[JAMA Network Open, 19 May 2023]

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.

[Infectious Disease Modelling, 14 December 2022]

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.

[PNAS, 10 August 2021]

Quantification of asymptomatic infections is fundamental for effective public health responses to the COVID-19 pandemic. Discrepancies regarding the extent of asymptomaticity have arisen from inconsistent terminology as well as conflation of index and secondary cases which biases toward lower asymptomaticity. We searched PubMed, Embase, Web of Science, and World Health Organization Global Research Database on COVID-19 between January 1, 2020 and April 2, 2021 to identify studies that reported silent infections at the time of testing, whether presymptomatic or asymptomatic. Index cases were removed to minimize representational bias that would result in overestimation of symptomaticity. By analyzing over 350 studies, we estimate that the percentage of infections that never developed clinical symptoms, and thus were truly asymptomatic, was 35.1% (95% CI: 30.7 to 39.9%). At the time of testing, 42.8% (95% prediction interval: 5.2 to 91.1%) of cases exhibited no symptoms, a group comprising both asymptomatic and presymptomatic infections. Asymptomaticity was significantly lower among the elderly, at 19.7% (95% CI: 12.7 to 29.4%) compared with children at 46.7% (95% CI: 32.0 to 62.0%). We also found that cases with comorbidities had significantly lower asymptomaticity compared to cases with no underlying medical conditions. Without proactive policies to detect asymptomatic infections, such as rapid contact tracing, prolonged efforts for pandemic control may be needed even in the presence of vaccination.

[The Lancet Infectious Diseases, 7 October 2021]

In July, 2021, another wave of COVID-19 began in the USA as the highly infectious delta (B.1.617.2) SARS-CoV-2 variant drove outbreaks predominantly affecting states with relatively low vaccination coverage. Some US states have shown the feasibility of rapidly achieving high vaccination coverage. Specifically, an average of 74·0% of adults had been fully vaccinated in Vermont, Connecticut, Massachusetts, Maine, and Rhode Island by July 31. By contrast, two states facing substantial delta-driven surges, Florida and Texas, had fully vaccinated only 59·5% and 55·8% of their adult residents, respectively.1 Here, we estimate the deaths, hospital admissions, and infections that could have been averted if Florida and Texas had matched the average vaccination pace of the top-performing states and vaccinated 74·0% of their adult populations by the end of July.

[JAMA Network Open, 21 November 2022]

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.

[Journal of Global Health, September 2022]

Since the start of COVID-19 vaccination in the United States (US), over 560 million doses of authorized vaccines were administered, and 69.7% of the eligible population were fully vaccinated as of March 31, 2022 [1]. Much attention has focused on the public health toll of the pandemic. The positive impact of the rapid development and deployment of highly efficacious vaccines, ie, the reduction in deaths, hospitalizations, and health care costs, remains unclear. We estimated the reduction in COVID-19 cases, hospitalizations and mortality, as well as averted health care costs achieved by the vaccination program from December 12, 2020 to March 31, 2022.

[BMC Public Health, 25 May 2022]

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.

[JAMA Network Open, 11 January 2022]

Introduction: The COVID-19 pandemic has caused more than 745 000 deaths in the US. However, the toll might have been higher without the rapid development and delivery of effective vaccines. As of October 28, 2021, 69% of 258 million US adults had been fully vaccinated.

Quantifying the population impact of COVID-19 vaccination can inform future vaccination strategies. Randomized clinical trials have established individual-level efficacy of authorized vaccines against the original strain, which exceeds 90% in preventing symptomatic and severe disease.1-3 However, the population-level effectiveness of the vaccination campaign in the US, in terms of association with reduced infections, hospitalizations, and deaths, is not as well documented, and we evaluated this using a simulation model.

Methods: This decision analytic model adheres to Consolidated Health Economic Evaluation Reporting Standards (CHEERS) reporting guideline. The institutional review of this study was waived by York University for the use of publicly available, deidentified data of the COVID-19 infections, deaths, and vaccination. Informed consent was not required to access the data.

We expanded our previous agent-based model4 to include transmission dynamics of the Alpha (B.1.1.7), Gamma (P.1), and Delta (B.1.617.2) variants in addition to the original strain (eMethods in the Supplement). The model was parameterized with the US demographics and age-specific risks of severe COVID-19 outcomes (eTable 1 and eTable 2 in the Supplement).5 A 2-dose vaccination strategy was implemented based on the daily vaccines administered in different age groups.6 Vaccine efficacies against infection, symptomatic disease and severe disease after each dose and for each variant were derived from published estimates (eTable 3 in the Supplement). The model was calibrated and fitted to reported national level incidence from October 1, 2020, to June 30, 2021 (eMethods in the Supplement).

We simulated pandemic trajectory under 2 counterfactuals: a no vaccination scenario and a program that achieved only half the daily vaccination rate of actual rollout. For each scenario, cumulative infections, hospitalizations, and deaths were compared with the simulated trends under the US vaccination program.

Credible intervals (CrIs) were generated from simulation outputs using the bias-corrected and accelerated bootstrap method (with 500 replications) in June 2021. The model was implemented in Julia Language Programming, version 1.6 (Julia), and outputs were analyzed in MATLAB, version 2017a (MathWorks). No significance tests were performed for this simulation study.

Results: Compared with the no vaccination scenario, the actual vaccination campaign saved an estimated 240 797 (95% CrI, 200 665-281 230) lives and prevented an estimated 1 133 617 (95% CrI, 967 487-1 301 881) hospitalizations from December 12, 2020, to June 30, 2021. The number of cases averted during the same period was projected to exceed 14 million. Vaccination prevented a wave of COVID-19 cases driven by the Alpha variant that would have occurred in April 2021 without vaccination (Figure 1), with a projected peak of 4409 (95% CrI, 2865-6312) deaths and 17 979 (95% CrI, 13 191-23 219) hospitalizations. Under the second counterfactual with daily vaccination rates at half the reported pace, we projected that the US would have still endured an additional 77 283 (95% CrI, 48 499-104 519) deaths and 336 000 (95% CrI, 225 330- 440 109) hospitalizations (Figure 2).

Discussion: Our analytical model suggested that the US COVID-19 vaccination program was associated with a reduction in the total hospitalizations and deaths by nearly half during the first 6 months of 2021. It was also associated with decreased impact of the more transmissible and lethal Alpha variant that was circulating during the same period. As new variants of SARS-CoV-2 continue to emerge, a renewed commitment to vaccine access, particularly among underserved groups and in counties with low vaccination coverage, will be crucial to preventing avoidable COVID-19 cases and bringing the pandemic to a close.

Limitations of our model included the use of reported cases for fitting, which may not reflect the true incidence. This fit does not completely match the temporal trends of reported hospitalizations and deaths. The model was nationally homogeneous; however, parameters may have varied across geographic regions. Furthermore, we did not consider waning immunity after vaccination or recovery within the study time frame.

[BMC Medicine, 23 November 2022]

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.

[Journal of Global Health, 18 September 2021]

The Republic of Seychelles is an archipelago of 115 islands in the Indian Ocean with a population of approximately 98 000. As of June 28, 2021, the Seychelles was one of only a dozen countries that had succeeded in fully vaccinating more than half of their population against COVID-19. The Seychelles began its vaccination campaign on January 13, 2021, with two-dose Sinopharm and AstraZeneca vaccines. Both vaccines reportedly have at least 78% efficacy against symptomatic disease 14 or more days after the second dose. With various non-pharmaceutical interventions (NPIs) in place and mounting vaccination coverage, the Seychelles suppressed its incidence to an average of 42 daily cases from January 1 to April 15, 2021. By May 5, over 61% of the population was fully vaccinated. Despite the high vaccination coverage, the country experienced a surge of COVID-19 infections soon after most NPIs were lifted in mid-April, reporting the world’s highest number of daily cases per capita and raising concerns about the efficacy of the vaccines. To understand the determinants of the recent surge, and the impact of the interplay between vaccination and NPIs, we used a previously established data-driven dynamic model and calibrated it to reported cases and vaccination rollout in the Seychelles…

[The Lancet Regional Health, 28 December 2022]

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.

Citerank: (7) 701037MfPH – Publications144B5ACA0, 703963Mobility859FDEF6, 704041Vaccination859FDEF6, 704045Covid-19859FDEF6, 704045Covid-19859FDEF6, 715328Nonpharmaceutical Interventions (NPIs)859FDEF6, 715831Diagnostic testing859FDEF6

[PNAS Nexus, 27 July 2022]

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.

[Communications Medicine, 9 July 2022]

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.