Evaluation of Strategies for Transitioning to Annual SARS-CoV-2 Vaccination Campaigns in the United States.

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.

An agent-based framework to study forced migration: A case study of Ukraine.

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.

Disease burden among Ukrainians forcibly displaced by the 2022 Russian invasion.

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.

Economic evaluation of COVID-19 rapid antigen screening programs in the workplace.

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.

Quarantine and serial testing for variants of SARS-CoV-2 with benefits of vaccination and boosting on consequent control of COVID-19.

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.

Testing for COVID-19 is Much More Effective When Performed Immediately Prior to Social Mixing.

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.

Comparative analyses of eighteen rapid antigen tests and RT-PCR for COVID-19 quarantine and surveillance-based isolation.

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.

Previous research on SARS-CoV-2 infection has determined optimal timing for testing in quarantine and the utility of different frequencies of testing for infection surveillance using RT-PCR and generalized rapid antigen tests. However, these strategies can depend on the specific rapid antigen test used. By examining 18 rapid antigen tests, we demonstrate that a single rapid antigen test performs better than RT-PCR when quarantines are two days or less in duration. In the context of infection surveillance, the ability of a rapid antigen test to provide results quickly counteracts its lower sensitivity with potentially more false positives. Our findings indicate that rapid antigen tests can be a suitable alternative to RT-PCR for application in quarantine and infection surveillance.

Quarantine and testing strategies to ameliorate transmission due to travel during the COVID-19 pandemic: a modelling study.

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).

Quarantine and testing strategies to ameliorate transmission due to travel during the COVID-19 pandemic: a modelling study.

BACKGROUND: Numerous countries imposed strict travel restrictions, contributing to the large socioeconomic burden during the COVID-19 pandemic. The long quarantines that apply 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).

Mechanistic basis of post-treatment control of SIV after anti-α4ß7 antibody therapy.

Treating macaques with an anti-α4ß7 antibody under the umbrella of combination antiretroviral therapy (cART) during early SIV infection can lead to viral remission, with viral loads maintained at < 50 SIV RNA copies/ml after removal of all treatment in a subset of animals. Depletion of CD8+ lymphocytes in controllers resulted in transient recrudescence of viremia, suggesting that the combination of cART and anti-α4ß7 antibody treatment led to a state where ongoing immune responses kept the virus undetectable in the absence of treatment. A previous mathematical model of HIV infection and cART incorporates immune effector cell responses and exhibits the property of two different viral load set-points. While the lower set-point could correspond to the attainment of long-term viral remission, attaining the higher set-point may be the result of viral rebound. Here we expand that model to include possible mechanisms of action of an anti-α4ß7 antibody operating in these treated animals. We show that the model can fit the longitudinal viral load data from both IgG control and anti-α4ß7 antibody treated macaques, suggesting explanations for the viral control associated with cART and an anti-α4ß7 antibody treatment. This effective perturbation to the virus-host interaction can also explain observations in other nonhuman primate experiments in which cART and immunotherapy have led to post-treatment control or resetting of the viral load set-point. Interestingly, because the viral kinetics in the various treated animals differed-some animals exhibited large fluctuations in viral load after cART cessation-the model suggests that anti-α4ß7 treatment could act by different primary mechanisms in different animals and still lead to post-treatment viral control. This outcome is nonetheless in accordance with a model with two stable viral load set-points, in which therapy can perturb the system from one set-point to a lower one through different biological mechanisms.

Racial disparities in COVID-19 mortality across Michigan, United States.

BACKGROUND: Black populations in the United States are being disproportionately affected by the COVID-19 pandemic, but the increased mortality burden after accounting for health and other demographic characteristics is not well understood. We examined characteristics of individuals who died from COVID-19 in Michigan by race stratified by their age, sex and comorbidity prevalence to illustrate and understand this disparity in mortality risk. METHODS: We evaluate COVID-19 mortality in Michigan by demographic and health characteristics, using individual-level linked death certificate and surveillance data collected by the Michigan Department of Health and Human Services from March 16 to October 26, 2020. We identified differences in demographics and comorbidity prevalence across race among individuals who died from COVID-19 and calculated mortality rates by age, sex, race, and number of comorbidities. FINDINGS: Among the 6,065 COVID-19 related deaths in Michigan, Black individuals are experiencing 3·6 times the mortality rate of White individuals (p<0.001), with a mortality rate for Black individuals under 65 years without comorbidities that is 12·6 times that of their White counterparts (p<0.001). After accounting for age, race, sex, and number of comorbidities, we find that Black individuals in all strata are at higher risk of COVID-19 mortality than their White counterparts. INTERPRETATION: Our findings demonstrate that Black populations are disproportionately burdened by COVID-19 mortality, even after accounting for demographic and underlying health characteristics. We highlight how disparities across race, which result from systemic racism, are compounded in crises. FUNDING: ASP, AP and APG were funded by NSF Expeditions grant 1918784, NIH grant 1R01AI151176-01, NSF Rapid Response Research for COVID-19 grant RAPID-2027755, and the Notsew Orm Sands Foundation. MCF was supported by NIH grant K01AI141576.

The Impact of Vaccination on Coronavirus Disease 2019 (COVID-19) Outbreaks in the United States.

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.

Optimal COVID-19 quarantine and testing strategies.

For COVID-19, it is vital to understand if quarantines shorter than 14 days can be equally effective with judiciously deployed testing. Here, we develop a mathematical model that quantifies the probability of post-quarantine transmission incorporating testing into travel quarantine, quarantine of traced contacts with an unknown time of infection, and quarantine of cases with a known time of exposure. We find that testing on exit (or entry and exit) can reduce the duration of a 14-day quarantine by 50%, while testing on entry shortens quarantine by at most one day. In a real-world test of our theory applied to offshore oil rig employees, 47 positives were obtained with testing on entry and exit to quarantine, of which 16 had tested negative at entry; preventing an expected nine offshore transmission events that each could have led to outbreaks. We show that appropriately timed testing can make shorter quarantines effective.

The impact of vaccination on COVID-19 outbreaks in the United States.

BACKGROUND: Global vaccine development efforts have been accelerated in response to the devastating 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 (US). METHODS: We developed an agent-based model of 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, while 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% pre-existing population immunity for the base-case scenario. The model was calibrated to an effective reproduction number of 1.2, accounting for current non-pharmaceutical interventions in the US. RESULTS: Vaccination reduced the overall attack rate to 4.6% (95% 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-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 non-pharmaceutical interventions is essential to achieve this impact.