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1.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21267959

Résumé

IntroductionUnderstanding human mixing patterns relevant to infectious diseases spread through close contact is vital for modelling transmission dynamics and optimisation of disease control strategies. Mixing patterns in low-income countries like Malawi are not well understood. MethodologyWe conducted a social mixing survey in urban Blantyre, Malawi between April and July 2021 (between the 2nd and 3rd wave of COVID-19 infections). Participants living in densely-populated neighbourhoods were randomly sampled and, if they consented, reported their physical and non-physical contacts within and outside homes lasting at least 5 minutes during the previous day. Age-specific mixing rates were calculated, and a negative binomial mixed effects model was used to estimate determinants of contact behaviour. ResultsOf 1,201 individuals enrolled, 702 (58.5%) were female, the median age was 15 years (interquartile range [IQR] 5-32) and 127 (10.6%) were HIV-positive. On average, participants reported 10.3 contacts per day (range: 1-25). Mixing patterns were highly age-assortative, particularly those within the community and with skin-to-skin contact. Adults aged 20-49y reported the most contacts (median:11, IQR: 8-15) of all age groups; 38% (95%CI: 16-63) more than infants (median: 8, IQR: 5-10), who had the least contacts. Household contact frequency increased by 3% (95%CI 2-5) per additional household member. Unemployed participants had 15% (95%CI: 9-21) fewer contacts than other adults. Among long range (>30 meters away from home) contacts, secondary school children had the largest median contact distance from home (257m, IQR 78-761). HIV-positive status in adults >18 years-old was not associated with increased contact patterns (1%, 95%CI -9-12). During this period of relatively low COVID-19 incidence in Malawi, 301 (25.1%) individuals stated that they had limited their contact with others due to COVID-19 precautions; however, their reported contacts were not fewer (8%, 95%CI 1-13). ConclusionIn urban Malawi, contact rates, are high and age-assortative, with little behavioural change due to either HIV-status or COVID-19 circulation. This highlights the limits of contact-restriction-based mitigation strategies in such settings and the need for pandemic preparedness to better understand how contact reductions can be enabled and motivated.

2.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21266930

Résumé

BackgroundIn settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine could let more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals for low- and middle-income countries of Europe. MethodsWe fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 low- and middle-income countries in the World Health Organization European Region (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Republic of Moldova, Russian Federation, Serbia, North Macedonia, Turkey, and Ukraine). A vaccine product with characteristics similar to the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies related to other COVID-19 vaccines. Both fixed dosing intervals at 4, 8, 12, 16, and 20 weeks and dose-specific intervals that prioritise specific doses for certain age groups were tested. Optimal intervals minimise COVID-19 mortality between March 2021 and December 2022. We incorporated the emergence of variants of concern into the model, and also conducted a benefit-risk assessment to quantify the trade-off between health benefits versus adverse events following immunisation. FindingsIn 12 of the 13 countries, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20-59 years). These strategies lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.2% [range: 4.0% - 22.5%; n = 13 (countries)] more deaths. There is generally a negative association between dosing interval and COVID-19 mortality within the range we investigated. Assuming a shorter first dose waning duration of 120 days, as opposed to 360 days in the base case, led to shorter optimal dosing intervals of 8-12 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks. InterpretationWe infer that longer dosing intervals of over six months, which are substantially longer than the current label recommendation for most vaccine products, could reduce COVID-19 mortality in low- and middle-income countries of WHO/Europe. Certain vaccine features, such as fast waning of first doses, significantly shorten the optimal dosing intervals. FundingWorld Health Organization

3.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21266401

Résumé

BackgroundThe ability of SARS-CoV-2 vaccines to protect against infection and onward transmission determines whether immunisation can control global circulation. We estimated effectiveness of BNT162b2 and ChAdOx1 vaccines against acquisition and transmission of the Alpha and Delta variants in a prospective household study in England. MethodsAdult index cases in the community and their household contacts took oral-nasal swabs on days 1, 3 and 7 after enrolment. Swabs were tested by RT-qPCR with genomic sequencing conducted on a subset. We used Bayesian logistic regression to infer vaccine effectiveness against acquisition and transmission, adjusted for age, vaccination history and variant. FindingsBetween 2 February 2021 and 10 September 2021 213 index cases and 312 contacts were followed up. After excluding households lacking genomic proximity (N=2) or with unlikely serial intervals (N=16), 195 households with 278 contacts remained of whom 113 (41%) became PCR positive. Delta lineages had 1.64 times the risk (95% Credible Interval: 1.15 - 2.44) of transmission than Alpha; contacts older than 18 years were 1.19 times (1.04 - 1.52) more likely to acquire infection than children. Effectiveness of two doses of BNT162b2 against transmission of Delta was 31% (-3%, 61%) and 42% (14%, 69%) for ChAdOx1, similar to their effectiveness for Alpha. Protection against infection with Alpha was higher than for Delta, 71% (12%,95%) vs 24% (-2%, 64%) respectively for BNT162b2 and 26% (-39%, 73%) vs 14% (-5%, 46%) respectively for ChAdOx1. InterpretationBNT162b2 and ChAdOx1 reduce transmission of the Delta variant from breakthrough infections in the household setting though their protection against infection is low. FundingThis study was funded by the UK Health Security Agency (formerly Public Health England) as part of the COVID-19 response.

4.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21260272

Résumé

BackgroundCountries in the World Health Organization (WHO) European Region differ in terms of the COVID-19 vaccine roll-out speed. We evaluated the health and economic impact of different age-based vaccine prioritisation strategies across this demographically and socio-economically diverse region. MethodsWe fitted country-specific age-stratified compartmental transmission models to reported COVID-19 mortality in the WHO European Region to inform the immunity level before vaccine roll-out. Building upon broad recommendations from the WHO Strategic Advisory Group of Experts on Immunisation (SAGE), we examined four strategies that prioritise: all adults (V+), younger (20-59 year-olds) followed by older adults (60+) (V20), older followed by younger adults (V60), and the oldest adults (75+) (V75) followed by incremental expansion to successively younger five-year age groups. We explored four roll-out scenarios based on projections or recent observations (R1-4) - the slowest scenario (R1) covers 30% of the total population by December 2022 and the fastest (R4) 80% by December 2021. Five decision-making metrics were summarised over 2021-22: mortality, morbidity, and losses in comorbidity-adjusted life expectancy (cLE), comorbidity- and quality-adjusted life years (cQALY), and the value of human capital (HC). Six sets of infection-blocking and disease-reducing vaccine efficacies were considered. FindingsThe optimal age-based vaccine prioritisation strategies were sensitive to country characteristics, decision-making metrics and roll-out speeds. Overall, V60 consistently performed better than or comparably to V75. There were greater benefits in prioritising older adults when roll-out is slow and when VE is low. Under faster roll-out, V+ was the most desirable option. InterpretationA prioritisation strategy involving more age-based stages (V75) does not necessarily lead to better health and economic outcomes than targeting broad age groups (V60). Countries expecting a slow vaccine roll-out may particularly benefit from prioritising older adults. FundingWorld Health Organization, Bill and Melinda Gates Foundation, the Medical Research Council (United Kingdom), the National Institute of Health Research (United Kingdom), the European Commission, the Foreign, Commonwealth and Development Office (United Kingdom), Wellcome Trust Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and medRxiv for articles published in English from inception to 9 Jun 2021, with the search terms: ("COVID-19" OR "SARS-CoV-2") AND ("priorit*) AND ("model*") AND ("vaccin*") and identified 66 studies on vaccine prioritization strategies. Of the 25 studies that compared two or more age-based prioritisation strategies, 12 found that targeting younger adults minimised infections while targeting older adults minimised mortality; an additional handful of studies found similar outcomes between different age-based prioritisation strategies where large outbreaks had already occurred. However, only two studies have explored age-based vaccine prioritisation using models calibrated to observed outbreaks in more than one country, and no study has explored the effectiveness of vaccine prioritisation strategies across settings with different population structures, contact patterns, and outbreak history. Added-value of this studyWe evaluated various age-based vaccine prioritisation strategies for 38 countries in the WHO European Region using various health and economic outcomes for decision-making, by parameterising models using observed outbreak history, known epidemiologic and vaccine characteristics, and a range of realistic vaccine roll-out scenarios. We showed that while targeting older adults was generally advantageous, broadly targeting everyone above 60 years might perform better than or comparably to a more detailed strategy that targeted the oldest age group above 75 years followed by those in the next younger five-year age band. Rapid vaccine roll-out has only been observed in a small number of countries. If vaccine coverage can reach 80% by the end of 2021, prioritising older adults may not be optimal in terms of health and economic impact. Lower vaccine efficacy was associated with greater relative benefits only under relatively slow roll-out scenarios considered. Implication of all the available evidenceCOVID-19 vaccine prioritization strategies that require more precise targeting of individuals of a specific and narrow age range may not necessarily lead to better outcomes compared to strategies that prioritise populations across broader age ranges. In the WHO European Region, prioritising all adults equally or younger adults first will only optimise health and economic impact when roll-out is rapid, which may raise between-country equity issues given the global demand for COVID-19 vaccines.

5.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21258924

Résumé

IntroductionIn countries with weak surveillance systems confirmed COVID-19 deaths are likely to underestimate the death toll of the pandemic. Many countries also have incomplete vital registration systems, hampering excess mortality estimation. Here, we fitted a dynamic transmission model to satellite imagery data on burial patterns in Mogadishu, Somalia during 2020 to estimate the date of introduction, transmissibility and other epidemiologic characteristics of SARS-CoV-2 in this low-income, crisis-affected setting. MethodsWe performed Markov chain Monte Carlo (MCMC) fitting with an age-structured compartmental COVID-19 model to provide median estimates and credible intervals for the date of introduction, the basic reproduction number (R0) and the effect of non-pharmaceutical interventions in Mogadishu up to September 2020. ResultsUnder the assumption that excess deaths in Mogadishu February-September 2020 were directly attributable to SARS-CoV-2 infection we arrived at median estimates of October-November 2019 for the date of introduction and low R0 estimates (1.3-1.5) stemming from the early and slow rise of excess deaths. The effect of control measures on transmissibility appeared small. ConclusionSubject to study assumptions, a very early SARS-CoV-2 introduction event may have occurred in Somalia. Estimated transmissibility in the first epidemic wave was lower than observed in European settings.

6.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21258735

Résumé

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.

7.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21257032

Résumé

We hypothesised that cross-protection from seasonal epidemics of human coronaviruses (HCoVs) could have affected SARS-CoV-2 transmission, including generating reduced susceptibility in children. To determine what the pre-pandemic distribution of immunity to HCoVs was, we fitted a mathematical model to 6 years of seasonal coronavirus surveillance data from England and Wales. We estimated a duration of immunity to seasonal HCoVs of 7.3 years (95%CI 6.8 - 7.9) and show that, while cross-protection between HCoV and SARS-CoV-2 may contribute to the age distribution, it is insufficient to explain the age pattern of SARS-CoV-2 infections in the first wave of the pandemic in England and Wales. Projections from our model illustrate how different strengths of cross-protection between circulating coronaviruses could determine the frequency and magnitude of SARS-CoV-2 epidemics over the coming decade, as well as the potential impact of cross-protection on future seasonal coronavirus transmission. Significance statementCross-protection from seasonal epidemics of human coronaviruses (HCoVs) has been hypothesised to contribute to the relative sparing of children during the early phase of the pandemic. Testing this relies on understanding the pre-pandemic age-distribution of recent HCoV infections, but little is known about their dynamics. Using England and Wales as a case study, we use a transmission model to estimate the duration of immunity to seasonal coronaviruses, and show how cross-protection could have affected the age distribution of susceptibility during the first wave, and alter SARS-CoV-2 transmission patterns over the coming decade.

8.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21257215

Résumé

BackgroundThe COVID-19 pandemic has disrupted delivery of immunisation services globally. Many countries have postponed vaccination campaigns out of concern about infection risks to staff delivering vaccination, the children being vaccinated and their families. The World Health Organization recommends considering both the benefit of preventive campaigns and the risk of SARS-CoV-2 transmission when making decisions about campaigns during COVID-19 outbreaks, but there has been little quantification of the risks. MethodsWe modelled excess SARS-CoV-2 infection risk to vaccinators, vaccinees and their caregivers resulting from vaccination campaigns delivered during a COVID-19 epidemic. Our model used population age-structure and contact patterns from three exemplar countries (Burkina Faso, Ethiopia, and Brazil). It combined an existing compartmental transmission model of an underlying COVID-19 epidemic with a Reed-Frost model of SARS-CoV-2 infection risk to vaccinators and vaccinees. We explored how excess risk depends on key parameters governing SARS-CoV-2 transmissibility, and aspects of campaign delivery such as campaign duration, number of vaccinations, and effectiveness of personal protective equipment (PPE) and symptomatic screening. ResultsInfection risks differ considerably depending on the circumstances in which vaccination campaigns are conducted. A campaign conducted at the peak of a SARS-CoV-2 epidemic with high prevalence and without special infection mitigation measures could increase absolute infection risk by 32% to 45% for vaccinators, and 0.3% to 0.5% for vaccinees and caregivers. However, these risks could be reduced to 3.6% to 5.3% and 0.1% to 0.2% respectively by use of PPE that reduces transmission by 90% (as might be achieved with N95 respirators or high-quality surgical masks) and symptomatic screening. ConclusionsSARS-CoV-2 infection risks to vaccinators, vaccinees and caregivers during vaccination campaigns can be greatly reduced by adequate PPE, symptomatic screening, and appropriate campaign timing. Our results support the use of adequate risk mitigation measures for vaccination campaigns held during SARS-CoV-2 epidemics, rather than cancelling them entirely.

9.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20240648

Résumé

Slovakia conducted multiple rounds of population-wide rapid antigen testing for SARS-CoV-2 in late 2020, combined with a period of additional contact restrictions. Observed prevalence decreased by 58% (95% CI: 57-58%) within one week in the 45 counties that were subject to two rounds of mass testing, an estimate that remained robust when adjusting for multiple potential confounders. Adjusting for epidemic growth of 4.4% (1.1-6.9%) per day preceding the mass testing campaign, the estimated decrease in prevalence compared to a scenario of unmitigated growth was 70% (67-73%). Modelling suggests that this decrease cannot be explained solely by infection control measures, but requires the additional impact of isolation as well as quarantine of household members of those testing positive.

10.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20186502

Résumé

As several countries gradually release social distancing measures, rapid detection of new localised 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 characterise 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 suggest ASMODEE compares favourably with a state-of-art outbreak-detection algorithm while being simpler and more flexible. We illustrate our method using publicly available data of NHS Pathways reporting potential COVID-19 cases in England at a fine spatial scale, for which we provide a template automated analysis pipeline. ASMODEE is implemented in the free R package trendbreaker.

11.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20181198

Résumé

BackgroundThe COVID-19 pandemic has disrupted routine measles immunisation and supplementary immunisation activities (SIAs) in most countries including Kenya. We assessed the risk of measles outbreaks during the pandemic in Kenya as a case study for the African Region. MethodsCombining measles serological data, local contact patterns, and vaccination coverage into a cohort model, we predicted the age-adjusted population immunity in Kenya and estimated the probability of outbreaks when contact-reducing COVID-19 interventions are lifted. We considered various scenarios for reduced measles vaccination coverage from April 2020. FindingsIn February 2020, when a scheduled SIA was postponed, population immunity was close to the herd immunity threshold and the probability of a large outbreak was 22% (0-46). As the COVID-19 restrictions to physical contact are lifted, from December 2020, the probability of a large measles outbreak increased to 31% (8-51), 35% (16-52) and 43% (31-56) assuming a 15%, 50% and 100% reduction in measles vaccination coverage. By December 2021, this risk increases further to 37% (17-54), 44% (29-57) and 57% (48-65) for the same coverage scenarios respectively. However, the increased risk of a measles outbreak following the lifting of restrictions on contact can be overcome by conducting an SIA with [≥] 95% coverage in under-fives. InterpretationWhile contact restrictions sufficient for SAR-CoV-2 control temporarily reduce measles transmissibility and the risk of an outbreak from a measles immunity gap, this risk rises rapidly once physical distancing is relaxed. Implementing delayed SIAs will be critical for prevention of measles outbreaks once contact restrictions are fully lifted in Kenya. FundingThe United Kingdoms Medical Research Council and the Department for International Development

12.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20177808

Résumé

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.

13.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20161281

Résumé

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.

14.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20141440

Résumé

BackgroundCountries achieving control of COVID-19 after an initial outbreak will continue to face the risk of SARS-CoV-2 resurgence. This study explores surveillance strategies for COVID-19 containment based on polymerase chain reaction tests. MethodsUsing a dynamic SEIR-type model to simulate the initial dynamics of a COVID-19 introduction, we investigate COVID-19 surveillance strategies among healthcare workers, hospital patients, and community members. We estimate surveillance sensitivity as the probability of COVID-19 detection using a hypergeometric sampling process. We identify test allocation strategies that maximise the probability of COVID-19 detection across different testing capacities. We use Beijing, China as a case study. FindingsSurveillance subgroups are more sensitive in detecting COVID-19 transmission when they are defined by more COVID-19 specific symptoms. In this study, fever clinics have the highest surveillance sensitivity, followed by respiratory departments. With a daily testing rate of 0.07/1000 residents, via exclusively testing at fever clinic and respiratory departments, there would have been 598 [95% eCI: 35, 2154] and 1373 [95% eCI: 47, 5230] cases in the population by the time of first case detection, respectively. Outbreak detection can occur earlier by including non-syndromic subgroups, such as younger adults in the community, as more testing capacity becomes available. InterpretationA multi-layer approach that considers both the surveillance sensitivity and administrative constraints can help identify the optimal allocation of testing resources and thus inform COVID-19 surveillance strategies. FundingBill & Melinda Gates Foundation, National Institute of Health Research (UK), National Institute of Health (US), the Royal Society, and Wellcome Trust.

15.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20123448

Résumé

BackgroundDuring the Covid-19 lockdown, contact clustering in social bubbles may allow extending contacts beyond the household at minimal additional risk and hence has been considered as part of modified lockdown policy or a gradual lockdown exit strategy. We estimated the impact of such strategies on epidemic and mortality risk using the UK as a case study. MethodsWe used an individual based model for a synthetic population similar to the UK, that is stratified into transmission risks from the community, within the household and from other households in the same social bubble. The base case considers a situation where non-essential shops and schools are closed, the secondary household attack rate is 20% and the initial reproduction number is 0.8. We simulate a number of strategies including variations of social bubbles, i.e. the forming of exclusive pairs of households, for particular subsets of households (households including children and single occupancy households), as well as for all households. We test the sensitivity of the results to a range of alternative model assumptions and parameters. ResultsClustering contacts outside the household into exclusive social bubbles is an effective strategy of increasing contacts while limiting some of the associated increase in epidemic risk. In the base case scenario social bubbles reduced cases and fatalities by 17% compared to an unclustered increase of contacts. We find that if all households were to form social bubbles the reproduction number would likely increase to 1.1 and therefore beyond the epidemic threshold of one. However, strategies that allow households with young children or single occupancy households to form social bubbles only increased the reproduction number by less than 10%. The corresponding increase in morbidity and mortality is proportional to the increase in the epidemic risk but is largely focussed in older adults independently of whether these are included in the social bubbles. ConclusionsSocial bubbles can be an effective way of extending contacts beyond the household limiting the increase in epidemic risk, if managed appropriately.

16.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20106278

Résumé

BackgroundNational immunisation programmes globally are at risk of suspension due to the severe health system constraints and physical distancing measures in place to mitigate the ongoing COVID-19 pandemic. Our aim is to compare the health benefits of sustaining routine childhood immunisation in Africa against the risk of acquiring SARS-CoV-2 infections through visiting routine vaccination service delivery points. MethodsWe used two scenarios to approximate the child deaths that may be caused by immunisation coverage reductions during COVID-19 outbreaks. First, we used previously reported country-specific child mortality impact estimates of childhood immunisation for diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, pneumococcal, rotavirus, measles, meningitis A, rubella, and yellow fever (DTP3, HepB3, Hib3, PCV3, RotaC, MCV1, MCV2, MenA, RCV, YFV) to approximate the future deaths averted before completing five years of age by routine childhood vaccination during a 6-month COVID-19 risk period without catch-up campaigns. Second, we analysed an alternative scenario that approximates the health benefits of sustaining routine childhood immunisation to only the child deaths averted from measles outbreaks during the COVID-19 risk period. The excess number of infections due to additional SARS-CoV-2 exposure during immunisation visits assumes that contact reducing interventions flatten the outbreak curve during the COVID-19 risk period, that 60% of the population will have been infected by the end of that period, that children can be infected by either vaccinators or during transport and that upon child infection the whole household would be infected. Country specific household age structure estimates and age dependent infection fatality rates are then applied to calculate the number of deaths attributable to the vaccination clinic visits. We present benefit-risk ratios for routine childhood immunisation alongside 95% uncertainty range estimates from probabilistic sensitivity analysis. FindingsFor every one excess COVID-19 death attributable to SARS-CoV-2 infections acquired during routine vaccination clinic visits, there could be 84 (14-267) deaths in children prevented by sustaining routine childhood immunisation in Africa. The benefit-risk ratio for the vaccinated children, siblings, parents or adult care-givers, and older adults in the households of vaccinated children are 85,000 (4,900 - 546,000), 75,000 (4,400 - 483,000), 769 (148 - 2,700), and 96 (14 - 307) respectively. In the alternative scenario that approximates the health benefits to only the child deaths averted from measles outbreaks, the benefit-risk ratio to the households of vaccinated children is 3 (0 - 10) under these highly conservative assumptions and if the risk to only the vaccinated children is considered, the benefit-risk ratio is 3,000 (182 - 21,000). InterpretationOur analysis suggests that the health benefits of deaths prevented by sustaining routine childhood immunisation in Africa far outweighs the excess risk of COVID-19 deaths associated with vaccination clinic visits, especially for the vaccinated children. However, there are other factors that must be considered for strategic decision making to sustain routine childhood immunisation in African countries during the COVID-19 pandemic. These include logistical constraints of vaccine supply chain problems caused by the COVID-19 pandemic, reallocation of immunisation providers to other prioritised health services, healthcare staff shortages caused by SARS-CoV-2 infections among the staff, decreased demand for vaccination arising from community reluctance to visit vaccination clinics for fear of contracting SARS-CoV-2 infections, and infection risk to healthcare staff providing immunisation services as well as to their households and onward SARS-CoV-2 transmission into the wider community. FundingGavi, the Vaccine Alliance and Bill & Melinda Gates Foundation (OPP1157270) Research in contextO_ST_ABSEvidence before the studyC_ST_ABSNational immunisation programmes globally are at risk of disruption due to the severe health system constraints caused by the ongoing COVID-19 pandemic and the physical distancing measures to mitigate the outbreak. The decrease in vaccination coverage increases the proportion of susceptible children at risk of increased morbidity and mortality from vaccine-preventable disease outbreaks. Outbreaks of vaccine preventable disease have been observed during previous interruptions to routine immunisation services during an ongoing infectious disease epidemic, such as during the 2013-2016 Ebola outbreak in West Africa, when most health resources were shifted towards the Ebola response which led to decreasing vaccination coverage and consequently outbreaks of measles and other vaccine-preventable diseases. Added value of this studyWe estimated the benefit-risk ratio by comparing the deaths prevented by sustaining routine childhood immunisation for diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, pneumococcal, rotavirus, measles, meningitis A, rubella, and yellow fever vaccines with the excess COVID-19 deaths associated with vaccination clinic visits. The benefit of routine childhood immunization programmes in all the 54 countries of Africa is higher than the COVID-19 risk associated with these vaccination clinic visits. Implications of all the available evidenceRoutine childhood immunisation programmes should be safeguarded for continued service delivery and prioritised for the prevention of infectious diseases, as logistically possible, as part of delivering essential health services during the COVID-19 pandemic in Africa. The current immunisation service models will require adaptation, including physical distancing measures, personal protective equipment, and good hygiene practices for infection control at the vaccination clinics, and have to be complemented by new immunisation service models for sustaining routine childhood immunisation in the African countries during the COVID-19 risk period.

17.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20093849

Résumé

BackgroundSome key gaps in the understanding of SARS-CoV-2 infection remain. One of them is the contribution to transmission from individuals experiencing asymptomatic infections. We aimed to characterise the proportion and infectiousness of asymptomatic infections using data from the outbreak on the Diamond Princess cruise ship. MethodsWe used a transmission model of COVID-19 with asymptomatic and presymptomatic states calibrated to outbreak data from the Diamond Princess, to quantify the contribution of asymptomatic infections to transmission. Data available included the date of symptom onset for symptomatic disease for passengers and crew, the number of symptom agnostic tests done each day, and date of positive test for asymptomatic and presymptomatic individuals. FindingsOn the Diamond Princess 74% (70-78%) of infections proceeded asymptomatically, i.e. a 1:3.8 case-to-infection ratio. Despite the intense testing 53%, (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. While the data did not allow identification of the infectiousness of asymptomatic infections, assuming no or low infectiousness resulted in posterior estimates for the net reproduction number of an individual progressing through presymptomatic and symptomatic stages in excess of 15. InterpretationAsymptomatic SARS-CoV-2 infections may contribute substantially to transmission. This is essential to consider for countries when assessing the potential effectiveness of ongoing control measures to contain COVID-19. FundingERC Starting Grant (#757699), Wellcome trust (208812/Z/17/Z), HDR UK (MR/S003975/1)

18.
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.

19.
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.

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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