Association between the COVID-19 pandemic and pertussis in France using multiple nationwide data sources (preprint)

Background: Interventions to mitigate coronavirus disease 19 (COVID-19) pandemic may impact other respiratory diseases such as pertussis. We aimed to study the course of pertussis in France over an 8-year period and its association with COVID-19 mitigation strategies, using multiple nationwide data sources. Methods: We analyzed the number of French pertussis cases between 2013 and 2020, using the PCR test results from nationwide outpatient laboratories (Source 1) and the pediatric network of 41 hospitals (Source 2), and using the reports of an office-based pediatric national network (Source 3). We conducted a quasi-experimental interrupted time-series analysis, relying on negative binomial regression models. The models accounted for seasonality, longterm cycles, and secular trend, and included a binary variable for the first national lockdown (ordered on March 16, 2021). Results: We identified 19,039 cases of pertussis from the three data sources during the study period. There was a significant decrease of pertussis cases following the implementation of mitigation measures, with adjusted incidence rate ratios of 0.102 (95% CI 0.040-0.256) and 0.216 (95% CI 0.071-0.656) for Source 1 and Source 2, respectively. The association was confirmed in Source 3 (median of 1 [IQR 0-2] vs. 0 [IQR 0-0] pertussis cases per month before and after lockdown, respectively, p=0.0048). Conclusion: The drastic reduction of outpatient and hospitalized cases of pertussis strongly suggests an impact of COVID-19 mitigation measures and their consequences on pertussis epidemiology. Pertussis vaccination recommendations should be carefully followed, and disease monitoring should be continued to detect any resurgence after relaxation of mitigation measures.

Adherence and sustainability of interventions informing optimal control against COVID-19 pandemic (preprint)

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

Colder and drier winter conditions are associated with greater SARS-CoV-2 transmission: a regional study of the first epidemic wave in north-west hemisphere countries. (preprint)

Higher transmissibility of SARS-CoV-2 in cold and dry weather conditions has been hypothesized since the onset of the COVID-19 pandemic but the level of epidemiological evidence remains low. During the first wave of the pandemic, Spain, Italy, France, Portugal, Canada and USA presented an early spread, a heavy COVID-19 burden, and low initial public health response until lockdowns. In a context when testing was limited, we calculated the basic reproduction number (R0) in 63 regions from the growth in regional death counts. After adjusting for population density, early spread of the epidemic, and age structure, temperature and humidity were negatively associated to SARS-CoV-2 transmissibility. A reduction of mean absolute humidity by 1g/m3 was associated with a 0.15-unit increase of R0. Below 10{degrees}C, a temperature reduction of 1{degrees}C was associated with a 0.16-unit increase of R0. Our results confirm a dependency of SARS-CoV-2 transmissibility to weather conditions in the absence of control measures during the first wave. The transition from summer-to winter-like conditions likely contributed to the intensification of the second wave in north-west hemisphere countries. Adjustments of the levels of social mobility restrictions need to account for increased SARS-CoV-2 transmissibility in winter conditions.

Monitoring the proportion infected by SARS-CoV-2 from age-stratified hospitalisation and serological data (preprint)

BackgroundRegional monitoring of the proportion infected by SARS-CoV-2 is important to guide local management of the epidemic, but is difficult in the absence of regular nationwide serosurveys. MethodsWe developed a method to reconstruct in real-time the proportion infected by SARS-CoV-2 and the proportion of infections being detected from the joint analysis of age-stratified seroprevalence, hospitalisation and case data. We applied our approach to the 13 French metropolitan regions. FindingsWe estimate that 5.7% [5.1%-6.4%] of adults in metropolitan France had been infected by SARS-CoV-2 by May 2020. This proportion remained stable until August and increased to 12.6% [11.2%-14.3%] by the end of November. With 23.8% [21.2%-26.8%] infected in the Paris region compared to 4.0% [3.5% - 4.6%] in Brittany, regional variations remained large (Coefficient of Variation CV: 0.53) although less so than in May (CV: 0.74). The proportion infected was twice higher (17.6% [13.4%-22.7%]) in 20-49 y.o. than in 50+ y.o (8.0% [5.7% - 11.5%]). Forty percent [33.7% - 45.4%] of infections in adults were detected in June-August compared to 55.7% [48.7% - 63.1%] in September-November. Our method correctly predicted seroprevalence in 11 regions in which only hospitalisation data were used. InterpretationIn the absence of contemporary serosurvey, our real-time monitoring indicates that the proportion infected by SARS-CoV-2 may be above 20% in some French regions. FundingEU RECOVER, ANR, Fondation pour la Recherche Medicale, Inserm.

Comparing the age and sex trajectories of SARS-CoV-2 morbidity with other respiratory pathogens points to potential immune mechanisms. (preprint)

Comparing age and sex differences in SARS-CoV-2 hospitalization and mortality with influenza and other health outcomes opens the way to generating hypotheses as to the underlying mechanisms, building on the extraordinary advances in immunology and physiology that have occurred over the last year. Notable departures in health outcomes starting around puberty suggest that burdens associated with influenza and other causes are reduced relative to the two emergent coronaviruses over much of adult life. Two possible hypotheses could explain this: protective adaptive immunity for influenza and other infections, or greater sensitivity to immunosenescence in the coronaviruses. Comparison of sex differences suggest an important role for adaptive immunity; but immunosenescence might also be relevant, if males experience faster immunosenescence. Involvement of the renin-angiotensin-system in SARS-CoV-2 infection might drive high sensitivity to disruptions of homeostasis. Overall, these results highlight the long tail of vulnerability in the age profile relevant to the emergent coronaviruses, which more transmissible variants have the potential to uncover at the younger end of the scale, and aging populations will expose at the other end of the scale.

Early chains of transmission of COVID-19 in France (preprint)

IntroductionSARS-CoV-2, which causes COVID-19, has spread rapidly across the world. A dedicated surveillance system was implemented in France in January 2020 to improve early detection of cases and their contacts and limit secondary transmission. Our objective was to use contact-tracing data collected during this initial phase of the epidemic to better characterize 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 characterized the risk of a contact becoming a case. We described chains of transmission and estimated key parameters of spread. ResultsOver the study period, 6,082 contacts of 735 confirmed cases were traced. The overall secondary clinical attack rate was 4.1% (95%CI 3.6-4.6) and increased with age of the index case and of the contact. Family contacts were at higher risk of becoming cases (adjusted odds ratio 2.1 (95%CI 1.4-3.0)) while nosocomial contacts were at lower risk (adjusted odds ratio 0.3 (95%CI 0.1-0.7)), compared to coworkers/friends. We identified 328 infector/infectee pairs, 49% of which were family members. The distribution of secondary cases was highly over-dispersed with 80% of secondary cases being caused by 10% of cases. The mean serial interval was 5.1 days (interquartile range 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 contributes to improving our knowledge of SARS-CoV-2 transmission, such as the importance of superspreading events. Contact-tracing data are challenging to collect but are key to better understand emerging pathogens. Funding statementThis work was supported by the LabEx "Integrative Biology of Emerging Infectious Diseases (IBEID)" (Grant Number ANR-10-LABX-62-IBEID), Sante Publique France, the INCEPTION project (PIA/ANR-16-CONV-0005), and the European Unions Horizon 2020 research and innovation program under grants 101003589 (RECOVER) and 874735 (VEO).

Ready for a BASE jump? Do not neglect SARS-CoV-2 hospitalization and fatality risks in the middle-aged adult population. (preprint)

Seroprevalence results coupled with surveillance data were used to estimate the SARS-CoV-2 infection hospitalization (IHR) and infection fatality ratios (IFR) in France. IHR and IFR were dramatically high in the very elderly (80-90 years: IHR: 30%, IFR: 11%), but also substantial in middle-aged adults (40-50 years: IHR: 1.2%, IFR: 0.05%).

Evaluating the impact of curfews and other measures on SARS-CoV-2 transmission in French Guiana (preprint)

While general lockdowns have proven effective to control SARS-CoV-2 epidemics, they come with enormous costs for society. It is therefore essential to identify control strategies with lower social and economic impact. Here, we report and evaluate the control strategy implemented during a large SARS-CoV-2 epidemic in June-July 2020 in French Guiana that relied on curfews, targeted lockdowns and other measures. We find that the combination of these interventions reduced the basic reproduction number of SARS-CoV-2 from 1.7 to 1.1, which was sufficient to avoid saturation of hospitals. We estimate that thanks to the young demographics across the territory, the risk of hospitalisation following infection was 0.3 times that of metropolitan France and that about 20% of the population was infected by July. Our model projections are consistent with a recent seroprevalence study. The study showcases how mathematical modeling can be used to support healthcare planning and decision making in a context of high uncertainty.

Age-specific mortality and immunity patterns of SARS-CoV-2 infection in 45 countries (preprint)

The number of COVID-19 deaths is often used as a key indicator of SARS-CoV-2 epidemic size. However, heterogeneous burdens in nursing homes and variable reporting of deaths in elderly individuals can hamper comparisons of deaths and the number of infections associated with them across countries. Using age-specific death data from 45 countries, we find that relative differences in the number of deaths by age amongst individuals aged <65 years old are highly consistent across locations. Combining these data with data from 15 seroprevalence surveys we demonstrate how age-specific infection fatality ratios (IFRs) can be used to reconstruct infected population proportions. We find notable heterogeneity in overall IFR estimates as suggested by individual serological studies and observe that for most European countries the reported number of deaths amongst [≥]65s are significantly greater than expected, consistent with high infection attack rates experienced by nursing home populations in Europe. Age-specific COVID-19 death data in younger individuals can provide a robust indicator of population immunity.

Estimating the burden of SARS-CoV-2 in France (preprint)

France has been heavily affected by the SARS-CoV-2 epidemic and went into lockdown on the 17th March 2020. Using models applied to hospital and death data, we estimate the impact of the lockdown and current population immunity. We find 2.6% of infected individuals are hospitalized and 0.53% die, ranging from 0.001% in those <20y to 8.3% in those >80y. Across all ages, men are more likely to be hospitalized, enter intensive care, and die than women. The lockdown reduced the reproductive number from 3.3 to 0.5 (84% reduction). By 11 May, when interventions are scheduled to be eased, we project 3.7 million (range: 2.3-6.7) people, 5.7% of the population, will have been infected. Population immunity appears insufficient to avoid a second wave if all control measures are released at the end of the lockdown.