Comparing the Performance of Three Models Incorporating Weather Data to Forecast Dengue Epidemics in Reunion Island, 2018-2019.

We developed mathematical models to analyze a large dengue virus (DENV) epidemic in Reunion Island in 2018-2019. Our models captured major drivers of uncertainty including the complex relationship between climate and DENV transmission, temperature trends, and underreporting. Early assessment correctly concluded that persistence of DENV transmission during the austral winter 2018 was likely and that the second epidemic wave would be larger than the first one. From November 2018, the detection probability was estimated at 10%-20% and, for this range of values, our projections were found to be remarkably accurate. Overall, we estimated that 8% and 18% of the population were infected during the first and second wave, respectively. Out of the 3 models considered, the best-fitting one was calibrated to laboratory entomological data, and accounted for temperature but not precipitation. This study showcases the contribution of modeling to strengthen risk assessments and planning of national and local authorities.

Impact of vaccination against severe COVID-19 in the French population aged 50 years and above: a retrospective population-based study.

BACKGROUND: Given the widespread implementation of COVID-19 vaccination to mitigate the pandemic from the end of 2020, it is important to retrospectively evaluate its impact, in particular by quantifying the number of severe outcomes prevented through vaccination. METHODS: We estimated the number of hospitalizations, intensive care unit (ICU) admissions and deaths directly averted by vaccination in France, in people aged ≥ 50 years, from December 2020 to March 2022, based on (1) the number of observed events, (2) vaccination coverage, and (3) vaccine effectiveness. We accounted for the effect of primary vaccination and the first booster dose, the circulating variants, the age groups, and the waning of vaccine-induced protection over time. RESULTS: An estimated 480,150 (95% CI: 260,072-582,516) hospitalizations, 132,156 (50,409-157,767) ICU admissions and 125,376 (53,792-152,037) deaths were directly averted by vaccination in people aged ≥ 50 years, which corresponds to a reduction of 63.2% (48.2-67.6), 68.7% (45.6-72.4) and 62.7% (41.9-67.1) respectively, compared to what would have been expected without vaccination over the study period. An estimated 5852 (2285-6853) deaths were directly averted among the 50-59 years old, 16,837 (6568-19,473) among the 60-69 years old, 32,136 (13,651-36,758) among the 70-79 years old and 70,551 (31,288-88,953) among the ≥ 80 years old. CONCLUSIONS: The vaccination campaign in France considerably reduced COVID-19 morbidity and mortality, as well as stress on the healthcare system.

Monitoring the reproductive number of COVID-19 in France: Comparative estimates from three datasets.

BACKGROUND: The effective reproduction number (Rt) quantifies the average number of secondary cases caused by one person with an infectious disease. Near-real-time monitoring of Rt during an outbreak is a major indicator used to monitor changes in disease transmission and assess the effectiveness of interventions. The estimation of Rt usually requires the identification of infected cases in the population, which can prove challenging with the available data, especially when asymptomatic people or with mild symptoms are not usually screened. The purpose of this study was to perform sensitivity analysis of Rt estimates for COVID-19 surveillance in France based on three data sources with different sensitivities and specificities for identifying infected cases. METHODS: We applied a statistical method developed by Cori et al. to estimate Rt using (1) confirmed cases identified from positive virological tests in the population, (2) suspected cases recorded by a national network of emergency departments, and (3) COVID-19 hospital admissions recorded by a national administrative system to manage hospital organization. RESULTS: Rt estimates in France from May 27, 2020, to August 12, 2022, showed similar temporal trends regardless of the dataset. Estimates based on the daily number of confirmed cases provided an earlier signal than the two other sources, with an average lag of 3 and 6 days for estimates based on emergency department visits and hospital admissions, respectively. CONCLUSION: The COVID-19 experience confirmed that monitoring temporal changes in Rt was a key indicator to help the public health authorities control the outbreak in real time. However, gaining access to data on all infected people in the population in order to estimate Rt is not straightforward in practice. As this analysis has shown, the opportunity to use more readily available data to estimate Rt trends, provided that it is highly correlated with the spread of infection, provides a practical solution for monitoring the COVID-19 pandemic and indeed any other epidemic.

Two-dose measles vaccine effectiveness remains high over time: A French observational study, 2017-2019.

BACKGROUND: From 2008 to 2019, France has experienced a resurgence of measles epidemics. Surveillance data have shown that the proportion of cases vaccinated with two doses of measles-containing vaccine (MCV) increased with age, raising concerns about the duration of vaccine protection. Our objectives were to investigate age-stratified vaccine effectiveness (VE) for the second dose of MCV (MCV2) and to quantify protection levels over time. METHODS: We analyzed data on measles cases aged 2-31 years, reported via mandatory notification to the French measles surveillance system from October 2017 to September 2019. We estimated an age-stratified VE for MCV2 using the screening method, which compares the vaccination status of cases with that of the general population. We improved this method by accounting for natural immunity, exploring four scenarios with four possible levels of natural immunity in the population. In addition, we quantified the decay rate of protection over time, by fitting an exponential decay model among individuals vaccinated in early life. RESULTS: In the baseline analysis (absence of natural immunity), VE estimates were high in all age groups and decreased with age, from 99.6 % (95 % confidence interval: 99.3-99.8) in 2-5 years old to 91.4 % (85.1-95.0) in 26-31 years old. Accounting for natural immunity increased VE in the older age group to 93.2-99.2 % depending on the scenario. We estimated that VE was slowly decreasing over time, with an exponential decay rate of 0.0022/year (0.0017-0.0028), leading to VE of 96.7 % (96.0-97.4) 16 years after MCV2 vaccination. This decline was most compatible with scenario 2, a scenario of 4.4 % naturally immunized, non-vaccinated individuals in the 26-31 years old. CONCLUSION: Our study confirms the continued high effectiveness of two doses of MCV with only slight degradation, decades after immunization. These findings support the importance of achieving a very high vaccination coverage with 2 doses of MCV.

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.

Vaccine effectiveness and duration of protection of COVID-19 mRNA vaccines against Delta and Omicron BA.1 symptomatic and severe COVID-19 outcomes in adults aged 50 years and over in France.

The emergence of SARS-CoV-2 variants calls for continuous monitoring of vaccine effectiveness (VE). We estimated the absolute effectiveness of complete 2-dose primary vaccination and booster vaccination with COVID-19 mRNA vaccines, and the duration of protection against Delta and Omicron BA.1 symptomatic infection and severe outcomes. French residents aged ≥50 years, who presented with SARS-CoV-2-like symptoms and tested for SARS-CoV-2 between June 6, 2021 and February 10, 2022 were included. A test-negative study was conducted to estimate VE against symptomatic infection, using conditional logistic regression models. Cox proportional hazard regressions were performed to assess additional protection against severe COVID-19 outcomes (any hospitalization, and intensive care units [ICU] admission or in-hospital death). In total, 273732 cases and 735 919 controls were included. VE against symptomatic infection after 2-doses vaccination was 86% (95% CI: 75-92%) for Delta and 70% (58-79%) for Omicron, 7-30 days post vaccination. Protection waned over time, reaching 60% (57-63%) against Delta and 20% (16.-24%) for Omicron BA.1 > 120 days after vaccination. The booster dose fully restored protection against symtpomatic Delta infection (95% [81-99%]) but only partially against symptomatic Omicron BA.1 infection (63% [59-67%]). VE against Delta-related severe outcomes was above 95% with 2 doses, and persisted for at least four months. Protection against any Omicron BA.1-hospitalization was 92% (65%-99%) at 8-30 days, and 82% (67%-91%) > 120 days from the second dose. Against BA.1 ICU admission or in-patient death, VE stood at 98% (0-100%) at 8-30 days, and was 90% (40-99%) > 120 days from the second dose. Protection confered by mRNA vaccines against severe disease caused by either Delta or Omicron BA.1 appeared high and sustained over time. Protection against symptomatic diseases after 2 doses decreased rapidly, especially against Omicron BA.1. A booster dose restored high protection against Delta but only a partial one against Omicron BA.1.

Modelling the end of a Zero-COVID strategy using nirmatrelvir/ritonavir, vaccination and NPIs in Wallis and Futuna.

Background: Ending Zero-COVID is challenging, particularly when vaccine coverage is low. Considering Wallis and Futuna, a French Zero-COVID territory affected by reluctance to vaccination, low immunity and high levels of comorbidities, we investigate how targeted use of nirmatrelvir/ritonavir (brand name Paxlovid) can complement vaccination and non-pharmaceutical interventions (NPIs), and mitigate the epidemic rebound expected when Zero-COVID ends. Methods: We developed a discrete age-stratified compartmental model describing SARS-CoV-2 spread and healthcare impact once Wallis and Futuna reopens. It accounts for comorbidity risk groups (CRG), vaccine coverage (2 doses, 3 doses), the effectiveness of vaccines (recent or old injection), treatments and NPIs. In our baseline scenario, cases aged 65+ in intermediate/high CRG and 40+ in high CRG are eligible for treatment. Findings: The epidemic is expected to start 13-20 days after reopening with a doubling time of 1.6-3.7 days. For medium transmission intensity (R0 = 5), 134 (115-156) hospital admissions are expected within 3 months, with no pharmaceutical measures. In our baseline scenario, admissions are reduced by 11%-21% if 50% of the target group receive treatment, with maximum impact when combined with NPIs and vaccination. The number of hospitalisations averted (HA) per patient treated (PT) is maximum when 65+ in high CRG are targeted (0.124 HA/PT), quickly followed by 65+ in intermediate/high CRG (0.097 HA/PT), and any 65+ (0.093 HA/PT). Expanding the target group increases both PT and HA, but marginal gains diminish. Interpretation: Modelling suggests that test and treat may contribute to the mitigation of epidemic rebounds at the end of Zero-COVID, particularly in populations with low immunity and high levels of comorbidities. Funding: RECOVER, VEO, AXA, Groupama, SpF, IBEID, INCEPTION, EMERGEN.

Reconstructing Mayotte 2018-19 Rift Valley Fever outbreak in humans by combining serological and surveillance data.

BACKGROUND: Rift Valley Fever (RVF) is a zoonosis that affects large parts of Africa and the Arabian Peninsula. RVF virus (RVFV) is transmitted to humans through contacts with infected animals, animal products, mosquito bites or aerosols. Its pathogenesis in humans ranges from asymptomatic forms to potentially deadly haemorrhagic fevers, and the true burden of human infections during outbreaks is generally unknown. METHODS: We build a model fitted to both passive surveillance data and serological data collected throughout a RVF epidemic that occurred in Mayotte Island in 2018-2019. RESULTS: We estimate that RVFV infected 10,797 (95% CrI 4,728-16,127) people aged ≥15 years old in Mayotte during the entire outbreak, among which only 1.2% (0.67%-2.2%) were reported to the syndromic surveillance system. RVFV IgG seroprevalence in people ≥15 years old was estimated to increase from 5.5% (3.6%-7.7%) before the outbreak to 12.9% (10.4%-16.3%) thereafter. CONCLUSIONS: Our results suggest that a large part of RVFV infected people present subclinical forms of the disease and/or do not reach medical care that could lead to their detection by the surveillance system. This may threaten the implementation of exhaustive RVF surveillance and adequate control programs in affected countries.

Rift Valley Fever (RVF) is a disease caused by a virus transmitted from livestock animals to humans by mosquito bites, aerosols or direct contact with infected animals or animal products. In some parts of Africa and the Arabian Peninsula, the virus can lead to large outbreaks in both humans and animals. Despite some infected people developing severe forms of the disease, some experience no or mild symptoms. Therefore, infection is often not detected by surveillance systems based on the reporting of symptoms by patients. Here, we use data collected during a RVF outbreak that occurred in 2018­2019 in Mayotte Island, in the Indian Ocean, to model the course of the outbreak in humans. We estimate that, throughout the epidemic, only 1.2% of infected people were detected by the surveillance system. Our results highlight that most human cases may go unreported during RVF outbreaks, making it difficult to monitor the burden of infections.

Seroepidemiology of enterovirus A71 infection in prospective cohort studies of children in southern China, 2013-2018.

Enterovirus A71 (EV-A71)-related hand, foot, and mouth disease (HFMD) imposes a substantial clinical burden in the Asia Pacific region. To inform policy on the introduction of the EV-A71 vaccine into the National Immunization Programme, we investigated the seroepidemiological characteristics of EV-A71 in two prospective cohorts of children in southern China conducted between 2013 and 2018. Our results show that maternal antibody titres declined rapidly in neonates, with over half becoming susceptible to EV-A71 at 1 month of age. Between 6 months and 2 years of age, over 80% of study participants were susceptible, while one third remained susceptible at 5 years old. The highest incidence of EV-A71 infections was observed in children aged 5-6 months. Our findings support EV-A71 vaccination before 6 months for birth cohorts in southern China, potentially with a one-time catch-up vaccination for children 6 months-5 years old. More regionally representative longitudinal seroepidemiological studies are needed to further validate these findings.

Analytical framework to evaluate and optimize the use of imperfect diagnostics to inform outbreak response: Application to the 2017 plague epidemic in Madagascar.

During outbreaks, the lack of diagnostic "gold standard" can mask the true burden of infection in the population and hamper the allocation of resources required for control. Here, we present an analytical framework to evaluate and optimize the use of diagnostics when multiple yet imperfect diagnostic tests are available. We apply it to laboratory results of 2,136 samples, analyzed with 3 diagnostic tests (based on up to 7 diagnostic outcomes), collected during the 2017 pneumonic (PP) and bubonic plague (BP) outbreak in Madagascar, which was unprecedented both in the number of notified cases, clinical presentation, and spatial distribution. The extent of these outbreaks has however remained unclear due to nonoptimal assays. Using latent class methods, we estimate that 7% to 15% of notified cases were Yersinia pestis-infected. Overreporting was highest during the peak of the outbreak and lowest in the rural settings endemic to Y. pestis. Molecular biology methods offered the best compromise between sensitivity and specificity. The specificity of the rapid diagnostic test was relatively low (PP: 82%, BP: 85%), particularly for use in contexts with large quantities of misclassified cases. Comparison with data from a subsequent seasonal Y. pestis outbreak in 2018 reveal better test performance (BP: specificity 99%, sensitivity: 91%), indicating that factors related to the response to a large, explosive outbreak may well have affected test performance. We used our framework to optimize the case classification and derive consolidated epidemic trends. Our approach may help reduce uncertainties in other outbreaks where diagnostics are imperfect.

Association between the COVID-19 pandemic and pertussis derived from multiple nationwide data sources, France, 2013 to 2020.

BackgroundInterventions to mitigate the COVID-19 pandemic may impact other respiratory diseases.AimsWe aimed to study the course of pertussis in France over an 8-year period including the beginning of the COVID-19 pandemic and its association with COVID-19 mitigation strategies, using multiple nationwide data sources and regression models.MethodsWe analysed the number of French pertussis cases between 2013 and 2020, using PCR test results from nationwide outpatient laboratories (Source 1) and a network of the paediatric wards from 41 hospitals (Source 2). We also used reports of a national primary care paediatric network (Source 3). We conducted a quasi-experimental interrupted time series analysis, relying on negative binomial regression models. The models accounted for seasonality, long-term cycles and secular trend, and included a binary variable for the first national lockdown (start 16 March 2020).ResultsWe identified 19,039 pertussis cases from these data sources. Pertussis cases decreased significantly following the implementation of mitigation measures, with adjusted incidence rate ratios of 0.10 (95% CI: 0.04-0.26) and 0.22 (95% CI: 0.07-0.66) for Source 1 and Source 2, respectively. The association was confirmed in Source 3 with a median of, respectively, one (IQR: 0-2) and 0 cases (IQR: 0-0) per month before and after lockdown (p = 0.0048).ConclusionsThe strong reduction in outpatient and hospitalised pertussis cases suggests an impact of COVID-19 mitigation measures on pertussis epidemiology. Pertussis vaccination recommendations should be followed carefully, and disease monitoring should be continued to detect any resurgence after relaxation of mitigation measures.

Comparing the age and sex trajectories of SARS-CoV-2 morbidity and mortality with other respiratory pathogens.

Comparing age and sex differences in SARS-CoV-2 hospitalization and mortality with MERS-CoV, seasonal coronaviruses, influenza and other health outcomes opens the way to generating hypotheses as to underlying mechanisms driving disease risk. Using 60-year-olds as a reference age group, we find that relative rates of hospitalization and mortality associated with the emergent coronaviruses are lower during childhood and start to increase earlier (around puberty) as compared with influenza and seasonal coronaviruses. The changing distribution of disease risk by age for emerging pathogens appears to broadly track the gradual deterioration of the immune system (immunosenescence), which starts around puberty. By contrast, differences in severe disease risk by age from endemic pathogens are more decoupled from the immune ageing process. Intriguingly, age-specific sex differences in hospitalizations are largely similar across endemic and emerging infections. We discuss potential mechanisms that may be associated with these patterns.

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.

Early chains of transmission of COVID-19 in France, January to March 2020.

IntroductionSARS-CoV-2, the virus that causes COVID-19, has spread rapidly worldwide. In January 2020, a surveillance system was implemented in France for early detection of cases and their contacts to help limit secondary transmissions.AimTo use contact-tracing data collected during the initial phase of the COVID-19 pandemic to better characterise SARS-CoV-2 transmission.MethodsWe analysed data collected during contact tracing and retrospective epidemiological investigations in France from 24 January to 30 March 2020. We assessed the secondary clinical attack rate and characterised the risk of a contact becoming a case. We described chains of transmission and estimated key parameters of spread.ResultsDuring the study period, 6,082 contacts of 735 confirmed cases were traced. The overall secondary clinical attack rate was 4.1% (95% confidence interval (CI): 3.6-4.6), increasing with age of index case and contact. Compared with co-workers/friends, family contacts were at higher risk of becoming cases (adjusted odds ratio (AOR): 2.1, 95% CI: 1.4-3.0) and nosocomial contacts were at lower risk (AOR: 0.3, 95% CI: 0.1-0.7). Of 328 infector/infectee pairs, 49% were family members. The distribution of secondary cases was highly over-dispersed: 80% of secondary cases were caused by 10% of cases. The mean serial interval was 5.1 days (interquartile range (IQR): 2-8 days) in contact tracing pairs, where late transmission events may be censored, and 6.8 (3-8) days in pairs investigated retrospectively.ConclusionThis study increases knowledge of SARS-CoV-2 transmission, including the importance of superspreading events during the onset of the pandemic.

Impact of booster vaccination on the control of COVID-19 Delta wave in the context of waning immunity: application to France in the winter 2021/22.

Europe has experienced a large COVID-19 wave caused by the Delta variant in winter 2021/22. Using mathematical models applied to Metropolitan France, we find that boosters administered to ≥ 65, ≥ 50 or ≥ 18 year-olds may reduce the hospitalisation peak by 25%, 36% and 43% respectively, with a delay of 5 months between second and third dose. A 10% reduction in transmission rates might further reduce it by 41%, indicating that even small increases in protective behaviours may be critical to mitigate the wave.

Effect of change in vaccine schedule on pertussis epidemiology in France: a modelling and serological study.

BACKGROUND: In April-May, 2013, France modified its pertussis vaccination schedule, which uses the acellular pertussis vaccine, from three primary doses at 2, 3, and 4 months of age and a first booster at 16-18 months of age (former schedule) to two primary doses at 2 and 4 months of age and a first booster at 11 months of age (new schedule). We aimed to assess the subsequent effect of the vaccine schedule change on pertussis epidemiology in France. METHODS: In this modelling study, using data collected between Jan 1, 2012, and Dec 31, 2019, from French national surveillance sources, we analysed the PCR test results of nasopharyngeal swabs collected from symptomatic outpatients aged 2-20 years with suspected pertussis. We developed a negative binomial regression model for the number of confirmed pertussis cases by year and age to assess the relative risks of pertussis depending on vaccine schedule. The linear predictor included the year, the age group, the population size, and a proxy of waning immunity. We tested different models in which waning immunity could vary with vaccine schedule and type of primary vaccine. The models were fitted to the 2012-18 data via Bayesian Markov chain Monte Carlo sampling, and the 2019 data were left out for external model validation. We also compared the anti-pertussis toxin (PT) antibody concentrations in leftover sera from children not tested for pertussis or recent respiratory tract infection aged 2-5 years born before and after the vaccine schedule change. FINDINGS: We collected data on 7493 confirmed cases of pertussis. The model that best fitted the 2012-18 epidemiological data supported a faster waning of immunity following vaccination with the new vaccine schedule. 3 years after vaccination, the risk of developing pertussis was 1·7 (95% CI 1·4-2·0) times higher for children vaccinated according to the new schedule than those vaccinated according to the former schedule. The model correctly predicted the age distribution of cases in 2019. Geometric mean concentrations (GMC) of anti-PT IgG were 50% lower in children aged 2 years vaccinated with the new schedule (GMC=5·85 IU/mL [95% CI 4·08-8·39]) than in children of the same age vaccinated with the former schedule (GMC=11·62 IU/mL [95% CI 9·05-14·92]; p=0·0016), and 43% lower in children aged 3 years vaccinated with the new schedule (GMC=3·88 IU/mL [95% CI 2·82-5·34]) than those with the former schedule (GMC=6·80 IU/mL [95% CI 4·77-9·70]; p=0·026). INTERPRETATION: A shorter-lived protection induced by the new vaccine schedule recommended in France since 2013 is associated with an increase of pertussis cases in children aged 2-5 years. If similar findings are observed in other countries and clinical trials, these findings should be considered in future pertussis vaccination policies. FUNDING: INCEPTION, Labex-IBEID, Institut Pasteur, and Santé Publique France.

Impact of SARS-CoV-2 Delta variant on incubation, transmission settings and vaccine effectiveness: Results from a nationwide case-control study in France.

BACKGROUND: We aimed to assess the settings and activities associated with SARS-CoV-2 infection in the context of B.1.617.2 (Delta) variant circulation in France, as well as the protection against symptomatic Delta infection. METHODS: In this nationwide case-control study, cases were SARS-CoV-2 infected adults recruited between 23 May and 13 August 2021. Controls were non-infected adults from a national representative panel matched to cases by age, sex, region, population density and calendar week. Participants completed an online questionnaire and multivariable logistic regression analysis was used to determine the association between acute SARS-CoV-2 infection and recent activity-related exposures, past history of SARS-CoV-2 infection, and COVID-19 vaccination. FINDINGS: We did not find any differences in the settings and activities associated with Delta versus non-Delta infections and grouped them for subsequent analyses. In multivariable analysis involving 12634 cases (8644 Delta and 3990 non-Delta) and 5560 controls, we found individuals under 40 years and attending bars (aOR:1.9; 95%CI:1.6-2.2) or parties (aOR:3.4; 95%CI:2.8-4.2) to be at increased risk of infection. In those aged 40 years and older, having children attend daycare (aOR:1.9; 95%CI:1.1-3.3), kindergarten (aOR:1.6; 95%CI:1.2-2.1), primary school (aOR:1.4; 95%CI:1.2-1.6) or middle school (aOR:1.3; 95%CI:1.2-1.6) were associated with increased risk of infection. We found strong protection against symptomatic Delta infection for those with prior infection whether it was recent (2-6 months) (95%; 95%CI:90-97) or associated with one dose (85%; 95%CI:78-90) or two doses of mRNA vaccine (96%; 95%CI:87-99). For those without past infection, protection was lower with two doses of mRNA vaccine (67%; 95%CI:63-71). INTERPRETATION: In line with other observational studies, we find reduced vaccine effectiveness against symptomatic Delta infections. The settings and activities at increased risk of infection indicate where efforts to reinforce individual and public health measures need to be concentrated.

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.

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.

Exposures associated with SARS-CoV-2 infection in France: A nationwide online case-control study.

BACKGROUND: We aimed to assess the role of different setting and activities in acquiring SARS-CoV-2 infection. METHODS: In this nationwide case-control study, cases were SARS-CoV-2 infected adults recruited between 27 October and 30 November 2020. Controls were individuals from the Ipsos market research database matched to cases by age, sex, region, population density and time period. Participants completed an online questionnaire on recent activity-related exposures. FINDINGS: Among 3426 cases and 1713 controls, in multivariable analysis, we found an increased risk of infection associated with any additional person living in the household (adjusted-OR: 1•16; 95%CI: 1•11-1•21); having children attending day-care (aOR: 1•31; 95%CI: 1•02-1•62), kindergarten (aOR: 1•27; 95%CI: 1•09-1•45), middle school (aOR: 1•30; 95%CI: 1•15-1•47), or high school (aOR: 1•18; 95%CI: 1•05-1•34); with attending professional (aOR: 1•15; 95%CI: 1•04-1•26) or private gatherings (aOR: 1•57; 95%CI: 1•45-1•71); and with having frequented bars and restaurants (aOR: 1•95; 95%CI: 1•76-2•15), or having practiced indoor sports activities (aOR: 1•36; 95%CI: 1•15-1•62). We found no increase in risk associated with frequenting shops, cultural or religious gatherings, or with transportation, except for carpooling (aOR: 1•47; 95%CI: 1•28-1•69). Teleworking was associated with decreased risk of infection (aOR: 0•65; 95%CI: 0•56-0•75). INTERPRETATION: Places and activities during which infection prevention and control measures may be difficult to fully enforce were those with increased risk of infection. Children attending day-care, kindergarten, middle and high schools, but not primary schools, were potential sources of infection for the household. FUNDING: Institut Pasteur, Research & Action Emerging Infectious Diseases (REACTing), Fondation de France (Alliance" Tous unis contre le virus").