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.

The implications of silent transmission for the control of COVID-19 outbreaks.

Since the emergence of coronavirus disease 2019 (COVID-19), unprecedented movement restrictions and social distancing measures have been implemented worldwide. The socioeconomic repercussions have fueled calls to lift these measures. In the absence of population-wide restrictions, isolation of infected individuals is key to curtailing transmission. However, the effectiveness of symptom-based isolation in preventing a resurgence depends on the extent of presymptomatic and asymptomatic transmission. We evaluate the contribution of presymptomatic and asymptomatic transmission based on recent individual-level data regarding infectiousness prior to symptom onset and the asymptomatic proportion among all infections. We found that the majority of incidences may be attributable to silent transmission from a combination of the presymptomatic stage and asymptomatic infections. Consequently, even if all symptomatic cases are isolated, a vast outbreak may nonetheless unfold. We further quantified the effect of isolating silent infections in addition to symptomatic cases, finding that over one-third of silent infections must be isolated to suppress a future outbreak below 1% of the population. Our results indicate that symptom-based isolation must be supplemented by rapid contact tracing and testing that identifies asymptomatic and presymptomatic cases, in order to safely lift current restrictions and minimize the risk of resurgence.

Impact of international travel and border control measures on the global spread of the novel 2019 coronavirus outbreak.

The novel coronavirus outbreak (COVID-19) in mainland China has rapidly spread across the globe. Within 2 mo since the outbreak was first reported on December 31, 2019, a total of 566 Severe Acute Respiratory Syndrome (SARS CoV-2) cases have been confirmed in 26 other countries. Travel restrictions and border control measures have been enforced in China and other countries to limit the spread of the outbreak. We estimate the impact of these control measures and investigate the role of the airport travel network on the global spread of the COVID-19 outbreak. Our results show that the daily risk of exporting at least a single SARS CoV-2 case from mainland China via international travel exceeded 95% on January 13, 2020. We found that 779 cases (95% CI: 632 to 967) would have been exported by February 15, 2020 without any border or travel restrictions and that the travel lockdowns enforced by the Chinese government averted 70.5% (95% CI: 68.8 to 72.0%) of these cases. In addition, during the first three and a half weeks of implementation, the travel restrictions decreased the daily rate of exportation by 81.3% (95% CI: 80.5 to 82.1%), on average. At this early stage of the epidemic, reduction in the rate of exportation could delay the importation of cases into cities unaffected by the COVID-19 outbreak, buying time to coordinate an appropriate public health response.

Projecting hospital utilization during the COVID-19 outbreaks in the United States.

In the wake of community coronavirus disease 2019 (COVID-19) transmission in the United States, there is a growing public health concern regarding the adequacy of resources to treat infected cases. Hospital beds, intensive care units (ICUs), and ventilators are vital for the treatment of patients with severe illness. To project the timing of the outbreak peak and the number of ICU beds required at peak, we simulated a COVID-19 outbreak parameterized with the US population demographics. In scenario analyses, we varied the delay from symptom onset to self-isolation, the proportion of symptomatic individuals practicing self-isolation, and the basic reproduction number R0 Without self-isolation, when R0 = 2.5, treatment of critically ill individuals at the outbreak peak would require 3.8 times more ICU beds than exist in the United States. Self-isolation by 20% of cases 24 h after symptom onset would delay and flatten the outbreak trajectory, reducing the number of ICU beds needed at the peak by 48.4% (interquartile range 46.4-50.3%), although still exceeding existing capacity. When R0 = 2, twice as many ICU beds would be required at the peak of outbreak in the absence of self-isolation. In this scenario, the proportional impact of self-isolation within 24 h on reducing the peak number of ICU beds is substantially higher at 73.5% (interquartile range 71.4-75.3%). Our estimates underscore the inadequacy of critical care capacity to handle the burgeoning outbreak. Policies that encourage self-isolation, such as paid sick leave, may delay the epidemic peak, giving a window of time that could facilitate emergency mobilization to expand hospital capacity.

Inferring the true number of SARS-CoV-2 infections in Japan.

INTRODUCTION: In Japan, as of December 31, 2021, more than 1.73 million laboratory-confirmed cases have been reported. However, the actual number of infections is likely to be under-ascertained due to the epidemiological characteristics such as mild and subclinical infections and limited testing availability in the early days of the pandemic. In this study, we infer the true number of infections in Japan between January 16, 2020, and December 31, 2021, using a statistical modelling framework that combines data on reported cases and fatalities. METHODS: We used reported COVID-19 deaths and age-specific infection fatality ratios (IFR) to impute the true number of infections. Estimates of IFR were informed from published studies and were adjusted to reflect the effects of pharmaceutical interventions, mass vaccination, and evolving variants. To account for the uncertainty in IFR, we sampled values from relevant distributions. RESULTS: We estimated that as of December 31, 2021, 3.07 million (CrI: 2.05-4.24 million) people had been infected in Japan, which is 1.77 times higher than the 1.73 million reported cases. Our meta-analysis confirmed that these findings were consistent with the intermittent seroprevalence studies conducted in Japan. CONCLUSIONS: We have estimated that a substantial number of COVID-19 infections in Japan were unreported, particularly in adults. Our approach provides a more realistic assessment of the true underlying burden of COVID-19. The results of this study can be used as fundamental components to strengthen population health control and surveillance measures.

Population Immunity Against COVID-19 in the United States.

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

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.

Projecting demand for critical care beds during COVID-19 outbreaks in Canada.

BACKGROUND: Increasing numbers of coronavirus disease 2019 (COVID-19) cases in Canada may create substantial demand for hospital admission and critical care. We evaluated the extent to which self-isolation of mildly ill people delays the peak of outbreaks and reduces the need for this care in each Canadian province. METHODS: We developed a computational model and simulated scenarios for COVID-19 outbreaks within each province. Using estimates of COVID-19 characteristics, we projected the hospital and intensive care unit (ICU) bed requirements without self-isolation, assuming an average number of 2.5 secondary cases, and compared scenarios in which different proportions of mildly ill people practised self-isolation 24 hours after symptom onset. RESULTS: Without self-isolation, the peak of outbreaks would occur in the first half of June, and an average of 569 ICU bed days per 10 000 population would be needed. When 20% of cases practised self-isolation, the peak was delayed by 2-4 weeks, and ICU bed requirement was reduced by 23.5% compared with no self-isolation. Increasing self-isolation to 40% reduced ICU use by 53.6% and delayed the peak of infection by an additional 2-4 weeks. Assuming current ICU bed occupancy rates above 80% and self-isolation of 40%, demand would still exceed available (unoccupied) ICU bed capacity. INTERPRETATION: At the peak of COVID-19 outbreaks, the need for ICU beds will exceed the total number of ICU beds even with self-isolation at 40%. Our results show the coming challenge for the health care system in Canada and the potential role of self-isolation in reducing demand for hospital-based and ICU care.

Cost-effectiveness of Prophylactic Zika Virus Vaccine in the Americas.

Zika virus remains a major public health concern because of its association with microcephaly and other neurologic disorders in newborns. A prophylactic vaccine has the potential to reduce disease incidence and eliminate birth defects resulting from prenatal Zika virus infection in future outbreaks. We evaluated the cost-effectiveness of a Zika vaccine candidate, assuming a protection efficacy of 60%-90%, for 18 countries in the Americas affected by the 2015-2017 Zika virus outbreaks. Encapsulating the demographics of these countries in an agent-based model, our results show that vaccinating women of reproductive age would be very cost-effective for sufficiently low (<$16) vaccination costs per recipient, depending on the country-specific Zika attack rate. In all countries studied, the median reduction of microcephaly was >75% with vaccination. These findings indicate that targeted vaccination of women of reproductive age is a noteworthy preventive measure for mitigating the effects of Zika virus infection in future outbreaks.

Cost-effectiveness of a potential Zika vaccine candidate: a case study for Colombia.

BACKGROUND: A number of Zika vaccine platforms are currently being investigated, some of which have entered clinical trials. We sought to evaluate the cost-effectiveness of a potential Zika vaccine candidate under the WHO Vaccine Target Product Profile for outbreak response, prioritizing women of reproductive age to prevent microcephaly and other neurological disorders. METHODS: Using an agent-based simulation model of ZIKV transmission dynamics in a Colombian population setting, we conducted cost-effectiveness analysis with and without pre-existing herd immunity. The model was parameterized with estimates associated with ZIKV infection, risks of microcephaly in different trimesters, direct medical costs, and vaccination costs. We assumed that a single dose of vaccine provides a protection efficacy in the range 60% to 90% against infection. Cost-effectiveness analysis was conducted from a government perspective. RESULTS: Under a favorable scenario when the reproduction number is relatively low (R0 = 2.2) and the relative transmissibility of asymptomatic infection is 10% compared with symptomatic infection, a vaccine is cost-saving (with negative incremental cost-effective ratio; ICER) for vaccination costs up to US$6 per individual without herd immunity, and up to US$4 per individual with 8% herd immunity. For positive ICER values, vaccination is highly cost-effective for vaccination costs up to US$10 (US$7) in the respective scenarios with the willingness-to-pay of US$6610 per disability-adjusted life-year, corresponding to the average per capita GDP of Colombia between 2013 and 2017. Our results indicate that the effect of other control measures targeted to reduce ZIKV transmission decreases the range of vaccination costs for cost-effectiveness due to reduced returns of vaccine-induced herd immunity. In all scenarios investigated, the median reduction of microcephaly exceeded 64% with vaccination. CONCLUSIONS: Our study suggests that a Zika vaccine with protection efficacy as low as 60% could significantly reduce the incidence of microcephaly. From a government perspective, Zika vaccination is highly cost-effective, and even cost-saving in Colombia if vaccination costs per individual is sufficiently low. Efficacy data from clinical trials and number of vaccine doses will be important requirements in future studies to refine our estimates, and conduct similar studies in other at-risk populations.

Projection de la demande de lits de soins intensifs durant l'épidémie de COVID-19 au Canada.

CONTEXTE: La hausse des cas de maladie à coronavirus 2019 (COVID-19) au Canada peut créer une forte demande de soins hospitaliers et de soins intensifs. Nous avons évalué la mesure dans laquelle l'isolement volontaire des personnes présentant des symptômes légers retarde le sommet épidémique et réduit la demande de soins dans chaque province canadienne. MÉTHODES: Nous avons conçu un modèle de calcul et fait des simulations de la propagation de la COVID-19 dans chaque province. À partir des estimations des caractéristiques de la COVID-19, nous avons évalué la demande de lits d'hôpital et de lits de soins intensifs en l'absence d'isolement volontaire en supposant une moyenne de 2,5 cas secondaires, et avons comparé des scénarios en faisant varier le taux d'isolement volontaire des cas légers 24 heures après l'apparition des symptômes. RÉSULTATS: En l'absence d'isolement volontaire, l'épidémie atteindrait son sommet dans la première moitié de juin, et il faudrait en moyenne 569 jours-lits de soins intensifs par 10 000 habitants. Avec un taux d'isolement volontaire de 20 %, l'atteinte du sommet serait repoussée de 2 à 4 semaines, et la demande de lits diminuerait de 23,5 %; avec un taux de 40 %, le sommet serait repoussé de 2 à 4 semaines supplémentaires, et la demande de lits connaîtrait une baisse de 53,6 %. En fixant le taux d'occupation actuel des lits de soins intensifs à plus de 80 % et le taux d'isolement volontaire à 40 %, la demande de lits demeure supérieure au nombre de lits disponibles. INTERPRÉTATION: Au sommet de l'épidémie de COVID-19 au Canada, la demande de lits de soins intensifs excédera le nombre total de lits disponibles, même avec un taux d'isolement volontaire de 40 %. Nos résultats montrent que la situation sera difficile pour le système de santé et que l'isolement volontaire pourrait réduire la demande de soins hospitaliers et de soins intensifs.

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 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.

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).

Lives saved and hospitalizations averted by COVID-19 vaccination in New York City: a modeling study.

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.

Timing is everything: the relationship between COVID outcomes and the date at which mask mandates are relaxed.

IMPORTANCE: Several states including Texas and Mississippi have lifted their mask mandates, sparking concerns that this policy change could lead to a surge in cases and hospitalizations. OBJECTIVE: To estimate the increase in incidence, hospitalizations, and deaths in Texas and Mississippi following the removal of mask mandates, and to evaluate the relative reduction of these outcomes if policy change is delayed by 90 days. DESIGN SETTING AND PARTICIPANTS: This study uses an age-stratified compartmental model parameterized to incidence data in Texas and Mississippi to simulate increased transmission following policy change in March or June 2021, and to estimate the resulting number of incidence, hospitalizations, and deaths. MAIN OUTCOMES AND MEASURES: The increase in incidence, hospitalizations, and deaths if mask mandates are lifted on March 14 compared to lifting on June 12. RESULTS: If transmission is increased by 67% when mask mandates are lifted, we projected 11.39 (CrI: 11.22 - 11.55) million infections, 170,909 (CrI: 167,454 - 174,379) hospitalizations, and 5647 (5511 - 5804) deaths (Figure 1) in Texas from March 14 through the end of 2021. Delaying NPI lift until June reduces the average number of infections, hospitalizations, and deaths by 36%, 65%, and 62%, respectively. Proportionate differences were similar for the state of Mississippi. Peak hospitalization rates would be reduced by 79% and 63% in Texas and Mississippi, respectively. CONCLUSIONS AND RELEVANCE: Removal of mask mandates in March 2021 is premature. Delaying this policy change until June 2021, when a larger fraction of the population has been vaccinated, will avert more than half of the expected COVID-19 hospitalizations and deaths, and avoid an otherwise likely strain on healthcare capacity.

Routine saliva testing for the identification of silent coronavirus disease 2019 (COVID-19) in healthcare workers.

OBJECTIVE: Current COVID-19 guidelines recommend symptom-based screening and regular nasopharyngeal (NP) testing for healthcare personnel in high-risk settings. We sought to estimate case detection percentages with various routine NP and saliva testing frequencies. DESIGN: Simulation modeling study. METHODS: We constructed a sensitivity function based on the average infectiousness profile of symptomatic coronavirus disease 2019 (COVID-19) cases to determine the probability of being identified at the time of testing. This function was fitted to reported data on the percent positivity of symptomatic COVID-19 patients using NP testing. We then simulated a routine testing program with different NP and saliva testing frequencies to determine case detection percentages during the infectious period, as well as the presymptomatic stage. RESULTS: Routine biweekly NP testing, once every 2 weeks, identified an average of 90.7% (SD, 0.18) of cases during the infectious period and 19.7% (SD, 0.98) during the presymptomatic stage. With a weekly NP testing frequency, the corresponding case detection percentages were 95.9% (SD, 0.18) and 32.9% (SD, 1.23), respectively. A 5-day saliva testing schedule had a similar case detection percentage as weekly NP testing during the infectious period, but identified ~10% more cases (mean, 42.5%; SD, 1.10) during the presymptomatic stage. CONCLUSION: Our findings highlight the utility of routine noninvasive saliva testing for frontline healthcare workers to protect vulnerable patient populations. A 5-day saliva testing schedule should be considered to help identify silent infections and prevent outbreaks in nursing homes and healthcare facilities.

Simulated identification of silent COVID-19 infections among children and estimated future infection rates with vaccination.

IMPORTANCE: A significant proportion of COVID-19 transmission occurs silently during the pre-symptomatic and asymptomatic stages of infection. Children, while being important drivers of silent transmission, are not included in the current COVID-19 vaccination campaigns. OBJECTIVE: To investigate the benefits of identifying silent infections among children as a proxy for their vaccination. DESIGN: This study used an age-structured disease transmission model, parameterized with census data and estimates from published literature, to simulate the synergistic effect of interventions in reducing attack rates over the course of one year. SETTING: A synthetic population representative of the United States (US) demographics. PARTICIPANTS: Six age groups of 0-4, 5-10, 11-18, 19-49, 50-64, 65+ years based on US census data. INTERVENTIONS: In addition to the isolation of symptomatic cases within 24 hours of symptom onset, vaccination of adults was implemented to reach a 40%-60% coverage over the course of one year with an efficacy of 95% against symptomatic and severe COVID-19. MAIN OUTCOMES AND MEASURES: The combinations of proportion and speed for detecting silent infections among children which would suppress future attack rates below 5%. RESULTS: In the base-case scenarios with an effective reproduction number R e = 1.2, a targeted approach that identifies 11% and 14% of silent infections among children within 2 or 3 days post-infection, respectively, would bring attack rates under 5% with 40% vaccination coverage of adults. If silent infections among children remained undetected, achieving the same attack rates would require an unrealistically high vaccination coverage (at least 81%) of this age group, in addition to 40% vaccination coverage of adults. The effect of identifying silent infections was robust in sensitivity analyses with respect to vaccine efficacy against infection and reduced susceptibility of children to infection. CONCLUSIONS AND RELEVANCE: In this simulation modeling study of a synthetic US population, in the absence of vaccine availability for children, a targeted approach to rapidly identify silent COVID-19 infections in this age group was estimated to significantly mitigate disease burden. Without measures to interrupt transmission chains from silent infections, vaccination of adults is unlikely to contain the outbreaks in the near term.

Simulated Identification of Silent COVID-19 Infections Among Children and Estimated Future Infection Rates With Vaccination.

Importance: A significant proportion of COVID-19 transmission occurs silently during the presymptomatic and asymptomatic stages of infection. Children, although important drivers of silent transmission, are not included in the current COVID-19 vaccination campaigns. Objective: To estimate the benefits of identifying silent infections among children as a proxy for their vaccination. Design, Setting, and Participants: This study used an age-structured disease transmission model, parameterized with census data and estimates from published literature, to simulate the estimated synergistic effect of interventions in reducing attack rates during the course of 1 year among a synthetic population representative of the US demographic composition. The population included 6 age groups of 0 to 4, 5 to 10, 11 to 18, 19 to 49, 50 to 64, and 65 years or older based on US census data. Data were analyzed from December 12, 2020, to February 26, 2021. Exposures: In addition to the isolation of symptomatic cases within 24 hours of symptom onset, vaccination of adults was implemented to reach a 40% to 60% coverage during 1 year with an efficacy of 95% against symptomatic and severe COVID-19. Main Outcomes and Measures: The combinations of proportion and speed for detecting silent infections among children that would suppress future attack rates to less than 5%. Results: In the base-case scenarios with an effective reproduction number Re = 1.2, a targeted approach that identifies 11% of silent infections among children within 2 days and 14% within 3 days after infection would bring attack rates to less than 5% with 40% vaccination coverage of adults. If silent infections among children remained undetected, achieving the same attack rates would require an unrealistically high vaccination coverage (≥81%) of this age group, in addition to 40% vaccination coverage of adults. The estimated effect of identifying silent infections was robust in sensitivity analyses with respect to vaccine efficacy against infection and reduced susceptibility of children to infection. Conclusions and Relevance: In this simulation modeling study of a synthetic US population, in the absence of vaccine availability for children, a targeted approach to rapidly identify silent COVID-19 infections in this age group was estimated to significantly mitigate disease burden. These findings suggest that without measures to interrupt transmission chains from silent infections, vaccination of adults is unlikely to contain the outbreaks in the near term.