Underdetection of cases of COVID-19 in France threatens epidemic control.

As countries in Europe gradually relaxed lockdown restrictions after the first wave, test-trace-isolate strategies became critical to maintain the incidence of coronavirus disease 2019 (COVID-19) at low levels1,2. Reviewing their shortcomings can provide elements to consider in light of the second wave that is currently underway in Europe. Here we estimate the rate of detection of symptomatic cases of COVID-19 in France after lockdown through the use of virological3 and participatory syndromic4 surveillance data coupled with mathematical transmission models calibrated to regional hospitalizations2. Our findings indicate that around 90,000 symptomatic infections, corresponding to 9 out 10 cases, were not ascertained by the surveillance system in the first 7 weeks after lockdown from 11 May to 28 June 2020, although the test positivity rate did not exceed the 5% recommendation of the World Health Organization (WHO)5. The median detection rate increased from 7% (95% confidence interval, 6-8%) to 38% (35-44%) over time, with large regional variations, owing to a strengthening of the system as well as a decrease in epidemic activity. According to participatory surveillance data, only 31% of individuals with COVID-19-like symptoms consulted a doctor in the study period. This suggests that large numbers of symptomatic cases of COVID-19 did not seek medical advice despite recommendations, as confirmed by serological studies6,7. Encouraging awareness and same-day healthcare-seeking behaviour of suspected cases of COVID-19 is critical to improve detection. However, the capacity of the system remained insufficient even at the low epidemic activity achieved after lockdown, and was predicted to deteriorate rapidly with increasing incidence of COVID-19 cases. Substantially more aggressive, targeted and efficient testing with easier access is required to act as a tool to control the COVID-19 pandemic. The testing strategy will be critical to enable partial lifting of the current restrictive measures in Europe and to avoid a third wave.

Preparedness and vulnerability of African countries against importations of COVID-19: a modelling study.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) epidemic has spread from China to 25 countries. Local cycles of transmission have already occurred in 12 countries after case importation. In Africa, Egypt has so far confirmed one case. The management and control of COVID-19 importations heavily rely on a country's health capacity. Here we evaluate the preparedness and vulnerability of African countries against their risk of importation of COVID-19. METHODS: We used data on the volume of air travel departing from airports in the infected provinces in China and directed to Africa to estimate the risk of importation per country. We determined the country's capacity to detect and respond to cases with two indicators: preparedness, using the WHO International Health Regulations Monitoring and Evaluation Framework; and vulnerability, using the Infectious Disease Vulnerability Index. Countries were clustered according to the Chinese regions contributing most to their risk. FINDINGS: Countries with the highest importation risk (ie, Egypt, Algeria, and South Africa) have moderate to high capacity to respond to outbreaks. Countries at moderate risk (ie, Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, and Kenya) have variable capacity and high vulnerability. We identified three clusters of countries that share the same exposure to the risk originating from the provinces of Guangdong, Fujian, and the city of Beijing, respectively. INTERPRETATION: Many countries in Africa are stepping up their preparedness to detect and cope with COVID-19 importations. Resources, intensified surveillance, and capacity building should be urgently prioritised in countries with moderate risk that might be ill-prepared to detect imported cases and to limit onward transmission. FUNDING: EU Framework Programme for Research and Innovation Horizon 2020, Agence Nationale de la Recherche.

Tracing and analysis of 288 early SARS-CoV-2 infections outside China: A modeling study.

BACKGROUND: In the early months of 2020, a novel coronavirus disease (COVID-19) spread rapidly from China across multiple countries worldwide. As of March 17, 2020, COVID-19 was officially declared a pandemic by the World Health Organization. We collected data on COVID-19 cases outside China during the early phase of the pandemic and used them to predict trends in importations and quantify the proportion of undetected imported cases. METHODS AND FINDINGS: Two hundred and eighty-eight cases have been confirmed out of China from January 3 to February 13, 2020. We collected and synthesized all available information on these cases from official sources and media. We analyzed importations that were successfully isolated and those leading to onward transmission. We modeled their number over time, in relation to the origin of travel (Hubei province, other Chinese provinces, other countries) and interventions. We characterized the importation timeline to assess the rapidity of isolation and epidemiologically linked clusters to estimate the rate of detection. We found a rapid exponential growth of importations from Hubei, corresponding to a doubling time of 2.8 days, combined with a slower growth from the other areas. We predicted a rebound of importations from South East Asia in the successive weeks. Time from travel to detection has considerably decreased since first importation, from 14.5 ± 5.5 days on January 5, 2020, to 6 ± 3.5 days on February 1, 2020. However, we estimated 36% of detection of imported cases. This study is restricted to the early phase of the pandemic, when China was the only large epicenter and foreign countries had not discovered extensive local transmission yet. Missing information in case history was accounted for through modeling and imputation. CONCLUSIONS: Our findings indicate that travel bans and containment strategies adopted in China were effective in reducing the exportation growth rate. However, the risk of importation was estimated to increase again from other sources in South East Asia. Surveillance and management of traveling cases represented a priority in the early phase of the epidemic. With the majority of imported cases going undetected (6 out of 10), countries experienced several undetected clusters of chains of local transmissions, fueling silent epidemics in the community. These findings become again critical to prevent second waves, now that countries have reduced their epidemic activity and progressively phase out lockdown.

Endemicity and prevalence of multipartite viruses under heterogeneous between-host transmission.

Multipartite viruses replicate through a puzzling evolutionary strategy. Their genome is segmented into two or more parts, and encapsidated in separate particles that appear to propagate independently. Completing the replication cycle, however, requires the full genome, so that a systemic infection of a host requires the concurrent presence of several particles. This represents an apparent evolutionary drawback of multipartitism, while its advantages remain unclear. A transition from monopartite to multipartite viral forms has been described in vitro under conditions of high multiplicity of infection, suggesting that cooperation between defective mutants is a plausible evolutionary pathway towards multipartitism. However, it is unknown how the putative advantages that multipartitism might enjoy at the microscopic level affect its epidemiology, or if an explicit advantange is needed to explain its ecological persistence. In order to disentangle which mechanisms might contribute to the rise and fixation of multipartitism, we here investigate the interaction between viral spreading dynamics and host population structure. We set up a compartmental model of the spread of a virus in its different forms and explore its epidemiology using both analytical and numerical techniques. We uncover that the impact of host contact structure on spreading dynamics entails a rich phenomenology of ecological relationships that includes cooperation, competition, and commensality. Furthermore, we find out that multipartitism might rise to fixation even in the absence of explicit microscopic advantages. Multipartitism allows the virus to colonize environments that could not be invaded by the monopartite form, while homogeneous contacts between hosts facilitate its spread. We conjecture that these features might have led to an increase in the diversity and prevalence of multipartite viral forms concomitantly with the expansion of agricultural practices.

Novel coronavirus (2019-nCoV) early-stage importation risk to Europe, January 2020.

As at 27 January 2020, 42 novel coronavirus (2019-nCoV) cases were confirmed outside China. We estimate the risk of case importation to Europe from affected areas in China via air travel. We consider travel restrictions in place, three reported cases in France, one in Germany. Estimated risk in Europe remains high. The United Kingdom, Germany and France are at highest risk. Importation from Beijing and Shanghai would lead to higher and widespread risk for Europe.

Epidemic Threshold in Continuous-Time Evolving Networks.

Current understanding of the critical outbreak condition on temporal networks relies on approximations (time scale separation, discretization) that may bias the results. We propose a theoretical framework to compute the epidemic threshold in continuous time through the infection propagator approach. We introduce the weak commutation condition allowing the interpretation of annealed networks, activity-driven networks, and time scale separation into one formalism. Our work provides a coherent connection between discrete and continuous time representations applicable to realistic scenarios.

Predicting epidemic risk from past temporal contact data.

Understanding how epidemics spread in a system is a crucial step to prevent and control outbreaks, with broad implications on the system's functioning, health, and associated costs. This can be achieved by identifying the elements at higher risk of infection and implementing targeted surveillance and control measures. One important ingredient to consider is the pattern of disease-transmission contacts among the elements, however lack of data or delays in providing updated records may hinder its use, especially for time-varying patterns. Here we explore to what extent it is possible to use past temporal data of a system's pattern of contacts to predict the risk of infection of its elements during an emerging outbreak, in absence of updated data. We focus on two real-world temporal systems; a livestock displacements trade network among animal holdings, and a network of sexual encounters in high-end prostitution. We define the node's loyalty as a local measure of its tendency to maintain contacts with the same elements over time, and uncover important non-trivial correlations with the node's epidemic risk. We show that a risk assessment analysis incorporating this knowledge and based on past structural and temporal pattern properties provides accurate predictions for both systems. Its generalizability is tested by introducing a theoretical model for generating synthetic temporal networks. High accuracy of our predictions is recovered across different settings, while the amount of possible predictions is system-specific. The proposed method can provide crucial information for the setup of targeted intervention strategies.

The importance of increasing primary vaccinations against COVID-19 in Europe.

In the European Union, mass vaccination against COVID-19 staved off the strict restrictions that had characterized early epidemic response. Now, vaccination campaigns are focusing on booster doses, and primary vaccinations have all but halted. Still, 52 million European adults are unvaccinated. We investigated if reaching the still unvaccinated population in future vaccination campaigns would substantially decrease the current burden of COVID-19, which is substantial. We focused on vaccination homophily, whereby those who are unvaccinated are mostly in contact with other unvaccinated, making COVID-19 circulation easier. We quantified vaccination homophily and estimated its impact on COVID-19 circulation. We used an online survey of 1,055,286 people from 22 European countries during early 2022. We computed vaccination homophily as the association between reported vaccination status and perceived vaccination uptake among one's own social contacts, using a case-referent design and a hierarchical logistic model. We used this information in an analysis of the COVID-19 reproduction ratio to determine the impact of vaccine homophily in transmission. Vaccination homophily was present and strong everywhere: the average odds ratio of being vaccinated for a 10-percentage-point increase in coverage among contacts was 1.66 (95% CI=(1.60, 1.72)). Homophily was positively associated with the strictness of COVID-19-related restrictions in 2020 (Pearson = 0.49, P = .03). In the countries studied, 12%-to-18% of the reproduction ratio would be attributable to vaccine homophily. Reducing vaccination homophily may curb the reproduction ratio substantially even to the point of preventing recurrent epidemic waves. In addition to boosting those already vaccinated, increasing primary vaccination should remain a high priority in future vaccination campaigns, to reduce vaccination homophily: this combined strategy may decrease COVID-19 burden.

Epidemic graph diagrams as analytics for epidemic control in the data-rich era.

COVID-19 highlighted modeling as a cornerstone of pandemic response. But it also revealed that current models may not fully exploit the high-resolution data on disease progression, epidemic surveillance and host behavior, now available. Take the epidemic threshold, which quantifies the spreading risk throughout epidemic emergence, mitigation, and control. Its use requires oversimplifying either disease or host contact dynamics. We introduce the epidemic graph diagrams to overcome this by computing the epidemic threshold directly from arbitrarily complex data on contacts, disease and interventions. A grammar of diagram operations allows to decompose, compare, simplify models with computational efficiency, extracting theoretical understanding. We use the diagrams to explain the emergence of resistant influenza variants in the 2007-2008 season, and demonstrate that neglecting non-infectious prodromic stages of sexually transmitted infections biases the predicted epidemic risk, compromising control. The diagrams are general, and improve our capacity to respond to present and future public health challenges.

Population mobility and the development of Botswana's generalized HIV epidemic: a network analysis.

The majority of people with HIV live in sub-Saharan Africa, where HIV epidemics are generalized. For these epidemics to develop, populations need to be mobile. However, population-level mobility has not yet been studied in the context of the development of generalized HIV epidemics. Here we do so by studying historical migration data from Botswana which has one of the most severe generalized HIV epidemics worldwide; in 2021, HIV prevalence was 21%. The country reported its first AIDS case in 1985 when it began to rapidly urbanize. We hypothesize that, during the development of Botswana's epidemic, the population was highly mobile and there were substantial urban-to-rural and rural-to-urban migratory flows. We test this hypothesis by conducting a network analysis using a historical time series (1981 to 2011) of micro-census data from Botswana. We found 10% of the population moved their residency annually, complex migration networks connected urban with rural areas, and there were very high rates of rural-to-urban migration. Notably, we also found mining towns were both important in-flow and out-flow migration hubs; consequently, there was a very high turnover of residents in towns. Our results support our hypothesis, and together, provide one explanation for the development of Botswana's generalized epidemic.

The role of migration networks in the development of Botswana's generalized HIV epidemic.

The majority of people with HIV live in sub-Saharan Africa, where epidemics are generalized. For these epidemics to develop, populations need to be mobile. However, the role of population-level mobility in the development of generalized HIV epidemics has not been studied. Here we do so by studying historical migration data from Botswana, which has one of the most severe generalized HIV epidemics worldwide; HIV prevalence was 21% in 2021. The country reported its first AIDS case in 1985 when it began to rapidly urbanize. We hypothesize that, during the development of Botswana's epidemic, the population was extremely mobile and the country was highly connected by substantial migratory flows. We test this mobility hypothesis by conducting a network analysis using a historical time series (1981-2011) of micro-census data from Botswana. Our results support our hypothesis. We found complex migration networks with very high rates of rural-to-urban, and urban-to-rural, migration: 10% of the population moved annually. Mining towns (where AIDS cases were first reported, and risk behavior was high) were important in-flow and out-flow migration hubs, suggesting that they functioned as 'core groups' for HIV transmission and dissemination. Migration networks could have dispersed HIV throughout Botswana and generated the current hyperendemic epidemic.

Over 25 million people in sub-Saharan Africa live with HIV. After reporting its first AIDS case in 1985, Botswana is one of the most severely affected countries in the region, with one in five adults now living with HIV. Movement of the population is likely to have contributed to a geographically dispersed, and high-prevalence, HIV epidemic in Botswana. Since 1985, urbanization, rapid economic and population growth, and migration have transformed Botswana. Yet, few studies have analyzed the role of population-level movement patterns in the spread of HIV during this time. By studying micro-census data from Botswana between 1981 and 2011, Song et al. found that the country's population was highly mobile during this period. Reconstructions of internal migration patterns show very high rates of rural-to-urban and urban-to-rural migration, with 10% of Botswana's population moving each year. The first reported AIDS cases in Botswana occurred in mining towns and cities where high-risk behavior was prevalent. These areas were also migration hubs during this period and could have contributed to the rapid spread of HIV throughout the country as infected individuals moved back to rural districts. Understanding human migration patterns and how they affect the spread of infectious diseases using current data could help public health authorities in Botswana and additional sub-Saharan African countries design control strategies for HIV and other important infections that occur in the region.

Attitudes towards booster, testing and isolation, and their impact on COVID-19 response in winter 2022/2023 in France, Belgium, and Italy: a cross-sectional survey and modelling study.

Background: European countries are focusing on testing, isolation, and boosting strategies to counter the 2022/2023 winter surge due to SARS-CoV-2 Omicron subvariants. However, widespread pandemic fatigue and limited compliance potentially undermine mitigation efforts. Methods: 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. 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. Findings: The vast majority of survey participants (N = 4594) 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). Epidemic model results estimate that testing and isolation protocols would confer significant benefit in reducing transmission (17-24% reduction, from R = 1.6 to R = 1.3 in France and Belgium, to R = 1.2 in Italy) with declared adherence. Achieving a mitigating level similar to the French protocol, the Belgian protocol would require 35% fewer tests (from 1 test to 0.65 test per infected person) 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. Interpretation: 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. Funding: The European Commission, ANRS-Maladies Infectieuses Émergentes, the Agence Nationale de la Recherche, the Chaires Blaise Pascal Program of the Île-de-France region.

Non-selective distribution of infectious disease prevention may outperform risk-based targeting.

Epidemic control often requires optimal distribution of available vaccines and prophylactic tools, to protect from infection those susceptible. Well-established theory recommends prioritizing those at the highest risk of exposure. But the risk is hard to estimate, especially for diseases involving stigma and marginalization. We address this conundrum by proving that one should target those at high risk only if the infection-averting efficacy of prevention is above a critical value, which we derive analytically. We apply this to the distribution of pre-exposure prophylaxis (PrEP) of the Human Immunodeficiency Virus (HIV) among men-having-sex-with-men (MSM), a population particularly vulnerable to HIV. PrEP is effective in averting infections, but its global scale-up has been slow, showing the need to revisit distribution strategies, currently risk-based. Using data from MSM communities in 58 countries, we find that non-selective PrEP distribution often outperforms risk-based, showing that a logistically simpler strategy is also more effective. Our theory may help design more feasible and successful prevention.

The potential impact of country-level migration networks on HIV epidemics in sub-Saharan Africa: the case of Botswana.

Generalised HIV epidemics in sub-Saharan Africa show substantial geographical variation in prevalence, which is considered when designing epidemic control strategies. We hypothesise that the migratory behaviour of the general population of countries in sub-Saharan Africa could have a substantial effect on HIV epidemics and challenge the elimination effort. To test this hypothesis, we used census data from 2017 to identify, construct, and visualise the migration network of the population of Botswana, which has one of the most severe HIV epidemics worldwide. We found that, over 12 months, approximately 14% of the population moved their residency from one district to another. Four types of migration occurred: urban-to-urban, rural-to-urban, urban-to-rural, and rural-to-rural. Migration is leading to a marked geographical redistribution of the population, causing high rates of population turnover in some areas, and further concentrating the population in urban areas. The migration network could potentially be having a substantial effect on the HIV epidemic of Botswana: changing the location of high-transmission areas, generating cross-country transmission corridors, creating source-sink dynamics, and undermining control strategies. Large-scale migration networks could present a considerable challenge to eliminating HIV in Botswana and in other countries in sub-Saharan Africa, and should be considered when designing epidemic control strategies.

Effect of delayed awareness and fatigue on the efficacy of self-isolation in epidemic control.

The isolation of infectious individuals is a key measure of public health for the control of communicable diseases. However, involving a strong perturbation of daily life, it often causes psychosocial distress, and severe financial and social costs. These may act as mechanisms limiting the adoption of the measure in the first place or the adherence throughout its full duration. In addition, difficulty of recognizing mild symptoms or lack of symptoms may impact awareness of the infection and further limit adoption. Here we study an epidemic model on a network of contacts accounting for limited adherence and delayed awareness to self-isolation, along with fatigue causing overhasty termination. The model allows us to estimate the role of each ingredient and analyze the tradeoff between adherence and duration of self-isolation. We find that the epidemic threshold is very sensitive to an effective compliance that combines the effects of imperfect adherence, delayed awareness and fatigue. If adherence improves for shorter quarantine periods, there exists an optimal duration of isolation, shorter than the infectious period. However, heterogeneities in the connectivity pattern, coupled to a reduced compliance for highly active individuals, may almost completely offset the effectiveness of self-isolation measures on the control of the epidemic.

Reorganization of nurse scheduling reduces the risk of healthcare associated infections.

Efficient prevention and control of healthcare associated infections (HAIs) is still an open problem. Using contact data from wearable sensors at a short-stay geriatric ward, we propose a proof-of-concept modeling study that reorganizes nurse schedules for efficient infection control. This strategy switches and reassigns nurses' tasks through the optimization of shift timelines, while respecting feasibility constraints and satisfying patient-care requirements. Through a Susceptible-Colonized-Susceptible transmission model, we found that schedules reorganization reduced HAI risk by 27% (95% confidence interval [24, 29]%) while preserving timeliness, number, and duration of contacts. More than 30% nurse-nurse contacts should be avoided to achieve an equivalent reduction through simple contact removal. Nurse scheduling can be reorganized to break potential chains of transmission and substantially limit HAI risk, while ensuring the timeliness and quality of healthcare services. This calls for including optimization of nurse scheduling practices in programs for infection control in hospitals.

Ignoring spatial heterogeneity in drivers of SARS-CoV-2 transmission in the US will impede sustained elimination.

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.

Using mobile phone data to reveal risk flow networks underlying the HIV epidemic in Namibia.

Twenty-six million people are living with HIV in sub-Saharan Africa; epidemics are widely dispersed, due to high levels of mobility. However, global elimination strategies do not consider mobility. We use Call Detail Records from 9 billion calls/texts to model mobility in Namibia; we quantify the epidemic-level impact by using a mathematical framework based on spatial networks. We find complex networks of risk flows dispersed risk countrywide: increasing the risk of acquiring HIV in some areas, decreasing it in others. Overall, 40% of risk was mobility-driven. Networks contained multiple risk hubs. All constituencies (administrative units) imported and exported risk, to varying degrees. A few exported very high levels of risk: their residents infected many residents of other constituencies. Notably, prevalence in the constituency exporting the most risk was below average. Large-scale networks of mobility-driven risk flows underlie generalized HIV epidemics in sub-Saharan Africa. In order to eliminate HIV, it is likely to become increasingly important to implement innovative control strategies that focus on disrupting risk flows.

Evaluating the effect of demographic factors, socioeconomic factors, and risk aversion on mobility during the COVID-19 epidemic in France under lockdown: a population-based study.

Background: On March 17, 2020, French authorities implemented a nationwide lockdown to respond to the COVID-19 epidemic and curb the surge of patients requiring critical care. Assessing the effect of lockdown on individual displacements is essential to quantify achievable mobility reductions and identify the factors driving the changes in social dynamics that affected viral diffusion. We aimed to use mobile phone data to study how mobility in France changed before and during lockdown, breaking down our findings by trip distance, user age and residency, and time of day, and analysing regional data and spatial heterogeneities. Methods: For this population-based study, we used temporally resolved travel flows among 1436 administrative areas of mainland France reconstructed from mobile phone trajectories. Data were stratified by age class (younger than 18 years, 18-64 years, and 65 years or older). We distinguished between residents and non-residents and used population data and regional socioeconomic indicators from the French National Statistical Institute. We measured mobility changes before and during lockdown at both local and country scales using a case-crossover framework. We analysed all trips combined and trips longer than 100 km (termed long trips), and separated trips by daytime or night-time, weekdays or weekends, and rush hours. Findings: Lockdown caused a 65% reduction in the countrywide number of displacements (from about 57 million to about 20 million trips per day) and was particularly effective in reducing work-related short-range mobility, especially during rush hour, and long trips. Geographical heterogeneities showed anomalous increases in long-range movements even before lockdown announcement that were tightly localised in space. During lockdown, mobility drops were unevenly distributed across regions (eg, Île-de-France, the region of Paris, went from 585 000 to 117 000 outgoing trips per day). They were strongly associated with active populations, workers employed in sectors highly affected by lockdown, and number of hospitalisations per region, and moderately associated with the socioeconomic level of the regions. Major cities largely shrank their pattern of connectivity, reducing it mainly to short-range commuting (95% of traffic leaving Paris was contained in a 201 km radius before lockdown, which was reduced to 29 km during lockdown). Interpretation: Lockdown was effective in reducing population mobility across scales. Caution should be taken in the timing of policy announcements and implementation, because anomalous mobility followed policy announcements, which might act as seeding events. Conversely, risk aversion might be beneficial in further decreasing mobility in highly affected regions. We also identified socioeconomic and demographic constraints to the efficacy of restrictions. The unveiled links between geography, demography, and timing of the response to mobility restrictions might help to design interventions that minimise invasiveness while contributing to the current epidemic response. Funding: Agence Nationale de la Recherche, EU, REACTing.