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1.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-22282676

RESUMEN

BackgroundThe SARS-CoV-2 transmission dynamics have been greatly modulated by human contact behaviour. To curb the spread of the virus, global efforts focused on implementing both Non-Pharmaceutical Interventions (NPIs) and pharmaceutical interventions such as vaccination. This study was conducted to explore the influence of COVID-19 vaccination status and risk perceptions related to SARS-CoV-2 on the number of social contacts of individuals in 16 European countries. This is important since insights derived from the study could be utilized in guiding the formulation of risk communication strategies. MethodsWe used data from longitudinal surveys conducted in the 16 European countries to measure social contact behaviour in the course of the pandemic. The data consisted of representative panels of participants in terms of gender, age and region of residence in each country. The surveys were conducted in several rounds between December 2020 and September 2021. We employed a multilevel generalized linear mixed effects model to explore the influence of risk perceptions and COVID-19 vaccination status on the number of social contacts of individuals. ResultsThe results indicated that perceived severity played a significant role in social contact behaviour during the pandemic after controlling for other variables. More specifically, participants who perceived COVID-19 to be a serious illness made fewer contacts compared to those who had low or neutral perceptions of the COVID-19 severity. Additionally, vaccinated individuals reported significantly higher number of contacts than the non-vaccinated. Further-more, individual-level factors played a more substantial role in influencing contact behaviour than country-level factors. ConclusionOur multi-country study yields significant insights on the importance of risk perceptions and vaccination in behavioral changes during a pandemic emergency. The apparent increase in social contact behaviour following vaccination would require urgent intervention in the event of emergence of an immune escaping variant. Hence, insights derived from this study could be taken into account when designing, implementing and communicating COVID-19 interventions.

2.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-22277998

RESUMEN

Most countries have enacted some restrictions to reduce social contacts to slow down disease transmission during the COVID-19 pandemic. For nearly two years, individuals likely also adopted new behaviours to avoid pathogen exposure based on personal circumstances. We aimed to understand the way in which different factors affect social contacts - a critical step to improving future pandemic responses. The analysis was based on repeated cross-sectional contact survey data collected in 21 European countries between March 2020 and March 2022. We calculated the mean daily contacts reported using a clustered bootstrap by country and by settings (at home, at work, or in other settings). Where data were available, contact rates during the study period were compared with rates recorded prior to the pandemic. We fitted censored individual-level generalized additive mixed models to examine the effects of various factors on the number of social contacts. The survey recorded 463,336 observations from 96,456 participants. In all countries where comparison data were available, contact rates over the previous two years were substantially lower than those seen prior to the pandemic (approximately from over 10 to <5), predominantly due to fewer contacts outside the home. Government restrictions imposed immediate effect on contacts, and these effects lingered after the restrictions were lifted. Across countries, the relationships between national policy, individual perceptions, or personal circumstances determining contacts varied. Our study, coordinated at the regional level, provides important insights into the understanding of the factors associated with social contacts to support future infectious disease outbreak responses.

3.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-22275775

RESUMEN

BackgroundEvidence and advice for pregnant women evolved during the COVID-19 pandemic. We studied social contact behaviour and vaccine uptake in pregnant women between March 2020 and September 2021 in 19 European countries. MethodsIn each country, repeated online survey data were collected from a panel of nationally-representative participants. We calculated the mean adjusted contacts reported with an individual-level generalized additive mixed model, modelled using the negative binomial distribution and a log link function. Mean proportion of people in isolation or quarantine, and vaccination coverage by pregnancy status and gender were calculated using a clustered bootstrap. FindingsWe recorded 4,129 observations from 1,041 pregnant women, and 115,359 observations from 29,860 non-pregnant individuals aged 18-49. Pregnant women made slightly fewer contacts (3.6, 95%CI=3.5-3.7) than non-pregnant women (4.0, 95%CI=3.9-4.0), driven by fewer work contacts but marginally more contacts in non-essential social settings. Approximately 15-20% pregnant and 5% of non-pregnant individuals reported to be in isolation and quarantine for large parts of the study period. COVID-19 vaccine coverage was higher in pregnant women than in non-pregnant women between January and April 2021. Since May 2021, vaccination in non-pregnant women began to increase and surpassed that in pregnant women. InterpretationSocial contacts and vaccine uptake protect pregnant women and their newborn babies. Recognition of maternal social support need, and efforts to promote the safety and effectiveness of the COVID-19 vaccines during pregnancy are high priorities in this vulnerable group.

4.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21267858

RESUMEN

The Omicron B.1.1.529 SARS-CoV-2 variant was first detected in late November 2021 and has since spread to multiple countries worldwide. We model the potential consequences of the Omicron variant on SARS-CoV-2 transmission and health outcomes in England between December 2021 and April 2022, using a deterministic compartmental model fitted to epidemiological data from March 2020 onwards. Because of uncertainty around the characteristics of Omicron, we explore scenarios varying the extent of Omicrons immune escape and the effectiveness of COVID-19 booster vaccinations against Omicron, assuming the level of Omicrons transmissibility relative to Delta to match the growth in observed S gene target failure data in England. We consider strategies for the re-introduction of control measures in response to projected surges in transmission, as well as scenarios varying the uptake and speed of COVID-19 booster vaccinations and the rate of Omicrons introduction into the population. These results suggest that Omicron has the potential to cause substantial surges in cases, hospital admissions and deaths in populations with high levels of immunity, including England. The reintroduction of additional non-pharmaceutical interventions may be required to prevent hospital admissions exceeding the levels seen in England during the previous peak in winter 2020-2021.

5.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21264701

RESUMEN

BackgroundThis study measured the long-term health-related quality of life of non-hospitalised COVID-19 cases with PCR-confirmed SARS-CoV-2(+) infection using the recommended instrument in England (the EQ-5D). MethodsProspective cohort study of SARS-CoV-2(+) cases aged 12-85 years and followed up for six months from 01 December 2020, with cross-sectional comparison to SARS-CoV-2(-) controls. Main outcomes were loss of quality-adjusted life days (QALDs); physical symptoms; and COVID-19-related private expenditures. We analysed results using multivariable regressions with post-hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls. ResultsOf 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of {pound}18.1 on non-prescription drugs (median: {pound}10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 15.9 (95%-CI: 12.1, 19.7) QALDs, while those reporting symptoms at month 6 lost 34.1 (29.0, 39.2) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 21% of the total COVID-19-related disease burden in England. ConclusionsOne in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms. summaryLosses of health-related quality of life in non-hospitalised COVID-19 cases increase by age and for cases with symptoms after 6 months. At a population level, at least 21% of the total COVID-19-related disease burden in England is attributable to morbidity.

6.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21260277

RESUMEN

BackgroundTo reduce the coronavirus disease burden in England, along with many other countries, the Government implemented a package of non-pharmaceutical interventions (NPIs) that have also impacted other transmissible infectious diseases such as norovirus. It is unclear what future norovirus disease incidence is likely to look like upon lifting these restrictions. MethodsHere we use a mathematical model of norovirus fitted to community incidence data in England to project forward expected incidence based on contact surveys that have been collected throughout 2020-2021. ResultsWe report that susceptibility to norovirus infection has likely increased between March 2020 to mid-2021. Depending upon assumptions of future contact patterns incidence of norovirus that is similar to pre-pandemic levels or an increase beyond what has been previously reported is likely to occur once restrictions are lifted. Should adult contact patterns return to 80% of pre-pandemic levels the incidence of norovirus will be similar to previous years. If contact patterns return to pre-pandemic levels there is a potential for the expected annual incidence to be up to 2-fold larger than in a typical year. The age-specific incidence is similar across all ages. ConclusionsContinued national surveillance for endemic diseases such as norovirus will be essential after NPIs are lifted to allow healthcare services to adequately prepare for a potential increase in cases and hospital pressures beyond what is typically experienced.

7.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21258735

RESUMEN

BackgroundMany countries require incoming air travellers to quarantine on arrival and/or undergo testing to limit importation of SARS-CoV-2. MethodsWe developed mathematical models of SARS-CoV-2 viral load trajectories over the course of infection to assess the effectiveness of quarantine and testing strategies. We consider the utility of pre and post-flight Polymerase Chain Reaction (PCR) and lateral flow testing (LFT) to reduce transmission risk from infected arrivals and to reduce the duration of, or replace, quarantine. We also estimate the effect of each strategy relative to domestic incidence, and limits of achievable risk reduction, for 99 countries where flight data and case numbers are estimated. ResultsWe find that LFTs immediately pre-flight are more effective than PCR tests 3 days before departure in decreasing the number of departing infectious travellers. Pre-flight LFTs and post-flight quarantines, with tests to release, may prevent the majority of transmission from infectious arrivals while reducing the required duration of quarantine; a pre-flight LFT followed by 5 days in quarantine with a test to release would reduce the expected number of secondary cases generated by an infected traveller compared to symptomatic self-isolation alone, Rs, by 85% (95% UI: 74%, 96%) for PCR and 85% (95% UI: 70%, 96%) for LFT, even assuming imperfect adherence to quarantine (28% of individuals) and self-isolation following a positive test (86%). Under the same adherence assumptions, 5 days of daily LFT testing would reduce Rs by 91% (95% UI: 75%, 98%). ConclusionsStrategies aimed at reducing the risk of imported cases should be considered with respect to: domestic incidence, transmission, and susceptibility; measures in place to support quarantining travellers; and incidence of new variants of concern in travellers origin countries. Daily testing with LFTs for 5 days is comparable to 5 days of quarantine with a test on exit or 14 days with no test.

8.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21257973

RESUMEN

BackgroundDuring the COVID-19 pandemic, the UK government imposed public health policies in England to reduce social contacts in hopes of curbing virus transmission. We measured contact patterns weekly from March 2020 to March 2021 to estimate the impact of these policies, covering three national lockdowns interspersed by periods of lower restrictions. MethodsData were collected using online surveys of representative samples of the UK population by age and gender. We calculated the mean daily contacts reported using a (clustered) bootstrap and fitted a censored negative binomial model to estimate age-stratified contact matrices and estimate proportional changes to the basic reproduction number under controlled conditions using the change in contacts as a scaling factor. ResultsThe survey recorded 101,350 observations from 19,914 participants who reported 466,710 contacts over 53 weeks. Contact patterns changed over time and by participants age, personal risk factors, and perception of risk. The mean of reported contacts among adults have reduced compared to previous surveys with adults aged 18 to 59 reporting a mean of 2.39 (95% CI 2.20 - 2.60) contacts to 4.93 (95% CI 4.65 - 5.19) contacts, and the mean contacts for school-age children was 3.07 (95% CI 2.89 - 3.27) to 15.11 (95% CI 13.87 - 16.41). The use of face coverings outside the home has remained high since the government mandated use in some settings in July 2020. ConclusionsThe CoMix survey provides a unique longitudinal data set for a full year since the first lockdown for use in statistical analyses and mathematical modelling of COVID-19 and other diseases. Recorded contacts reduced dramatically compared to pre-pandemic levels, with changes correlated to government interventions throughout the pandemic. Despite easing of restrictions in the summer of 2020, mean reported contacts only returned to about half of that observed pre-pandemic.

9.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21257315

RESUMEN

BackgroundCOVID-19 outbreaks are still occurring in English care homes despite the non-pharmaceutical interventions (NPIs) in place. MethodsWe developed a stochastic compartmental model to simulate the spread of SARS-CoV-2 within an English care home. We quantified the outbreak risk under the NPIs already in place, the role of community prevalence in driving outbreaks, and the relative contribution of all importation routes into the care home. We also considered the potential impact of additional control measures, namely: increasing staff and resident testing frequency, using lateral flow antigen testing (LFD) tests instead of PCR, enhancing infection prevention and control (IPC), increasing the proportion of residents isolated, shortening the delay to isolation, improving the effectiveness of isolation, restricting visitors and limiting staff to working in one care home. FindingsThe model suggests that importation of SARS-CoV-2 by staff, from the community, is the main driver of outbreaks, that importation by visitors or from hospitals is rare, and that the past testing strategy (monthly testing of residents and daily testing of staff by PCR) likely provides negligible benefit in preventing outbreaks. Daily staff testing by LFD was 39% (95% 18-55%) effective in preventing outbreaks at 30 days compared to no testing. InterpretationIncreasing the frequency of testing in staff and enhancing IPC are important to preventing importations to the care home. Further work is needed to understand the impact of vaccination in this population, which is likely to be very effective in preventing outbreaks. FundingThe National Institute for Health Research, European Union Horizon 2020, Canadian Institutes of Health Research, French National Research Agency, UK Medical Research Council. The World Health Organisation funded the development of the COS-LTCF Shiny application. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSCare homes have been identified as being at increased risk of COVID-19 outbreaks, and a number of modelling studies have considered the transmission dynamics of SARS-CoV-2 in this setting. We searched the PubMed database and bioRxiv and medRxivs COVID-19 SARS-CoV-2 preprints for English-language articles on the 11th May 2021, with the search terms ("COVID-19" OR "SARS-CoV-2" OR "coronavirus") AND ("care home" OR "LTCF" OR "long term care facility" OR "nursing home") AND ("model"). In addition to these searches, we identified articles relevant to this work through informal networks. These searches returned 87 studies, of which 12 explicitly modelled SARS-CoV-2 transmission within care homes and explored the effectiveness of non-pharmaceutical interventions in these settings. These studies employed a number of modelling approaches (agent-based and compartmental models) and considered various strategies for mitigating epidemic spread within care homes. Only one of these studies modelled care homes in England, but didnt consider individual care homes as separate entities (transmission between residents in separate facilities was equally likely as within one facility) and only modelled one intervention within the care home: the effect of restricting visitors. Another study modelled a different type of long-term care facility, a rehabilitation facility in France. Other studies modelled care homes in Canada, Scotland, and the US. These modelled care homes were larger than the average English care home. Only one study included importation of SARS-CoV-2 to care homes from hospitals through resident hospitalisation. Added value of this studyWe developed a stochastic compartmental model describing the transmission dynamics of SARS-CoV-2 within English care homes. This study is the first to assess the relative importance of all SARS-CoV-2 importation routes to care homes (including resident hospitalisation) and to quantify the impact of a range of non-pharmaceutical interventions against SARS-CoV-2 particularly for English care homes. We found that community prevalence, through staff importations, was the main driver of outbreaks in care homes at 30 days, not importation from hospital visits nor by visitors. In line with this, we found daily testing of staff to be the most effective testing strategy in preventing outbreaks. We show the previous testing strategy (PCR testing residents once every 28 days and staff once a week) to be ineffective in preventing outbreaks and suggest that more frequent testing of staff is required. Restricting visitors bore little effect on the probability of an outbreak occurring by day 30. Interventions focusing on decreasing the transmission of SARS-CoV-2 in the care home were the most effective in reducing the frequency of outbreaks. We provide a Shiny application for users to explore alternative care home characteristics, outbreak characteristics and interventions. Implications of all the available evidencePreventing the importation of SARS-CoV-2 to care homes from the community through staff is key to preventing outbreaks. Infection prevention and control (IPC) measures targeting transmission within the care home and frequent testing of staff, ideally daily, are the most effective strategies considered. Many care homes in England are currently unable to meet the additional workload daily testing would entail, therefore additional support should be considered to enable these measures. Allowing visitors should be considered given their general positive contribution to residents physical and mental health and likely negligible contribution to outbreaks.

10.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21252964

RESUMEN

BackgroundSchools have been closed in England since the 4th of January 2021 as part of the national restrictions to curb transmission of SARS-CoV-2. The UK Government plans to reopen schools on the 8th of March. Although there is evidence of lower individual-level transmission risk amongst children compared to adults, the combined effects of this with increased contact rates in school settings are not clear. MethodsWe measured social contacts when schools were both open or closed, amongst other restrictions. We combined these data with estimates of the susceptibility and infectiousness of children compared with adults to estimate the impact of reopening schools on the reproduction number. ResultsOur results suggest that reopening all schools could increase R from an assumed baseline of 0.8 to between 1.0 and 1.5, or to between 0.9 and 1.2 reopening primary or secondary schools alone. ConclusionOur results suggest that reopening schools is likely to halt the fall in cases observed in recent months and risks returning to rising infections, but these estimates rely heavily on the current estimates or reproduction number and the current validity of the susceptibility and infectiousness profiles we use.

11.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21250959

RESUMEN

SARS-CoV-2 lineage B.1.1.7, a variant first detected in the United Kingdom in September 20201, has spread to multiple countries worldwide. Several studies have established that B.1.1.7 is more transmissible than preexisting variants, but have not identified whether it leads to any change in disease severity2. We analyse a dataset linking 2,245,263 positive SARS-CoV-2 community tests and 17,452 COVID-19 deaths in England from 1 September 2020 to 14 February 2021. For 1,146,534 (51%) of these tests, the presence or absence of B.1.1.7 can be identified because of mutations in this lineage preventing PCR amplification of the spike gene target (S gene target failure, SGTF1). Based on 4,945 deaths with known SGTF status, we estimate that the hazard of death associated with SGTF is 55% (95% CI 39-72%) higher after adjustment for age, sex, ethnicity, deprivation, care home residence, local authority of residence and test date. This corresponds to the absolute risk of death for a 55-69-year-old male increasing from 0.6% to 0.9% (95% CI 0.8-1.0%) within 28 days after a positive test in the community. Correcting for misclassification of SGTF and missingness in SGTF status, we estimate a 61% (42-82%) higher hazard of death associated with B.1.1.7. Our analysis suggests that B.1.1.7 is not only more transmissible than preexisting SARS-CoV-2 variants, but may also cause more severe illness.

12.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20248822

RESUMEN

A novel SARS-CoV-2 variant, VOC 202012/01 (lineage B.1.1.7), emerged in southeast England in November 2020 and is rapidly spreading towards fixation. Using a variety of statistical and dynamic modelling approaches, we estimate that this variant has a 43-90% (range of 95% credible intervals 38-130%) higher reproduction number than preexisting variants. A fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases. Without stringent control measures, including limited closure of educational institutions and a greatly accelerated vaccine roll-out, COVID-19 hospitalisations and deaths across England in 2021 will exceed those in 2020. Concerningly, VOC 202012/01 has spread globally and exhibits a similar transmission increase (59-74%) in Denmark, Switzerland, and the United States.

13.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20220962

RESUMEN

BackgroundShort-term forecasts of infectious disease can aid situational awareness and planning for outbreak response. Here, we report on multi-model forecasts of Covid-19 in the UK that were generated at regular intervals starting at the end of March 2020, in order to monitor expected healthcare utilisation and population impacts in real time. MethodsWe evaluated the performance of individual model forecasts generated between 24 March and 14 July 2020, using a variety of metrics including the weighted interval score as well as metrics that assess the calibration, sharpness, bias and absolute error of forecasts separately. We further combined the predictions from individual models into ensemble forecasts using a simple mean as well as a quantile regression average that aimed to maximise performance. We compared model performance to a null model of no change. ResultsIn most cases, individual models performed better than the null model, and ensembles models were well calibrated and performed comparatively to the best individual models. The quantile regression average did not noticeably outperform the mean ensemble. ConclusionsEnsembles of multi-model forecasts can inform the policy response to the Covid-19 pandemic by assessing future resource needs and expected population impact of morbidity and mortality.

14.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20200857

RESUMEN

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.

15.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20167965

RESUMEN

BackgroundSchool closures are a well-established non-pharmaceutical intervention in the event of infectious disease outbreaks, and have been implemented in many countries across the world, including the UK, to slow down the spread of SARS-CoV-2. As governments begin to relax restrictions on public life there is a need to understand the potential impact that reopening schools may have on transmission. MethodsWe used data provided by the UK Department for Education to construct a network of English schools, connected through pairs of pupils resident at the same address. We used the network to evaluate the potential for transmission between schools, and for long range propagation across the network, under different reopening scenarios. ResultsAmongst the options evaluated we found that reopening only Reception, Year 1 and Year 6 (4-6 and 10-11 year olds) resulted in the lowest risk of transmission between schools, with outbreaks within a single school unlikely to result in outbreaks in adjacent schools in the network. The additional reopening of Years 10 and 12 (14-15 and 16-17 year olds) resulted in an increase in the risk of transmission between schools comparable to reopening all primary school years (4-11 year olds). However, the majority of schools presented low risk of initiating widespread transmission through the school system. Reopening all secondary school years (11-18 year olds) resulted in large potential outbreak clusters putting up to 50% of households connected to schools at risk of infection if sustained transmission within schools was possible. ConclusionsReopening secondary school years is likely to have a greater impact on community transmission than reopening primary schools in England. Keeping transmission within schools limited is essential for reducing the risk of large outbreaks amongst school-aged children and their household members.

16.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20177808

RESUMEN

Previous work has indicated that contact tracing and isolation of index case and quarantine of potential secondary cases can, in concert with physical distancing measures, be an effective strategy for reducing transmission of SARS-CoV-2 (1). Currently, contacts traced manually through the NHS Test and Trace scheme in the UK are asked to self-isolate for 14 days from the day they were exposed to the index case, which represents the upper bound for the incubation period (2). However, following previous work on screening strategies for air travellers (3,4) it may be possible that this quarantine period could be reduced if combined with PCR testing. Adapting the simulation model for contact tracing, we find that quarantine periods of at least 10 days combined with a PCR test on day 9 may largely emulate the results from a 14-day quarantine period in terms of the averted transmission potential from secondary cases (72% (95%UI: 3%, 100%) vs 75% (4%, 100%), respectively). These results assume the delays from testing index cases and tracing their contacts are minimised (no longer than 4.5 days on average). If secondary cases are traced and quarantined 1 day earlier on average, shorter quarantine periods of 8 days with a test on day 7 (76% (7%, 100%)) approach parity with the 14 day quarantine period with a 1 day longer delay to the index cases test. However, the risk of false-negative PCR tests early in a traced cases infectious period likely prevents the use of testing to reduce quarantine periods further than this, and testing immediately upon tracing, with release if negative, will avert just 17% of transmission potential on average. In conclusion, the use of PCR testing is an effective strategy for reducing quarantine periods for secondary cases, while still reducing transmission of SARS-CoV-2, especially if delays in the test and trace system can be reduced, and may improve quarantine compliance rates.

17.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20161281

RESUMEN

To mitigate SARS-CoV-2 transmission risks from international travellers, many countries currently use a combination of up to 14 days of self-quarantine on arrival and testing for active infection. We used a simulation model of air travellers arriving to the UK from the EU or the USA and the timing of their stages of infection to evaluate the ability of these strategies to reduce the risk of seeding community transmission. We find that a quarantine period of 8 days on arrival with a PCR test on day 7 (with a 1-day delay for test results) can reduce the number of infectious arrivals released into the community by a median 94% compared to a no quarantine, no test scenario. This reduction is similar to that achieved by a 14-day quarantine period (median 99% reduction). Shorter quarantine periods still can prevent a substantial amount of transmission; all strategies in which travellers spend at least 5 days (the mean incubation period) in quarantine and have at least one negative test before release are highly effective (e.g. a test on day 5 with release on day 6 results in a median 88% reduction in transmission potential). Without intervention, the current high prevalence in the US (40 per 10,000) results in a higher expected number of infectious arrivals per week (up to 23) compared to the EU (up to 12), despite an estimated 8 times lower volume of travel in July 2020. Requiring a 14-day quarantine period likely results in less than 1 infectious traveller each entering the UK per week from the EU and the USA (97.5th percentile). We also find that on arrival the transmission risk is highest from pre-symptomatic travellers; quarantine policies will shift this risk increasingly towards asymptomatic infections if eventually-symptomatic individuals self-isolate after the onset of symptoms. As passenger numbers recover, strategies to reduce the risk of re-introduction should be evaluated in the context of domestic SARS-CoV-2 incidence, preparedness to manage new outbreaks, and the economic and psychological impacts of quarantine.

18.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20049908

RESUMEN

BackgroundNon-pharmaceutical interventions have been implemented to reduce transmission of SARS-CoV-2 in the UK. Projecting the size of an unmitigated epidemic and the potential effect of different control measures has been critical to support evidence-based policymaking during the early stages of the epidemic. MethodsWe used a stochastic age-structured transmission model to explore a range of intervention scenarios, including the introduction of school closures, social distancing, shielding of elderly groups, self-isolation of symptomatic cases, and extreme "lockdown"-type restrictions. We simulated different durations of interventions and triggers for introduction, as well as combinations of interventions. For each scenario, we projected estimated new cases over time, patients requiring inpatient and critical care (intensive care unit, ICU) treatment, and deaths. FindingsWe found that mitigation measures aimed at reducing transmission would likely have decreased the reproduction number, but not sufficiently to prevent ICU demand from exceeding NHS availability. To keep ICU bed demand below capacity in the model, more extreme restrictions were necessary. In a scenario where "lockdown"-type interventions were put in place to reduce transmission, these interventions would need to be in place for a large proportion of the coming year in order to prevent healthcare demand exceeding availability. InterpretationThe characteristics of SARS-CoV-2 mean that extreme measures are likely required to bring the epidemic under control and to prevent very large numbers of deaths and an excess of demand on hospital beds, especially those in ICUs. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSAs countries have moved from early containment efforts to planning for the introduction of large-scale non-pharmaceutical interventions to control COVID-19 outbreaks, epidemic modelling studies have explored the potential for extensive social distancing measures to curb transmission. However, it remains unclear how different combinations of interventions, timings, and triggers for the introduction and lifting of control measures may affect the impact of the epidemic on health services, and what the range of uncertainty associated with these estimates would be. Added value of this studyUsing a stochastic, age-structured epidemic model, we explored how eight different intervention scenarios could influence the number of new cases and deaths, as well as intensive care beds required over the projected course of the epidemic. We also assessed the potential impact of local versus national targeting of interventions, reduction in leisure events, impact of increased childcare by grandparents, and timing of triggers for different control measures. We simulated multiple realisations for each scenario to reflect uncertainty in possible epidemic trajectories. Implications of all the available evidenceOur results support early modelling findings, and subsequent empirical observations, that in the absence of control measures, a COVID-19 epidemic could quickly overwhelm a healthcare system. We found that even a combination of moderate interventions - such as school closures, shielding of older groups and self-isolation - would be unlikely to prevent an epidemic that would far exceed available ICU capacity in the UK. Intermittent periods of more intensive lockdown-type measures are predicted to be effective for preventing the healthcare system from being overwhelmed.

19.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20049023

RESUMEN

BackgroundTo mitigate and slow the spread of COVID-19, many countries have adopted unprecedented physical distancing policies, including the UK. We evaluate whether these measures might be sufficient to control the epidemic by estimating their impact on the reproduction number (R0, the average number of secondary cases generated per case). MethodsWe asked a representative sample of UK adults about their contact patterns on the previous day. The questionnaire documents the age and location of contacts and as well as a measure of their intimacy (whether physical contact was made or not). In addition, we asked about adherence to different physical distancing measures. The first surveys were sent on Tuesday 24th March, one day after a " lockdown" was implemented across the UK. We compared measured contact patterns during the " lockdown" to patterns of social contact made during a non-epidemic period. By comparing these, we estimated the change in reproduction number as a consequence of the physical distancing measures imposed. We used a meta-analysis of published estimates to inform our estimates of the reproduction number before interventions were put in place. FindingsWe found a 73% reduction in the average daily number of contacts observed per participant (from 10.2 to 2.9). This would be sufficient to reduce R0 from 2.6 prior to lockdown to 0.62 (95% confidence interval [CI] 0.37 - 0.89) after the lockdown, based on all types of contact and 0.37 (95% CI = 0.22 - 0.53) for physical contacts only. InterpretationThe physical distancing measures adopted by the UK public have substantially reduced contact levels and will likely lead to a substantial impact and a decline in cases in the coming weeks. However, this projected decline in incidence will not occur immediately as there are significant delays between infection, the onset of symptomatic disease and hospitalisation, as well as further delays to these events being reported. Tracking behavioural change can give a more rapid assessment of the impact of physical distancing measures than routine epidemiological surveillance. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSMany governments have adopted physical distancing measures to mitigate the impact of the COVID-19 pandemic. However, it is unclear to what extent these measures reduce the number of contacts and therefore transmission. We searched PubMed and medRxiv on March 28, 2020, with the terms " (coronavirus OR COVID-19 OR influenza) AND ((school OR work) AND (closure OR holiday)) AND (contact OR mixing)" and identified 59 and 17 results, respectively. Only one study conducted in China during the COVID-19 pandemic reported a reduction in daily contacts outside the home during the period of " lockdown". We found no other published articles that empirically quantify the impact of these measures on age- and location-specific mixing patterns. Added value of this studyBy surveying adults behaviour in the UK during a period of stringent physical distancing (" lockdown") and comparing the results to previously collected data, we found a large reduction in daily contacts particularly outside the home, resulting in a marked reduction in the estimated reproduction number from 2.6 to 0.62 (95% bootstrapped confidence interval [CI] 0.37 - 0.89). This method allows for rapid assessment of changes in the reproduction number that is unaffected by reporting delays. Implications of all the available evidenceChanges in human contact behaviour drive respiratory infection rates. Understanding these changes at different stages of the COVID-19 pandemic allows us to rapidly quantify the impact of physical distancing measures on the transmission of pathogens.

20.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20021162

RESUMEN

BackgroundTo assess the viability of isolation and contact tracing to control onwards transmission from imported cases of 2019-nCoV. MethodsWe developed a stochastic transmission model, parameterised to the 2019-nCoV outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a 2019 nCoV-like pathogen. We considered scenarios that varied in: the number of initial cases; the basic reproduction number R0; the delay from symptom onset to isolation; the probability contacts were traced; the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort. FindingsWhile simulated outbreaks starting with only 5 initial cases, R0 of 1.5 and little transmission before symptom onset could be controlled even with low contact tracing probability, the prospects of controlling an outbreak dramatically dropped with the number of initial cases, with higher R0, and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R0 of 1.5 were controllable with under 50% of contacts successfully traced. For R0 of 2.5 and 3.5, more than 70% and 90% of contacts respectively had to be traced to control the majority of outbreaks. The delay between symptom onset and isolation played the largest role in determining whether an outbreak was controllable for lower values of R0. For higher values of R0 and a large initial number of cases, contact tracing and isolation was only potentially feasible when less than 1% of transmission occurred before symptom onset. InterpretationWe found that in most scenarios contact tracing and case isolation alone is unlikely to control a new outbreak of 2019-nCov within three months. The probability of control decreases with longer delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts. FundingWellcome Trust, Global Challenges Research Fund, and HDR UK. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSContact tracing and isolation of cases is a commonly used intervention for controlling infectious disease outbreaks. This intervention can be effective, but may require intensive public health effort and cooperation to effectively reach and monitor all contacts. When the pathogen has infectiousness before symptom onset, control of outbreaks using contact tracing and isolation is more challenging. Added value of this studyThis study uses a mathematical model to assess the feasibility of contact tracing and case isolation to control outbreaks of 2019-nCov, a newly emerged pathogen. We used disease transmission characteristics specific to the pathogen and therefore give the best available evidence if contact tracing and isolation can achieve control of outbreaks. Implications of all the available evidenceContact tracing and isolation may not contain outbreaks of 2019-nCoV unless very high levels of contact tracing are achieved. Even in this case, if there is asymptomatic transmission, or a high fraction of transmission before onset of symptoms, this strategy may not achieve control within three months.

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