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1.
Preprint in English | medRxiv | ID: ppmedrxiv-21266598

ABSTRACT

1Forecasts based on epidemiological modelling have played an important role in shaping public policy throughout the COVID-19 pandemic. This modelling combines knowledge about infectious disease dynamics with the subjective opinion of the researcher who develops and refines the model and often also adjusts model outputs. Developing a forecast model is difficult, resource- and time-consuming. It is therefore worth asking what modelling is able to add beyond the subjective opinion of the researcher alone. To investigate this, we analysed different real-time forecasts of cases of and deaths from COVID-19 in Germany and Poland over a 1-4 week horizon submitted to the German and Polish Forecast Hub. We compared crowd forecasts elicited from researchers and volunteers, against a) forecasts from two semi-mechanistic models based on common epidemiological assumptions and b) the ensemble of all other models submitted to the Forecast Hub. We found crowd forecasts, despite being overconfident, to outperform all other methods across all forecast horizons when forecasting cases (weighted interval score relative to the Hub ensemble 2 weeks ahead: 0.89). Forecasts based on computational models performed comparably better when predicting deaths (rel. WIS 1.26), suggesting that epidemiological modelling and human judgement can complement each other in important ways.

2.
Preprint in English | medRxiv | ID: ppmedrxiv-20200857

ABSTRACT

BackgroundIn response to the coronavirus disease 2019 (COVID-19), the UK adopted mandatory physical distancing measures in March 2020. Vaccines against the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may become available as early as late 2020. We explored the health and economic value of introducing SARS-CoV-2 immunisation alongside physical distancing scenarios in the UK. MethodsWe used an age-structured dynamic-transmission and economic model to explore different scenarios of immunisation programmes over ten years. Assuming vaccines are effective in 5-64 year olds, we compared vaccinating 90% of individuals in this age group to no vaccination. We assumed either vaccine effectiveness of 25% and 1-year protection and 90% re-vaccinated annually, or 75% vaccine effectiveness and 10-year protection and 10% re-vaccinated annually. Natural immunity was assumed to last 45 weeks in the base case. We also explored the additional impact of physical distancing. We considered benefits from disease prevented in terms of quality-adjusted life-years (QALYs), and costs to the healthcare payer versus the national economy. We discounted at 3.5% annually and monetised health impact at {pound}20,000 per QALY to obtain the net monetary value, which we explored in sensitivity analyses. FindingsWithout vaccination and physical distancing, we estimated 147.9 million COVID-19 cases (95% uncertainty interval: 48.5 million, 198.7 million) and 2.8 million (770,000, 4.2 million) deaths in the UK over ten years. Vaccination with 75% vaccine effectiveness and 10-year protection may stop community transmission entirely for several years, whereas SARS-CoV-2 becomes endemic without highly effective vaccines. Introducing vaccination compared to no vaccination leads to economic gains (positive net monetary value) of {pound}0.37 billion to +{pound}1.33 billion across all physical distancing and vaccine effectiveness scenarios from the healthcare perspective, but net monetary values of physical distancing scenarios may be negative from societal perspective if the daily national economy losses are persistent and large. InterpretationOur model findings highlight the substantial health and economic value of introducing SARS-CoV-2 vaccination. Given uncertainty around both characteristics of the eventually licensed vaccines and long-term COVID-19 epidemiology, our study provides early insights about possible future scenarios in a post-vaccination era from an economic and epidemiological perspective. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and medRxiv for economic evaluations of SARS-CoV-2 vaccines with the search string (coronavirus OR COVID OR SARS-CoV-2) AND (vaccin* OR immunisation) AND ((economic evaluation) OR (cost effectiveness analysis)) AND 2020[dp] on September 21, 2020, with no language restrictions. We found one pre-print that valued health outcomes in monetary terms and explored the additional impact of vaccines in a cost-benefit analysis of physical distancing for the USA; no study focused on vaccines in a full economic evaluation. Added value of this studyWith a growing number of vaccine candidates under development and having entered clinical trials, our study is to our knowledge the first to explore the health and economic value of introducing a national SARS-CoV-2 immunisation programme. A programme with high vaccine effectiveness and long-lasting protection may stop the community transmission entirely for a couple of years, but even a vaccine with 25% vaccine effectiveness is worthwhile to use; even at short-lived natural and vaccine-induced protections. After an initial lockdown, voluntary physical distancing as a sole strategy risks a large second epidemic peak, unless accompanied by highly effective immunisation. Compared to no vaccination, introducing vaccination leads to positive net monetary value across physical distancing scenarios from the healthcare perspective, subject to the long-run vaccine price and cost-effectiveness of other treatments (e.g. new drugs). The net monetary value of immunisation decreases if vaccine introduction is delayed, natural immunity is long or vaccine-induced protection is short. Intermittent physical distancing leads to negative net benefits from the perspective of the wider economy if the daily national income losses are persistent and large. Implications of all the available evidenceOur model findings highlight the health and economic value of introducing SARS-CoV-2 vaccination to control the COVID-19 epidemic. Despite the many uncertainties, continued physical distancing may be needed to reduce community transmission until vaccines with sufficiently high vaccine effectiveness and long-lasting protection are available. Our study provides first broad health-economic insights rather than precise quantitative projections given the many uncertainties and unknown characteristics of the vaccine candidates and aspects of the long-term COVID-19 epidemiology, and the value of vaccines will ultimately depend on other socioeconomic and health-related policies and population behaviours.

3.
Preprint in English | medRxiv | ID: ppmedrxiv-20159772

ABSTRACT

Mathematical models have played a key role in understanding the spread of directly-transmissible infectious diseases such as Coronavirus Disease 2019 (COVID-19), as well as the effectiveness of public health responses. As the risk of contracting directly-transmitted infections depends on who interacts with whom, mathematical models often use contact matrices to characterise the spread of infectious pathogens. These contact matrices are usually generated from diary-based contact surveys. However, the majority of places in the world do not have representative empirical contact studies, so synthetic contact matrices have been constructed using more widely available setting-specific survey data on household, school, classroom, and workplace composition combined with empirical data on contact patterns in Europe. In 2017, the largest set of synthetic contact matrices to date were published for 152 geographical locations. In this study, we update these matrices with the most recent data and extend our analysis to 177 geographical locations. Due to the observed geographic differences within countries, we also quantify contact patterns in rural and urban settings where data is available. Further, we compare both the 2017 and 2020 synthetic matrices to out-of-sample empirically-constructed contact matrices, and explore the effects of using both the empirical and synthetic contact matrices when modelling physical distancing interventions for the COVID-19 pandemic. We found that the synthetic contact matrices reproduce the main traits of the contact patterns in the empirically-constructed contact matrices. Models parameterised with the empirical and synthetic matrices generated similar findings with few differences observed in age groups where the empirical matrices have missing or aggregated age groups. This finding means that synthetic contact matrices may be used in modelling outbreaks in settings for which empirical studies have yet to be conducted. Author summaryThe risk of contracting a directly transmitted infectious disease such as the Coronavirus Disease 2019 (COVID-19) depends on who interacts with whom. Such person-to-person interactions vary by age and locations--e.g., at home, at work, at school, or in the community--due to the different social structures. These social structures, and thus contact patterns, vary across and within countries. Although social contact patterns can be measured using contact surveys, the majority of countries around the world, particularly low- and middle-income countries, lack nationally representative contact surveys. A simple way to present contact data is to use matrices where the elements represent the rate of contact between subgroups such as age groups represented by the columns and rows. In 2017, we generated age- and location-specific synthetic contact matrices for 152 geographical regions by adapting contact pattern data from eight European countries using country-specific data on household size, school and workplace composition. We have now updated these matrices with the most recent data (Demographic Household Surveys, World Bank, UN Population Division) extending the coverage to 177 geographical locations, covering 97.2% of the worlds population. We also quantified contact patterns in rural and urban settings. When compared to out-of-sample empirically-measured contact patterns, we found that the synthetic matrices reproduce the main features of these contact patterns.

4.
Preprint in English | medRxiv | ID: ppmedrxiv-20033761

ABSTRACT

We estimate the number of COVID-19 cases from newly reported deaths in a population without previous reports. Our results suggest that by the time a single death occurs, hundreds to thousands of cases are likely to be present in that population. This suggests containment via contact tracing will be challenging at this point, and other response strategies should be considered. Our approach is implemented in a publicly available, user-friendly, online tool.

5.
Preprint in English | medRxiv | ID: ppmedrxiv-20033050

ABSTRACT

BACKGROUNDIn December 2019, a novel strain of SARS-CoV-2 emerged in Wuhan, China. Since then, the city of Wuhan has taken unprecedented measures and efforts in response to the outbreak. METHODSWe quantified the effects of control measures on population contact patterns in Wuhan, China, to assess their effects on the progression of the outbreak. We included the latest estimates of epidemic parameters from a transmission model fitted to data on local and internationally exported cases from Wuhan in the age-structured epidemic framework. Further, we looked at the age-distribution of cases. Lastly, we simulated lifting of the control measures by allowing people to return to work in a phased-in way, and looked at the effects of returning to work at different stages of the underlying outbreak. FINDINGSChanges in mixing patterns may have contributed to reducing the number of infections in mid-2020 by 92% (interquartile range: 66-97%). There are benefits to sustaining these measures until April in terms of reducing the height of the peak, overall epidemic size in mid-2020 and probability that a second peak may occur after return to work. However, the modelled effects of social distancing measures vary by the duration of infectiousness and the role school children play in the epidemic. INTERPRETATIONRestrictions on activities in Wuhan, if maintained until April, would likely contribute to the reduction and delay the epidemic size and peak, respectively. However, there are some limitations to the analysis, including large uncertainties around estimates of R0 and the duration of infectiousness. FUNDINGBill and Melinda Gates Foundation, National Institute for Health Research, Wellcome Trust, and Health Data Research UK.

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