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1.
JMIR Res Protoc ; 2022 Apr 21.
Article in English | MEDLINE | ID: covidwho-1875278

ABSTRACT

BACKGROUND: One of the most debated questions in the COVID-19 pandemic has been the role of schools in SARS-CoV-2 transmission. The COVID-19 Schools Infection Survey (SIS) aims to provide much-needed evidence addressing this. OBJECTIVE: This paper presents the study protocol and participation profile for the SIS study, aimed at assessing the role of schools in SARS-CoV-2 infection and transmission within school settings, and investigating how transmission within and from schools could be mitigated through implementation of school COVID-19 control measures. METHODS: SIS was a multisite, prospective, observational cohort study conducted in a stratified random sample of primary and secondary schools in selected local authorities in England. Six bio-behavioural surveys were planned among participating students and staff during the 2020/21 academic year, between November 2020 and July 2021. Key measurements were SARS-CoV-2 virus prevalence, assessed by nasal swab polymerase chain reaction; anti-SARS-CoV-2 (nucleocapsid protein) antibody prevalence and conversion, assessed in finger-prick-blood for staff and oral-fluid for students; student and staff school attendance rates; feasibility and acceptability of school-level implementation of SARS-CoV-2 control measures; and investigation of selected school outbreaks. The study received approvals from the UK Health Security Agency Research Support and Governance Office (NR0237) and London School of Hygiene & Tropical Medicine Ethics Review Committee (ref:22657). RESULTS: Data collection and laboratory analyses were completed by September 2021. A total of 22,585 individuals: 1,891 staff and 4,654 students from 59 primary schools and 5,852 staff and 10,188 students from 97 secondary schools participated in at least one survey. On average, across survey rounds, staff and student participation rates were 45.2% and 16.4% respectively in primary schools and 30.0% and 15.2% in secondary schools. While primary student participation increased over time, and secondary student participation remained reasonably consistent, staff participation declined across rounds, especially for secondary school staff (41.7% in Round 1 and 22.1% in Round 6). While staff participation overall was generally reflective of the eligible staff population, student participation was higher in schools with low absenteeism, a lower proportion of students eligible for free school meals and from schools in the least deprived locations (in primary schools 9.6% participants were from schools in the least deprived quintile compared with 5.7% of eligible students). CONCLUSIONS: We outline the study design, methods and participation, and reflect on the strengths of the SIS study as well as the practical challenges encountered, and the strategies implemented to address these challenges. The SIS study, by measuring current and incident infection over time, alongside the implementation of control measures in schools, across a range of settings in England, aims to inform national guidance and public health policy for educational settings.

2.
Clin Infect Dis ; 2022 Mar 05.
Article in English | MEDLINE | ID: covidwho-1852990

ABSTRACT

BACKGROUND: We aimed to quantify the unknown losses in health-related quality of life of COVID-19 cases using quality-adjusted life days (QALDs) and the recommended EQ-5D instrument in England. METHODS: Prospective cohort study of non-hospitalised, PCR-confirmed SARSCoV2(+) cases aged 12-85 years and followed up for six months from 01 December 2020, with cross-sectional comparison to SARSCoV2() controls. Main outcomes were QALD losses; 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. RESULTS: Of 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 £18.1 on non-prescription drugs (median: £10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 13.7 (95%-CI: 9.7, 17.7) QALDs, while those reporting symptoms at month 6 lost 32.9 (24.5, 37.6) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 18% of the total COVID-19-related disease burden in England. CONCLUSIONS: One 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.

3.
BMC Infect Dis ; 22(1): 324, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1770492

ABSTRACT

BACKGROUND: COVID-19 outbreaks still occur in English care homes despite the interventions in place. METHODS: We developed a stochastic compartmental model to simulate the spread of SARS-CoV-2 within an English care home. We quantified the outbreak risk with baseline non-pharmaceutical interventions (NPIs) already in place, the role of community prevalence in driving outbreaks, and the relative contribution of all importation routes into a fully susceptible care home. We also considered the potential impact of additional control measures in care homes with and without immunity, namely: increasing staff and resident testing frequency, using lateral flow antigen testing (LFD) tests instead of polymerase chain reaction (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. We additionally present a Shiny application for users to apply this model to their facility of interest, specifying care home, outbreak and intervention characteristics. RESULTS: The 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. CONCLUSIONS: Increasing 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.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , Disease Outbreaks/prevention & control , Humans , Infection Control , Vaccination
4.
Sci Rep ; 12(1): 5192, 2022 03 25.
Article in English | MEDLINE | ID: covidwho-1764203

ABSTRACT

Human behaviour is known to be crucial in the propagation of infectious diseases through respiratory or close-contact routes like the current SARS-CoV-2 virus. Intervention measures implemented to curb the spread of the virus mainly aim at limiting the number of close contacts, until vaccine roll-out is complete. Our main objective was to assess the relationships between SARS-CoV-2 perceptions and social contact behaviour in Belgium. Understanding these relationships is crucial to maximize interventions' effectiveness, e.g. by tailoring public health communication campaigns. In this study, we surveyed a representative sample of adults in Belgium in two longitudinal surveys (survey 1 in April 2020 to August 2020, and survey 2 in November 2020 to April 2021). Generalized linear mixed effects models were used to analyse the two surveys. Participants with low and neutral perceptions on perceived severity made a significantly higher number of social contacts as compared to participants with high levels of perceived severity after controlling for other variables. Our results highlight the key role of perceived severity on social contact behaviour during a pandemic. Nevertheless, additional research is required to investigate the impact of public health communication on severity of COVID-19 in terms of changes in social contact behaviour.


Subject(s)
COVID-19 , Communicable Diseases , Adult , COVID-19/epidemiology , COVID-19/prevention & control , Humans , Pandemics , Public Health , SARS-CoV-2
5.
PLoS Negl Trop Dis ; 16(2): e0010163, 2022 02.
Article in English | MEDLINE | ID: covidwho-1745362

ABSTRACT

BACKGROUND: The evaluation of ring vaccination and other outbreak-containment interventions during severe and rapidly-evolving epidemics presents a challenge for the choice of a feasible study design, and subsequently, for the estimation of statistical power. To support a future evaluation of a case-area targeted intervention against cholera, we have proposed a prospective observational study design to estimate the association between the strength of implementation of this intervention across several small outbreaks (occurring within geographically delineated clusters around primary and secondary cases named 'rings') and its effectiveness (defined as a reduction in cholera incidence). We describe here a strategy combining mathematical modelling and simulation to estimate power for a prospective observational study. METHODOLOGY AND PRINCIPAL FINDINGS: The strategy combines stochastic modelling of transmission and the direct and indirect effects of the intervention in a set of rings, with a simulation of the study analysis on the model results. We found that targeting 80 to 100 rings was required to achieve power ≥80%, using a basic reproduction number of 2.0 and a dispersion coefficient of 1.0-1.5. CONCLUSIONS: This power estimation strategy is feasible to implement for observational study designs which aim to evaluate outbreak containment for other pathogens in geographically or socially defined rings.


Subject(s)
Cholera/epidemiology , Computer Simulation , Basic Reproduction Number , Disease Outbreaks , Humans , Models, Theoretical , Prospective Studies
6.
BMJ Open ; 12(3): e055596, 2022 03 08.
Article in English | MEDLINE | ID: covidwho-1736069

ABSTRACT

INTRODUCTION: Ebola virus disease (EVD) continues to be a significant public health problem in sub-Saharan Africa, especially in the Democratic Republic of the Congo (DRC). Large-scale vaccination during outbreaks may reduce virus transmission. We established a large population-based clinical trial of a heterologous, two-dose prophylactic vaccine during an outbreak in eastern DRC to determine vaccine effectiveness. METHODS AND ANALYSIS: This open-label, non-randomised, population-based trial enrolled eligible adults and children aged 1 year and above. Participants were offered the two-dose candidate EVD vaccine regimen VAC52150 (Ad26.ZEBOV, Modified Vaccinia Ankara (MVA)-BN-Filo), with the doses being given 56 days apart. After vaccination, serious adverse events (SAEs) were passively recorded until 1 month post dose 2. 1000 safety subset participants were telephoned at 1 month post dose 2 to collect SAEs. 500 pregnancy subset participants were contacted to collect SAEs at D7 and D21 post dose 1 and at D7, 1 month, 3 months and 6 months post dose 2, unless delivery was before these time points. The first 100 infants born to these women were given a clinical examination 3 months post delivery. Due to COVID-19 and temporary suspension of dose 2 vaccinations, at least 50 paediatric and 50 adult participants were enrolled into an immunogenicity subset to examine immune responses following a delayed second dose. Samples collected predose 2 and at 21 days post dose 2 will be tested using the Ebola viruses glycoprotein Filovirus Animal Non-Clinical Group ELISA. For qualitative research, in-depth interviews and focus group discussions were being conducted with participants or parents/care providers of paediatric participants. ETHICS AND DISSEMINATION: Approved by Comité National d'Ethique et de la Santé du Ministère de la santé de RDC, Comité d'Ethique de l'Ecole de Santé Publique de l'Université de Kinshasa, the LSHTM Ethics Committee and the MSF Ethics Review Board. Findings will be presented to stakeholders and conferences. Study data will be made available for open access. TRIAL REGISTRATION NUMBER: NCT04152486.


Subject(s)
Ebola Vaccines , Hemorrhagic Fever, Ebola , Adult , COVID-19 , Child , Clinical Trials, Phase III as Topic , Democratic Republic of the Congo/epidemiology , Ebola Vaccines/adverse effects , Female , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/prevention & control , Humans , Immunization Schedule
7.
PLoS Med ; 19(3): e1003907, 2022 03.
Article in English | MEDLINE | ID: covidwho-1714705

ABSTRACT

BACKGROUND: During the Coronavirus Disease 2019 (COVID-19) pandemic, the United Kingdom government imposed public health policies in England to reduce social contacts in hopes of curbing virus transmission. We conducted a repeated cross-sectional study to measure contact patterns weekly from March 2020 to March 2021 to estimate the impact of these policies, covering 3 national lockdowns interspersed by periods of less restrictive policies. METHODS AND FINDINGS: The repeated cross-sectional survey data were collected using online surveys of representative samples of the UK population by age and gender. Survey participants were recruited by the online market research company Ipsos MORI through internet-based banner and social media ads and email campaigns. The participant data used for this analysis are restricted to those who reported living in England. 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. To put the findings in perspective, we discuss contact rates recorded throughout the year in terms of previously recorded rates from the POLYMOD study social contact study. The survey recorded 101,350 observations from 19,914 participants who reported 466,710 contacts over 53 weeks. We observed changes in social contact patterns in England over time and by participants' age, personal risk factors, and perception of risk. The mean reported contacts for adults 18 to 59 years old ranged between 2.39 (95% confidence interval [CI] 2.20 to 2.60) contacts and 4.93 (95% CI 4.65 to 5.19) contacts during the study period. The mean contacts for school-age children (5 to 17 years old) ranged from 3.07 (95% CI 2.89 to 3.27) to 15.11 (95% CI 13.87 to 16.41). This demonstrates a sustained decrease in social contacts compared to a mean of 11.08 (95% CI 10.54 to 11.57) contacts per participant in all age groups combined as measured by the POLYMOD social contact study in 2005 to 2006. Contacts measured during periods of lockdowns were lower than in periods of eased social restrictions. The use of face coverings outside the home has remained high since the government mandated use in some settings in July 2020. The main limitations of this analysis are the potential for selection bias, as participants are recruited through internet-based campaigns, and recall bias, in which participants may under- or overreport the number of contacts they have made. CONCLUSIONS: In this study, we observed that recorded contacts reduced dramatically compared to prepandemic levels (as measured in the POLYMOD study), with changes in reported contacts correlated with government interventions throughout the pandemic. Despite easing of restrictions in the summer of 2020, the mean number of reported contacts only returned to about half of that observed prepandemic at its highest recorded level. The CoMix survey provides a unique repeated cross-sectional data set for a full year in England, from the first day of the first lockdown, for use in statistical analyses and mathematical modelling of COVID-19 and other diseases.


Subject(s)
COVID-19/psychology , Social Interaction , Adolescent , Adult , Aged , Attitude to Health , Cross-Sectional Studies , England , Female , Humans , Male , Middle Aged , Models, Psychological , Pandemics , Surveys and Questionnaires , Young Adult
8.
BMC Med ; 19(1): 299, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1511749

ABSTRACT

BACKGROUND: To 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. METHODS: Here 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. RESULTS: We report that susceptibility to norovirus infection has likely increased between March 2020 and 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. CONCLUSIONS: Continued 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.


Subject(s)
COVID-19 , Norovirus , England/epidemiology , Humans , Models, Theoretical , SARS-CoV-2
9.
BMC Med ; 19(1): 254, 2021 09 29.
Article in English | MEDLINE | ID: covidwho-1496170

ABSTRACT

BACKGROUND: SARS-CoV-2 dynamics are driven by human behaviour. Social contact data are of utmost importance in the context of transmission models of close-contact infections. METHODS: Using online representative panels of adults reporting on their own behaviour as well as parents reporting on the behaviour of one of their children, we collect contact mixing (CoMix) behaviour in various phases of the COVID-19 pandemic in over 20 European countries. We provide these timely, repeated observations using an online platform: SOCRATES-CoMix. In addition to providing cleaned datasets to researchers, the platform allows users to extract contact matrices that can be stratified by age, type of day, intensity of the contact and gender. These observations provide insights on the relative impact of recommended or imposed social distance measures on contacts and can inform mathematical models on epidemic spread. CONCLUSION: These data provide essential information for policymakers to balance non-pharmaceutical interventions, economic activity, mental health and wellbeing, during vaccine rollout.


Subject(s)
COVID-19 , Pandemics , Adult , Child , Europe/epidemiology , Humans , Models, Theoretical , SARS-CoV-2
10.
Science ; 372(6538)2021 04 09.
Article in English | MEDLINE | ID: covidwho-1476375

ABSTRACT

A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, VOC 202012/01 (lineage B.1.1.7), emerged in southeast England in September 2020 and is rapidly spreading toward fixation. Using a variety of statistical and dynamic modeling approaches, we estimate that this variant has a 43 to 90% (range of 95% credible intervals, 38 to 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 rollout, COVID-19 hospitalizations and deaths across England in the first 6 months of 2021 were projected to exceed those in 2020. VOC 202012/01 has spread globally and exhibits a similar transmission increase (59 to 74%) in Denmark, Switzerland, and the United States.


Subject(s)
COVID-19/transmission , COVID-19/virology , SARS-CoV-2 , Adolescent , Adult , Aged , Aged, 80 and over , Basic Reproduction Number , COVID-19/epidemiology , COVID-19/mortality , COVID-19 Vaccines , Child , Child, Preschool , Communicable Disease Control , England/epidemiology , Europe/epidemiology , Female , Humans , Infant , Male , Middle Aged , Models, Theoretical , Mutation , SARS-CoV-2/genetics , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity , Severity of Illness Index , Socioeconomic Factors , United States/epidemiology , Viral Load , Young Adult
11.
Euro Surveill ; 26(39)2021 09.
Article in English | MEDLINE | ID: covidwho-1448678

ABSTRACT

BackgroundTo mitigate SARS-CoV-2 transmission risks from international air travellers, many countries implemented a combination of up to 14 days of self-quarantine upon arrival plus PCR testing in the early stages of the COVID-19 pandemic in 2020.AimTo assess the effectiveness of quarantine and testing of international travellers to reduce risk of onward SARS-CoV-2 transmission into a destination country in the pre-COVID-19 vaccination era.MethodsWe used a simulation model of air travellers arriving in the United Kingdom from the European Union or the United States, incorporating timing of infection stages while varying quarantine duration and timing and number of PCR tests.ResultsQuarantine upon arrival with a PCR test on day 7 plus a 1-day delay for results can reduce the number of infectious arriving travellers released into the community by a median 94% (95% uncertainty interval (UI): 89-98) compared with a no quarantine/no test scenario. This reduction is similar to that achieved by a 14-day quarantine period (median > 99%; 95% UI: 98-100). Even shorter quarantine periods can prevent a substantial amount of transmission; all strategies in which travellers spend at least 5 days (mean incubation period) in quarantine and have at least one negative test before release are highly effective (median reduction 89%; 95% UI: 83-95)).ConclusionThe effect of different screening strategies impacts asymptomatic and symptomatic individuals differently. The choice of an optimal quarantine and testing strategy for unvaccinated air travellers may vary based on the number of possible imported infections relative to domestic incidence.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Vaccines , Humans , Pandemics , Quarantine , United Kingdom/epidemiology
12.
BMC Med ; 19(1): 233, 2021 09 10.
Article in English | MEDLINE | ID: covidwho-1403237

ABSTRACT

BACKGROUND: Schools were closed in England on 4 January 2021 as part of increased national restrictions to curb transmission of SARS-CoV-2. The UK government reopened schools on 8 March. Although there was evidence of lower individual-level transmission risk amongst children compared to adults, the combined effects of this with increased contact rates in school settings and the resulting impact on the overall transmission rate in the population were not clear. METHODS: We measured social contacts of > 5000 participants weekly from March 2020, including periods when schools were both open and 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. RESULTS: Our analysis indicates that reopening all schools under the same measures as previous periods that combined lockdown with face-to-face schooling would be likely to increase the reproduction number substantially. Assuming a baseline of 0.8, we estimated a likely increase to between 1.0 and 1.5 with the reopening of all schools or to between 0.9 and 1.2 reopening primary or secondary schools alone. CONCLUSION: Our results suggest that reopening schools would likely halt the fall in cases observed between January and March 2021 and would risk a return to rising infections, but these estimates relied heavily on the latest estimates or reproduction number and the validity of the susceptibility and infectiousness profiles we used at the time of reopening.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Child , Communicable Disease Control , England/epidemiology , Humans , Reproduction , Schools
13.
Philos Trans R Soc Lond B Biol Sci ; 376(1829): 20200266, 2021 07 19.
Article in English | MEDLINE | ID: covidwho-1309686

ABSTRACT

As several countries gradually release social distancing measures, rapid detection of new localized COVID-19 hotspots and subsequent intervention will be key to avoiding large-scale resurgence of transmission. We introduce ASMODEE (automatic selection of models and outlier detection for epidemics), a new tool for detecting sudden changes in COVID-19 incidence. Our approach relies on automatically selecting the best (fitting or predicting) model from a range of user-defined time series models, excluding the most recent data points, to characterize the main trend in an incidence. We then derive prediction intervals and classify data points outside this interval as outliers, which provides an objective criterion for identifying departures from previous trends. We also provide a method for selecting the optimal breakpoints, used to define how many recent data points are to be excluded from the trend fitting procedure. The analysis of simulated COVID-19 outbreaks suggests ASMODEE compares favourably with a state-of-art outbreak-detection algorithm while being simpler and more flexible. As such, our method could be of wider use for infectious disease surveillance. We illustrate ASMODEE using publicly available data of National Health Service (NHS) Pathways reporting potential COVID-19 cases in England at a fine spatial scale, showing that the method would have enabled the early detection of the flare-ups in Leicester and Blackburn with Darwen, two to three weeks before their respective lockdown. ASMODEE is implemented in the free R package trendbreaker. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.


Subject(s)
COVID-19/epidemiology , Models, Theoretical , Pandemics , SARS-CoV-2/pathogenicity , Algorithms , COVID-19/transmission , COVID-19/virology , Communicable Disease Control , England/epidemiology , Humans , United Kingdom/epidemiology
14.
Lancet Public Health ; 6(3): e175-e183, 2021 03.
Article in English | MEDLINE | ID: covidwho-1164723

ABSTRACT

BACKGROUND: In most countries, contacts of confirmed COVID-19 cases are asked to quarantine for 14 days after exposure to limit asymptomatic onward transmission. While theoretically effective, this policy places a substantial social and economic burden on both the individual and wider society, which might result in low adherence and reduced policy effectiveness. We aimed to assess the merit of testing contacts to avert onward transmission and to replace or reduce the length of quarantine for uninfected contacts. METHODS: We used an agent-based model to simulate the viral load dynamics of exposed contacts, and their potential for onward transmission in different quarantine and testing strategies. We compared the performance of quarantines of differing durations, testing with either PCR or lateral flow antigen (LFA) tests at the end of quarantine, and daily LFA testing without quarantine, against the current 14-day quarantine strategy. We also investigated the effect of contact tracing delays and adherence to both quarantine and self-isolation on the effectiveness of each strategy. FINDINGS: Assuming moderate levels of adherence to quarantine and self-isolation, self-isolation on symptom onset alone can prevent 37% (95% uncertainty interval [UI] 12-56) of onward transmission potential from secondary cases. 14 days of post-exposure quarantine reduces transmission by 59% (95% UI 28-79). Quarantine with release after a negative PCR test 7 days after exposure might avert a similar proportion (54%, 95% UI 31-81; risk ratio [RR] 0·94, 95% UI 0·62-1·24) to that of the 14-day quarantine period, as would quarantine with a negative LFA test 7 days after exposure (50%, 95% UI 28-77; RR 0·88, 0·66-1·11) or daily testing without quarantine for 5 days after tracing (50%, 95% UI 23-81; RR 0·88, 0·60-1·43) if all tests are returned negative. A stronger effect might be possible if individuals isolate more strictly after a positive test and if contacts can be notified faster. INTERPRETATION: Testing might allow for a substantial reduction in the length of, or replacement of, quarantine with a small excess in transmission risk. Decreasing test and trace delays and increasing adherence will further increase the effectiveness of these strategies. Further research is required to empirically evaluate the potential costs (increased transmission risk, false reassurance) and benefits (reduction in the burden of quarantine, increased adherence) of such strategies before adoption as policy. FUNDING: National Institute for Health Research, UK Research and Innovation, Wellcome Trust, EU Horizon 2021, and the Bill & Melinda Gates Foundation.


Subject(s)
COVID-19 Testing/methods , COVID-19/prevention & control , Contact Tracing , Quarantine , COVID-19/epidemiology , Humans , Models, Theoretical
15.
Nat Commun ; 12(1): 1942, 2021 03 29.
Article in English | MEDLINE | ID: covidwho-1157906

ABSTRACT

In early 2020 many countries closed schools to mitigate the spread of SARS-CoV-2. Since then, governments have sought to relax the closures, engendering a need to understand associated risks. Using address records, we construct a network of schools in England connected through pupils who share households. We evaluate the risk of transmission between schools under different reopening scenarios. We show that whilst reopening select year-groups causes low risk of large-scale transmission, reopening secondary schools could result in outbreaks affecting up to 2.5 million households if unmitigated, highlighting the importance of careful monitoring and within-school infection control to avoid further school closures or other restrictions.


Subject(s)
COVID-19/transmission , Family Characteristics , Schools/organization & administration , Adolescent , COVID-19/epidemiology , COVID-19/virology , Child , Child, Preschool , Disease Transmission, Infectious/prevention & control , England/epidemiology , Humans , Pandemics , Risk Assessment , Risk Factors , SARS-CoV-2/isolation & purification , Schools/statistics & numerical data
16.
Lancet Infect Dis ; 21(7): 962-974, 2021 07.
Article in English | MEDLINE | ID: covidwho-1145004

ABSTRACT

BACKGROUND: In response to the COVID-19 pandemic, the UK first adopted physical distancing measures in March, 2020. Vaccines against SARS-CoV-2 became available in December, 2020. We explored the health and economic value of introducing SARS-CoV-2 immunisation alongside physical distancing in the UK to gain insights about possible future scenarios in a post-vaccination era. METHODS: We used an age-structured dynamic transmission and economic model to explore different scenarios of UK mass immunisation programmes over 10 years. We compared vaccinating 75% of individuals aged 15 years or older (and annually revaccinating 50% of individuals aged 15-64 years and 75% of individuals aged 65 years or older) to no vaccination. We assumed either 50% vaccine efficacy against disease and 45-week protection (worst-case scenario) or 95% vaccine efficacy against infection and 3-year protection (best-case scenario). Natural immunity was assumed to wane within 45 weeks. We also explored the additional impact of physical distancing on vaccination by assuming either an initial lockdown followed by voluntary physical distancing, or an initial lockdown followed by increased physical distancing mandated above a certain threshold of incident daily infections. We considered benefits in terms of quality-adjusted life-years (QALYs) and costs, both to the health-care payer and the national economy. We discounted future costs and QALYs at 3·5% annually and assumed a monetary value per QALY of £20 000 and a conservative long-run cost per vaccine dose of £15. We explored and varied these parameters in sensitivity analyses. We expressed the health and economic benefits of each scenario with the net monetary value: QALYs × (monetary value per QALY) - costs. FINDINGS: Without the initial lockdown, vaccination, and increased physical distancing, we estimated 148·0 million (95% uncertainty interval 48·5-198·8) COVID-19 cases and 3·1 million (0·84-4·5) deaths would occur in the UK over 10 years. In the best-case scenario, vaccination minimises community transmission without future periods of increased physical distancing, whereas SARS-CoV-2 becomes endemic with biannual epidemics in the worst-case scenario. Ongoing transmission is also expected in intermediate scenarios with vaccine efficacy similar to published clinical trial data. From a health-care perspective, introducing vaccination leads to incremental net monetary values ranging from £12·0 billion to £334·7 billion in the best-case scenario and from -£1·1 billion to £56·9 billion in the worst-case scenario. Incremental net monetary values of increased physical distancing might be negative from a societal perspective if national economy losses are persistent and large. INTERPRETATION: Our model findings highlight the substantial health and economic value of introducing SARS-CoV-2 vaccination. Smaller outbreaks could continue even with vaccines, but population-wide implementation of increased physical distancing might no longer be justifiable. Our study provides early insights about possible future post-vaccination scenarios from an economic and epidemiological perspective. FUNDING: National Institute for Health Research, European Commission, Bill & Melinda Gates Foundation.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Physical Distancing , SARS-CoV-2/immunology , Vaccination/economics , Adolescent , Adult , Aged , COVID-19/epidemiology , COVID-19/transmission , COVID-19/virology , COVID-19 Vaccines/economics , Cost-Benefit Analysis , Humans , Middle Aged , Models, Biological , Models, Economic , Pandemics/economics , Pandemics/prevention & control , Pandemics/statistics & numerical data , Patient Admission/economics , Patient Admission/statistics & numerical data , Quality-Adjusted Life Years , SARS-CoV-2/pathogenicity , United Kingdom/epidemiology , Young Adult
17.
Nature ; 593(7858): 270-274, 2021 05.
Article in English | MEDLINE | ID: covidwho-1135672

ABSTRACT

SARS-CoV-2 lineage B.1.1.7, a variant that was first detected in the UK in September 20201, has spread to multiple countries worldwide. Several studies have established that B.1.1.7 is more transmissible than pre-existing variants, but have not identified whether it leads to any change in disease severity2. Here we analyse a dataset that links 2,245,263 positive SARS-CoV-2 community tests and 17,452 deaths associated with COVID-19 in England from 1 November 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 mutations in this lineage prevent PCR amplification of the spike (S) gene target (known as S gene target failure (SGTF)1). On the basis of 4,945 deaths with known SGTF status, we estimate that the hazard of death associated with SGTF is 55% (95% confidence interval, 39-72%) higher than in cases without SGTF after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55-69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8-1.0%) within 28 days of a positive test in the community. Correcting for misclassification of SGTF and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42-82%) higher than with pre-existing variants. Our analysis suggests that B.1.1.7 is not only more transmissible than pre-existing SARS-CoV-2 variants, but may also cause more severe illness.


Subject(s)
COVID-19/mortality , COVID-19/virology , Phylogeny , SARS-CoV-2/classification , SARS-CoV-2/pathogenicity , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , England/epidemiology , Evolution, Molecular , Female , Homes for the Aged , Humans , Infant , Male , Middle Aged , Proportional Hazards Models , Risk Assessment , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Survival Analysis , Time Factors , Young Adult
18.
BMC Med ; 19(1): 52, 2021 02 19.
Article in English | MEDLINE | ID: covidwho-1090667

ABSTRACT

BACKGROUND: England's COVID-19 response transitioned from a national lockdown to localised interventions. In response to rising cases, these were supplemented by national restrictions on contacts (the Rule of Six), then 10 pm closing for bars and restaurants, and encouragement to work from home. These were quickly followed by a 3-tier system applying different restrictions in different localities. As cases continued to rise, a second national lockdown was declared. We used a national survey to quantify the impact of these restrictions on epidemiologically relevant contacts. METHODS: We compared paired measures on setting-specific contacts before and after each restriction started and tested for differences using paired permutation tests on the mean change in contacts and the proportion of individuals decreasing their contacts. RESULTS: Following the imposition of each measure, individuals tended to report fewer contacts than they had before. However, the magnitude of the changes was relatively small and variable. For instance, although early closure of bars and restaurants appeared to have no measurable effect on contacts, the work from home directive reduced mean daily work contacts by 0.99 (95% confidence interval CI] 0.03-1.94), and the Rule of Six reduced non-work and school contacts by a mean of 0.25 (0.01-0.5) per day. Whilst Tier 3 appeared to also reduce non-work and school contacts, the evidence for an effect of the lesser restrictions (Tiers 1 and 2) was much weaker. There may also have been some evidence of saturation of effects, with those who were in Tier 1 (least restrictive) reducing their contacts markedly when they entered lockdown, which was not reflected in similar changes in those who were already under tighter restrictions (Tiers 2 and 3). CONCLUSIONS: The imposition of various local and national measures in England during the summer and autumn of 2020 has gradually reduced contacts. However, these changes are smaller than the initial lockdown in March. This may partly be because many individuals were already starting from a lower number of contacts.


Subject(s)
COVID-19/epidemiology , COVID-19/prevention & control , Physical Distancing , Quarantine/trends , Adolescent , Adult , Aged , Child , Child, Preschool , England/epidemiology , Female , Humans , Infant , Infant, Newborn , Longitudinal Studies , Male , Middle Aged , Schools/trends , Workplace , Young Adult
19.
Lancet Public Health ; 6(1): e12-e20, 2021 01.
Article in English | MEDLINE | ID: covidwho-1072035

ABSTRACT

BACKGROUND: Countries have restricted international arrivals to delay the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These measures carry a high economic and social cost, and might have little effect on COVID-19 epidemics if there are many more cases resulting from local transmission compared with imported cases. Our study aims to investigate the extent to which imported cases contribute to local transmission under different epidemic conditions. METHODS: To inform decisions about international travel restrictions, we calculated the ratio of expected COVID-19 cases from international travel (assuming no travel restrictions) to expected cases arising from internal spread, expressed as a proportion, on an average day in May and September, 2020, in each country. COVID-19 prevalence and incidence were estimated using a modelling framework that adjusts reported cases for under-ascertainment and asymptomatic infections. We considered different travel scenarios for May and September, 2020: an upper bound with estimated travel volumes at the same levels as May and September, 2019, and a lower bound with estimated travel volumes adjusted downwards according to expected reductions in May and September, 2020. Results were interpreted in the context of local epidemic growth rates. FINDINGS: In May, 2020, imported cases are likely to have accounted for a high proportion of total incidence in many countries, contributing more than 10% of total incidence in 102 (95% credible interval 63-129) of 136 countries when assuming no reduction in travel volumes (ie, with 2019 travel volumes) and in 74 countries (33-114) when assuming estimated 2020 travel volumes. Imported cases in September, 2020, would have accounted for no more than 10% of total incidence in 106 (50-140) of 162 countries and less than 1% in 21 countries (4-71) when assuming no reductions in travel volumes. With estimated 2020 travel volumes, imported cases in September, 2020, accounted for no more than 10% of total incidence in 125 countries (65-162) and less than 1% in 44 countries (8-97). Of these 44 countries, 22 (2-61) had epidemic growth rates far from the tipping point of exponential growth, making them the least likely to benefit from travel restrictions. INTERPRETATION: Countries can expect travellers infected with SARS-CoV-2 to arrive in the absence of travel restrictions. Although such restrictions probably contribute to epidemic control in many countries, in others, imported cases are likely to contribute little to local COVID-19 epidemics. Stringent travel restrictions might have little impact on epidemic dynamics except in countries with low COVID-19 incidence and large numbers of arrivals from other countries, or where epidemics are close to tipping points for exponential growth. Countries should consider local COVID-19 incidence, local epidemic growth, and travel volumes before implementing such restrictions. FUNDING: Wellcome Trust, UK Foreign, Commonwealth & Development Office, European Commission, National Institute for Health Research, Medical Research Council, and Bill & Melinda Gates Foundation.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , Communicable Diseases, Imported/epidemiology , Epidemics , Internationality , COVID-19/prevention & control , Communicable Diseases, Imported/prevention & control , Humans , Models, Theoretical , Travel/legislation & jurisprudence
20.
Wellcome Open Res ; 5: 78, 2020.
Article in English | MEDLINE | ID: covidwho-1068023

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.

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