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1.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.01.02.23284109

ABSTRACT

SARS-CoV-2 variants of concern (VOCs) arise against the backdrop of increasingly heterogeneous human connectivity and population immunity. Through a large-scale phylodynamic analysis of 115,622 Omicron genomes, we identified >6,000 independent introductions of the antigenically distinct virus into England and reconstructed the dispersal history of resulting local transmission. Travel restrictions on southern Africa did not reduce BA.1 importation intensity as secondary hubs became major exporters. We explored potential drivers of BA.1 spread across England and discovered an early period during which viral lineage movements mainly occurred between larger cities, followed by a multi-focal spatial expansion shaped by shorter distance mobility patterns. We also found evidence that disease incidence impacted human commuting behaviours around major travel hubs. Our results offer a detailed characterisation of processes that drive the invasion of an emerging VOC across multiple spatial scales and provide unique insights on the interplay between disease spread and human mobility.

2.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.12.30.22283726

ABSTRACT

European countries are focusing on testing, isolation, and boosting strategies to counter the 2022/2023 winter surge due to Omicron subvariants. However, widespread pandemic fatigue and limited compliance potentially undermine mitigation efforts. To establish a baseline for interventions, we ran a multicountry survey to assess respondents' willingness to receive booster vaccination and comply with testing and isolation mandates. The vast majority of survey participants (N=4,594) was willing to adhere to testing (>91%) and rapid isolation (>88%) across the three countries. Pronounced differences emerged in the declared senior adherence to booster vaccination (73% in France, 94% in Belgium, 86% in Italy). Next, we inferred the vaccine-induced population immunity profile at the winter start from prior vaccination data, immunity waning, and declared booster uptake. Integrating survey and estimated immunity data in a branching process epidemic spreading model, we evaluated the effectiveness and costs of current protocols in France, Belgium, and Italy to manage the winter wave. Model results estimate that testing and isolation protocols would confer significant benefit in reducing transmission (17-24%) with declared adherence. Achieving a mitigating level similar tothe French protocol, the Belgian protocol would require 30% fewer tests and avoid the long isolation periods of the Italian protocol (average of 6 days vs. 11). A cost barrier to test would significantly decrease adherence in France and Belgium, undermining protocols' effectiveness. Simpler mandates for isolation may increase awareness and actual compliance, reducing testing costs, without compromising mitigation. High booster vaccination uptake remains key for the control of the winter wave.

3.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.10.10.22280897

ABSTRACT

COVID-19 highlighted how modeling is an integral part of pandemic response. But it also exposed fundamental methodological challenges. As high-resolution data on disease progression, epidemic surveillance, and host behavior are now available, can models turn them into accurate epidemic estimates and reliable public health recommendations? Take the epidemic threshold, which estimates the potential for an infection to spread in a host population, quantifying epidemic risk throughout epidemic emergence, mitigation, and control. While models increasingly integrated realistic host contacts, no parallel development occurred with matching detail in disease progression and interventions. This narrowed the use of the epidemic threshold to oversimplified disease and control descriptions. Here, we introduce the epidemic graph diagrams (EGDs), novel representations to compute the epidemic threshold directly from arbitrarily complex data on contacts, disease and control efforts. We define a grammar of diagram operations to decompose, compare, simplify models, extracting new theoretical understanding and improving computational efficiency. We test EGDs on two public health challenges, influenza and sexually-transmitted infections, to (i) explain the emergence of resistant influenza variants in the 2007-2008 season, and (ii) demonstrate that neglecting non-infectious prodromic stages biases the predicted epidemic risk, compromising control. EGDs are however general, and increase the performance of mathematical modeling to respond to present and future public health challenges.

4.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.07.15.22277497

ABSTRACT

Influenza circulation declined during the COVID-19 pandemic. The timing and extent of decline and its association with interventions against COVID-19 were described for some regions. Here, we provide a global analysis of the influenza decline between March 2020 and September 2021 and investigate its potential drivers. We computed influenza change by country and trimester relative to the 2014-2019 period using the number of samples in the FluNet database. We used random forests to determine important predictors in a list of 20 covariates including demography, weather, pandemic preparedness, COVID-19 incidence, and COVID-19 pandemic response. With a regression tree we then classified observations according to these predictors. We found that influenza circulation decreased globally, with COVID-19 incidence and pandemic preparedness being the two most important predictors of this decrease. The regression tree showed interpretable groups of observations by country and trimester: Europe and North America clustered together in spring 2020, with limited influenza decline despite strong COVID-19 restrictions; in the period afterwards countries of temperate regions, with high pandemic preparedness, high COVID-19 incidence and stringent social restrictions grouped together having strong influenza decline. Conversely, countries in the tropics, with altogether low pandemic preparedness, low reported COVID-19 incidence and low strength of COVID-19 response showed low influenza decline overall. A final group singled out four "zero-Covid" countries, with the lowest residual influenza levels. The spatiotemporal decline of influenza during the COVID-19 pandemic was global, yet heterogeneous. The sociodemographic context and stage of the COVID-19 pandemic showed non-linear associations with this decline. Zero-Covid countries maintained the lowest levels of reduction with strict border controls and despite close-to-normal social activity. These results suggest that the resurgence of influenza could take equally diverse paths. It also emphasizes the importance of influenza reseeding in driving countries' seasonal influenza epidemics.

5.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.02.28.22271600

ABSTRACT

Computational models offer a unique setting to test strategies to mitigate infectious diseases’ spread, providing useful insights to applied public health. To be actionable, models need to be informed by data, which can be available at different levels of detail. While high resolution data describing contacts between individuals are increasingly available, data gathering remains challenging, especially during a health emergency: many models thus use synthetic data or coarse information to evaluate intervention protocols. Here, we evaluate how the representation of contact data might affect the impact of various strategies in models, in the realm of COVID-19 transmission in educational and work contexts. Starting from high resolution contact data, we use data representations ranging from very detailed to very coarse to inform a model for the spread of SARS-CoV-2 and simulate several mitigation strategies. We find that coarse data representations underestimate the risk of super-spreading events. However, the rankings of protocols according to their efficiency or cost remain coherent across representations, ensuring the consistency of model findings to inform public health advice. Caution should be taken, however, on the quantitative estimations of those benefits and costs that may trigger the adoption of protocols, as these may depend on data representation.

6.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.02.04.22270473

ABSTRACT

As record cases due to the Omicron variant are currently registered in Europe, schools remain a vulnerable setting suffering large disruption. Extending previous modeling of SARS-CoV-2 transmission in schools in France, we estimate that at high incidence rates reactive screening protocols (as currently applied in France) require comparable test resources as weekly screening (as currently applied in some Swiss cantons), for considerably lower control. Our findings can be used to define incidence levels triggering school protocols and optimizing their cost-effectiveness.

7.
researchsquare; 2021.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-1143391.v1

ABSTRACT

Background: Several countries are implementing COVID-19 booster vaccination campaigns. The objective of this study was to model the impact of different primary and booster vaccination strategies. Methods. We used a compartmental model fitted to hospital admission data in France to analyze the impact of primary and booster vaccination strategies on morbidity and mortality, assuming waning of immunity and various levels of virus transmissibility during winter. Results. Strategies prioritizing primary vaccinations were systematically more effective than strategies prioritizing boosters. Regarding booster strategies targeting different age groups, their effectiveness varied with immunity and virus transmissibility levels. If waining of immunity affects all adults, people aged 30 to 49 years should be boosted in priority, even for low transmissibility levels. Discussion. Increasing the primary vaccination coverage should remain a priority. If a plateau has been reached, boosting immunity of younger adults could be the most effective strategy, especially if SARS-CoV-2 transmissibility is high.

8.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.12.01.21267122

ABSTRACT

Background. As evidence shows that vaccine immunity to COVID-19 wanes with time and decreases due to variants, several countries are implementing booster vaccination campaigns. The objective of this study was to analyze the morbidity and mortality burdens of different primary and booster vaccination strategies against COVID-19, using France as a case study. Methods. We used a deterministic, age-structured, compartmental model fitted to hospital admission data and validated against sero-prevalence data in France to analyze the impact of primary and booster vaccination strategies on morbidity and mortality assuming waning of immunity and increased virus transmissibility during winter. Findings. Strategies prioritizing primary vaccinations were systematically more effective than strategies prioritizing boosters. Regarding booster strategies targeting different age groups, their effectiveness varied with the levels of virus transmissibility, and according to the assumed loss of immunity for each age group. If the immunity reduction affects all age groups, people aged 30 to 49 years should be boosted in priority, even for low transmissibility levels. If the immunity reduction is restricted to people older than 65 years, boosting younger people becomes effective only above certain levels of transmissibility. Interpretation. Increasing the primary vaccination coverage should remain a priority to reduce morbidity and mortality due to COVID-19. If a plateau of primary vaccination has been reached, boosting immunity in younger age-groups could prevent more hospitalizations and deaths than boosting the immunity of older people, especially under conditions increasing SARS-CoV-2 transmissibility, or when facing new variants. Funding. The study was partially funded by the French national research agency through project SPHINX-17-CE36-0008-0.

9.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.11.15.21266187

ABSTRACT

SARS-CoV-2 remains a worldwide emergency. While vaccines have been approved and are widely administered, these are only available to adults and adolescents in Europe. Therefore, in order to mitigate the spread of more transmissible SARS-CoV-2 variants among children, the use of non-pharmaceutical interventions is still warranted. We investigate the impact of different testing strategies on the SARS-CoV-2 infection dynamics in a primary school environment, using an individual-based modelling approach. Specifically, we consider three testing strategies: 1) symptomatic isolation, where we test symptomatic individuals and isolate them when they test positive, 2) reactive screening, where a class is screened once one symptomatic individual was identified, and 3) repetitive screening, where the school in its entirety is screened on regular time intervals. Through this analysis, we demonstrate that repetitive testing strategies can significantly reduce the attack rate in schools, contrary to a reactive screening approach. Furthermore, we investigate the impact of these testing strategies on the average number of school days lost per child.

10.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.08.15.21261243

ABSTRACT

Schools were largely closed in 2020-2021 to counter COVID-19 spread, impacting students education and well-being. With highly contagious variants expanding in Europe while vaccine hesitancy persists, safe options to maintain schools open are urgently needed. We developed an agent-based model of SARS-CoV-2 transmission in school. We used empirical contact data measured in a primary and a secondary school in France, and field estimates for adherence to screening from 683 schools during the spring 2021 wave. Examining different screening protocols, we performed a cost-benefit analysis for varying epidemic conditions and vaccination scenarios. In a partially immunized school population, weekly screening would reduce the number of cases on average by 24% in the primary and 53% in the secondary school compared to symptom-based testing alone, if R=1.3 and 50% adhered to screening. This adherence was met in primary schools (53% (95% confidence interval 21-85%)), but insufficient participation was recorded in secondary schools (10% (1-38%) in middle schools, 6% (2-12%) in high schools). Regular screening would also reduce by 90% the number of student-days lost compared to reactive class closure. No difference was predicted when fully vaccinating teachers, due to their limited number and mixing. Partially vaccinating adolescents would still require regular screening for additional control (20% case reduction with 50% vaccinated students). In the upcoming fall, COVID-19 epidemic will likely continue to pose a risk to the safe opening of schools. Increasing vaccination coverage in adolescents and implementing regular testing while largely incentivizing adherence are essential steps to keep schools open.

11.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.08.09.21261807

ABSTRACT

To dissect the transmission dynamics of SARS-CoV-2 in the United States, we integrate parallel streams of high-resolution data on contact, mobility, seasonality, vaccination and seroprevalence within a metapopulation network. We find the COVID-19 pandemic in the US is characterized by a geographically localized mosaic of transmission along an urban-rural gradient, with many outbreaks sustained by between-county transmission. We detect a dynamic tension between the spatial scale of public health interventions and population susceptibility as pre-pandemic contact is resumed. Further, we identify regions rendered particularly at risk from invasion by variants of concern due to spatial connectivity. These findings emphasize the public health importance of accounting for the hierarchy of spatial scales in transmission and the heterogeneous impacts of mobility on the landscape of contagion risk.

12.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.07.26.21261133

ABSTRACT

As vaccination against COVID-19 stalls in some countries, increased accessibility and more adaptive approaches may be useful to keep the epidemic under control. Here we study the impact of reactive vaccination targeting schools and workplaces where cases have been detected, with an agent-based model accounting for COVID-19 natural history, vaccine characteristics, individuals' demography and behaviour and social distancing. We study epidemic scenarios ranging from sustained spread to flare-up of cases, and we consider reactive vaccination alone and in combination with mass vaccination. With the same number of doses, reactive vaccination reduces cases more than non-reactive approaches, but may require concentrating a high number of doses over a short time in case of sustained spread. In case of flare-ups, quick implementation of reactive vaccination supported by enhanced test-trace-isolate practices would limit further spread. These results provide key information to promote an adaptive vaccination plan in the months to come.

13.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.05.13.21257088

ABSTRACT

After one year of stop-and-go COVID-19 mitigation, some European countries still experience sustained viral circulation due to the B.1.1.7 variant. As the prospect of phasing out this stage through vaccination draws closer, it is critical to balance the efficacy of long-lasting interventions and their impact on the quality of life. Focusing on the current situation in France, we show that moderate interventions require a much longer time to achieve the same result as high intensity lockdowns, with the additional risk of deteriorating control as adherence wanes. Integrating intensity and duration of social distancing in a data-driven "distress" index, we show that shorter strict lockdowns are largely more performant than longer moderate lockdowns, for similar intermediate distress and infringement on individual freedom. Our study shows that favoring milder interventions over more stringent short approaches on the basis of perceived acceptability could be detrimental in the long term, especially with waning adherence.

14.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.04.21.21255876

ABSTRACT

Several countries have implemented lockdowns to control their COVID-19 epidemic. However, questions like “where” and “when” still require answers. We assessed the impact of national and regional lockdowns considering the French first epidemic wave of COVID-19 as a case study. In a regional lockdown scenario aimed at preventing intensive care units (ICU) saturation, almost all French regions would have had to implement a lockdown within 10 days and 96% of ICU capacities would have been used. For slowly growing epidemics, with a lower reproduction number, the expected delays between regional lockdowns increases. However, the public health costs associated with these delays tend to grow exponentially with time. In a quickly growing pandemic wave, defining the timing of lockdowns at a regional rather than national level delays by a few days the implementation of a nationwide lockdown but leads to substantially higher morbidity, mortality and stress on the healthcare system.

15.
researchsquare; 2021.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-371058.v1

ABSTRACT

Background: The knowledge of risk perceptions in primary care could help health authorities to manage epidemics. Methods A European multi-center study was conducted in France, Belgium and Spain to describe the perceptions, the level of anxiety and the feeling of preparedness of primary healthcare physicians towards the COVID-19 infection at the beginning of the pandemic. The factors associated with the feeling of preparedness were studied using multivariate logistic regressions. Results A total of 511 physicians participated to the study. Among them, only 16.3% (n = 82) were highly anxious about the pandemic, 50.6% (n = 254) had the feeling to have a high level of information, 80.5% (n = 409) found the measures taken by the health authorities suitable to limit the spread of COVID-19, and 45.2% (n = 229) felt prepared to face the epidemic. Factors associated with feeling prepared were: being a Spanish practitioner (adjusted OR = 4.34; 95%CI [2.47; 7.80]), being a man (aOR = 2.57, 95%CI [1.69; 3.96]), finding the measures taken by authorities appropriate (aOR = 1.72, 95%CI [1.01; 3.00]) and being highly informed (aOR = 4.82, 95%CI [2.62; 9.19]). Conclusions Regarding the dramatic evolution of the pandemic in Europe in the weeks following the study, it appears that information available at this time and transmitted to the physicians could have given a wrong assessment of the spread and the severity of the disease. It seems essential to better integrate the primary care physicians into the information, training and protection channels. A comparison between countries could help to select the most effective measures in terms of information and communication.

16.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.02.14.21251708

ABSTRACT

Facing B.1.1.7 variant, social distancing was strengthened in France in January 2021. Using a 2-strain mathematical model calibrated on genomic surveillance, we estimated that curfew measures allowed hospitalizations to plateau, by decreasing transmission of the historical strain while B.1.1.7 continued to grow. School holidays appear to have further slowed down progression in February. Without progressively strengthened social distancing, a rapid surge of hospitalizations is expected, despite the foreseen increase in vaccination rhythm.

17.
arxiv; 2021.
Preprint in English | PREPRINT-ARXIV | ID: ppzbmed-2102.05445v1

ABSTRACT

Digital contact tracing is a public health intervention. It should be integrated with local health policy, provide rapid and accurate notifications to exposed individuals, and encourage high app uptake and adherence to quarantine. Real-time monitoring and evaluation of effectiveness of app-based contact tracing is key for improvement and public trust.

18.
researchsquare; 2021.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-208849.v1

ABSTRACT

Following the first wave of SARS-CoV-2 infections in spring 2020, Europe experienced a resurgence of the virus starting late summer that was deadlier and more difficult to contain. Relaxed intervention measures and summer travel have been implicated as drivers of the second wave. Here, we build a phylogeographic model to evaluate how newly introduced lineages, as opposed to the rekindling of persistent lineages, contributed to the COVID-19 resurgence in Europe. We inform this model using genomic, mobility and epidemiological data from 10 West European countries and estimate that in many countries more than 50% of the lineages circulating in late summer resulted from new introductions since June 15th. The success in onwards transmission of these lineages is predicted by SARS-CoV-2 incidence during this period. Relatively early introductions from Spain into the United Kingdom contributed to the successful spread of the 20A.EU1/B.1.177 variant. The pervasive spread of variants that have not been associated with an advantage in transmissibility highlights the threat of novel variants of concern that emerged more recently and have been disseminated by holiday travel. Our findings indicate that more effective and coordinated measures are required to contain spread through cross-border travel.

19.
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.08.10.20171744

ABSTRACT

A novel testing policy was implemented in May in France to systematically screen potential COVID-19 infections and suppress local outbreaks while lifting lockdown restrictions. 20,736 virologically-confirmed cases were reported in mainland France from May 13, 2020 (week 20, end of lockdown) to June 28 (week 26). Accounting for missing data and the delay from symptom onset to confirmation test, this corresponds to 7,258 [95% CI 7,160-7,336] cases with symptom onset during this period, a likely underestimation of the real number. Using age-stratified transmission models parameterized to behavioral data and calibrated to regional hospital admissions, we estimated that 69,115 [58,072-77,449] COVID-19 symptomatic cases occurred, suggesting that 9 out of 10 cases with symptoms were not ascertained. Median detection rate increased from 7% [6-9]% to 31% [28-35]% over time, with regional estimates varying from 11% (Grand Est) to 78% (Normandy) by the end of June. Healthcare-seeking behavior in COVID-19 suspect cases remained low (31%) throughout the period. Model projections for the incidence of symptomatic cases (4.5 [3.9-5.0] per 100,000) were compatible with estimates integrating participatory and virological surveillance data, assuming all suspect cases consulted. Encouraging healthcare-seeking behavior and awareness in suspect cases is critical to improve detection. Substantially more aggressive and efficient testing with easier access is required to act as a pandemic-fighting tool. These elements should be considered in light of the currently observed resurgence of cases in France and other European countries.

20.
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.07.22.20158352

ABSTRACT

The efficacy of digital contact tracing against COVID-19 epidemic is debated: smartphone penetration is limited in many countries, non-uniform across age groups, with low coverage among elderly, the most vulnerable to SARS-CoV-2. We developed an agent-based model to precise the impact of digital contact tracing and household isolation on COVID-19 transmission. The model, calibrated on French population, integrates demographic, contact-survey and epidemiological information to describe the risk factors for exposure and transmission of COVID-19. We explored realistic levels of case detection, app adoption, population immunity and transmissibility. Assuming a reproductive ratio R = 2.6 and 50% detection of clinical cases, a ~20% app adoption reduces peak incidence by ~35%. With R = 1.7, >30% app adoption lowers the epidemic to manageable levels. Higher coverage among adults, playing a central role in COVID-19 transmission, yields an indirect benefit for elderly. These results may inform the inclusion of digital contact tracing within a COVID-19 response plan.

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