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  • COVID-19
  • 2017-2021
  • French National Research Agency (AN...
  • INCEPTION
  • Hal-Diderot

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Tran Kiem, Cécile; Bosetti, Paolo; Paireau, Juliette; Crépey, Pascal; +8 Authors

    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. Funder: We acknowledge financial support from the Investissement d'Avenir program, the Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases program (grant ANR-10-LABX-62-IBEID), Sant�� Publique France, the INCEPTION project (PIA/ANR-16-COV-0005), the European Union���s Horizon 2020 research and innovation program under grant 101003589 (RECOVER) and 874735 (VEO), AXA and Groupama. Funder: AXA Research Fund (Le Fonds AXA pour la Recherche); doi: https://doi.org/10.13039/501100001961

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Article . 2021 . Peer-reviewed
    Data sources: PubMed Central
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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    Apollo
    Other literature type . 2021
    Data sources: Apollo
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    Apollo
    Other literature type . 2021
    License: CC BY
    Data sources: Apollo
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    Apollo
    Article . 2022
    License: CC BY
    Data sources: Datacite
    HAL Descartes
    Article . 2021
    License: CC BY
    Data sources: HAL Descartes
    Apollo
    Article . 2021
    Data sources: Datacite
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  • Authors: Fillâtre, Pierre; Dufour, Marie-José; Behillil, Sylvie; Vatan, Remi; +24 Authors

    International audience; Objectives - In early January 2021 an outbreak of nosocomial cases of coronavirus disease 2019 (COVID-19) emerged in Western France; RT-PCR tests were repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole-genome sequencing (WGS) revealed a new variant, currently defining a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.616. In March, the WHO classified this as a 'variant under investigation' (VUI). We analysed the characteristics and outcomes of COVID-19 cases related to this new variant. Methods - Clinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled those inpatients with: (a) positive SARS-CoV-2 RT-PCR on a respiratory sample, (b) seroconversion with anti-SARS-CoV-2 IgG/IgM, or (c) suggestive symptoms and typical features of COVID-19 on a chest CT scan. Cases were categorized as B.1.616, a variant of concern (VOC), or unknown. Results - From 1st January to 24th March 2021, 114 patients fulfilled the inclusion criteria: B.1.616 (n = 39), VOC (n = 32), and unknown (n = 43). B.1.616-related cases were older than VOC-related cases (81 years, interquartile range (IQR) 73-88 versus 73 years, IQR 67-82, p < 0.05) and their first RT-PCR tests were rarely positive (6/39, 15% versus 31/32, 97%, p < 0.05). The B.1.616 variant was independently associated with severe disease (multivariable Cox model HR 4.0, 95%CI 1.5-10.9) and increased lethality (28-day mortality 18/39 (46%) for B.1.616 versus 5/32 (16%) for VOC, p = 0.006). Conclusion - We report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, which is poorly detected by RT-PCR on nasopharyngeal samples and is associated with high lethality.

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Cécile Tran Kiem; Clément Massonnaud; Daniel Lévy-Bruhl; Chiara Poletto; +9 Authors

    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. Funding: We acknowledge financial support from Haute Autorite de Sante, the Investissement d'Avenir program, the Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases program (grant ANR-10-LABX-62-IBEID), Sante Publique France, the INCEPTION project (PIA/ANR-16-CONV-0005), AXA, Groupama and the European Union's Horizon 2020 research and innovation program under grants 101003589 (RECOVER) and 874735 (VEO).

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    EClinicalMedicine
    Other literature type . Article . 2021 . Peer-reviewed
    License: Elsevier TDM
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    EClinicalMedicine
    Article . 2021
    Data sources: DOAJ-Articles
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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    EClinicalMedicine
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    Data sources: UnpayWall
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    Article . 2021
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      EClinicalMedicine
      Other literature type . Article . 2021 . Peer-reviewed
      License: Elsevier TDM
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      EClinicalMedicine
      Article . 2021
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      EClinicalMedicine
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      Article . 2021
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Arnaud Fontanet; Laura Tondeur; Rebecca Grant; Sarah Temmam; +23 Authors

    Background Children’s role in SARS-CoV-2 epidemiology remains unclear. We investigated an initially unnoticed SARS-CoV-2 outbreak linked to schools in northern France, beginning as early as mid-January 2020. Aims This retrospective observational study documents the extent of SARS-CoV-2 transmission, linked to an affected high school (n = 664 participants) and primary schools (n = 1,340 study participants), in the context of unsuspected SARS-CoV-2 circulation and limited control measures. Methods Between 30 March and 30 April 2020, all school staff, as well as pupils and their parents and relatives were invited for SARS-CoV-2 antibody testing and to complete a questionnaire covering symptom history since 13 January 2020. Results In the high school, infection attack rates were 38.1% (91/239), 43.4% (23/53), and 59.3% (16/27), in pupils, teachers, and non-teaching staff respectively vs 10.1% (23/228) and 12.0% (14/117) in the pupils’ parents and relatives (p < 0.001). Among the six primary schools, three children attending separate schools at the outbreak start, while symptomatic, might have introduced SARS-CoV-2 there, but symptomatic secondary cases related to them could not be definitely identified. In the primary schools overall, antibody prevalence in pupils sharing classes with symptomatic cases was higher than in pupils from other classes: 15/65 (23.1%) vs 30/445 (6.7%) (p < 0.001). Among 46 SARS-CoV-2 seropositive pupils < 12 years old, 20 were asymptomatic. Whether past HKU1 and OC43 seasonal coronavirus infection protected against SARS-CoV-2 infection in 6–11 year olds could not be inferred. Conclusions Viral circulation can occur in high and primary schools so keeping them open requires consideration of appropriate control measures and enhanced surveillance.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Eurosurveillance
    Article . 2021 . Peer-reviewed
    License: CC BY
    Data sources: Crossref
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Eurosurveillance
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Andronico, Alessio; Tran Kiem, Cécile; Paireau, Juliette; Succo, Tiphanie; +9 Authors

    Abstract: 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 coincided with a reduction in the basic reproduction number of SARS-CoV-2 from 1.7 to 1.1, which was sufficient to avoid hospital saturation. We estimate that thanks to the young demographics, 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 modelling can be used to support healthcare planning in a context of high uncertainty. Funder: We acknowledge financial support from the Investissement d'Avenir program, the Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases program (Grant ANR-10-LABX-62-IBEID), Sante Publique France, the INCEPTION project (PIA/ANR-16-CONV-0005) and European Union V.E.O and RECOVER projects.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Nature Communication...arrow_drop_down
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    Europe PubMed Central
    Article . 2021 . Peer-reviewed
    Data sources: PubMed Central
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    Apollo
    Other literature type . 2021
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    Apollo
    Other literature type . 2021
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    Article . 2021
    License: CC BY
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    Article . 2021
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Nature Communication...arrow_drop_down
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      Europe PubMed Central
      Article . 2021 . Peer-reviewed
      Data sources: PubMed Central
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      Apollo
      Other literature type . 2021
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      Apollo
      Other literature type . 2021
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      Article . 2021
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      Article . 2021
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    Authors: Marion Plaze; David Attali; Matthieu Prot; Anne-Cécile Petit; +10 Authors

    Introduction Urgent action is needed to fight the ongoing COVID-19 pandemic by reducing the number of infected people along with the infection contagiousness and severity. Chlorpromazine (CPZ), the prototype of typical antipsychotics from the phenothiazine group, is known to inhibit clathrin-mediated endocytosis and acts as an antiviral, in particular against SARS-CoV-1 and MERS-CoV. The aim of this in vitro study was to test CPZ against a SARS-CoV-2 isolate in monkey and human cells. Material and methods Monkey VeroE6 cells and human alveolar basal epithelial A549-ACE2 cells were infected with SARS-CoV-2 in presence of different concentrations of CPZ. Supernatants were harvested at day 2 and analysed by RT-qPCR for the presence of SARS-CoV-2 RNA. Cell viability was assessed on non-infected cells. Results We evidenced an antiviral activity of CPZ against SARS-CoV-2 in monkey VeroE6 cells with an IC50 of 8.2 µM, a CC50 of 13.5µM and a SI of 1.65. In human A549-ACE2 cells, CPZ was also associated with an anti-SARS-CoV-2 activity, with an IC50 of 11.3 µM, a CC50 of 23.1 µM and a SI of 2.04. Discussion Even though the measured SI are low, such IC50 measured in vitro may translate to CPZ dosage used in clinical routine because of CPZ high biodistribution in lungs and in saliva. Also, CPZ brain distribution could be of high interest for treating or preventing the neurological and psychiatric forms of COVID-19. Conclusions These preclinical findings support clinical investigation of the repurposing of CPZ, a largely used drug with mild side effects, in COVID-19 treatment. Highlights • Chlorpromazine, an FDA-approved drug, inhibits clathrin-mediated endocytosis • CPZ acts as an antiviral against SARS-CoV-1 and MERS-CoV • We evidenced antiviral activity of CPZ against SARS-CoV-2 in monkey and human cells • Because of CPZ high distribution in lungs, CPZ IC50 may translate in clinical routine • CPZ brain distribution could be of high interest for neurological forms of COVID-19

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    International Journal of Antimicrobial Agents
    Article . 2021 . Peer-reviewed
    License: Elsevier TDM
    Hal-Diderot
    Article . 2021
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    Authors: Elena Rensen; Stefano Pietropaoli; Christian Weber; Sylvie Souquere; +9 Authors

    AbstractThe current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The positive-sense single-stranded RNA virus contains a single linear RNA segment that serves as a template for transcription and replication, leading to the synthesis of positive and negative-stranded viral RNA (vRNA) in infected cells. Tools to visualize viral RNA directly in infected cells are critical to analyze its replication cycle, screen for therapeutic molecules or study infections in human tissue. Here, we report the design, validation and initial application of fluorescencein situhybridization (FISH) probes to visualize positive or negative RNA of SARS-CoV-2 (CoronaFISH). We demonstrate sensitive visualization of vRNA in African green monkey and several human cell lines, in patient samples and human tissue. We further demonstrate the adaptation of CoronaFISH probes to electron microscopy (EM). We provide all required oligonucleotide sequences, source code to design the probes, and a detailed protocol. We hope that CoronaFISH will complement existing techniques for research on SARS-CoV-2 biology and COVID-19 pathophysiology, drug screening and diagnostics.

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    Authors: Fabiana Gámbaro; Sylvie Behillil; Artem Baidaliuk; Flora Donati; +10 Authors

    International audience; Following SARS-CoV-2 emergence in China, a specific surveillance was implemented in France. Phylogenetic analysis of sequences retrieved through this surveillance suggests that detected initial introductions, involving non-clade G viruses, did not seed local transmission. Nevertheless, identification of clade G variants subsequently circulating in the country, with the earliest from a patient who neither travelled to risk areas nor had contact with travellers, suggests that SARS-CoV-2 might have been present before the first recorded local cases.

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    Eurosurveillance
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    Eurosurveillance
    Article . 2020 . Peer-reviewed
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      Eurosurveillance
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      Eurosurveillance
      Article . 2020 . Peer-reviewed
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    Authors: Fontanet, Arnaud; Grant, Rebecca; Tondeur, Laura; Madec, Yoann; +13 Authors

    AbstractBackgroundThe extent of SARS-CoV-2 transmission among pupils in primary schools and their families is unknown.MethodsBetween 28-30 April 2020, a retrospective cohort study was conducted among pupils, their parents and relatives, and staff of primary schools exposed to SARS-CoV-2 in February and March 2020 in a city north of Paris, France. Participants completed a questionnaire that covered sociodemographic information and history of recent symptoms. A blood sample was tested for the presence of anti-SARS-CoV-2 antibodies using a flow-cytometry-based assay.ResultsThe infection attack rate (IAR) was 45/510 (8.8%), 3/42 (7.1%), 1/28 (3.6%), 76/641 (11.9%) and 14/119 (11.8%) among primary school pupils, teachers, non-teaching staff, parents, and relatives, respectively (P = 0.29). Prior to school closure on February 14, three SARS-CoV-2 infected pupils attended three separate schools with no secondary cases in the following 14 days among pupils, teachers and non-teaching staff of the same schools. Familial clustering of cases was documented by the high proportion of antibodies among parents and relatives of infected pupils (36/59 = 61.0% and 4/9 = 44.4%, respectively). In children, disease manifestations were mild, and 24/58 (41.4%) of infected children were asymptomatic.InterpretationIn young children, SARS-CoV-2 infection was largely mild or asymptomatic and there was no evidence of onwards transmission from children in the school setting.

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    Authors: Fontanet, Arnaud; Tondeur, Laura; Madec, Yoann; Grant, Rebecca; +21 Authors

    SummaryBackgroundThe Oise department in France has been heavily affected by COVID-19 in early 2020.MethodsBetween 30 March and 4 April 2020, we conducted a retrospective closed cohort study among pupils, their parents and siblings, as well as teachers and non-teaching staff of a high-school located in Oise. Participants completed a questionnaire that covered history of fever and/or respiratory symptoms since 13 January 2020 and had blood tested for the presence of anti-SARS-CoV-2 antibodies. The infection attack rate (IAR) was defined as the proportion of participants with confirmed SARS-CoV-2 infection based on antibody detection. Blood samples from two blood donor centres collected between 23 and 27 March 2020 in the Oise department were also tested for presence of anti-SARS-CoV-2 antibodies.FindingsOf the 661 participants (median age: 37 years), 171 participants had anti-SARS-CoV-2 antibodies. The overall IAR was 25.9% (95% confidence interval (CI) = 22.6-29.4), and the infection fatality rate was 0% (one-sided 97.5% CI = 0 - 2.1). Nine of the ten participants hospitalised since mid-January were in the infected group, giving a hospitalisation rate of 5.3% (95% CI = 2.4 –9.8). Anosmia and ageusia had high positive predictive values for SARS-CoV-2 infection (84.7% and 88.1%, respectively). Smokers had a lower IAR compared to non-smokers (7.2% versus 28.0%, P <0.001). The proportion of infected individuals who had no symptoms during the study period was 17.0% (95% CI = – 23.4). The proportion of donors with anti-SARS-CoV-2 antibodies in two nearby blood banks of the Oise department was 3.0% (95% CI = 1.1 - 6.4).InterpretationThe relatively low IAR observed in an area where SARS-CoV-2 actively circulated weeks before confinement measures indicates that establishing herd immunity will take time, and that lifting these measures in France will be long and complex.FundingInstitut Pasteur, CNRS, Université de Paris, Santé publique France, Labex IBEID (ANR-10-LABX-62-IBEID), REACTing, EU grant Recover, INCEPTION project (PIA/ANR-16-CONV-0005).Research in contextEvidence before the studyThe first COVID-19 cases in France were reported on 24 January 2020. Substantial transmission has occurred since then, with the Oise department, north of Paris, one of the heaviest affected areas in the early stages of the epidemic in France. As of 13 April 2020, 98,076 cases had been diagnosed in France, including 5,379 deaths.Epidemiological and clinical characteristics of patients with COVID-19 have been widely reported, but this has largely been centred on cases requiring medical care. What remains unclear at this stage is the extent to which SARS-CoV-2 infections may be asymptomatic or present as subclinical, non-specific symptoms. While extensive contact tracing has identified asymptomatic infections using RT-PCR testing, serologic detection of anti-SARS-CoV-2 antibodies is needed to determine the real infection attack rate and the proportion of all infections that are asymptomatic or subclinical.Added value of this studyUsing a combination of serologic assays with high sensitivity and specificity for anti-SARS-CoV-2 antibodies, we conducted a retrospective closed cohort study. In a high school linked to a cluster of COVID-19 in the Oise department, we showed an overall infection attack rate (IAR) of 40.9% in the high school group, and 10.9% in parents and siblings of the pupils. The proportion of infected individuals who had no symptoms during the study period was 17.0%.Implications of all of the available evidenceThe relatively low IAR in this area where SARS-CoV-2 actively circulated before confinement measures were introduced indicates that establishing herd immunity will take time, and that the lifting of these measures in France will be long and complex.

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Tran Kiem, Cécile; Bosetti, Paolo; Paireau, Juliette; Crépey, Pascal; +8 Authors

    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. Funder: We acknowledge financial support from the Investissement d'Avenir program, the Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases program (grant ANR-10-LABX-62-IBEID), Sant�� Publique France, the INCEPTION project (PIA/ANR-16-COV-0005), the European Union���s Horizon 2020 research and innovation program under grant 101003589 (RECOVER) and 874735 (VEO), AXA and Groupama. Funder: AXA Research Fund (Le Fonds AXA pour la Recherche); doi: https://doi.org/10.13039/501100001961

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    Europe PubMed Central
    Article . 2021 . Peer-reviewed
    Data sources: PubMed Central
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    Apollo
    Other literature type . 2021
    Data sources: Apollo
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    Apollo
    Article . 2022
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    HAL Descartes
    Article . 2021
    License: CC BY
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    Apollo
    Article . 2021
    Data sources: Datacite
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  • Authors: Fillâtre, Pierre; Dufour, Marie-José; Behillil, Sylvie; Vatan, Remi; +24 Authors

    International audience; Objectives - In early January 2021 an outbreak of nosocomial cases of coronavirus disease 2019 (COVID-19) emerged in Western France; RT-PCR tests were repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole-genome sequencing (WGS) revealed a new variant, currently defining a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.616. In March, the WHO classified this as a 'variant under investigation' (VUI). We analysed the characteristics and outcomes of COVID-19 cases related to this new variant. Methods - Clinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled those inpatients with: (a) positive SARS-CoV-2 RT-PCR on a respiratory sample, (b) seroconversion with anti-SARS-CoV-2 IgG/IgM, or (c) suggestive symptoms and typical features of COVID-19 on a chest CT scan. Cases were categorized as B.1.616, a variant of concern (VOC), or unknown. Results - From 1st January to 24th March 2021, 114 patients fulfilled the inclusion criteria: B.1.616 (n = 39), VOC (n = 32), and unknown (n = 43). B.1.616-related cases were older than VOC-related cases (81 years, interquartile range (IQR) 73-88 versus 73 years, IQR 67-82, p < 0.05) and their first RT-PCR tests were rarely positive (6/39, 15% versus 31/32, 97%, p < 0.05). The B.1.616 variant was independently associated with severe disease (multivariable Cox model HR 4.0, 95%CI 1.5-10.9) and increased lethality (28-day mortality 18/39 (46%) for B.1.616 versus 5/32 (16%) for VOC, p = 0.006). Conclusion - We report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, which is poorly detected by RT-PCR on nasopharyngeal samples and is associated with high lethality.

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    Authors: Cécile Tran Kiem; Clément Massonnaud; Daniel Lévy-Bruhl; Chiara Poletto; +9 Authors

    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. Funding: We acknowledge financial support from Haute Autorite de Sante, the Investissement d'Avenir program, the Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases program (grant ANR-10-LABX-62-IBEID), Sante Publique France, the INCEPTION project (PIA/ANR-16-CONV-0005), AXA, Groupama and the European Union's Horizon 2020 research and innovation program under grants 101003589 (RECOVER) and 874735 (VEO).

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    EClinicalMedicine
    Other literature type . Article . 2021 . Peer-reviewed
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    EClinicalMedicine
    Article . 2021
    Data sources: DOAJ-Articles
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    EClinicalMedicine
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    Article . 2021
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      EClinicalMedicine
      Other literature type . Article . 2021 . Peer-reviewed
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      EClinicalMedicine
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      EClinicalMedicine
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    Authors: Arnaud Fontanet; Laura Tondeur; Rebecca Grant; Sarah Temmam; +23 Authors

    Background Children’s role in SARS-CoV-2 epidemiology remains unclear. We investigated an initially unnoticed SARS-CoV-2 outbreak linked to schools in northern France, beginning as early as mid-January 2020. Aims This retrospective observational study documents the extent of SARS-CoV-2 transmission, linked to an affected high school (n = 664 participants) and primary schools (n = 1,340 study participants), in the context of unsuspected SARS-CoV-2 circulation and limited control measures. Methods Between 30 March and 30 April 2020, all school staff, as well as pupils and their parents and relatives were invited for SARS-CoV-2 antibody testing and to complete a questionnaire covering symptom history since 13 January 2020. Results In the high school, infection attack rates were 38.1% (91/239), 43.4% (23/53), and 59.3% (16/27), in pupils, teachers, and non-teaching staff respectively vs 10.1% (23/228) and 12.0% (14/117) in the pupils’ parents and relatives (p < 0.001). Among the six primary schools, three children attending separate schools at the outbreak start, while symptomatic, might have introduced SARS-CoV-2 there, but symptomatic secondary cases related to them could not be definitely identified. In the primary schools overall, antibody prevalence in pupils sharing classes with symptomatic cases was higher than in pupils from other classes: 15/65 (23.1%) vs 30/445 (6.7%) (p < 0.001). Among 46 SARS-CoV-2 seropositive pupils < 12 years old, 20 were asymptomatic. Whether past HKU1 and OC43 seasonal coronavirus infection protected against SARS-CoV-2 infection in 6–11 year olds could not be inferred. Conclusions Viral circulation can occur in high and primary schools so keeping them open requires consideration of appropriate control measures and enhanced surveillance.

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    Eurosurveillance
    Article . 2021 . Peer-reviewed
    License: CC BY
    Data sources: Crossref
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    Eurosurveillance
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    Authors: Andronico, Alessio; Tran Kiem, Cécile; Paireau, Juliette; Succo, Tiphanie; +9 Authors

    Abstract: 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 coincided with a reduction in the basic reproduction number of SARS-CoV-2 from 1.7 to 1.1, which was sufficient to avoid hospital saturation. We estimate that thanks to the young demographics, 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 modelling can be used to support healthcare planning in a context of high uncertainty. Funder: We acknowledge financial support from the Investissement d'Avenir program, the Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases program (Grant ANR-10-LABX-62-IBEID), Sante Publique France, the INCEPTION project (PIA/ANR-16-CONV-0005) and European Union V.E.O and RECOVER projects.

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    Europe PubMed Central
    Article . 2021 . Peer-reviewed
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    Apollo
    Other literature type . 2021
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    Apollo
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    Apollo
    Article . 2021
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    Apollo
    Article . 2021
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      Europe PubMed Central
      Article . 2021 . Peer-reviewed
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      Apollo
      Other literature type . 2021
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      Article . 2021
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      Article . 2021
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    Authors: Marion Plaze; David Attali; Matthieu Prot; Anne-Cécile Petit; +10 Authors

    Introduction Urgent action is needed to fight the ongoing COVID-19 pandemic by reducing the number of infected people along with the infection contagiousness and severity. Chlorpromazine (CPZ), the prototype of typical antipsychotics from the phenothiazine group, is known to inhibit clathrin-mediated endocytosis and acts as an antiviral, in particular against SARS-CoV-1 and MERS-CoV. The aim of this in vitro study was to test CPZ against a SARS-CoV-2 isolate in monkey and human cells. Material and methods Monkey VeroE6 cells and human alveolar basal epithelial A549-ACE2 cells were infected with SARS-CoV-2 in presence of different concentrations of CPZ. Supernatants were harvested at day 2 and analysed by RT-qPCR for the presence of SARS-CoV-2 RNA. Cell viability was assessed on non-infected cells. Results We evidenced an antiviral activity of CPZ against SARS-CoV-2 in monkey VeroE6 cells with an IC50 of 8.2 µM, a CC50 of 13.5µM and a SI of 1.65. In human A549-ACE2 cells, CPZ was also associated with an anti-SARS-CoV-2 activity, with an IC50 of 11.3 µM, a CC50 of 23.1 µM and a SI of 2.04. Discussion Even though the measured SI are low, such IC50 measured in vitro may translate to CPZ dosage used in clinical routine because of CPZ high biodistribution in lungs and in saliva. Also, CPZ brain distribution could be of high interest for treating or preventing the neurological and psychiatric forms of COVID-19. Conclusions These preclinical findings support clinical investigation of the repurposing of CPZ, a largely used drug with mild side effects, in COVID-19 treatment. Highlights • Chlorpromazine, an FDA-approved drug, inhibits clathrin-mediated endocytosis • CPZ acts as an antiviral against SARS-CoV-1 and MERS-CoV • We evidenced antiviral activity of CPZ against SARS-CoV-2 in monkey and human cells • Because of CPZ high distribution in lungs, CPZ IC50 may translate in clinical routine • CPZ brain distribution could be of high interest for neurological forms of COVID-19

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    International Journal of Antimicrobial Agents
    Article . 2021 . Peer-reviewed
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    Hal-Diderot
    Article . 2021
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    Authors: Elena Rensen; Stefano Pietropaoli; Christian Weber; Sylvie Souquere; +9 Authors

    AbstractThe current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The positive-sense single-stranded RNA virus contains a single linear RNA segment that serves as a template for transcription and replication, leading to the synthesis of positive and negative-stranded viral RNA (vRNA) in infected cells. Tools to visualize viral RNA directly in infected cells are critical to analyze its replication cycle, screen for therapeutic molecules or study infections in human tissue. Here, we report the design, validation and initial application of fluorescencein situhybridization (FISH) probes to visualize positive or negative RNA of SARS-CoV-2 (CoronaFISH). We demonstrate sensitive visualization of vRNA in African green monkey and several human cell lines, in patient samples and human tissue. We further demonstrate the adaptation of CoronaFISH probes to electron microscopy (EM). We provide all required oligonucleotide sequences, source code to design the probes, and a detailed protocol. We hope that CoronaFISH will complement existing techniques for research on SARS-CoV-2 biology and COVID-19 pathophysiology, drug screening and diagnostics.

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    Authors: Fabiana Gámbaro; Sylvie Behillil; Artem Baidaliuk; Flora Donati; +10 Authors

    International audience; Following SARS-CoV-2 emergence in China, a specific surveillance was implemented in France. Phylogenetic analysis of sequences retrieved through this surveillance suggests that detected initial introductions, involving non-clade G viruses, did not seed local transmission. Nevertheless, identification of clade G variants subsequently circulating in the country, with the earliest from a patient who neither travelled to risk areas nor had contact with travellers, suggests that SARS-CoV-2 might have been present before the first recorded local cases.

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    Eurosurveillance
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    Eurosurveillance
    Article . 2020 . Peer-reviewed
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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      Eurosurveillance
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      Eurosurveillance
      Article . 2020 . Peer-reviewed
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Fontanet, Arnaud; Grant, Rebecca; Tondeur, Laura; Madec, Yoann; +13 Authors

    AbstractBackgroundThe extent of SARS-CoV-2 transmission among pupils in primary schools and their families is unknown.MethodsBetween 28-30 April 2020, a retrospective cohort study was conducted among pupils, their parents and relatives, and staff of primary schools exposed to SARS-CoV-2 in February and March 2020 in a city north of Paris, France. Participants completed a questionnaire that covered sociodemographic information and history of recent symptoms. A blood sample was tested for the presence of anti-SARS-CoV-2 antibodies using a flow-cytometry-based assay.ResultsThe infection attack rate (IAR) was 45/510 (8.8%), 3/42 (7.1%), 1/28 (3.6%), 76/641 (11.9%) and 14/119 (11.8%) among primary school pupils, teachers, non-teaching staff, parents, and relatives, respectively (P = 0.29). Prior to school closure on February 14, three SARS-CoV-2 infected pupils attended three separate schools with no secondary cases in the following 14 days among pupils, teachers and non-teaching staff of the same schools. Familial clustering of cases was documented by the high proportion of antibodies among parents and relatives of infected pupils (36/59 = 61.0% and 4/9 = 44.4%, respectively). In children, disease manifestations were mild, and 24/58 (41.4%) of infected children were asymptomatic.InterpretationIn young children, SARS-CoV-2 infection was largely mild or asymptomatic and there was no evidence of onwards transmission from children in the school setting.

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Fontanet, Arnaud; Tondeur, Laura; Madec, Yoann; Grant, Rebecca; +21 Authors

    SummaryBackgroundThe Oise department in France has been heavily affected by COVID-19 in early 2020.MethodsBetween 30 March and 4 April 2020, we conducted a retrospective closed cohort study among pupils, their parents and siblings, as well as teachers and non-teaching staff of a high-school located in Oise. Participants completed a questionnaire that covered history of fever and/or respiratory symptoms since 13 January 2020 and had blood tested for the presence of anti-SARS-CoV-2 antibodies. The infection attack rate (IAR) was defined as the proportion of participants with confirmed SARS-CoV-2 infection based on antibody detection. Blood samples from two blood donor centres collected between 23 and 27 March 2020 in the Oise department were also tested for presence of anti-SARS-CoV-2 antibodies.FindingsOf the 661 participants (median age: 37 years), 171 participants had anti-SARS-CoV-2 antibodies. The overall IAR was 25.9% (95% confidence interval (CI) = 22.6-29.4), and the infection fatality rate was 0% (one-sided 97.5% CI = 0 - 2.1). Nine of the ten participants hospitalised since mid-January were in the infected group, giving a hospitalisation rate of 5.3% (95% CI = 2.4 –9.8). Anosmia and ageusia had high positive predictive values for SARS-CoV-2 infection (84.7% and 88.1%, respectively). Smokers had a lower IAR compared to non-smokers (7.2% versus 28.0%, P <0.001). The proportion of infected individuals who had no symptoms during the study period was 17.0% (95% CI = – 23.4). The proportion of donors with anti-SARS-CoV-2 antibodies in two nearby blood banks of the Oise department was 3.0% (95% CI = 1.1 - 6.4).InterpretationThe relatively low IAR observed in an area where SARS-CoV-2 actively circulated weeks before confinement measures indicates that establishing herd immunity will take time, and that lifting these measures in France will be long and complex.FundingInstitut Pasteur, CNRS, Université de Paris, Santé publique France, Labex IBEID (ANR-10-LABX-62-IBEID), REACTing, EU grant Recover, INCEPTION project (PIA/ANR-16-CONV-0005).Research in contextEvidence before the studyThe first COVID-19 cases in France were reported on 24 January 2020. Substantial transmission has occurred since then, with the Oise department, north of Paris, one of the heaviest affected areas in the early stages of the epidemic in France. As of 13 April 2020, 98,076 cases had been diagnosed in France, including 5,379 deaths.Epidemiological and clinical characteristics of patients with COVID-19 have been widely reported, but this has largely been centred on cases requiring medical care. What remains unclear at this stage is the extent to which SARS-CoV-2 infections may be asymptomatic or present as subclinical, non-specific symptoms. While extensive contact tracing has identified asymptomatic infections using RT-PCR testing, serologic detection of anti-SARS-CoV-2 antibodies is needed to determine the real infection attack rate and the proportion of all infections that are asymptomatic or subclinical.Added value of this studyUsing a combination of serologic assays with high sensitivity and specificity for anti-SARS-CoV-2 antibodies, we conducted a retrospective closed cohort study. In a high school linked to a cluster of COVID-19 in the Oise department, we showed an overall infection attack rate (IAR) of 40.9% in the high school group, and 10.9% in parents and siblings of the pupils. The proportion of infected individuals who had no symptoms during the study period was 17.0%.Implications of all of the available evidenceThe relatively low IAR in this area where SARS-CoV-2 actively circulated before confinement measures were introduced indicates that establishing herd immunity will take time, and that the lifting of these measures in France will be long and complex.

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