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.

Impact and cost-effectiveness analyses of vaccination for prevention of respiratory syncytial virus disease among older adults in Ontario: A Canadian Immunization Research Network (CIRN) study.

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.

Cost-effectiveness analysis of nirsevimab and maternal RSVpreF vaccine strategies for prevention of Respiratory Syncytial Virus disease among infants in Canada: a simulation study.

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.

Cost-effectiveness of Prefusion F Protein-based Vaccines Against Respiratory Syncytial Virus Disease for Older Adults in the United States.

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.

Modelling the effect of travel-related policies on disease control in a meta-population structure.

Travel restrictions, while delaying the spread of an emerging disease from the source, could inflict substantial socioeconomic burden. Travel-related policies, such as quarantine and testing of travelers, may be considered as alternative strategies to mitigate the negative impact of travel bans. We developed a meta-population, delay-differential model to evaluate a strategy that combines testing of travelers prior to departure from the source of infection with quarantine and testing at exit from quarantine in the destination population. Our results, based on early parameter estimates of SARS-CoV-2 infection, indicate that testing travelers at exit from quarantine is more effective in delaying case importation than testing them before departure or upon arrival. We show that a 1-day quarantine with an exit test could outperform a longer, 3-day quarantine without testing in delaying the outbreak peak. Rapid, large-scale testing capacities with short turnaround times provide important means of detecting infectious cases and reducing case importation, while shortening quarantine duration for travelers at destination.

Modelling the impact of a high-uptake bivalent booster scenario on the COVID-19 burden and healthcare costs in New York City.

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.

Epidemic dynamics with time-varying transmission risk reveal the role of disease stage-dependent infectiousness.

A key characteristic of acute communicable diseases is the infectiousness that varies over time as the infection dynamics evolve within a host, which influences the risk of transmission in different stages of the disease. Despite the evidence of time-varying transmission risk, most dynamic models of epidemics assume a constant transmission rate during the infectious period. Recent work has shown the difference in epidemic dynamics when this assumption is relaxed and different transmission rates are used by discretizing the infectious period into multiple sub-periods. Here, we develop an age-structured model to integrate a continuous time-varying transmission risk, based on an established correlation between the viral dynamics and infectiousness profile. Taking into account the natural history and parameter estimates of COVID-19 caused by the original strain of SARS-CoV-2, we demonstrate the difference in temporal epidemic dynamics when a continuous time-varying transmission probability is used as compared to multiple constant transmission probabilities. Our results show a significant difference between the incidence curves in terms of the magnitude and peak time, even when the reproduction number and total number of infections are the same for continuous and discrete transmission probabilities. Finally, we demonstrate the spurious outcome of preventing an epidemic through the isolation of infectious individuals when constant transmission probabilities are used, highlighting the importance of integrating a continuous time-dependent transmission parameter in dynamic models. These findings suggest a more cautious interpretation of model outcomes, especially those that are intended to evaluate the effectiveness of interventions and inform policy decisions for disease mitigation strategies.

Cost-Effectiveness of Prefusion F Protein-Based Vaccines Against Respiratory Syncytial Virus Disease for Older Adults in the United States.

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 US. Taking into account the costs associated with these RSV-related outcomes, we calculated the net monetary benefit using quality-adjusted life-years (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 under $120 with Arexvy and $111 with Abrysvo over the first RSV season. Achieving an influenza-like vaccination coverage of 66% for the population of older adults in the US, the budget impact of these programs at the maximum PPD ranged from $5.74 to $6.10 billion. If the benefits of vaccination extend to a second RSV season as reported in clinical trials, we estimated a maximum PPD of $250 for Arexvy and $233 for Abrysvo, with two-year budget impacts of $11.59 and $10.89 billion, respectively. Conclusions: Vaccination of older adults would provide substantial direct health benefits by reducing outcomes associated with RSV-related illness in this population.

Estimated US Pediatric Hospitalizations and School Absenteeism Associated With Accelerated COVID-19 Bivalent Booster Vaccination.

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.

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.

Modelling the impact of timelines of testing and isolation on disease control.

Testing and isolation remain a key component of public health responses to both persistent and emerging infectious diseases. Although the value of these measures have been demonstrated in combating recent outbreaks including the COVID-19 pandemic and monkeypox, their impact depends critically on the timelines of testing and start of isolation during the course of disease. To investigate this impact, we developed a delay differential model and incorporated age-since-symptom-onset as a parameter for delay in testing. We then used the model to compare the outcomes of reverse-transcription polymerase chain reaction (RT-PCR) and rapid antigen (RA) testing methods when isolation starts either at the time of testing or at the time of test result. Parameterizing the model with estimates of SARS-CoV-2 infection and diagnostic sensitivity of the tests, we found that the reduction of disease transmission using the RA test can be comparable to that achieved by applying the RT-PCR test. Given constraints and inevitable delays associated with sample collection and laboratory assays in RT-PCR testing post symptom onset, self-administered RA tests with short turnaround times present a viable alternative for timely isolation of infectious cases.

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.

Return on Investment of the COVID-19 Vaccination Campaign in New York City.

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.

Evaluation of TB elimination strategies in Canadian Inuit populations: Nunavut as a case study.

Tuberculosis (TB) continues to disproportionately affect Inuit populations in Canada with some communities having over 300 times higher rate of active TB than Canadian-born, non-Indigenous people. Inuit Tuberculosis Elimination Framework has set the goal of reducing active TB incidence by at least 50% by 2025, aiming to eliminate it by 2030. Whether these goals are achievable with available resources and treatment regimens currently in practice has not been evaluated. We developed an agent-based model of TB transmission to evaluate timelines and milestones attainable in Nunavut, Canada by including case findings, contact-tracing and testing, treatment of latent TB infection (LTBI), and the government investment on housing infrastructure to reduce the average household size. The model was calibrated to ten years of TB incidence data, and simulated for 20 years to project program outcomes. We found that, under a range of plausible scenarios with tracing and testing of 25%-100% of frequent contacts of detected active cases, the goal of 50% reduction in annual incidence by 2025 is not achievable. If active TB cases are identified rapidly within one week of becoming symptomatic, then the annual incidence would reduce below 100 per 100,000 population, with 50% reduction being met between 2025 and 2030. Eliminating TB from Inuit populations would require high rates of contact-tracing and would extend beyond 2030. The findings indicate that time-to-identification of active TB is a critical factor determining program effectiveness, suggesting that investment in resources for rapid case detection is fundamental to controlling TB.

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.

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.

Impact of non-pharmaceutical interventions and vaccination on COVID-19 outbreaks in Nunavut, Canada: a Canadian Immunization Research Network (CIRN) study.

BACKGROUND: Nunavut, the northernmost Arctic territory of Canada, experienced three community outbreaks of the coronavirus disease 2019 (COVID-19) from early November 2020 to mid-June 2021. We sought to investigate how non-pharmaceutical interventions (NPIs) and vaccination affected the course of these outbreaks. METHODS: We used an agent-based model of disease transmission to simulate COVID-19 outbreaks in Nunavut. The model encapsulated demographics and household structure of the population, the effect of NPIs, and daily number of vaccine doses administered. We fitted the model to inferred, back-calculated infections from incidence data reported from October 2020 to June 2021. We then compared the fit of the scenario based on case count data with several counterfactual scenarios without the effect of NPIs, without vaccination, and with a hypothetical accelerated vaccination program whereby 98% of the vaccine supply was administered to eligible individuals. RESULTS: We found that, without a territory-wide lockdown during the first COVID-19 outbreak in November 2020, the peak of infections would have been 4.7 times higher with a total of 5,404 (95% CrI: 5,015-5,798) infections before the start of vaccination on January 6, 2021. Without effective NPIs, we estimated a total of 4,290 (95% CrI: 3,880-4,708) infections during the second outbreak under the pace of vaccination administered in Nunavut. In a hypothetical accelerated vaccine rollout, the total infections during the second Nunavut outbreak would have been 58% lower, to 1,812 (95% CrI: 1,593-2,039) infections. Vaccination was estimated to have the largest impact during the outbreak in April 2021, averting 15,196 (95% CrI: 14,798-15,591) infections if the disease had spread through Nunavut communities. Accelerated vaccination would have further reduced the total infections to 243 (95% CrI: 222-265) even in the absence of NPIs. CONCLUSIONS: NPIs have been essential in mitigating pandemic outbreaks in this large, geographically distanced and remote territory. While vaccination has the greatest impact to prevent infection and severe outcomes, public health implementation of NPIs play an essential role in the short term before attaining high levels of immunity in the population.

COVID-19 hospitalizations and deaths averted under an accelerated vaccination program in northeastern and southern regions of the USA.

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).