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1.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-22282676

Résumé

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 Dans Anglais | medRxiv | ID: ppmedrxiv-22281248

Résumé

The COVID-19 pandemic was in 2020 and 2021 for a large part mitigated by reducing contacts in the general population. To monitor how these contacts changed over the course of the pandemic in the Netherlands, a longitudinal survey was conducted where participants reported on their at-risk contacts every two weeks, as part of the European CoMix survey. The survey included 1659 participants from April to August 2020 and 2514 participants from December 2020 to September 2021. We categorized the number of unique contacted persons excluding household members, reported per participant per day into six activity levels, defined as 0, 1, 2, 3-4, 5-9 and 10 or more reported contacts. After correcting for age, vaccination status, risk status for severe outcome of infection, and frequency of participation, activity levels increased over time, coinciding with relaxation of COVID-19 control measures.

3.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-22277998

Résumé

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.

4.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-22275775

Résumé

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.

5.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-22271001

Résumé

BackgroundThe SARS-CoV-2 Omicron variant (B.1.1.529) has rapidly replaced the Delta variant (B.1.617.2) to become dominant in England. This epidemiological study assessed differences in transmissibility between the Omicron and Delta using two methods and data sources. MethodsOmicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5-11 December 2021. Secondary attack rates for Omicron and Delta using named contacts and household clustering were calculated using national surveillance and contact tracing data. We used multivariable logistic regression was used to control for factors associated with transmission. FindingsAnalysis of contact tracing data identified elevated secondary attack rates for Omicron vs Delta in household (15.0% vs 10.8%) and non-household (8.2% vs 3.7%) settings. The proportion of index cases resulting in residential clustering was twice as high for Omicron (16.1%) compared to Delta (7.3%). Transmission was significantly less likely from cases, or in named contacts, in receipt of three compared to two vaccine doses in household settings, but less pronounced for Omicron (aRR 0.78 and 0.88) compared to Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed for Delta cases and contacts (aRR 0.84 and 0.51) but only for Omicron contacts (aRR 0.76, 95% CI: 0.58-0.93) and not cases in receipt of three vs two doses (aRR 0.95, 0.77-1.16). InterpretationOur study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron. FundingStudy funded by the UK Health Security Agency.

6.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21260277

Résumé

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 Dans Anglais | medRxiv | ID: ppmedrxiv-21257973

Résumé

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.

8.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21252964

Résumé

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.

9.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21250959

Résumé

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.

10.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20248822

Résumé

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.

11.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20148460

Résumé

BackgroundAsymptomatic or subclinical SARS-CoV-2 infections are often unreported, which means that confirmed case counts may not accurately reflect underlying epidemic dynamics. Understanding the level of ascertainment (the ratio of confirmed symptomatic cases to the true number of symptomatic individuals) and undetected epidemic progression is crucial to informing COVID-19 response planning, including the introduction and relaxation of control measures. Estimating case ascertainment over time allows for accurate estimates of specific outcomes such as seroprevalence, which is essential for planning control measures. MethodsUsing reported data on COVID-19 cases and fatalities globally, we estimated the proportion of symptomatic cases (i.e. any person with any of fever >= 37.5{degrees}C, cough, shortness of breath, sudden onset of anosmia, ageusia or dysgeusia illness) that were reported in 210 countries and territories, given those countries had experienced more than ten deaths. We used published estimates of the case fatality ratio (CFR) as an assumed baseline. We then calculated the ratio of this baseline CFR to an estimated local delay-adjusted CFR to estimate the level of under-ascertainment in a particular location. We then fit a Bayesian Gaussian process model to estimate the temporal pattern of under-ascertainment. ResultsWe estimate that, during March 2020, the median percentage of symptomatic cases detected across the 84 countries which experienced more than ten deaths ranged from 2.38% (Bangladesh) to 99.6% (Chile). Across the ten countries with the highest number of total confirmed cases as of 6th July 2020, we estimated that the peak number of symptomatic cases ranged from 1.4 times (Chile) to 17.8 times (France) larger than reported. Comparing our model with national and regional seroprevalence data where available, we find that our estimates are consistent with observed values. Finally, we estimated seroprevalence for each country. Despite low case detection in some countries, our results that adjust for this still suggest that all countries have had only a small fraction of their populations infected as of July 2020. ConclusionsWe found substantial under-ascertainment of symptomatic cases, particularly at the peak of the first wave of the SARS-CoV-2 pandemic, in many countries. Reported case counts will therefore likely underestimate the rate of outbreak growth initially and underestimate the decline in the later stages of an epidemic. Although there was considerable under-reporting in many locations, our estimates were consistent with emerging serological data, suggesting that the proportion of each countrys population infected with SARS-CoV-2 worldwide is generally low. FundingWellcome Trust, Bill & Melinda Gates Foundation, DFID, NIHR, GCRF, ARC.

12.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20122689

Résumé

BackgroundMany low- and middle-income countries have implemented control measures against coronavirus disease 2019 (COVID-19). However, it is not clear to what extent these measures explain the low numbers of recorded COVID-19 cases and deaths in Africa. One of the main aims of control measures is to reduce respiratory pathogen transmission through direct contact with others. In this study we collect contact data from residents of informal settlements around Nairobi, Kenya to assess if control measures have changed contact patterns, and estimate the impact of changes on the basic reproduction number (R0). MethodsWe conducted a social contact survey with 213 residents of five informal settlements around Nairobi in early May 2020, four weeks after the Kenyan government introduced enhanced physical distancing measures and a curfew between 7pm and 5am. Respondents were asked to report all direct physical and non-physical contacts made the previous day, alongside a questionnaire asking about the social and economic impact of COVID-19 and control measures. We examined contact patterns by demographic factors, including socioeconomic status. We described the impact of COVID-19 and control measures on income and food security. We compared contact patterns during control measures to patterns from non-pandemic periods to estimate the change in R0. FindingsWe estimate that control measures reduced physical and non-physical contacts, reducing the R0 from around 2.6 to between 0.5 and 0.7, depending on the pre-COVID-19 comparison matrix used. Masks were worn by at least one person in 92% of contacts. Respondents in the poorest socioeconomic quintile reported 1.5 times more contacts than those in the richest. 86% of respondents reported a total or partial loss of income due to COVID-19, and 74% reported eating less or skipping meals due to having too little money for food. InterpretationCOVID-19 control measures have had a large impact on direct contacts and therefore transmission, but have also caused considerable economic and food insecurity. Reductions in R0 are consistent with the linear epidemic growth in Kenya and other sub-Saharan African countries that implemented similar, early control measures. However, negative and inequitable impacts on economic and food security may mean control measures are not sustainable in the longer term. Research in context Evidence before this studyWe conducted a PubMed search on 6 June 2020 with no language restrictions for studies published since inception, using the search terms ("social mix*" OR "social cont*" OR "contact pattern*) AND ("covid*"). The search yielded 53 articles, two of which reported changes in social contacts after COVID-19 control measures. The first study reported changes in contact patterns in Wuhan and Shanghai, and the second changes in contact patterns in the UK. We found no studies examining changes in contact patterns due to control measures in sub-Saharan Africa, and no studies disaggregating contacts by socioeconomic status. Added value of this studyThis is the first study to estimate the reproduction number of COVID-19 under control measures in sub-Saharan Africa using primary contact data. This study also moves beyond existing work to i) measure contacts in densely populated informal settlements, ii) explore how social contacts vary across socioeconomic status, and iii) assess the impact of control measures on economic and food security in these areas. Implications of all the evidenceCOVID-19 control measures have substantially reduced social contacts and disease transmission. People of lower socioeconomic status face greater transmission risk as they report more contacts. Control measures have led to considerable economic and food insecurity, and may not be sustainable in the long term without efforts to reduce the burden of control measures on households.

13.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20101824

Résumé

Understanding changes in human mobility in the early stages of the COVID-19 pandemic is crucial for assessing the impacts of travel restrictions designed to reduce disease spread. Here, relying on data from mainland China, we investigated the spatio-temporal characteristics of human mobility between 1st January and 1st March 2020 and discussed their public health implications. An outbound travel surge from Wuhan before travel restrictions were implemented was also observed across China due to the Lunar New Year, indicating that holiday travel may have played a larger role in mobility changes compared to impending travel restrictions. Holiday travel also shifted healthcare pressure related to COVID-19 towards locations with lower access to care. Network analyses showed no sign of major changes in the transportation network after Lunar New Year. Changes observed were temporary and have not yet led to structural reorganisation of the transportation network at the time of this study. One sentence summaryUnderstanding travel before, during, and after the introduction of travel restrictions in China in response to the COVID-19 Pandemic.

14.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20099135

Résumé

BackgroundThere is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of morbidity and mortality from symptomatic SARS-Cov-2 infection or coronavirus disease 2019 (Covid-19). Most studies investigating racial and ethnic disparities to date have focused on hospitalized patients or have not characterized who received testing or those who tested positive for Covid-19. ObjectiveTo compare patterns of testing and test results for coronavirus 2019 (Covid-19) and subsequent mortality by race and ethnicity in the largest integrated healthcare system in the United States. DesignRetrospective cohort study. SettingUnited States Department of Veterans Affairs (VA). Participants5,834,543 individuals in care, among whom 62,098 were tested and 5,630 tested positive for Covid-19 between February 8 and May 4, 2020. ExposuresSelf-reported race/ethnicity. Main outcome measuresWe evaluated associations between race/ethnicity and receipt of Covid-19 testing, a positive test result, and 30-day mortality, accounting for a wide range of demographic and clinical risk factors including comorbid conditions, site of care, and urban versus rural residence. ResultsAmong all individuals in care, 74% were non-Hispanic white (white), 19% non-Hispanic black (black), and 7% Hispanic. Compared with white individuals, black and Hispanic individuals were more likely to be tested for Covid-19 (tests per 1000: white=9.0, [95% CI 8.9 to 9.1]; black=16.4, [16.2 to 16.7]; and Hispanic=12.2, [11.9 to 12.5]). While individuals from minority backgrounds were more likely to test positive (black vs white: OR 1.96, 95% CI 1.81 to 2.12; Hispanic vs white: OR 1.73, 95% CI 1.53 to 1.96), 30-day mortality did not differ by race/ethnicity (black vs white: OR 0.93, 95% CI 0.64 to 1.33; Hispanic vs white: OR 1.07, 95% CI 0.61 to 1.87). ConclusionsBlack and Hispanic individuals are experiencing an excess burden of Covid-19 not entirely explained by underlying medical conditions or where they live or receive care. While there was no observed difference in mortality by race or ethnicity, our findings may underestimate risk in the broader US population as health disparities tend to be reduced in VA.

15.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20081711

Résumé

BackgroundThe health impact of COVID-19 may differ in African settings as compared to countries in Europe or China due to demographic, epidemiological, environmental and socio-economic factors. We evaluated strategies to reduce SARS-CoV-2 burden in African countries, so as to support decisions that balance minimising mortality, protecting health services and safeguarding livelihoods. MethodsWe used a Susceptible-Exposed-Infectious-Recovered mathematical model, stratified by age, to predict the evolution of COVID-19 epidemics in three countries representing a range of age distributions in Africa (from oldest to youngest average age: Mauritius, Nigeria and Niger), under various effectiveness assumptions for combinations of different non-pharmaceutical interventions: self-isolation of symptomatic people, physical distancing, and shielding (physical isolation) of the high-risk population. We adapted model parameters to better represent uncertainty about what might be expected in African populations, in particular by shifting the distribution of severity risk towards younger ages and increasing the case-fatality ratio. ResultsWe predicted median clinical attack rates over the first 12 months of 17% (Niger) to 39% (Mauritius), peaking at 2-4 months, if epidemics were unmitigated. Self-isolation while symptomatic had a maximum impact of about 30% on reducing severe cases, while the impact of physical distancing varied widely depending on percent contact reduction and R0. The effect of shielding high-risk people, e.g. by rehousing them in physical isolation, was sensitive mainly to residual contact with low-risk people, and to a lesser extent to contact among shielded individuals. Response strategies incorporating self-isolation of symptomatic individuals, moderate physical distancing and high uptake of shielding reduced predicted peak bed demand by 46% to 54% and mortality by 60% to 75%. Lockdowns delayed epidemics by about 3 months. Estimates were sensitive to differences in age-specific social mixing patterns, as published in the literature. DiscussionIn African settings, as elsewhere, current evidence suggests large COVID-19 epidemics are expected. However, African countries have fewer means to suppress transmission and manage cases. We found that self-isolation of symptomatic persons and general physical distancing are unlikely to avert very large epidemics, unless distancing takes the form of stringent lockdown measures. However, both interventions help to mitigate the epidemic. Shielding of high-risk individuals can reduce health service demand and, even more markedly, mortality if it features high uptake and low contact of shielded and unshielded people, with no increase in contact among shielded people. Strategies combining self-isolation, moderate physical distancing and shielding will probably achieve substantial reductions in mortality in African countries. Temporary lockdowns, where socioeconomically acceptable, can help gain crucial time for planning and expanding health service capacity.

16.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20073049

Résumé

BackgroundReporting of daily hospital COVID-19 deaths in the UK are promoted by the government and scientific advisers alike as a key metric for assessing the progress in the control of the epidemic. These data, however, have certain limitations, among which one of the most significant concerns the fact that the daily totals span deaths that have occurred between 1 and 10 days or more in the past. Data and methodsWe obtained daily data published published by NHS England up to and including April 25 in the form of Excel spreadsheets in which deaths counts are presented by date of death according to age and region. Simple descriptive analyses were conducted and presented in graphical and tabular form which were aimed at illustrating the biases inherent in focussing on daily counts regardless of when the deaths occurred. We then looked at how a less biased picture could be obtained by looking at trends in death counts stratifying by individual period of delay in days between occurrence of death and when the death was included in the daily announcement. FindingsThe number of hospital COVID-19 deaths announced daily overestimates the maximum number of deaths actually occurring so far in the epidemic in the UK, and also obscures the pattern of decline in deaths. Taking account of reporting delays suggests that for England as a whole a peak in hospital COVID-19 deaths may have been reached on April 8 with a subsequent gradual decline suggested. The same peak is also seen among those aged 60-79 and 80+, although there is slightly shallower decline in the oldest age group (80+ years). Among those aged 40-59 years a later peak on April 11 is evident. London shows a peak on April 8 and a clearer and steeper pattern of subsequent decline compared to England as a whole. InterpretationAnalyses of mortality trends must take account of delay, and in communication with the public more emphasis should be placed on looking at trends based on deaths that occurred 5 or more days prior to the announcement day. The slightly weaker decline seen at age 80+ may reflect increased hospitalisation of people from care homes, whereas the later peak under the age of 60 years may reflect the higher proportions at these younger ages being admitted to critical care resulting in an extension of life of several days. Competing interestsAll authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years other than LS who reported grants from Wellcome, MRC, NIHR, GSK, BHF, Diabetes UK all outside the submitted work; no other relationships or activities that could appear to have influenced the submitted work other than LS who is a Trustee of the British Heart Foundation and AJM who is a member of the Royal Society Delve Committee.

17.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20067504

Résumé

BackgroundTo contain the spread of COVID-19, a cordon sanitaire was put in place in Wuhan prior to the Lunar New Year, on 23 January 2020, restricting travel to other parts of China. We assess the efficacy of the cordon sanitaire to delay the introduction and onset of local transmission of COVID-19 in other major cities in mainland China. MethodsWe estimated the number of infected travellers from Wuhan to other major cities in mainland China from November 2019 to March 2020 using previously estimated COVID-19 prevalence in Wuhan and publicly available mobility data. We focused on Beijing, Chongqing, Hangzhou, and Shenzhen as four representative major cities to identify the potential independent contribution of the cordon sanitaire and holiday travel. To do this, we simulated outbreaks generated by infected arrivals in these destination cities using stochastic branching processes. We also modelled the effect of the cordon sanitaire in combination with reduced transmissibility scenarios representing the effect of local non-pharmaceutical interventions. FindingsIn the four cities, given the potentially high prevalence of COVID-19 in Wuhan between Dec 2019 and early Jan 2020, local transmission may have been seeded as early as 2 - 8 January 2020. By the time the cordon sanitaire was imposed, simulated case counts were likely in the hundreds. The cordon sanitaire alone did not substantially affect the epidemic progression in these cities, although it may have had some effect in smaller cities. InterpretationOur results indicate that the cordon sanitaire may not have prevented COVID-19 spread in major Chinese cities; local non-pharmaceutical interventions were likely more important for this. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSIn late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in Wuhan, China. In response to the outbreak, authorities enacted a cordon sanitaire in order to limit spread. Several studies have sought to determine the efficacy of the policy; a search of PubMed for "coronavirus AND (travel restrictions OR travel ban OR shutdown OR cordon sanitaire) AND (Wuhan OR China)" returned 24 results. However other studies have relied on reported cases to determine efficacy, which are likely subject to reporting and testing biases. Early outbreak dynamics are also subject to a significant degree of stochastic uncertainty due to small numbers of cases. Added value of this studyHere we use publicly-available mobility data and a stochastic branching process model to evaluate the efficacy of the cordon sanitaire to limiting the spread of COVID-19 from Wuhan to other cities in mainland China, while accounting for underreporting and uncertainty. We find that although travel restrictions led to a significant decrease in the number of individuals leaving Wuhan during the busy post-Lunar New Year holiday travel period, local transmission was likely already established in major cities. Thus, the travel restrictions likely did not affect the epidemic trajectory substantially in these cities. Implications of all the available evidenceA cordon sanitaire around the epicentre alone may not be able to reduce COVID-19 incidence when implemented after local transmission has occurred in highly connected neighbors. Local non-pharmaceutical interventions to reduce transmissibility (e.g., school and workplace closures) may have contributed more to the observed decrease in incidence in mainland China.

18.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20059964

Résumé

ImportanceSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (Covid-19), an evolving pandemic. Limited data are available characterizing SARS-Cov-2 infection in the United States. ObjectiveTo determine associations between demographic and clinical factors and testing positive for coronavirus 2019 (Covid-19+), and among Covid-19+ subsequent hospitalization and intensive care. Design, Setting, and ParticipantsRetrospective cohort study including all patients tested for Covid-19 between February 8 and March 30, 2020, inclusive. We extracted electronic health record data from the national Veterans Affairs Healthcare System, the largest integrated healthcare system in the United States, on 2,026,227 patients born between 1945 and 1965 and active in care. ExposuresDemographic data, comorbidities, medication history, substance use, vital signs, and laboratory measures. Laboratory tests were analyzed first individually and then grouped into a validated summary measure of physiologic injury (VACS Index). Main Outcomes and MeasuresWe evaluated which factors were associated with Covid-19+ among all who tested. Among Covid-19+ we identified factors associated with hospitalization or intensive care. We identified independent associations using multivariable and conditional multivariable logistic regression with multiple imputation of missing values. ResultsAmong Veterans aged 54-75 years, 585/3,789 (15.4%) tested Covid-19+. In adjusted analysis (C-statistic=0.806) black race was associated with Covid-19+ (OR 4.68, 95% CI 3.79-5.78) and the association remained in analyses conditional on site (OR 2.56, 95% CI 1.89-3.46). In adjusted models, laboratory abnormalities (especially fibrosis-4 score [FIB-4] >3.25 OR 8.73, 95% CI 4.11-18.56), and VACS Index (per 5-point increase OR 1.62, 95% CI 1.43-1.84) were strongly associated with hospitalization. Associations were similar for intensive care. Although significant in unadjusted analyses, associations with comorbid conditions and medications were substantially reduced and, in most cases, no longer significant after adjustment. Conclusions and RelevanceBlack race was strongly associated with Covid-19+, but not with hospitalization or intensive care. Among Covid-19+, risk of hospitalization and intensive care may be better characterized by laboratory measures and vital signs than by comorbid conditions or prior medication exposure. Key PointsO_ST_ABSQuestionC_ST_ABSWhat are the demographic and clinical characteristics associated with testing positive for coronavirus 2019 (Covid-19+), and among Covid-19+ subsequent hospitalization and intensive care among Veterans in the United States? FindingsIn this retrospective cohort study of 2,026,227 Veterans aged 54-75 years and active in care, 585/3,789 (15.4%) tested Covid-19+. Black race was strongly associated with Covid-19+, but not with hospitalization or intensive care. Among Covid-19+, laboratory abnormalities and a summary measure of physiologic injury were strongly associated with hospitalization and intensive care. MeaningRacial differences in testing positive for Covid-19 may be an underestimate of the general population as racial health disparities in the Veterans Affairs Healthcare System tend to be smaller than in the private sector. Risk of hospitalization and intensive care may be better characterized by laboratory measures and vital signs than by comorbid conditions or prior medication exposure.

19.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20049023

Résumé

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 Dans Anglais | medRxiv | ID: ppmedrxiv-20031773

Résumé

Adjusting for delay from confirmation-to-death, we estimated case and infection fatality ratios (CFR, IFR) for COVID-19 on the Diamond Princess ship as 2.3% (0.75%-5.3%) and 1.2% (0.38-2.7%). Comparing deaths onboard with expected deaths based on naive CFR estimates using China data, we estimate IFR and CFR in China to be 0.5% (95% CI: 0.2-1.2%) and 1.1% (95% CI: 0.3-2.4%) respectively. AimTo estimate the infection and case fatality ratio of COVID-19, using data from passengers of the Diamond Princess cruise ship while correcting for delays between confirmation-and-death, and age-structure of the population.

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