Impact of non-pharmaceutical interventions, weather, vaccination, and variants on COVID-19 transmission across departments in France.

BACKGROUND: Multiple factors shape the temporal dynamics of the COVID-19 pandemic. Quantifying their relative contributions is key to guide future control strategies. Our objective was to disentangle the individual effects of non-pharmaceutical interventions (NPIs), weather, vaccination, and variants of concern (VOC) on local SARS-CoV-2 transmission. METHODS: We developed a log-linear model for the weekly reproduction number (R) of hospital admissions in 92 French metropolitan departments. We leveraged (i) the homogeneity in data collection and NPI definitions across departments, (ii) the spatial heterogeneity in the timing of NPIs, and (iii) an extensive observation period (14 months) covering different weather conditions, VOC proportions, and vaccine coverage levels. FINDINGS: Three lockdowns reduced R by 72.7% (95% CI 71.3-74.1), 70.4% (69.2-71.6) and 60.7% (56.4-64.5), respectively. Curfews implemented at 6/7 pm and 8/9 pm reduced R by 34.3% (27.9-40.2) and 18.9% (12.04-25.3), respectively. School closures reduced R by only 4.9% (2.0-7.8). We estimated that vaccination of the entire population would have reduced R by 71.7% (56.4-81.6), whereas the emergence of VOC (mainly Alpha during the study period) increased transmission by 44.6% (36.1-53.6) compared with the historical variant. Winter weather conditions (lower temperature and absolute humidity) increased R by 42.2% (37.3-47.3) compared to summer weather conditions. Additionally, we explored counterfactual scenarios (absence of VOC or vaccination) to assess their impact on hospital admissions. INTERPRETATION: Our study demonstrates the strong effectiveness of NPIs and vaccination and quantifies the role of weather while adjusting for other confounders. It highlights the importance of retrospective evaluation of interventions to inform future decision-making.

SARS-CoV-2 in Nursing Homes: Analysis of Routine Surveillance Data in Four European Countries.

Transmission of SARS-CoV-2 in nursing homes is poorly documented. Using surveillance data of 228 European private nursing homes, we estimated weekly SARS-CoV-2 incidences among 21,467 residents and 14,371 staff members, compared to that in the general population, between August 3, 2020, and February 20, 2021. We studied the outcomes of "episodes of introduction" where one case was first detected and computed attack rates, reproduction ratio (R), and dispersion parameter (k). Out of 502 episodes of SARS-CoV-2 introduction, 77.1% (95%CI, 73.2%-80.6%) led to additional cases. Attack rates were highly variable, ranging from 0.4% to 86.5%. The R was 1.16 (95%CI, 1.11-1.22) with k at 2.5 (95%CI, 0.5-4.5). The timing of viral circulation in nursing homes did not mirror that in the general population (p-values<0.001). We estimated the impact of vaccination in preventing SARS-CoV-2 transmission. Before vaccination's roll-out, a cumulated 5,579 SARS-CoV-2 infections were documented among residents and 2,321 among staff. Higher staffing ratio and previous natural immunization reduced the probability of an outbreak following introduction. Despite strong preventive measures, transmission likely occurred, regardless of building characteristics. Vaccination started on January 15, 2021, and coverage reached 65.0% among residents, and 42.0% among staff by February 20, 2021. Vaccination yielded a 92% reduction (95%CI, 71%-98%) of outbreak probability, and lowered R to 0.87 (95%CI, 0.69-1.10). In the post-pandemic era, much attention will have to be paid to multi-lateral collaboration, policy making, and prevention plans.

Global patterns and drivers of influenza decline during the COVID-19 pandemic.

OBJECTIVES: The influenza circulation reportedly declined during the COVID-19 pandemic in many countries. The occurrence of this change has not been studied worldwide nor its potential drivers. METHODS: The change in the proportion of positive influenza samples reported by country and trimester was computed relative to the 2014-2019 period using the FluNet database. Random forests were used to determine predictors of change from demographical, weather, pandemic preparedness, COVID-19 incidence, and pandemic response characteristics. Regression trees were used to classify observations according to these predictors. RESULTS: During the COVID-19 pandemic, the influenza decline relative to prepandemic levels was global but heterogeneous across space and time. It was more than 50% for 311 of 376 trimesters-countries and even more than 99% for 135. COVID-19 incidence and pandemic preparedness were the two most important predictors of the decline. Europe and North America initially showed limited decline despite high COVID-19 restrictions; however, there was a strong decline afterward in most temperate countries, where pandemic preparedness, COVID-19 incidence, and social restrictions were high; the decline was limited in countries where these factors were low. The "zero-COVID" countries experienced the greatest decline. CONCLUSION: Our findings set the stage for interpreting the resurgence of influenza worldwide.

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.

Adherence and sustainability of interventions informing optimal control against the COVID-19 pandemic.

BACKGROUND: After one year of stop-and-go COVID-19 mitigation, in the spring of 2021 European countries still experienced sustained viral circulation due to the Alpha variant. As the prospect of entering a new pandemic phase through vaccination was drawing closer, a key challenge remained on how to balance the efficacy of long-lasting interventions and their impact on the quality of life. METHODS: Focusing on the third wave in France during spring 2021, we simulate intervention scenarios of varying intensity and duration, with potential waning of adherence over time, based on past mobility data and modeling estimates. We identify optimal strategies by balancing efficacy of interventions with a data-driven "distress" index, integrating intensity and duration of social distancing. RESULTS: We show that moderate interventions would require a much longer time to achieve the same result as high intensity lockdowns, with the additional risk of deteriorating control as adherence wanes. Shorter strict lockdowns are largely more effective than longer moderate lockdowns, for similar intermediate distress and infringement on individual freedom. CONCLUSIONS: 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.

In the spring of 2021, social distancing measures were strengthened in France to control the third wave of COVID-19 cases. While such measures are needed to slow the spread of the virus, they have a significant impact on the population's quality of life. Here, we use mathematical modelling based on hospital admission data and behavioural and health data (including data on mobility, indicators of social distancing, risk perception, and mental health) to evaluate optimal COVID-19 control strategies. We look at the effects of interventions, their sustainability and the population's adherence to them over time. We find that shorter, more stringent measures are likely to have similar effects on viral circulation and healthcare burden to long-lasting, less stringent but less sustainable interventions. Our findings have implications for the design and implementation of public health measures to control future COVID-19 waves.

An ensemble model based on early predictors to forecast COVID-19 health care demand in France.

Short-term forecasting of the COVID-19 pandemic is required to facilitate the planning of COVID-19 health care demand in hospitals. Here, we evaluate the performance of 12 individual models and 19 predictors to anticipate French COVID-19-related health care needs from September 7, 2020, to March 6, 2021. We then build an ensemble model by combining the individual forecasts and retrospectively test this model from March 7, 2021, to July 6, 2021. We find that the inclusion of early predictors (epidemiological, mobility, and meteorological predictors) can halve the rms error for 14-d­ahead forecasts, with epidemiological and mobility predictors contributing the most to the improvement. On average, the ensemble model is the best or second-best model, depending on the evaluation metric. Our approach facilitates the comparison and benchmarking of competing models through their integration in a coherent analytical framework, ensuring that avenues for future improvements can be identified.

Screening and vaccination against COVID-19 to minimise school closure: a modelling study.

BACKGROUND: Schools were closed extensively in 2020-21 to counter SARS-CoV-2 spread, impacting students' education and wellbeing. With highly contagious variants expanding in Europe, safe options to maintain schools open are urgently needed. By estimating school-specific transmissibility, our study evaluates costs and benefits of different protocols for SARS-CoV-2 control at school. METHODS: We developed an agent-based model of SARS-CoV-2 transmission in schools. We used empirical contact data in a primary and a secondary school and data from pilot screenings in 683 schools during the alpha variant (B.1.1.7) wave in March-June, 2021, in France. We fitted the model to observed school prevalence to estimate the school-specific effective reproductive number for the alpha (Ralpha) and delta (B.1.617.2; Rdelta) variants and performed a cost-benefit analysis examining different intervention protocols. FINDINGS: We estimated Ralpha to be 1·40 (95% CI 1·35-1·45) in the primary school and 1·46 (1·41-1·51) in the secondary school during the spring wave, higher than the time-varying reproductive number estimated from community surveillance. Considering the delta variant and vaccination coverage in Europe as of mid-September, 2021, we estimated Rdelta to be 1·66 (1·60-1·71) in primary schools and 1·10 (1·06-1·14) in secondary schools. Under these conditions, weekly testing of 75% of unvaccinated students (PCR tests on saliva samples in primary schools and lateral flow tests in secondary schools), in addition to symptom-based testing, would reduce cases by 34% (95% CI 32-36) in primary schools and 36% (35-39) in secondary schools compared with symptom-based testing alone. Insufficient adherence was recorded in pilot screening (median ≤53%). Regular testing would also reduce student-days lost up to 80% compared with reactive class closures. Moderate vaccination coverage in students would still benefit from regular testing for additional control-ie, weekly testing 75% of unvaccinated students would reduce cases compared with symptom-based testing only, by 23% in primary schools when 50% of children are vaccinated. INTERPRETATION: The COVID-19 pandemic will probably continue to pose a risk to the safe and normal functioning of schools. Extending vaccination coverage in students, complemented by regular testing with good adherence, are essential steps to keep schools open when highly transmissible variants are circulating. FUNDING: EU Framework Programme for Research and Innovation Horizon 2020, Horizon Europe Framework Programme, Agence Nationale de la Recherche, ANRS-Maladies Infectieuses Émergentes.

Agent-based modelling of reactive vaccination of workplaces and schools against COVID-19.

With vaccination against COVID-19 stalled in some countries, increasing vaccine accessibility and distribution could help keep transmission under control. Here, we study the impact of reactive vaccination targeting schools and workplaces where cases are detected, with an agent-based model accounting for COVID-19 natural history, vaccine characteristics, demographics, behavioural changes and social distancing. In most scenarios, reactive vaccination leads to a higher reduction in cases compared with non-reactive strategies using the same number of doses. The reactive strategy could however be less effective than a moderate/high pace mass vaccination program if initial vaccination coverage is high or disease incidence is low, because few people would be vaccinated around each case. In case of flare-ups, reactive vaccination could better mitigate spread if it is implemented quickly, is supported by enhanced test-trace-isolate and triggers an increased vaccine uptake. These results provide key information to plan an adaptive vaccination rollout.

Lockdown impact on age-specific contact patterns and behaviours, France, April 2020.

BackgroundMany countries implemented national lockdowns to contain the rapid spread of SARS-CoV-2 and avoid overburdening healthcare capacity.AimWe aimed to quantify how the French lockdown impacted population mixing, contact patterns and behaviours.MethodsWe conducted an online survey using convenience sampling and collected information from participants aged 18 years and older between 10 April and 28 April 2020.ResultAmong the 42,036 survey participants, 72% normally worked outside their home, and of these, 68% changed to telework during lockdown and 17% reported being unemployed during lockdown. A decrease in public transport use was reported from 37% to 2%. Participants reported increased frequency of hand washing and changes in greeting behaviour. Wearing masks in public was generally limited. A total of 138,934 contacts were reported, with an average of 3.3 contacts per individual per day; 1.7 in the participants aged 65 years and older compared with 3.6 for younger age groups. This represented a 70% reduction compared with previous surveys, consistent with SARS-CoV2 transmission reduction measured during the lockdown. For those who maintained a professional activity outside home, the frequency of contacts at work dropped by 79%.ConclusionThe lockdown affected the population's behaviour, work, risk perception and contact patterns. The frequency and heterogeneity of contacts, both of which are critical factors in determining how viruses spread, were affected. Such surveys are essential to evaluate the impact of lockdowns more accurately and anticipate epidemic dynamics in these conditions.

SARS-CoV-2 transmission across age groups in France and implications for control.

The shielding of older individuals has been proposed to limit COVID-19 hospitalizations while relaxing general social distancing in the absence of vaccines. Evaluating such approaches requires a deep understanding of transmission dynamics across ages. Here, we use detailed age-specific case and hospitalization data to model the rebound in the French epidemic in summer 2020, characterize age-specific transmission dynamics and critically evaluate different age-targeted intervention measures in the absence of vaccines. We find that while the rebound started in young adults, it reached individuals aged ≥80 y.o. after 4 weeks, despite substantial contact reductions, indicating substantial transmission flows across ages. We derive the contribution of each age group to transmission. While shielding older individuals reduces mortality, it is insufficient to allow major relaxations of social distancing. When the epidemic remains manageable (R close to 1), targeting those most contributing to transmission is better than shielding at-risk individuals. Pandemic control requires an effort from all age groups.

Common communicable diseases in the general population in France during the COVID-19 pandemic.

In France, social distancing measures have been adopted to contain the spread of COVID-19, culminating in national Lockdowns. The use of hand washing, hydro-alcoholic rubs and mask-wearing also increased over time. As these measures are likely to impact the transmission of many communicable diseases, we studied the changes in common infectious diseases incidence in France during the first year of COVID-19 circulation. We examined the weekly incidence of acute gastroenteritis, chickenpox, acute respiratory infections and bronchiolitis reported in general practitioner networks since January 2016. We obtained search engine query volume for French terms related to these diseases and sales data for relevant drugs over the same period. A periodic regression model was fit to disease incidence, drug sales and search query volume before the COVID-19 period and extrapolated afterwards. We compared the expected values with observations made in 2020. During the first lockdown period, incidence dropped by 67% for gastroenteritis, by 79% for bronchiolitis, by 49% for acute respiratory infection and 90% for chickenpox compared to the past years. Reductions with respect to the expected incidence reflected the strength of implemented measures. Incidence in children was impacted the most. Reduction in primary care consultations dropped during a short period at the beginning of the first lockdown period but remained more than 95% of the expected value afterwards. In primary care, the large decrease in reported gastroenteritis, chickenpox or bronchiolitis observed during the period where many barrier measures were implemented imply that the circulation of common viruses was reduced and informs on the overall effect of these measures.

Risk of COVID-19 variant importation - How useful are travel control measures?

We consider models for the importation of a new variant COVID-19 strain in a location already seeing propagation of a resident variant. By distinguishing contaminations generated by imported cases from those originating in the community, we are able to evaluate the contribution of importations to the dynamics of the disease in a community. We find that after an initial seeding, the role of importations becomes marginal compared to that of community-based propagation. We also evaluate the role of two travel control measures, quarantine and travel interruptions. We conclude that quarantine is an efficacious way of lowering importation rates, while travel interruptions have the potential to delay the consequences of importations but need to be applied within a very tight time window following the initial emergence of the variant.

A modelling study investigating short and medium-term challenges for COVID-19 vaccination: From prioritisation to the relaxation of measures.

BACKGROUND: The roll-out of COVID-19 vaccines is a multi-faceted challenge whose performance depends on pace of vaccination, vaccine characteristics and heterogeneities in individual risks. METHODS: We developed a mathematical model accounting for the risk of severe disease by age and comorbidity, and transmission dynamics. We compared vaccine prioritisation strategies in the early roll-out stage and quantified the extent to which measures could be relaxed as a function of the vaccine coverage achieved in France. FINDINGS: Prioritizing at-risk individuals reduces morbi-mortality the most if vaccines only reduce severity, but is of less importance if vaccines also substantially reduce infectivity or susceptibility. Age is the most important factor to consider for prioritization; additionally accounting for comorbidities increases the performance of the campaign in a context of scarce resources. Vaccinating 90% of ≥65 y.o. and 70% of 18-64 y.o. before autumn 2021 with a vaccine that reduces severity by 90% and susceptibility by 80%, we find that control measures reducing transmission rates by 15-27% should be maintained to remain below 1000 daily hospital admissions in France with a highly transmissible variant (basic reproduction number R0  = 4). Assuming 90% of ≥65 y.o. are vaccinated, full relaxation of control measures might be achieved with a vaccine coverage of 89-100% in 18-64 y.o or 60-69% of 0-64 y.o. INTERPRETATION: Age and comorbidity-based vaccine prioritization strategies could reduce the burden of the disease. Very high vaccination coverage may be required to completely relax control measures. Vaccination of children, if possible, could lower coverage targets necessary to achieve this objective.

Benefits and risks associated with different uses of the COVID-19 vaccine Vaxzevria: a modelling study, France, May to September 2021.

Thrombosis with thrombocytopenia (TTS) has been identified as a rare adverse event following COVID-19 vaccination with Vaxzevria. We modelled the benefits and risks of Vaxzevria distribution from May to September 2021 in metropolitan France where other vaccines are available, considering French hospitalisation data and European data on TTS. Across different scenarios, benefits of Vaxzevria distribution in people 55 years and older exceeded the risk of death from COVID-19. In young adults, risks were at least of similar magnitude as benefits.

Lockdown as a last resort option in case of COVID-19 epidemic rebound: a modelling study.

BackgroundGiven its high economic and societal cost, policymakers might be reluctant to implement a large-scale lockdown in case of coronavirus disease (COVID-19) epidemic rebound. They may consider it as a last resort option if alternative control measures fail to reduce transmission.AimWe developed a modelling framework to ascertain the use of lockdown to ensure intensive care unit (ICU) capacity does not exceed a peak target defined by policymakers.MethodsWe used a deterministic compartmental model describing transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the trajectories of COVID-19 patients in healthcare settings, accounting for age-specific mixing patterns and an increasing probability of severe outcomes with age. The framework is illustrated in the context of metropolitan France.ResultsThe daily incidence of ICU admissions and the number of occupied ICU beds are the most robust indicators to decide when a lockdown should be triggered. When the doubling time of hospitalisations estimated before lockdown is between 8 and 20 days, lockdown should be enforced when ICU admissions reach 3.0-3.7 and 7.8-9.5 per million for peak targets of 62 and 154 ICU beds per million (4,000 and 10,000 beds for metropolitan France), respectively. When implemented earlier, the lockdown duration required to get back below a desired level is also shorter.ConclusionsWe provide simple indicators and triggers to decide if and when a last-resort lockdown should be implemented to avoid saturation of ICU. These metrics can support the planning and real-time management of successive COVID-19 pandemic waves.

SARS-CoV-2 transmission among children and staff in daycare centres during a nationwide lockdown in France: a cross-sectional, multicentre, seroprevalence study.

BACKGROUND: The extent to which very young children contribute to the transmission of SARS-CoV-2 is unclear. We aimed to estimate the seroprevalence of antibodies against SARS-CoV-2 in daycare centres that remained open for key workers' children during a nationwide lockdown in France. METHODS: Children and staff who attended one of 22 daycare centres during a nationwide lockdown in France (between March 15 and May 9, 2020) were included in this cross-sectional, multicentre, seroprevalence study. Hospital staff not occupationally exposed to patients with COVID-19, or to children, were enrolled in a comparator group. The primary outcome was SARS-CoV-2 seroprevalence in children, daycare centre staff, and the comparator group. The presence of antibodies against SARS-CoV-2 in capillary whole blood was measured with a rapid chromatographic immunoassay. We computed raw prevalence as the percentage of individuals with a positive IgG or IgM test, and used Bayesian smoothing to account for imperfect sensitivity and specificity of the assay. This study is registered with ClinicalTrials.gov, NCT04413968. FINDINGS: Between June 4 and July 3, 2020, we enrolled 327 children (mean age 1·9 [SD 0·9] years; range 5 months to 4·4 years), 197 daycare centre staff (mean age 40 [12] years), and 164 adults in the comparator group (42 [12] years). Positive serological tests were observed for 14 children (raw seroprevalence 4·3%; 95% CI 2·6-7·1) and 14 daycare centre staff (7·7%; 4·2-11·6). After accounting for imperfect sensitivity and specificity of the assay, we estimated that 3·7% (95% credible interval [95% CrI] 1·3-6·8) of the children and 6·8% (3·2-11·5) of daycare centre staff had SARS-CoV-2 infection. The comparator group fared similarly to the daycare centre staff; nine participants had a positive serological test (raw seroprevalence 5·5%; 95% CI 2·9-10·1), leading to a seroprevalence of 5·0% (95% CrI 1·6-9·8) after accounting for assay characteristics. An exploratory analysis suggested that seropositive children were more likely than seronegative children to have been exposed to an adult household member with laboratory-confirmed COVID-19 (six [43%] of 14 vs 19 [6%] of 307; relative risk 7·1 [95% CI 2·2-22·4]). INTERPRETATION: According to serological test results, the proportion of young children in our sample with SARS-CoV-2 infection was low. Intrafamily transmission seemed more plausible than transmission within daycare centres. Further epidemiological studies are needed to confirm this exploratory hypothesis. FUNDING: Assistance Publique-Hôpitaux de Paris; Mairie de Paris, Conseil Départemental de Seine Saint Denis. TRANSLATIONS: For the French translation of the abstract see Supplementary Materials section.

Evolution of outcomes for patients hospitalised during the first 9 months of the SARS-CoV-2 pandemic in France: A retrospective national surveillance data analysis.

BACKGROUND: As SARS-CoV-2 continues to spread, a thorough characterisation of healthcare needs and patient outcomes, and how they have changed over time, is essential to inform planning. METHODS: We developed a probabilistic framework to analyse detailed patient trajectories from 198,846 hospitalisations in France during the first nine months of the pandemic. Our model accounts for the varying age- and sex- distribution of patients, and explore changes in outcome probabilities as well as length of stay. FINDINGS: We found that there were marked changes in the age and sex of hospitalisations over the study period. In particular, the proportion of hospitalised individuals that were >80y varied between 27% and 48% over the course of the epidemic, and was lowest during the inter-peak period. The probability of hospitalised patients entering ICU dropped from 0·25 (0·24-0·26) to 0·13 (0·12-0·14) over the four first months as case numbers fell, before rising to 0·19 (0·19-0·20) during the second wave. The probability of death followed a similar trajectory, falling from 0·25 (0·24-0·26) to 0·10 (0·09-0·11) after the first wave before increasing again during the second wave to 0·19 (0·18-0·19). Overall, we find both the probability of death and the probability of entering ICU were significantly correlated with COVID-19 ICU occupancy. INTERPRETATION: There are large scale trends in patients outcomes by age, sex and over time. These need to be considered in ongoing healthcare planning efforts. FUNDING: INCEPTION.