The societal value of SARS-CoV-2 booster vaccination in Indonesia.

OBJECTIVES: To estimate the expected socio-economic value of booster vaccination in terms of averted deaths and averted closures of businesses and schools using simulation modelling. METHODS: The value of booster vaccination in Indonesia is estimated by comparing simulated societal costs under a twelve-month, 187-million-dose Moderna booster vaccination campaign to costs without boosters. The costs of an epidemic and its mitigation consist of lost lives, economic closures and lost education; cost-minimising non-pharmaceutical mitigation is chosen for each scenario. RESULTS: The cost-minimising non-pharmaceutical mitigation depends on the availability of vaccines: the differences between the two scenarios are 14 to 19 million years of in-person education and $153 to $204 billion in economic activity. The value of the booster campaign ranges from $2,500 ($1,400-$4,100) to $2,800 ($1,700-$4,600) per dose in the first year, depending on life-year valuations. CONCLUSIONS: The societal benefits of booster vaccination are substantial. Much of the value of vaccination resides in the reduced need for costly non-pharmaceutical mitigation. We propose cost minimisation as a tool for policy decision-making and valuation of vaccination, taking into account all socio-economic costs, and not averted deaths alone.

The Societal Value of Vaccines: Expert-Based Conceptual Framework and Methods Using COVID-19 Vaccines as a Case Study.

Health technology assessments (HTAs) of vaccines typically focus on the direct health benefits to individuals and healthcare systems. COVID-19 highlighted the widespread societal impact of infectious diseases and the value of vaccines in averting adverse clinical consequences and in maintaining or resuming social and economic activities. Using COVID-19 as a case study, this research work aimed to set forth a conceptual framework capturing the broader value elements of vaccines and to identify appropriate methods to quantify value elements not routinely considered in HTAs. A two-step approach was adopted, combining a targeted literature review and three rounds of expert elicitation based on a modified Delphi method, leading to a conceptual framework of 30 value elements related to broader health effects, societal and economic impact, public finances, and uncertainty value. When applying the framework to COVID-19 vaccines in post-pandemic settings, 13 value elements were consensually rated highly important by the experts for consideration in HTAs. The experts reviewed over 10 methods that could be leveraged to quantify broader value elements and provided technical forward-looking recommendations. Limitations of the framework and the identified methods were discussed. This study supplements ongoing efforts aimed towards a broader recognition of the full societal value of vaccines.

Data needs for integrated economic-epidemiological models of pandemic mitigation policies.

The COVID-19 pandemic and the mitigation policies implemented in response to it have resulted in economic losses worldwide. Attempts to understand the relationship between economics and epidemiology has led to a new generation of integrated mathematical models. The data needs for these models transcend those of the individual fields, especially where human interaction patterns are closely linked with economic activity. In this article, we reflect upon modelling efforts to date, discussing the data needs that they have identified, both for understanding the consequences of the pandemic and policy responses to it through analysis of historic data and for the further development of this new and exciting interdisciplinary field.

Modelling the impact of vaccine hesitancy in prolonging the need for Non-Pharmaceutical Interventions to control the COVID-19 pandemic.

Background: Vaccine hesitancy - a delay in acceptance or refusal of vaccines despite availability - has the potential to threaten the successful roll-out of SARS-CoV-2 vaccines globally. In this study, we aim to understand the likely impact of vaccine hesitancy on the control of the COVID-19 pandemic. Methods: We modelled the potential impact of vaccine hesitancy on the control of the pandemic and the relaxation of non-pharmaceutical interventions (NPIs) by combining an epidemiological model of SARS-CoV-2 transmission with data on vaccine hesitancy from population surveys. Results: Our simulations suggest that the mortality over a 2-year period could be up to 7.6 times higher in countries with high vaccine hesitancy compared to an ideal vaccination uptake if NPIs are relaxed. Alternatively, high vaccine hesitancy could prolong the need for NPIs to remain in place. Conclusions: While vaccination is an individual choice, vaccine-hesitant individuals have a substantial impact on the pandemic trajectory, which may challenge current efforts to control COVID-19. In order to prevent such outcomes, addressing vaccine hesitancy with behavioural interventions is an important priority in the control of the COVID-19 pandemic.

Clinical Characteristics and Predictors of Outcomes of Hospitalized Patients With Coronavirus Disease 2019 in a Multiethnic London National Health Service Trust: A Retrospective Cohort Study.

BACKGROUND: Emerging evidence suggests ethnic minorities are disproportionately affected by coronavirus disease 2019 (COVID-19). Detailed clinical analyses of multicultural hospitalized patient cohorts remain largely undescribed. METHODS: We performed regression, survival, and cumulative competing risk analyses to evaluate factors associated with mortality in patients admitted for COVID-19 in 3 large London hospitals between 25 February and 5 April, censored as of 1 May 2020. RESULTS: Of 614 patients (median age, 69 [interquartile range, 25] years) and 62% male), 381 (62%) were discharged alive, 178 (29%) died, and 55 (9%) remained hospitalized at censoring. Severe hypoxemia (adjusted odds ratio [aOR], 4.25 [95% confidence interval {CI}, 2.36-7.64]), leukocytosis (aOR, 2.35 [95% CI, 1.35-4.11]), thrombocytopenia (aOR [1.01, 95% CI, 1.00-1.01], increase per 109 decrease), severe renal impairment (aOR, 5.14 [95% CI, 2.65-9.97]), and low albumin (aOR, 1.06 [95% CI, 1.02-1.09], increase per gram decrease) were associated with death. Forty percent (n = 244) were from black, Asian, and other minority ethnic (BAME) groups, 38% (n = 235) were white, and ethnicity was unknown for 22% (n = 135). BAME patients were younger and had fewer comorbidities. Although the unadjusted odds of death did not differ by ethnicity, when adjusting for age, sex, and comorbidities, black patients were at higher odds of death compared to whites (aOR, 1.69 [95% CI, 1.00-2.86]). This association was stronger when further adjusting for admission severity (aOR, 1.85 [95% CI, 1.06-3.24]). CONCLUSIONS: BAME patients were overrepresented in our cohort; when accounting for demographic and clinical profile of admission, black patients were at increased odds of death. Further research is needed into biologic drivers of differences in COVID-19 outcomes by ethnicity.

The impact of the COVID-19 pandemic on patterns of attendance at emergency departments in two large London hospitals: an observational study.

BACKGROUND: Hospitals in England have undergone considerable change to address the surge in demand imposed by the COVID-19 pandemic. The impact of this on emergency department (ED) attendances is unknown, especially for non-COVID-19 related emergencies. METHODS: This analysis is an observational study of ED attendances at the Imperial College Healthcare NHS Trust (ICHNT). We calibrated auto-regressive integrated moving average time-series models of ED attendances using historic (2015-2019) data. Forecasted trends were compared to present year ICHNT data for the period between March 12, 2020 (when England implemented the first COVID-19 public health measure) and May 31, 2020. We compared ICHTN trends with publicly available regional and national data. Lastly, we compared hospital admissions made via the ED and in-hospital mortality at ICHNT during the present year to the historic 5-year average. RESULTS: ED attendances at ICHNT decreased by 35% during the period after the first lockdown was imposed on March 12, 2020 and before May 31, 2020, reflecting broader trends seen for ED attendances across all England regions, which fell by approximately 50% for the same time frame. For ICHNT, the decrease in attendances was mainly amongst those aged < 65 years and those arriving by their own means (e.g. personal or public transport) and not correlated with any of the spatial dependencies analysed such as increasing distance from postcode of residence to the hospital. Emergency admissions of patients without COVID-19 after March 12, 2020 fell by 48%; we did not observe a significant change to the crude mortality risk in patients without COVID-19 (RR 1.13, 95%CI 0.94-1.37, p = 0.19). CONCLUSIONS: Our study findings reflect broader trends seen across England and give an indication how emergency healthcare seeking has drastically changed. At ICHNT, we find that a larger proportion arrived by ambulance and that hospitalisation outcomes of patients without COVID-19 did not differ from previous years. The extent to which these findings relate to ED avoidance behaviours compared to having sought alternative emergency health services outside of hospital remains unknown. National analyses and strategies to streamline emergency services in England going forward are urgently needed.

The impact of a COVID-19 lockdown on work productivity under good and poor compliance.

BACKGROUND: In response to the COVID-19 pandemic, governments across the globe have imposed strict social distancing measures. Public compliance to such measures is essential for their success, yet the economic consequences of compliance are unknown. This is the first study to analyze the effects of good compliance compared with poor compliance to a COVID-19 suppression strategy (i.e. lockdown) on work productivity. METHODS: We estimate the differences in work productivity comparing a scenario of good compliance with one of poor compliance to the UK government COVID-19 suppression strategy. We use projections of the impact of the UK suppression strategy on mortality and morbidity from an individual-based epidemiological model combined with an economic model representative of the labour force in Wales and England. RESULTS: We find that productivity effects of good compliance significantly exceed those of poor compliance and increase with the duration of the lockdown. After 3 months of the lockdown, work productivity in good compliance is £398.58 million higher compared with that of poor compliance; 75% of the differences is explained by productivity effects due to morbidity and non-health reasons and 25% attributed to avoided losses due to pre-mature mortality. CONCLUSION: Good compliance to social distancing measures exceeds positive economic effects, in addition to health benefits. This is an important finding for current economic and health policy. It highlights the importance to set clear guidelines for the public, to build trust and support for the rules and if necessary, to enforce good compliance to social distancing measures.

A Systematic Review of the Costs Relating to Non-pharmaceutical Interventions Against Infectious Disease Outbreaks.

BACKGROUND: Non-pharmaceutical interventions (NPIs) are the cornerstone of infectious disease outbreak response in the absence of effective pharmaceutical interventions. Outbreak strategies often involve combinations of NPIs that may change according to disease prevalence and population response. Little is known with regard to how costly each NPI is to implement. This information is essential to inform policy decisions for outbreak response. OBJECTIVE: To address this gap in existing literature, we conducted a systematic review on outbreak costings and simulation studies related to a number of NPI strategies, including isolating infected individuals, contact tracing and quarantine, and school closures. METHODS: Our search covered the MEDLINE and EMBASE databases, studies published between 1990 and 24 March 2020 were included. We included studies containing cost data for our NPIs of interest in pandemic, epidemic, and outbreak response scenarios. RESULTS: We identified 61 relevant studies. There was substantial heterogeneity in the cost components recorded for NPIs in outbreak costing studies. The direct costs of NPIs for which costing studies existed also ranged widely: isolating infected individuals per case: US$141.18 to US$1042.68 (2020 values), tracing and quarantine of contacts per contact: US$40.73 to US$93.59, social distancing: US$33.76 to US$167.92, personal protection and hygiene: US$0.15 to US$895.60. CONCLUSION: While there are gaps and heterogeneity in available cost data, the findings of this review and the collated cost database serve as an important resource for evidence-based decision-making for estimating costs pertaining to NPI implementation in future outbreak response policies.

The J-IDEA Pandemic Planner: A Framework for Implementing Hospital Provision Interventions During the COVID-19 Pandemic.

BACKGROUND: Planning for extreme surges in demand for hospital care of patients requiring urgent life-saving treatment for coronavirus disease 2019 (COVID-19), while retaining capacity for other emergency conditions, is one of the most challenging tasks faced by health care providers and policymakers during the pandemic. Health systems must be well-prepared to cope with large and sudden changes in demand by implementing interventions to ensure adequate access to care. We developed the first planning tool for the COVID-19 pandemic to account for how hospital provision interventions (such as cancelling elective surgery, setting up field hospitals, or hiring retired staff) will affect the capacity of hospitals to provide life-saving care. METHODS: We conducted a review of interventions implemented or considered in 12 European countries in March to April 2020, an evaluation of their impact on capacity, and a review of key parameters in the care of COVID-19 patients. This information was used to develop a planner capable of estimating the impact of specific interventions on doctors, nurses, beds, and respiratory support equipment. We applied this to a scenario-based case study of 1 intervention, the set-up of field hospitals in England, under varying levels of COVID-19 patients. RESULTS: The Abdul Latif Jameel Institute for Disease and Emergency Analytics pandemic planner is a hospital planning tool that allows hospital administrators, policymakers, and other decision-makers to calculate the amount of capacity in terms of beds, staff, and crucial medical equipment obtained by implementing the interventions. Flexible assumptions on baseline capacity, the number of hospitalizations, staff-to-beds ratios, and staff absences due to COVID-19 make the planner adaptable to multiple settings. The results of the case study show that while field hospitals alleviate the burden on the number of beds available, this intervention is futile unless the deficit of critical care nurses is addressed first. DISCUSSION: The tool supports decision-makers in delivering a fast and effective response to the pandemic. The unique contribution of the planner is that it allows users to compare the impact of interventions that change some or all inputs.

Impacts of introducing and lifting nonpharmaceutical interventions on COVID-19 daily growth rate and compliance in the United States

We evaluate the impacts of implementing and lifting non-pharmaceutical interventions (NPIs) in US counties on the daily growth rate of COVID-19 cases and compliance, measured through the percentage of devices staying home, and evaluate whether introducing and lifting NPIs protecting selective populations is an effective strategy. We use difference-in-differences methods, leveraging on daily county-level data and exploit the staggered introduction and lifting of policies across counties over time. We also assess heterogenous impacts due to counties' population characteristics, namely ethnicity and household income. Results show that introducing NPIs led to a reduction in cases through the percentage of devices staying home. When counties lifted NPIs, they benefited from reduced mobility outside of the home during the lockdown, but only for a short period. In the long term, counties experienced diminished health and mobility gains accrued from previously implemented policies. Notably, we find heterogenous impacts due to population characteristics implying that measures can mitigate the disproportionate burden of COVID-19 on marginalized populations and find that selectively targeting populations may not be effective. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

A systematic examination of international funding flows for Ebola virus and Zika virus outbreaks 2014-2019: donors, recipients and funding purposes.

INTRODUCTION: There has been no systematic comparison of how the policy response to past infectious disease outbreaks and epidemics was funded. This study aims to collate and analyse funding for the Ebola epidemic and Zika outbreak between 2014 and 2019 in order to understand the shortcomings in funding reporting and suggest improvements. METHODS: Data were collected via a literature review and analysis of financial reporting databases, including both amounts donated and received. Funding information from three financial databases was analysed: Institute of Health Metrics and Evaluation's Development Assistance for Health database, the Georgetown Infectious Disease Atlas and the United Nations Financial Tracking Service. A systematic literature search strategy was devised and applied to seven databases: MEDLINE, EMBASE, HMIC, Global Health, Scopus, Web of Science and EconLit. Funding information was extracted from articles meeting the eligibility criteria and measures were taken to avoid double counting. Funding was collated, then amounts and purposes were compared within, and between, data sources. RESULTS: Large differences between funding reported by different data sources, and variations in format and methodology, made it difficult to arrive at precise estimates of funding amounts and purpose. Total disbursements reported by the databases ranged from $2.5 to $3.2 billion for Ebola and $150-$180 million for Zika. Total funding reported in the literature is greater than reported in databases, suggesting that databases may either miss funding, or that literature sources overreport. Databases and literature disagreed on the main purpose of funding for socioeconomic recovery versus outbreak response. One of the few consistent findings across data sources and diseases is that the USA was the largest donor. CONCLUSION: Implementation of several recommendations would enable more effective mapping and deployment of outbreak funding for response activities relating to COVID-19 and future epidemics.

Within-country age-based prioritisation, global allocation, and public health impact of a vaccine against SARS-CoV-2: A mathematical modelling analysis.

The worldwide endeavour to develop safe and effective COVID-19 vaccines has been extraordinary, and vaccination is now underway in many countries. However, the doses available in 2021 are likely to be limited. We extend a mathematical model of SARS-CoV-2 transmission across different country settings to evaluate the public health impact of potential vaccines using WHO-developed target product profiles. We identify optimal vaccine allocation strategies within- and between-countries to maximise averted deaths under constraints on dose supply. We find that the health impact of SARS-CoV-2 vaccination depends on the cumulative population-level infection incidence when vaccination begins, the duration of natural immunity, the trajectory of the epidemic prior to vaccination, and the level of healthcare available to effectively treat those with disease. Within a country we find that for a limited supply (doses for < 20% of the population) the optimal strategy is to target the elderly. However, with a larger supply, if vaccination can occur while other interventions are maintained, the optimal strategy switches to targeting key transmitters to indirectly protect the vulnerable. As supply increases, vaccines that reduce or block infection have a greater impact than those that prevent disease alone due to the indirect protection provided to high-risk groups. Given a 2 billion global dose supply in 2021, we find that a strategy in which doses are allocated to countries proportional to population size is close to optimal in averting deaths and aligns with the ethical principles agreed in pandemic preparedness planning.

Modelling intensive care unit capacity under different epidemiological scenarios of the COVID-19 pandemic in three Western European countries.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has placed enormous strain on intensive care units (ICUs) in Europe. Ensuring access to care, irrespective of COVID-19 status, in winter 2020-2021 is essential. METHODS: An integrated model of hospital capacity planning and epidemiological projections of COVID-19 patients is used to estimate the demand for and resultant spare capacity of ICU beds, staff and ventilators under different epidemic scenarios in France, Germany and Italy across the 2020-2021 winter period. The effect of implementing lockdowns triggered by different numbers of COVID-19 patients in ICUs under varying levels of effectiveness is examined, using a 'dual-demand' (COVID-19 and non-COVID-19) patient model. RESULTS: Without sufficient mitigation, we estimate that COVID-19 ICU patient numbers will exceed those seen in the first peak, resulting in substantial capacity deficits, with beds being consistently found to be the most constrained resource. Reactive lockdowns could lead to large improvements in ICU capacity during the winter season, with pressure being most effectively alleviated when lockdown is triggered early and sustained under a higher level of suppression. The success of such interventions also depends on baseline bed numbers and average non-COVID-19 patient occupancy. CONCLUSION: Reductions in capacity deficits under different scenarios must be weighed against the feasibility and drawbacks of further lockdowns. Careful, continuous decision-making by national policymakers will be required across the winter period 2020-2021.

Reduction in mobility and COVID-19 transmission.

In response to the COVID-19 pandemic, countries have sought to control SARS-CoV-2 transmission by restricting population movement through social distancing interventions, thus reducing the number of contacts. Mobility data represent an important proxy measure of social distancing, and here, we characterise the relationship between transmission and mobility for 52 countries around the world. Transmission significantly decreased with the initial reduction in mobility in 73% of the countries analysed, but we found evidence of decoupling of transmission and mobility following the relaxation of strict control measures for 80% of countries. For the majority of countries, mobility explained a substantial proportion of the variation in transmissibility (median adjusted R-squared: 48%, interquartile range - IQR - across countries [27-77%]). Where a change in the relationship occurred, predictive ability decreased after the relaxation; from a median adjusted R-squared of 74% (IQR across countries [49-91%]) pre-relaxation, to a median adjusted R-squared of 30% (IQR across countries [12-48%]) post-relaxation. In countries with a clear relationship between mobility and transmission both before and after strict control measures were relaxed, mobility was associated with lower transmission rates after control measures were relaxed indicating that the beneficial effects of ongoing social distancing behaviours were substantial.

SARIMA-modelled greater severity and mortality during the 2010/11 post-pandemic influenza season compared to the 2009 H1N1 pandemic in English hospitals.

OBJECTIVE: The COVID-19 pandemic demonstrates the need for understanding pathways to healthcare demand, morbidity, and mortality of pandemic patients. We estimate H1N1 (1) hospitalization rates, (2) severity rates (length of stay, ventilation, pneumonia, and death) of those hospitalized, (3) mortality rates, and (4) time lags between infections and hospitalizations during the pandemic (June 2009 to March 2010) and post-pandemic influenza season (November 2010 to February 2011) in England. METHODS: Estimates of H1N1 infections from a dynamic transmission model are combined with hospitalizations and severity using time series econometric analyses of administrative patient-level hospital data. RESULTS: Hospitalization rates were 34% higher and severity rates of those hospitalized were 20%-90% higher in the post-pandemic period than the pandemic. Adults (45-64-years-old) had the highest ventilation and pneumonia hospitalization rates. Hospitalizations did not lag infection during the pandemic for the young (<24-years-old) but lagged by one or more weeks for all ages in the post-pandemic period. DISCUSSION: The post-pandemic flu season exhibited heightened H1N1 severity, long after the pandemic was declared over. Policymakers should remain vigilant even after pandemics seem to have subsided. Analysis of administrative hospital data and epidemiological modelling estimates can provide valuable insights to inform responses to COVID-19 and future influenza and other disease pandemics.

Characteristics and outcomes of clinically diagnosed RT-PCR swab negative COVID-19: a retrospective cohort study.

Patients with strong clinical features of COVID-19 with negative real time polymerase chain reaction (RT-PCR) SARS-CoV-2 testing are not currently included in official statistics. The scale, characteristics and clinical relevance of this group are not well described. We performed a retrospective cohort study in two large London hospitals to characterize the demographic, clinical, and hospitalization outcome characteristics of swab-negative clinical COVID-19 patients. We found 1 in 5 patients with a negative swab and clinical suspicion of COVID-19 received a clinical diagnosis of COVID-19 within clinical documentation, discharge summary or death certificate. We compared this group to a similar swab positive cohort and found similar demographic composition, symptomology and laboratory findings. Swab-negative clinical COVID-19 patients had better outcomes, with shorter length of hospital stay, reduced need for > 60% supplementary oxygen and reduced mortality. Patients with strong clinical features of COVID-19 that are swab-negative are a common clinical challenge. Health systems must recognize and plan for the management of swab-negative patients in their COVID-19 clinical management, infection control policies and epidemiological assessments.

Database of epidemic trends and control measures during the first wave of COVID-19 in mainland China.

OBJECTIVES: In this data collation study, we aimed to provide a comprehensive database describing the epidemic trends and responses during the first wave of coronavirus disease 2019 (COVID-19) throughout the main provinces in China. METHODS: From mid-January to March 2020, we extracted publicly available data regarding the spread and control of COVID-19 from 31 provincial health authorities and major media outlets in mainland China. Based on these data, we conducted descriptive analyses of the epidemic in the six most-affected provinces. RESULTS: School closures, travel restrictions, community-level lockdown, and contact tracing were introduced concurrently around late January but subsequent epidemic trends differed among provinces. Compared with Hubei, the other five most-affected provinces reported a lower crude case fatality ratio and proportion of critical and severe hospitalised cases. From March 2020, as the local transmission of COVID-19 declined, switching the focus of measures to the testing and quarantine of inbound travellers may have helped to sustain the control of the epidemic. CONCLUSIONS: Aggregated indicators of case notifications and severity distributions are essential for monitoring an epidemic. A publicly available database containing these indicators and information regarding control measures is a useful resource for further research and policy planning in response to the COVID-19 epidemic.

Adapting hospital capacity to meet changing demands during the COVID-19 pandemic.

BACKGROUND: To calculate hospital surge capacity, achieved via hospital provision interventions implemented for the emergency treatment of coronavirus disease 2019 (COVID-19) and other patients through March to May 2020; to evaluate the conditions for admitting patients for elective surgery under varying admission levels of COVID-19 patients. METHODS: We analysed National Health Service (NHS) datasets and literature reviews to estimate hospital care capacity before the pandemic (pre-pandemic baseline) and to quantify the impact of interventions (cancellation of elective surgery, field hospitals, use of private hospitals, deployment of former medical staff and deployment of newly qualified medical staff) for treatment of adult COVID-19 patients, focusing on general and acute (G&A) and critical care (CC) beds, staff and ventilators. RESULTS: NHS England would not have had sufficient capacity to treat all COVID-19 and other patients in March and April 2020 without the hospital provision interventions, which alleviated significant shortfalls in CC nurses, CC and G&A beds and CC junior doctors. All elective surgery can be conducted at normal pre-pandemic levels provided the other interventions are sustained, but only if the daily number of COVID-19 patients occupying CC beds is not greater than 1550 in the whole of England. If the other interventions are not maintained, then elective surgery can only be conducted if the number of COVID-19 patients occupying CC beds is not greater than 320. However, there is greater national capacity to treat G&A patients: without interventions, it takes almost 10,000 G&A COVID-19 patients before any G&A elective patients would be unable to be accommodated. CONCLUSIONS: Unless COVID-19 hospitalisations drop to low levels, there is a continued need to enhance critical care capacity in England with field hospitals, use of private hospitals or deployment of former and newly qualified medical staff to allow some or all elective surgery to take place.