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566 Research products, page 1 of 57

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  • Publication . Other literature type . Article . 2020
    Open Access English
    Authors: 
    Ali Moussaoui; Pierre Auger;
    Publisher: HAL CCSD
    Country: France

    The first case of coronavirus disease 2019 (COVID-19) in Algeria was reported on 25 February 2020. Since then, it has progressed rapidly and the number of cases grow exponentially each day. In this article, we utilize SEIR modelling to forecast COVID-19 outbreak in Algeria under two scenarios by using the real-time data from March 01 to April 10, 2020. In the first scenario: no control measures are put into place, we estimate that the basic reproduction number for the epidemic in Algeria is 2.1, the number of new cases in Algeria will peak from around late May to early June and up to 82% of the Algerian population will likely contract the coronavirus. In the second scenario, at a certain date T, drastic control measures are taken, people are being advised to self-isolate or to quarantine and will be able to leave their homes only if necessary. We use SEIR model with fast change between fully protected and risky states. We prove that the final size of the epidemic depends strongly on the cumulative number of cases at the date when we implement intervention and on the fraction of the population in confinement. Our analysis shows that the longer we wait, the worse the situation will be and this very quickly produces.

  • Open Access English
    Authors: 
    Moritz U. G. Kraemer; Chia-Hung Yang; Bernardo Gutierrez; Chieh-Hsi Wu; Brennan Klein; David M. Pigott; Louis du Plessis; Nuno R. Faria; Ruoran Li; William P. Hanage; +7 more
    Countries: United Kingdom, France, United Kingdom, United Kingdom, United Kingdom, United Kingdom, United Kingdom
    Project: NIH | MIDAS Center for Communic... (1U54GM088558-01), NIH | MIDAS Center for Communic... (1U54GM088558-01)

    The ongoing COVID-19 outbreak has expanded rapidly throughout China. Major behavioral, clinical, and state interventions are underway currently to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, have affected COVID-19 spread in China. We use real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation on transmission in cities across China and ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was well explained by human mobility data. Following the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases are still indicative of local chains of transmission outside Wuhan. This study shows that the drastic control measures implemented in China have substantially mitigated the spread of COVID-19. One sentence summary: The spread of COVID-19 in China was driven by human mobility early on and mitigated substantially by drastic control measures implemented since the end of January.

  • Open Access English
    Authors: 
    Bastien Reyné; Christian Selinger; Mircea T. Sofonea; Stéphanie Miot; Amandine Pisoni; Edouard Tuaillon; Jean Bousquet; Hubert Blain; Samuel Alizon;
    Publisher: HAL CCSD
    Country: France

    AbstractBackgroundCOVID-19 is spreading rapidly in nursing homes (NHs). It is urgent to evaluate the effect of infection prevention and control (IPC) measures to reduce COVID spreading.MethodsWe analysed COVID-19 outbreaks in 12 NH using rRT-PCR for SARS-CoV-2. We estimated secondary attack risks (SARs) and identified cofactors associated with the proportion of infected residents.ResultsThe SAR was below 5%, suggesting a high efficiency of IPC measures. Mask-wearing or establishment of COVID-19 zones for infected residents were associated with lower SAR.ConclusionsWearing masks and isolating potentially infected residents appear to limit SARS-CoV-2 spread in nursing homes.

  • Publication . Article . Preprint . 2020
    Open Access English
    Authors: 
    Alexandre J. Vivanti; Christelle Vauloup-Fellous; Sophie Prevot; Veronique Zupan; Cecile Suffee; Jeremy Do Cao; Alexandra Benachi; Daniele De Luca;
    Publisher: Nature Publishing Group
    Country: France

    SARS-CoV-2 outbreak is the first pandemic of the century. SARS-CoV-2 infection is transmitted through droplets; other transmission routes are hypothesized but not confirmed. So far, it is unclear whether and how SARS-CoV-2 can be transmitted from the mother to the fetus. We demonstrate the transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the last trimester and presenting with neurological compromise. The transmission is confirmed by comprehensive virological and pathological investigations. In detail, SARS-CoV-2 causes: (1) maternal viremia, (2) placental infection demonstrated by immunohistochemistry and very high viral load; placental inflammation, as shown by histological examination and immunohistochemistry, and (3) neonatal viremia following placental infection. The neonate is studied clinically, through imaging, and followed up. The neonate presented with neurological manifestations, similar to those described in adult patients. Congenital infection of SARS-CoV-2 has been described, but the transmission routes remain unclear. Here, the authors report evidence of transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the last trimester and presenting with neurological compromise.

  • English
    Authors: 
    Collin, Annabelle; Prague, Mélanie; Moireau, Philippe;
    Publisher: HAL CCSD
    Country: France

    International audience; Estimation of dynamical systems - in particular, identification of their parameters - is fundamental in computational biology, e.g., pharmacology, virology, or epidemiology, to reconcile model runs with available measurements. Unfortunately, the mean and variance priorities of the parameters must be chosen very appropriately to balance our distrust of the measurements when the data are sparse or corrupted by noise. Otherwise, the identification procedure fails. One option is to use repeated measurements collected in configurations with common priorities - for example, with multiple subjects in a clinical trial or clusters in an epidemiological investigation. This shared information is beneficial and is typically modeled in statistics using nonlinear mixed-effects models. In this paper, we present a data assimilation method that is compatible with such a mixed-effects strategy without being compromised by the potential curse of dimensionality. We define population-based estimators through maximum likelihood estimation. We then develop an equivalent robust sequential estimator for large populations based on filtering theory that sequentially integrates data. Finally, we limit the computational complexity by defining a reduced-order version of this population-based Kalman filter that clusters subpopulations with common observational backgrounds. The performance of the resulting algorithm is evaluated against classical pharmacokinetics benchmarks. Finally, the versatility of the proposed method is tested in an epidemiological study using real data on the hospitalisation of COVID-19 patients in the regions and departments of France.

  • Open Access English
    Authors: 
    Alice Mac Kain; Ghizlane Maarifi; Sophie-Marie Aicher; Nathalie J. Arhel; Artem Baidaliuk; Thomas Vallet; Quang Dinh Tran; Alexandra Hardy; Maxime Chazal; Françoise Porrot; +11 more
    Publisher: HAL CCSD
    Country: France

    AbstractInterferon restricts SARS-CoV-2 replication in cell culture, but only a handful of Interferon Stimulated Genes with antiviral activity against SARS-CoV-2 have been identified. Here, we describe a functional CRISPR/Cas9 screen aiming at identifying SARS-CoV-2 restriction factors. We identified DAXX, a scaffold protein residing in PML nuclear bodies known to limit the replication of DNA viruses and retroviruses, as a potent inhibitor of SARS-CoV-2 and SARS-CoV replication in human cells. Basal expression of DAXX was sufficient to limit the replication of SARS-CoV-2, and DAXX over-expression further restricted infection. In contrast with most of its previously described antiviral activities, DAXX-mediated restriction of SARS-CoV-2 was independent of the SUMOylation pathway. SARS-CoV-2 infection triggered the re-localization of DAXX to cytoplasmic sites and promoted its degradation. Mechanistically, this process was mediated by the viral papain-like protease (PLpro) and the proteasome. Together, these results demonstrate that DAXX restricts SARS-CoV-2, which in turn has evolved a mechanism to counteract its action.

  • Open Access English
    Authors: 
    Paul Brandily; Clément Brébion; Simon Briole; Laura Khoury;
    Publisher: HAL CCSD
    Country: France
    Project: ANR | PGSE (ANR-17-EURE-0001)

    Mortality inequalities remain substantial in many countries, and large shocks such as pandemics could amplify them further. The unequal distribution of COVID-19 confirmed cases suggests that this is the case. Yet, evidence on the causal effect of the epidemic on mortality inequalities remains scarce. In this paper, we exploit exhaustive municipality-level data in France, one of the most severely hit country in the world, to identify a negative relationship between income and excess mortality within urban areas, that persists over COVID-19 waves. Over the year 2020, the poorest municipalities experienced a 30% higher increase in excess mortality. Our analyses can rule out an independent contribution of lockdown policies to this heterogeneous impact. Finally, we find evidence that both labour-market exposure and housing conditions are major determinants of the epidemic-induced effects of COVID-19 on mortality inequalities, but that their respective role depends on the state of the epidemic.

  • English
    Authors: 
    Abidi, Hani; Amami, Rim; Trabelsi, Chiraz;
    Publisher: HAL CCSD
    Country: France

    The model descibes the epidemic dynamics of Covid-19 in a population after vaccination. Using the maximum principale, our goal is to prove the existence of an optimal strategy such that it minimize the number of infected people after vaccination. Finally, some numerical results are provided.

  • Publication . Other literature type . Article . Preprint . 2019
    Open Access English
    Authors: 
    Cindy Kundlacz; Marie Pourcelot; Aurore Fablet; Rayane Amaral Da Silva Moraes; Thibaut Léger; Bastien Morlet; Cyril Viarouge; Corinne Sailleau; Mathilde Turpaud; Axel Gorlier; +6 more
    Countries: Netherlands, South Africa, France

    AbstractBluetongue virus (BTV) is an arbovirus transmitted by blood-feeding midges to a wide range of wild and domestic ruminants. In this report, we showed that BTV, through its virulence non-structural protein NS3 (BTV-NS3), is able to activate the MAPK/ERK pathway. In response to growth factors, the MAPK/ERK pathway activates cell survival, differentiation, proliferation and protein translation but can also lead to the production of several inflammatory cytokines. By combining immunoprecipitation of BTV-NS3 and mass spectrometry analysis from both BTV-infected and NS3-transfected cells, we identified the serine/threonine-protein kinase B-Raf (BRAF), a crucial player of the MAPK/ERK pathway, as a new cellular interactor of BTV-NS3. BRAF silencing led to a significant decrease of the MAPK/ERK activation by BTV supporting a model where BTV-NS3 interacts with BRAF to activate this signaling cascade. Furthermore, the intrinsic ability of BTV-NS3 to bind BRAF and activate the MAPK/ERK pathway is conserved throughout multiple serotypes/strains but appears to be specific to BTV compared to other members ofOrbivirusgenus. Inhibition of MAPK/ERK pathway with U0126 reduced viral titers, suggesting that BTV manipulates this pathway for its own replication. Therefore, the activation of the MAPK/ERK pathway by BTV-NS3 could benefit to BTV replication by promoting its own viral protein synthesis but could also explain the deleterious inflammation associated with tissue damages as already observed in severe cases of BT disease. Altogether, our data provide molecular mechanisms to explain the role of BTV-NS3 as a virulence factor and determinant of pathogenesis.ImportanceBluetongue Virus (BTV) is responsible of the non-contagious arthropod-borne disease Bluetongue (BT) transmitted to ruminants by blood-feeding midges. Despite the fact that BTV has been extensively studied, we still have little understanding of the molecular determinants of BTV virulence. In this report, we found that the virulence protein NS3 interacts with BRAF, a key component of the MAPK/ERK pathway. In response to growth factors, this pathway promotes cell survival, increases protein translation but also contributes to the production of inflammatory cytokines. We showed that BTV-NS3 enhances the MAPK/ERK pathway and this activation is BRAF-dependent. Our results demonstrate, at the molecular level, how a single virulence factor has evolved to target a cellular function to ensure its viral replication. On the other hand, our findings could also explain the deleterious inflammation associated with tissue damages as already observed in severe cases of BT disease.

  • Open Access English
    Authors: 
    Stuart P. Weisberg; Thomas J. Connors; Yun Zhu; Matthew R. Baldwin; Wen-Hsuan W. Lin; Sandeep N. Wontakal; Peter A. Szabo; Steven B. Wells; Pranay Dogra; Joshua I. Gray; +18 more
    Publisher: HAL CCSD
    Country: France
    Project: NIH | Development of therapeuti... (1R01NS105699-01A1), NIH | Bioinformatics (5P01AI106697-02), NIH | Development of Localized ... (1K23AI141686-01)

    ABSTRACTClinical manifestations of COVID-19 caused by the novel coronavirus SARS-CoV-2 are associated with age. While children are largely spared from severe respiratory disease, they can present with a SARS-CoV-2-associated multisystem inflammatory syndrome (MIS-C) similar to Kawasaki’s disease. Here, we show distinct antibody (Ab) responses in children with MIS-C compared to adults with severe COVID-19 causing acute respiratory distress syndrome (ARDS), and those who recovered from mild disease. There was a reduced breadth and specificity of anti-SARS-CoV-2-specific antibodies in MIS-C patients compared to the COVID patient groups; MIS-C predominantly generated IgG Abs specific for the Spike (S) protein but not for the nucleocapsid (N) protein, while the COVID-19 cohorts had anti-S IgG, IgM and IgA Abs, as well as anti-N IgG Abs. Moreover, MIS-C patients had reduced neutralizing activity compared to both COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children and adults who develop severe disease, with implications for optimizing treatments based on symptom and age.

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