a Pfizer vaccine trial, outside the submitted work. MMM reports personal fees from law firms representing retail pharmacies and generic drug companies that have sued other drug companies for antitrust law violations, outside the submitted work, and served as an advisor to Verily Life Sciences on an app designed to facilitate safe return to work and school during the COVID-19 epidemic. DJO reports grants from the US National Institutes of Health, outside the submitted work. DAS reports grants from Merck and personal fees from Pfizer and Janssen, outside the submitted work. The other authors declare no competing interests.

The durability of vaccine-mediated immunity to SARS-CoV-2, the durations to breakthrough infection, and the optimal timings of booster vaccination are crucial knowledge for pandemic response. Here, we applied comparative evolutionary analyses to estimate the durability of immunity and the likelihood of breakthrough infections over time following vaccination by BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), ChAdOx1 (Oxford-AstraZeneca), and Ad26.COV2.S (Johnson & Johnson/Janssen). We evaluated anti-Spike (S) immunoglobulin G (IgG) antibody levels elicited by each vaccine relative to natural infection. We estimated typical trajectories of waning and corresponding infection probabilities, providing the distribution of times to breakthrough infection for each vaccine under endemic conditions. Peak antibody levels elicited by messenger RNA (mRNA) vaccines mRNA-1273 and BNT1262b2 exceeded that of natural infection and are expected to typically yield more durable protection against breakthrough infections (median 29.6 mo; 5 to 95% quantiles 10.9 mo to 7.9 y) than natural infection (median 21.5 mo; 5 to 95% quantiles 3.5 mo to 7.1 y). Relative to mRNA-1273 and BNT1262b2, viral vector vaccines ChAdOx1 and Ad26.COV2.S exhibit similar peak anti-S IgG antibody responses to that from natural infection and are projected to yield lower, shorter-term protection against breakthrough infection (median 22.4 mo and 5 to 95% quantiles 4.3 mo to 7.2 y; and median 20.5 mo and 5 to 95% quantiles 2.6 mo to 7.0 y; respectively). These results leverage the tools from evolutionary biology to provide a quantitative basis for otherwise unknown parameters that are fundamental to public health policy decision-making.

Background: Before widespread vaccination, the United States was disproportionately affected by COVID-19 with a mortality rate several times that of other affluent societies. Comparing regions with different rates of health insurance, we assess how much of this excess mortality may be due to the relatively large population without health insurance., Methods: We use daily surveillance data from the US Centers for Disease Control and Prevention (CDC) stratified by region, age group, gender, and race in regression analysis of daily COVID-19 cases, hospitalization, and mortality. COVID-19 data have been matched with structural characteristics of the region including average proportion with health insurance. As checks, we have estimated regressions for different time periods, different groups of states, and by comparing adjacent counties between states with and without Medicaid expansion., Findings: Groups with lower health insurance coverage had significantly higher mortality as well as greater case counts and hospitalization. Early in the pandemic, they were also less likely to be tested for COVID-19. Applying our regression estimates, we estimate that had there been full health insurance coverage of the population, there would have been 60,000 fewer deaths, 26% of the total death toll in the period of this analysis., Interpretation: Our study demonstrates that a significant share of COVID-19 mortality in the United States, and much of the excess mortality in the United States compared with other countries, is due to our reliance on a system of market-driven healthcare. Providing universal insurance coverage should be part of our campaign to reduce COVID-19 mortality. It also suggests that these concerns should not be restricted to COVID-19 but apply across all diseases, contributing to many unnecessary deaths in the United States each year even apart from the COVID-19 pandemic., Competing Interests: None., (© 2022 The Authors.)

Objective: To quantify the utility of RT-PCR and rapid antigen tests in preventing post-arrival transmission based on timing of the pre-departure test. Methods: We derived analytical expressions to compute post-arrival transmission when no test is performed, and when either an RT-PCR or any of 18 rapid antigen tests is performed at specified times before arrival. We determined the diagnostic sensitivity of the rapid antigen tests by propagating their RT-PCR percent positive agreement onto known RT-PCR diagnostic sensitivity. Results: Depending on the rapid antigen test used, conducting a rapid antigen test immediately before departure reduces post-arrival transmission between 37.4% (95% CrI: 28.2%-40.7%) and 46.7% (95% CrI:40.0%-49.3%), compared to a 31.1% (95% CrI: 26.3%-33.5%) reduction using an RT-PCR 12 h before arrival. Performance of each rapid antigen test differed by diagnostic sensitivity over the course of disease. However, these differences were smaller than those engendered by testing too early. Conclusion: Testing closer to arrival-ideally on the day of arrival-is more effective at reducing post-arrival transmission than testing earlier. Rapid antigen tests perform the best in this application due to their short turnaround time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wells, Gokcebel, Pandey, Galvani and Townsend.)

Quarantine and serial testing strategies for a disease depend principally on its incubation period and infectiousness profile. In the context of COVID-19, these primary public health tools must be modulated with successive SARS CoV-2 variants of concern that dominate transmission. Our analysis shows that (1) vaccination status of an individual makes little difference to the determination of the appropriate quarantine duration of an infected case, whereas vaccination coverage of the population can have a substantial effect on this duration, (2) successive variants can challenge disease control efforts by their earlier and increased transmission in the disease time course relative to prior variants, and (3) sufficient vaccine boosting of a population substantially aids the suppression of local transmission through frequent serial testing. For instance, with Omicron, increasing immunity through vaccination and boosters-for instance with 100% of the population is fully immunized and at least 24% having received a third dose-can reduce quarantine durations by up to 2 d, as well as substantially aid in the repression of outbreaks through serial testing. Our analysis highlights the paramount importance of maintaining high population immunity, preferably by booster uptake, and the role of quarantine and testing to control the spread of SARS CoV-2., (© The Author(s) 2022. Published by Oxford University Press on behalf of National Academy of Sciences.)

Four studies demonstrate that the public's understanding of government budgetary expenditures is hampered by difficulty in representing large numerical magnitudes. Despite orders of magnitude difference between millions and billions, study participants struggle with the budgetary magnitudes of government programs. When numerical values are rescaled as smaller magnitudes (in the thousands or lower), lay understanding improves, as indicated by greater sensitivity to numerical ratios and more accurate rank ordering of expenses. A robust benefit of numerical rescaling is demonstrated across a variety of experimental designs, including policy relevant choices and incentive-compatible accuracy measures. This improved sensitivity ultimately impacts funding choices and public perception of respective budgets, indicating the importance of numerical cognition for good citizenship.

Background: Rapid antigen (RA) tests are being increasingly employed to detect SARS-CoV-2 infections in quarantine and surveillance. Prior research has focused on RT-PCR testing, a single RA test, or generic diagnostic characteristics of RA tests in assessing testing strategies., Methods: We have conducted a comparative analysis of the post-quarantine transmission, the effective reproduction number during serial testing, and the false-positive rates for 18 RA tests with emergency use authorization from The United States Food and Drug Administration and an RT-PCR test. To quantify the extent of transmission, we developed an analytical mathematical framework informed by COVID-19 infectiousness, test specificity, and temporal diagnostic sensitivity data., Results: We demonstrate that the relative effectiveness of RA tests and RT-PCR testing in reducing post-quarantine transmission depends on the quarantine duration and the turnaround time of testing results. For quarantines of two days or shorter, conducting a RA test on exit from quarantine reduces onward transmission more than a single RT-PCR test (with a 24-h delay) conducted upon exit. Applied to a complementary approach of performing serial testing at a specified frequency paired with isolation of positives, we have shown that RA tests outperform RT-PCR with a 24-h delay. The results from our modeling framework are consistent with quarantine and serial testing data collected from a remote industry setting., Conclusions: These RA test-specific results are an important component of the tool set for policy decision-making, and demonstrate that judicious selection of an appropriate RA test can supply a viable alternative to RT-PCR in efforts to control the spread of disease., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2022.)

The fragmented and inefficient healthcare system in the United States leads to many preventable deaths and unnecessary costs every year. During a pandemic, the lives saved and economic benefits of a single-payer universal healthcare system relative to the status quo would be even greater. For Americans who are uninsured and underinsured, financial barriers to COVID-19 care delayed diagnosis and exacerbated transmission. Concurrently, deaths beyond COVID-19 accrued from the background rate of uninsurance. Universal healthcare would alleviate the mortality caused by the confluence of these factors. To evaluate the repercussions of incomplete insurance coverage in 2020, we calculated the elevated mortality attributable to the loss of employer-sponsored insurance and to background rates of uninsurance, summing with the increased COVID-19 mortality due to low insurance coverage. Incorporating the demography of the uninsured with age-specific COVID-19 and nonpandemic mortality, we estimated that a single-payer universal healthcare system would have saved about 212,000 lives in 2020 alone. We also calculated that US$105.6 billion of medical expenses associated with COVID-19 hospitalization could have been averted by a single-payer universal healthcare system over the course of the pandemic. These economic benefits are in addition to US$438 billion expected to be saved by single-payer universal healthcare during a nonpandemic year.

Competing Interests: We declare no competing interests.

Objective: Despite their effectiveness in preventing the transmission of HIV among people who inject drugs (PWID), syringe services programs (SSPs) in many settings are hampered by social and political opposition. We aimed to estimate the impact of closure and temporary interruption of SSP on the HIV epidemic in a rural United States setting., Methods: Using an agent-based model (ABM) calibrated to observed surveillance data, we simulated HIV risk behaviors and transmission in adult populations who inject and do not inject drugs in Scott County, Indiana. We projected HIV incidence and prevalence between 2020 and 2025 for scenarios with permanent closure, delayed closure (one additional renewal for 24 months before closure), and temporary closure (lasting 12 months) of an SSP in comparison to persistent SSP operation., Results: With sustained SSP operation, we projected an incidence rate of 0.15 per 100 person-years among the overall population (95% simulation interval: 0.06-0.28). Permanently closing the SSP would cause an average of 58.4% increase in the overall incidence rate during 2021-2025, resulting in a higher prevalence of 60.8% (50.9-70.6%) (18.7% increase) among PWID by 2025. A delayed closure would increase the incidence rate by 38.9%. A temporary closure would cause 12 (35.3%) more infections during 2020-2021., Conclusion: Our analysis suggests that temporary interruption and permanent closure of existing SSPs operating in rural United States may lead to 'rebound' HIV outbreaks among PWID. To reach and sustain HIV epidemic control, it will be necessary to maintain existing and implement new SSPs in combination with other prevention interventions., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The Lancet Commission on Vaccine Refusal, Acceptance, and Demand in the USA is co-hosted by the Yale Institute for Global Health and the Baylor College of Medicine. The Commissioners are Saad B Omer, Regina M Benjamin, Noel T Brewer, Alison M Buttenheim, Timothy Callaghan, Arthur Caplan, Richard M Carpiano, Chelsea Clinton, Renee DiResta, Jad A Elharake, Lisa C Flowers, Alison P Galvani, Rekha Lakshmanan, Yvonne A Maldonado, Michelle M Mello, Douglas J Opel, Daniel A Salmon, Jason L Schwartz, Joshua M Sharfstein, and Peter J Hotez. PJH is a developer of a COVID-19 vaccine construct, which was licensed by Baylor College of Medicine to Biological E Ltd, a commercial vaccine manufacturer for scale-up, production, testing and licensure. NTB reports personal fees from WHO, CDC, and Merck outside the submitted work. RMC reports receiving research grant funding from Novo Nordisk Foundation (Denmark), outside the submitted work. RL reports grants from Pfizer, GlaxoSmithKline, Sanofi Pasteur, and Merck and personal fees from BIO, outside the submitted work. YAM is a member of a Data Safety Monitoring Board for Pfizer and a site PI for a Pfizer vaccine trial, outside the submitted work. MMM reports personal fees from law firms representing retail pharmacies and generic drug companies that have sued other drug companies for antitrust law violations, outside the submitted work, and serves as an advisor to Verily Life Sciences LLC on an app designed to facilitate safe return to work and school during COVID-19. DJO reports grants from the U.S. National Institutes of Health, outside the submitted work. DAS reports grants from Merck and personal fees from Pfizer and Janssen, outside the submitted work. The other authors declare no competing interests.

Background: As SARS-CoV-2 vaccines are administered worldwide, the COVID-19 pandemic continues to exact significant human and economic costs. Mass testing of unvaccinated individuals followed by isolation of positive cases can substantially mitigate risks and be tailored to local epidemiological conditions to ensure cost effectiveness., Methods: Using a multi-scale model that incorporates population-level SARS-CoV-2 transmission and individual-level viral load kinetics, we identify the optimal frequency of proactive SARS-CoV-2 testing, depending on the local transmission rate and proportion immunized., Findings: Assuming a willingness-to-pay of US$100,000 per averted year of life lost (YLL) and a price of $10 per test, the optimal strategy under a rapid transmission scenario ( R e ∼ 2.5) is daily testing until one third of the population is immunized and then weekly testing until half the population is immunized, combined with a 10-day isolation period of positive cases and their households. Under a low transmission scenario ( R e ∼ 1.2), the optimal sequence is weekly testing until the population reaches 10% partial immunity, followed by monthly testing until 20% partial immunity, and no testing thereafter., Interpretation: Mass proactive testing and case isolation is a cost effective strategy for mitigating the COVID-19 pandemic in the initial stages of the global SARS-CoV-2 vaccination campaign and in response to resurgences of vaccine-evasive variants., Funding: US National Institutes of Health, US Centers for Disease Control and Prevention, HK Innovation and Technology Commission, China National Natural Science Foundation, European Research Council, and EPSRC Impact Acceleration Grant., Competing Interests: We declare no competing interests. Dr Chinazzi, Dr Pastore y Piontti and Prof. Alessandro Vespignani report grants from Metabiota Inc, outside the submitted work. Prof. Benjamin J. Cowling reports honoraria from AstraZeneca, GSK, Moderna, Pfizer, Roche and Sanofi Pasteur. The authors report no other potential conflicts of interest., (© 2022 The Author(s).)

Background: Numerous countries have imposed strict travel restrictions during the COVID-19 pandemic, contributing to a large socioeconomic burden. The long quarantines that have been applied to contacts of cases may be excessive for travel policy., Methods: We developed an approach to evaluate imminent countrywide COVID-19 infections after 0-14-day quarantine and testing. We identified the minimum travel quarantine duration such that the infection rate within the destination country did not increase compared to a travel ban, defining this minimum quarantine as "sufficient.", Findings: We present a generalised analytical framework and a specific case study of the epidemic situation on November 21, 2021, for application to 26 European countries. For most origin-destination country pairs, a three-day or shorter quarantine with RT-PCR or antigen testing on exit suffices. Adaptation to the European Union traffic-light risk stratification provided a simplified policy tool. Our analytical approach provides guidance for travel policy during all phases of pandemic diseases., Interpretation: For nearly half of origin-destination country pairs analysed, travel can be permitted in the absence of quarantine and testing. For the majority of pairs requiring controls, a short quarantine with testing could be as effective as a complete travel ban. The estimated travel quarantine durations are substantially shorter than those specified for traced contacts., Funding: EasyJet (JPT and APG), the Elihu endowment (JPT), the Burnett and Stender families' endowment (APG), the Notsew Orm Sands Foundation (JPT and APG), the National Institutes of Health (MCF), Canadian Institutes of Health Research (SMM) and Natural Sciences and Engineering Research Council of Canada EIDM-MfPH (SMM)., Competing Interests: JPT and APG declare the following competing interests: received funding from EasyJet to conduct research on travel quarantine durations. CRW, AP, WSC, MCF, BHS, and SMM declare no competing interest. The funders had no role in designing the study, conducting the analyses, deriving the findings, or the decision to publish the outcomes., (© 2021 The Authors.)

Background: The fourth wave of COVID-19 pandemic peaked in the US at 160,000 daily cases, concentrated primarily in southern states. As the Delta variant has continued to spread, we evaluated the impact of accelerated vaccination on reducing hospitalization and deaths across northeastern and southern regions of the US census divisions., Methods: We used an age-stratified agent-based model of COVID-19 to simulate outbreaks in all states within two U.S. regions. The model was calibrated using reported incidence in each state from October 1, 2020 to August 31, 2021, and parameterized with characteristics of the circulating SARS-CoV-2 variants and state-specific daily vaccination rate. We then projected the number of infections, hospitalizations, and deaths that would be averted between September 2021 and the end of March 2022 if the states increased their daily vaccination rate by 20 or 50% compared to maintaining the status quo pace observed during August 2021., Findings: A 50% increase in daily vaccine doses administered to previously unvaccinated individuals is projected to prevent a total of 30,727 hospitalizations and 11,937 deaths in the two regions between September 2021 and the end of March 2022. Southern states were projected to have a higher weighted average number of hospitalizations averted (18.8) and lives saved (8.3) per 100,000 population, compared to the weighted average of hospitalizations (12.4) and deaths (2.7) averted in northeastern states. On a per capita basis, a 50% increase in daily vaccinations is expected to avert the most hospitalizations in Kentucky (56.7 hospitalizations per 100,000 averted with 95% CrI: 45.56 - 69.9) and prevent the most deaths in Mississippi, (22.1 deaths per 100,000 population prevented with 95% CrI: 18.0 - 26.9)., Interpretation: Accelerating progress to population-level immunity by raising the daily pace of vaccination would prevent substantial hospitalizations and deaths in the US, even in those states that have passed a Delta-driven peak in infections., Funding: This study was supported by The Commonwealth Fund. SMM acknowledges the support from the Canadian Institutes of Health Research [OV4 - 170643, COVID-19 Rapid Research] and the Natural Sciences and Engineering Research Council of Canada, Emerging Infectious Disease Modelling, MfPH grant. MCF acknowledges support from the National Institutes of Health (5 K01 AI141576)., Competing Interests: None, (© 2021 The Authors.)

Background: Following the start of COVID-19 vaccination in New York City (NYC), cases have declined over 10-fold from the outbreak peak in January 2020, despite the emergence of highly transmissible variants. We evaluated the impact of NYC's vaccination campaign on saving lives as well as averting hospitalizations and cases., Methods: We used an age-stratified agent-based model of COVID-19 to include transmission dynamics of Alpha, Gamma, Delta and Iota variants as identified in NYC. The model was calibrated and fitted to reported incidence in NYC, accounting for the relative transmissibility of each variant and vaccination rollout data. We simulated COVID-19 outbreak in NYC under the counterfactual scenario of no vaccination and compared the resulting disease burden with the number of cases, hospitalizations and deaths reported under the actual pace of vaccination., Findings: We found that without vaccination, there would have been a spring-wave of COVID-19 in NYC due to the spread of Alpha and Delta variants. The COVID-19 vaccination campaign in NYC prevented such a wave, and averted 290,467 (95% CrI: 232,551 - 342,664) cases, 48,076 (95% CrI: 42,264 - 53,301) hospitalizations, and 8,508 (95% CrI: 7,374 - 9,543) deaths from December 14, 2020 to July 15, 2021., Interpretation: Our study demonstrates that the vaccination program in NYC was instrumental to substantially reducing the COVID-19 burden and suppressing a surge of cases attributable to more transmissible variants . As the Delta variant sweeps predominantly among unvaccinated individuals, our findings underscore the urgent need to accelerate vaccine uptake and close the vaccination coverage gaps., Funding: This study was supported by The Commonwealth Fund., Competing Interests: None., (© 2021 Published by Elsevier Ltd.)

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.)