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.

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.

Evaluation of COVID-19 vaccination strategies with a delayed second dose.

Two of the Coronavirus Disease 2019 (COVID-19) vaccines currently approved in the United States require 2 doses, administered 3 to 4 weeks apart. Constraints in vaccine supply and distribution capacity, together with a deadly wave of COVID-19 from November 2020 to January 2021 and the emergence of highly contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants, sparked a policy debate on whether to vaccinate more individuals with the first dose of available vaccines and delay the second dose or to continue with the recommended 2-dose series as tested in clinical trials. We developed an agent-based model of COVID-19 transmission to compare the impact of these 2 vaccination strategies, while varying the temporal waning of vaccine efficacy following the first dose and the level of preexisting immunity in the population. Our results show that for Moderna vaccines, a delay of at least 9 weeks could maximize vaccination program effectiveness and avert at least an additional 17.3 (95% credible interval [CrI]: 7.8-29.7) infections, 0.69 (95% CrI: 0.52-0.97) hospitalizations, and 0.34 (95% CrI: 0.25-0.44) deaths per 10,000 population compared to the recommended 4-week interval between the 2 doses. Pfizer-BioNTech vaccines also averted an additional 0.60 (95% CrI: 0.37-0.89) hospitalizations and 0.32 (95% CrI: 0.23-0.45) deaths per 10,000 population in a 9-week delayed second dose (DSD) strategy compared to the 3-week recommended schedule between doses. However, there was no clear advantage of delaying the second dose with Pfizer-BioNTech vaccines in reducing infections, unless the efficacy of the first dose did not wane over time. Our findings underscore the importance of quantifying the characteristics and durability of vaccine-induced protection after the first dose in order to determine the optimal time interval between the 2 doses.

Asymptomatic SARS-CoV-2 infection: A systematic review and meta-analysis.

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.

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.

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.

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.

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.

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.

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.

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.

Multifaceted strategies for the control of COVID-19 outbreaks in long-term care facilities in Ontario, Canada.

The novel coronavirus disease 2019 (COVID-19) has caused severe outbreaks in Canadian long-term care facilities (LTCFs). In Canada, over 80% of COVID-19 deaths during the first pandemic wave occurred in LTCFs. We sought to evaluate the effect of mitigation measures in LTCFs including frequent testing of staff, and vaccination of staff and residents. We developed an agent-based transmission model and parameterized it with disease-specific estimates, temporal sensitivity of nasopharyngeal and saliva testing, results of vaccine efficacy trials, and data from initial COVID-19 outbreaks in LTCFs in Ontario, Canada. Characteristics of staff and residents, including contact patterns, were integrated into the model with age-dependent risk of hospitalization and death. Estimates of infection and outcomes were obtained and 95% credible intervals were generated using a bias-corrected and accelerated bootstrap method. Weekly routine testing of staff with 2-day turnaround time reduced infections among residents by at least 25.9% (95% CrI: 23.3%-28.3%), compared to baseline measures of mask-wearing, symptom screening, and staff cohorting alone. A similar reduction of hospitalizations and deaths was achieved in residents. Vaccination averted 2-4 times more infections in both staff and residents as compared to routine testing, and markedly reduced hospitalizations and deaths among residents by 95.9% (95% CrI: 95.4%-96.3%) and 95.8% (95% CrI: 95.5%-96.1%), respectively, over 200 days from the start of vaccination. Vaccination could have a substantial impact on mitigating disease burden among residents, but may not eliminate the need for other measures before population-level control of COVID-19 is achieved.

Simulating the effect of school closure during COVID-19 outbreaks in Ontario, Canada.

BACKGROUND: The province of Ontario, Canada, has instituted indefinite school closures (SC) as well as other social distancing measures to mitigate the impact of the novel coronavirus disease 2019 (COVID-19) pandemic. We sought to evaluate the effect of SC on reducing attack rate and the need for critical care during COVID-19 outbreaks, while considering scenarios with concurrent implementation of self-isolation (SI) of symptomatic cases. METHODS: We developed an age-structured agent-based simulation model and parameterized it with the demographics of Ontario stratified by age and the latest estimates of COVID-19 epidemiologic characteristics. Disease transmission was simulated within and between different age groups by considering inter- and intra-group contact patterns. The effect of SC of varying durations on the overall attack rate, magnitude and peak time of the outbreak, and requirement for intensive care unit (ICU) admission in the population was estimated. Secondly, the effect of concurrent community-based voluntary SI of symptomatic COVID-19 cases was assessed. RESULTS: SC reduced attack rates in the range of 7.2-12.7% when the duration of SC increased from 3 to 16 weeks, when contacts among school children were restricted by 60-80%, and in the absence of SI by mildly symptomatic persons. Depending on the scenario, the overall reduction in ICU admissions attributed to SC throughout the outbreak ranged from 3.3 to 6.7%. When SI of mildly symptomatic persons was included and practiced by 20%, the reduction of attack rate and ICU admissions exceeded 6.3% and 9.1% (on average), respectively, in the corresponding scenarios. CONCLUSION: Our results indicate that SC may have limited impact on reducing the burden of COVID-19 without measures to interrupt the chain of transmission during both pre-symptomatic and symptomatic stages. While highlighting the importance of SI, our findings indicate the need for better understanding of the epidemiologic characteristics of emerging diseases on the effectiveness of social distancing measures.

Temporal estimates of case-fatality rate for COVID-19 outbreaks in Canada and the United States.

BACKGROUND: Estimates of the case-fatality rate (CFR) associated with coronavirus disease 2019 (COVID-19) vary widely in different population settings. We sought to estimate and compare the COVID-19 CFR in Canada and the United States while adjusting for 2 potential biases in crude CFR. METHODS: We used the daily incidence of confirmed COVID-19 cases and deaths in Canada and the US from Jan. 31 to Apr. 22, 2020. We applied a statistical method to minimize bias in the crude CFR by accounting for the survival interval as the lag time between disease onset and death, while considering reporting rates of COVID-19 cases less than 50% (95% confidence interval 10%-50%). RESULTS: Using data for confirmed cases in Canada, we estimated the crude CFR to be 4.9% on Apr. 22, 2020, and the adjusted CFR to be 5.5% (credible interval [CrI] 4.9%-6.4%). After we accounted for various reporting rates less than 50%, the adjusted CFR was estimated at 1.6% (CrI 0.7%-3.1%). The US crude CFR was estimated to be 5.4% on Apr. 20, 2020, with an adjusted CFR of 6.1% (CrI 5.4%-6.9%). With reporting rates of less than 50%, the adjusted CFR for the US was 1.78 (CrI 0.8%-3.6%). INTERPRETATION: Our estimates suggest that, if the reporting rate is less than 50%, the adjusted CFR of COVID-19 in Canada is likely to be less than 2%. The CFR estimates for the US were higher than those for Canada, but the adjusted CFR still remained below 2%. Quantification of case reporting can provide a more accurate measure of the virulence and disease burden of severe acute respiratory syndrome coronavirus 2.

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.

Risk of influenza infection with low vaccine effectiveness: the role of avoidance behaviour.

Low vaccine-effectiveness has been recognised as a key factor undermining efforts to improve strategies and uptake of seasonal influenza vaccination. Aiming to prevent disease transmission, vaccination may influence the perceived risk-of-infection and, therefore, alter the individual-level behavioural responses, such as the avoidance of contact with infectious cases. We asked how the avoidance behaviour of vaccinated individuals changes disease dynamics, and specifically the epidemic size, in the context of imperfect vaccination. For this purpose, we developed an agent-based simulation model, and parameterised it with published estimates and relevant databases for population demographics and agent characteristics. Encapsulating an age-stratified structure, we evaluated the per-contact risk-of-infection and estimated the epidemic size. Our results show that vaccination could lead to a larger epidemic size if the level of avoidance behaviour in vaccinated individuals reduces below that of susceptible individuals. Furthermore, the risk-of-infection in vaccinated individuals, which follows the pattern of age-dependent frailty index of the population, increases for older age groups, and may reach, or even exceed, the risk-of-infection in susceptible individuals. Our findings indicate that low engagement in avoidance behaviour can potentially offset the benefits of vaccination even for vaccines with high effectiveness. While highlighting the protective effects of vaccination, seasonal influenza immunisation programmes should enhance strategies to promote avoidance behaviour despite being vaccinated.