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51. Nasopharyngeal and serological anti SARS-CoV-2 IgG/IgA responses in COVID-19 patients

Author: Sylvie van der Werf, Caroline Demeret, Bernadette Crescenzo-Chaigne, Lila Bouadma, Jade Ghosn, Vincent Enouf, Sarah Tubiana, Stéphane Petres, Marie Noelle Ungeheuer, Sylvie Behillil, Nicolas Escriou, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], Plateforme de Microbiologie Mutualisée (PIBnet) - Mutualized Platform for Microbiology (P2M), Laboratoire d’innovation : vaccins – Innovation lab : vaccines, Plateforme technologique Production et purification de protéines recombinantes – Production and Purification of Recombinant Proteins Technological Platform (PPR), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigations Cliniques [CHU Bichat] (CIC plurithématique), This work was supported by the « URGENCE COVID-19 » fundraising campaign of Institut Pasteur, by REACTING (Research & Action Emerging Infectious Diseases) and by the H2020 project 101003589 (RECOVER). The French Covid Cohort is funded through the Ministry of Health and Social Affairs (PHRC n°20-0424) and Ministry of Higher Education and Research dedicated COVID19 fund., List of the membership of the French COVID cohort study group : Mélanie RORIZ, Patrick RISPAL, Sarah REDL (CHG d'Agen), Laurent LEFEBVRE, Pascal GRANIER, Laurence MAULIN (CH du Pays d'Aix, Aix en Provence), Cédric JOSEPH, Julien MOYET, Sylvie LION-DAOLIO (CHU Amiens Nord), Rafael MAHIEU, Alexandra DU-CANCELLE, Vincent DUBEE (CHU d'Angers), Stéphane SALLA-BERRY, Aldric MANUEL, Gabriel MACHEDA, Mylène MAILLET, Bruno CHANZY (CH d'Annecy Genevois), Jean-Charles GAGNARD (Hôpital privé d'Antony), Guillermo GIORDANO, Clara MOUTON PERROT, Vincent PESTRE (CH Henri Duffaut, Avignon), Cécile FICKO, Marie GOMINET, Aurore BOUSQUET (Hôpital d'instruction des armées Begin), Charline VAUCHY, Kévin BOUILLER, Maïder PAGADOY, Solène MARTY-QUINTERNET, Quentin LEPILLER (CHU Jean Minjoz, Besançon), Cyril LE BRIS, Benoit THILL, Marie-Laure CASANOVA, Georges LE FALHER, Eric OZIOL (CH de Béziers), Hugues CORDEL, Nathalie DOURNON, Olivier BOUCHAUD, Ségolène BRICHLER (Hôpital Avicenne, Bobigny), Duc NGUYEN, Pantxika BELLECAVE, Camille CICCONE, Marie-Edith LAFON (CHU Pellegrin, Bordeaux), Ségolène GREFFE (CHU Ambroise Paré, Boulogne Billancourt), Camille BOUISSE, Nicholas SEDILLOT, Damien BOUHOUR (CH Fleyriat, Bourg en Bresse), Camille CHASSIN (CH Pierre Oudot, Bourgoin-Jallieu), Erwan L'HER, Séverine ANSART, Cécile TROMEUR, Dewi GUELLEC (CHRU de Brest), Antoine MERCKX (CH de Cahors), Felix DJOSSOU (CH Andrée Rosemon, Cayenne), Vincent PEIGNE, Carola PIEROBON, Marie-Christine CARRET, Florence JEGO, Margaux ISNARD (CHMS Chambéry NH), Johann AUCHABIE, Roxane COURTOIS (CH de Cholet), Olivier LESENS (CHU Gabriel Montpied, Clermont-Ferrand), Martin MARTINOT (Hôpital Pasteur, Colmar), Olivier PICONE (Hôpital Louis Mourier, Colombes), Marie LACOSTE (CH Alpes Leman Contamine sur Arve), Brigitte ELHAR-RAR, Valérie GARRAIT, Isabelle DELACROIX, Thomas MAITRE, Jean Baptiste ASSIE (Centre Hospitalier Intercommunal de Créteil), Elsa NYAMANKOLLY (CH de Dax), François Xavier CATHERINE, Ma-thieu BLOT, Sophie MAHY, Marielle BUISSON, Lionel PIROTH, Florence GUILLOTIN, Alexis DE ROUGEMONT (CHU de Dijon Bourgogne), Valentine CAMPANA, Jérémie PASQUIER, André CABIE (CHU de Martinique, Fort de France), Simon BESSIS (Hôpital Raymond Poincaré, Garches), Olivier EPAULARD, Nicolas TERZI, Jean-François PAYEN, Laurence BOUILLET, Rebecca HAMIDFAR, Marion Le MARECHAL (CHU de Grenoble), Moïse MACHADO, Audrey BARRELET, Alexandra BEDOSSA (Grand Hôpital de l'Est Francilien site Marne-la-Vallée, Jossigny), Gwenhaël COLIN, Romain DECOURS, Thomas GUIMARD (CHD Les Oudairies, La Roche Sur Yon), Cécile GOUJARD, Stéphane JAUREGUIBERRY, Antoine CHERET (Hôpital Universitaire Bicêtre, Le Kremlin-Bicêtre), Anne Sophie RESSEGUIER (CH Emile Roux, Le Puy en Velay), Julien POISSY, Daniel MATHIEU, Saad NSEIR, Ilka ENGELMANN, Martine REMY (CHRU de Lille, Hôpital Salengro), Fanny VUOTTO, Benoit GACHET, Karine FAURE, Marielle BOYER-BESSEYRE, Kazali Enagnon (CHRU de Lille, Hôpital Fourrier), Marc LAMBERT, Arnaud SCHERPEREEL, Dominique DEPLANQUE, Stéphanie FRY, Cécile YELNIK (CHRU de Lille, Hôpital Albert Calmette), Laurent BITKER, Mehdi MEZIDI, Hodane YONIS, Nicolas BENECH, Thomas PERPOINT, Anne CONRAD, Vinca ICARD, Martine VALETTE (Hôpital de la Croix Rousse, Lyon), Simon-Djamel THIBERVILLE (Hôpital Louis Raffalli, Manosque), Stanislas REBAUDET (Hôpital Européen de Marseille), Bertrand DUSSOL (Hôpital Conception, Marseille), Sylvain DIAMANTIS, Catherine CHAKVEATZE, Clara FLATEAU (Groupe Hospitalier Sud Ile De France, hôpital de Melun), Vincent DINOT, Rostane GACI, Nadia OUAMARA (Hôpital de Mercy, CHR Metz-Thionville, Ars laquenexy), Hajnal-Gabriela ILLES, Louis GER-BAUD MORLAES, Jérôme DIMET (CH de Mont Marsan), Vincent LE MOING, Nathalie PANSU, Clément LE BIHAN, Brigitte MONTES (CHU de Montpellier), Anne Sophie BOUREAU, Clotilde ALLAVENA, Sabelline BOUCHEZ, Romain GUERY, Paul LE TURNIER, Cécile MEAR-PASSARD, Virginie FERRE (CHU de Nantes), Christophe RAPP (Hôpital Américain de Paris, Neuilly sur Seine), Elisa DE-MONCHY, Céline MICHELANGELLI, Karine RISSO (CHU de Nice), Paul LOUBET, Jean-Phillippe LAVIGNE (CHU Caremeau, Nîmes), Etienne DE MONTMOLLIN, Juliette PATRIER, Paul Henri WICKY, Lucie LE FEVRE, Pierre JACQUET, Raphael BORIE, Antoine DOSSIER, Dominique LUTON, Valentina ISERNIA, Sylvie LE GAC (Hôpital Bichat, Paris), Cécile AZOULAY, Nicolas CARLIER, Liem LUONG, Marie LACHATRE, Odile LAUNAY (Hôpital Cochin, Paris), Younes KERROUMI, Vanina MEYSSONNIER (Groupe Hospitalier Diaconesses Croix Saint-Simon, Paris), Jean-Luc DIEHL, Jean-Sébastien HULOT, Bernard CHOLLEY, Jean-Benoît ARLET, Olivier SANCHEZ (Hôpital Européen Georges Pompidou, Paris), Victoria MANDA, Laurène AZEMAR, Guylaine CASTOR-ALEXANDRE (Hôpital Lariboisière, Paris), Karine LACOMBE, Thibault CHIARABINI, Bénédicte LEFEBVRE, Laurence MORAND-JOUBERT, Djeneba FOFANA, Aurélie SCHNURIGER (Hôpital Saint Antoine, Paris), Nathalie DE CASTRO, Constance DELAUGERRE, Marie-Laure CHAIX (Hôpital Saint Louis, Paris), Julie CHAS (Hôpital Tenon, Paris), Valérie GABORIEAU, Eve LE COUSTUMIER, Walter PICARD (CH de Pau), Jean-Benoît ZABBE, Florent PEELMAN, Edouard SOUM (CH de Périgueux), Hugues AUMAÎTRE (CH de Perpignan), Elodie CURLIER, Rachida OUISSA, Isabelle FABRE (CHU de Pointe à Pitre, Guadeloupe), Blandine RAMMAERT (CHU de Poitiers), Nadia SAIDANI (CH Quimper), Firouzé BANI-SADR, Maxime HENTZIEN, Yohan N 'GUYEN, Juliette ROMARU, Kévin DIDIER (CHU Reims), Isabelle ENDERLE, Vincent THIBAULT, Fabrice LAINE, Matthieu LESOU-HAITIER, Matthieu REVEST, Pierre TATTEVIN (CHU Rennes), Jean-Christophe PLANTIER, Manuel ETIENNE, Véronique LEMEE, Eglantine FERRAND DEVOUGE, Kévin ALEXANDRE, Elise ARTAUD-MACCARI (CHU Rouen), Nathalie ALLOU, Marie LAGRANGE, Julien JABOT (CH Saint Denis et Saint Pierre, La réunion), Benoît ROZE, Delphine BREGEAUD, Younes AIT TAMLIHAT (CH Saintes), Ali HACHEMI (CH Soisson), Hélène SALVATOR, Erwan FOURN, David ZUCMAN (Hôpital Foch, Suresnes), Eric DELAVEUVE, Coline JAUD-FISCHER, Paul DUNAND (Hôpital Bel Air, Thionville), François BISSUEL (CH Thonon les Bains), Karen DELAVIGNE, Marie PIEL-JULIAN, Pierre DELOBEL, Benjamine SARTON, Marie RAFIQ, Guillaume MARTIN-BLONDEL, Laurent GUILLEMINAULT, Marlène MURRIS, Agnès SOMMET (CHU de Toulouse), Eric SENNEVILLE, Olivier ROBINEAU, Agnès MEYBECK (CH Tourcoing), Denis GAROT, Laurent PLANTIER, Valérie GISSOT, Julien MARLET, Karl STEFIC, Catherine GAUDY-GRAFFIN, Francis BARIN, Adrien LEMAIGNEN (CHU Bretonneau, Tours), Grégory CORVAISIER, Delphine LARIVIERE, Marie LANGELOT-RICHARD (CH Vannes), Elisabeth BOTELHO-NEVERS , Amandine GAGNEUX-BRUNON, Tiffany TROUILLON, Thomas BOURLET, Thomas BOURLET, Sylvie PILLET, Bruno POZZETTO (CHU de St Etienne), Antoine KIMMOUM, Bruno LEVY, Mathieu MATTEI, François GOEHRINGER, Christian RABAUD, Sibylle BEVILACQUA, Benjamin LEFEVRE, Anne GUILLAUMOT, Véronique VENARD, Hélène JEULIN, Evelyne SCHVOERER, Cédric HARTARD (CHU de Nancy, Vandoeuvre les Nancy), Pauline CARAUX PAZ, Laurent RICHIER, Mohamed EL SANHARAWI (CH Villeneuve St Georges)., European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord
Subjects: Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Severe disease, Infectious and parasitic diseases, RC109-216, Article, Serology, 03 medical and health sciences, 0302 clinical medicine, Medicine, Mucosal Immunity, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, business.industry, Epithelium, 3. Good health, Nucleoprotein, medicine.anatomical_structure, Antibody response, SARS CoV, 030220 oncology & carcinogenesis, Immunology, biology.protein, Antibody, business
Abstract: BackgroundThe systemic antibody responses to SARS-CoV-2 in COVID-19 patients has been extensively studied. However, much less is known about the mucosal responses in the upper airways at the site of initial SARS-CoV-2 replication. Local antibody responses in the nasopharyngeal epithelium, that are likely to determine the course of infection, have not been analysed so far nor their correlation with antibody responses in serum.MethodsThe IgG and IgA antibody responses were analysed in the plasma as well as in nasopharyngeal swabs (NPS) from the first four COVID-19 patients confirmed by RT-qPCR in France. Two were pauci-symptomatic while two developed severe disease. Taking advantage of a comprehensive series of plasma and nasopharyngeal samples, we characterized their antibody profiles from the second week post symptoms onset, by using an in-house ELISA to detect anti-SARS-CoV-2 Nucleoprotein (N) IgG and IgA.ResultsAnti-N IgG and IgA antibodies were detected in the NPS of severe patients. Overall, the levels of IgA and IgG antibodies in plasma and NPS appeared specific to each patient.ConclusionsAnti-N IgG and IgA antibodies are detected in NPS, and their levels are related to antibody levels in plasma. The two patients with severe disease exhibited different antibody profiles that may reflect different disease outcome. For the pauci-symptomatic patients, one showed a low anti-N IgG and IgA response in the plasma only, while the other one did not exhibit overt serological response.
Published: 2021

52. Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies

Author: Ludivine Grzelak, Mélanie Albert, María González, Vincent Enouf, Françoise Porrot, Hélène Péré, Marianne Maquart, Flora Donati, Timothée Bruel, Maaran Michael Rajah, Olivier Schwartz, Jérôme De Seze, Isabelle Staropoli, Julian Buchrieser, Sylvie van der Werf, Aymeric Sève, Florence Guivel-Benhassine, Laurent Hocqueloux, Samira Fafi-Kremer, Karl Stefic, David Veyer, Cyril Planchais, Etienne Simon-Loriere, Delphine Planas, Elodie Bishop, Thierry Prazuck, Hugo Mouquet, and Sylvie Behillil
Subjects: biology, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Virology, Virus, Neutralization, Vaccination, Titer, Nasal Swab, Humoral immunity, biology.protein, Medicine, Antibody, business
Abstract: SARS-CoV-2 B.1.1.7 and B.1.351 variants emerged respectively in United Kingdom and South Africa and spread in many countries. Here, we isolated infectious B.1.1.7 and B.1.351 strains and examined their sensitivity to anti-SARS-CoV-2 antibodies present in sera and nasal swabs, in comparison with a D614G reference virus. We established a novel rapid neutralization assay, based on reporter cells that become GFP+ after overnight infection. B.1.1.7 was neutralized by 79/83 sera from convalescent patients collected up to 9 months post symptoms, almost similar to D614G. There was a mean 6-fold reduction in titers and even loss of activity against B.1.351 in 40% of convalescent sera after 9 months. Early sera from 19 vaccinated individuals were almost as potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Nasal swabs from vaccine recipients were not neutralizing, except in individuals who were diagnosed COVID-19+ before vaccination. Thus, faster-spreading variants acquired a partial resistance to humoral immunity generated by natural infection or vaccination, mostly visible in individuals with low antibody levels.
Published: 2021

53. Absence of association between 2019‐20 influenza vaccination and COVID‐19: Results of the European I‐MOVE‐COVID‐19 primary care project, March‐August 2020

Author: Alessandra Falchi, Itziar Casado Buesa, Theresa Enkirch, Ana-Maria Vilcu, Mia Brytting, Adam Meijer, Janneke Hendriksen, Josie Murray, Jesús Castilla, Debbie Sigerson, Diogo F P Marques, Vincent Enouf, Sylvie Behillil, Mariëtte Hooiveld, AnnaSara Carnahan, Iván Martínez-Baz, Marta Valenciano, Esther Kissling, Frederika Dijkstra, Naoma William, Marit M A de Lange, EpiConcept [Paris], Netherlands Institute for Health Services Research [Utrecht] (NIVEL), Public Health Agency of Sweden, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), CIBER de Epidemiología y Salud Pública (CIBERESP), Public Health Scotland [Glasgow], Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de Virologie [UNIV Corse-Inserm] (EA7310), Université Pascal Paoli (UPP)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Union. Grant Number: 101003673, European Project: 101003673,H2020-SC1-PHE-CORONAVIRUS-2020,I-MOVE-COVID-19(2020), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pascal Paoli (UPP), and University of St Andrews. School of Medicine
Subjects: Male, Epidemiology, [SDV]Life Sciences [q-bio], Target groups, E-DAS, Logistic regression, SARS‐CoV‐2, 0302 clinical medicine, RA0421, RA0421 Public health. Hygiene. Preventive Medicine, Odds Ratio, 030212 general & internal medicine, Respiratory Tract Infections, 0303 health sciences, Vaccination, Respiratory infection, Case-control study, Orthomyxoviridae, influenza vaccination, multicentre study, 3. Good health, Europe, Infectious Diseases, Influenza Vaccines, Original Article, Female, Test-negative design, Pulmonary and Respiratory Medicine, RM, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Influenza vaccination status, case-control study, Primary care, Multicentre study, 03 medical and health sciences, SDG 3 - Good Health and Well-being, COVID‐19, Internal medicine, Influenza, Human, medicine, Humans, 030304 developmental biology, Primary Health Care, case‐control study, business.industry, SARS-CoV-2, test-negative design, Public Health, Environmental and Occupational Health, COVID-19, Original Articles, Odds ratio, NIS, Influenza vaccination, RM Therapeutics. Pharmacology, Logistic Models, test‐negative design, Case-Control Studies, business
Abstract: The I‐MOVE‐COVID‐19 network has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no 101003673. Background : Claims of influenza vaccination increasing COVID-19 risk are circulating. Within the I-MOVE-COVID-19 primary care multicentre study, we measured the association between 2019-20 influenza vaccination and COVID-19. Methods : We conducted a multicentre test-negative case-control study at primary care level, in study sites in five European countries, from March to August 2020. Patients presenting with acute respiratory infection were swabbed, with demographic, 2019-20 influenza vaccination and clinical information documented. Using logistic regression, we measured the adjusted odds ratio (aOR), adjusting for study site and age, sex, calendar time, presence of chronic conditions. The main analysis included patients swabbed ≤7 days after onset from the three countries with
Published: 2021

54. Performing point-of-care molecular testing for SARS-CoV-2 with RNA extraction and isothermal amplification

Author: Daniel Felipe Gonzalez Obando, Pierre Garneret, Vincent Enouf, Jean Claude Manuguerra, Elian Martin, Patrick Tabeling, Elodie Brient-Litzler, Sylvie van der Werf, Jean-Christophe Olivo-Marin, Jessica Vanhomwegen, Fabrice Monti, Etienne Coz, Chimie-Biologie-Innovation (UMR 8231) (CBI), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre-Gilles de Gennes pour la Microfluidique, Cellule d'Intervention Biologique d'Urgence (Centre National de Référence) - Laboratory for Urgent Response to Biological Threats (National Reference Center) (CIBU), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris] (IP)-Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Analyse d'images biologiques - Biological Image Analysis (BIA), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Microfluidique, MEMS, Nanostructures (MMN), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), IPGG platform (ANR-10-EQPX-34) (PT,PG,EC,EM), Carnot Pasteur Maladies Infectieuses program (ANR 11-CARN 017-01) (JV,JCM), ANR-20-COVI-000 (EB,JV,JCM,PT,EM,C), FONDS ESPCI (EC), ANR-10-EQPX-0034,IPGG,Institut Pierre Gilles de Gennes pour la microfluidique(2010), Université Paris sciences et lettres (PSL), and The authors thank ESPCI, CNRS, IPGG platform (ANR-10-EQPX-34), PSL, PSL-VALO, PASTEUR, Carnot Pasteur Maladies Infectieuses program (ANR 11-CARN 017–01), PARIS City, ANR Flash, DIM ELICIT, Fonds de l’ESPCI, Bettencourt Fondation for their support. They thank DNA SCRIPT, France Ambassador in JAPAN, M.Ban, Bertin-Technology, Withings, T.Coulhon, JL.Missika, MC.Lemardeley, V.Croquette, A.Boquet-Pujadas, C.Batéjat, D.Hoinard, L.Dehove, D.Freitas, A.Kwasiborski, Q.Grassin, M.Feher, for discussion and help.
Subjects: RNA viruses, Viral Diseases, Time Factors, Coronaviruses, Computer science, [SDV]Life Sciences [q-bio], Artificial Gene Amplification and Extension, Polymerase Chain Reaction, Genome, Medical Conditions, COVID-19 Testing, Limit of Detection, Medicine and Health Sciences, Signal Amplification, Pathology and laboratory medicine, Virus Testing, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Multidisciplinary, Equipment Design, Medical microbiology, Viral Load, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Infectious Diseases, Molecular Diagnostic Techniques, Point-of-Care Testing, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Viruses, Engineering and Technology, RNA, Viral, Medicine, RNA extraction, SARS CoV 2, Pathogens, Nucleic Acid Amplification Techniques, Research Article, SARS coronavirus, Science, Loop-mediated isothermal amplification, Computational biology, Research and Analysis Methods, Microbiology, Extraction techniques, Diagnostic Medicine, Virology, Genetics, Humans, Nucleic Acid Amplification Tests, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, Molecular Biology Techniques, Molecular Biology, Point of care, Gene amplification, Biology and life sciences, SARS-CoV-2, Organisms, Viral pathogens, COVID-19, RNA, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Covid 19, Reverse Transcriptase-Polymerase Chain Reaction, Gold standard (test), Microbial pathogens, RNA amplification, Signal Processing, Nucleic acid, Viral Transmission and Infection
Abstract: Déposé dans medRxiv le 4 août 2020 : https://doi.org/10.1101/2020.08.01.20166538; International audience; To respond to the urgent need for COVID-19 testing, countries perform nucleic acid amplification tests (NAAT) for the detection of SARS-CoV-2 in centralized laboratories. Real-time RT-PCR (Reverse transcription-Polymerase Chain Reaction), used to amplify and detect the viral RNA., is considered, as the current gold standard for diagnostics. It is an efficient process, but the complex engineering required for automated RNA extraction and temperature cycling makes it incompatible for use in point of care settings [1]. In the present work, by harnessing progress made in the past two decades in isothermal amplification and paper microfluidics, we created a portable test, in which SARS-CoV-2 RNA is extracted, amplified isothermally by RT-LAMP (Loop-mediated Isothermal Amplification), and detected using intercalating dyes or fluorescent probes. Depending on the viral load in the tested samples, the detection takes between twenty minutes and one hour. Using a set of 16 pools of naso-pharyngal swab eluates, we estimated a limit of detection comparable to real-time RT-PCR (i.e. 1 genome copies per microliter of clinical sample) and no cross-reaction with eight major respiratory viruses currently circulating in Europe. We designed and fabricated an easy-to-use portable device called "COVIDISC" to carry out the test at the point of care. The low cost of the materials along with the absence of complex equipment will expedite the widespread dissemination of this device. What is proposed here is a new efficient tool to help managing the pandemics.
Published: 2021

55. Linked transmission chains of imported SARS-CoV-2 variant B.1.351 across mainland France, January 2021

Author: Diane Descamps, Arnaud Tarantola, Lucile Trutt, Josselin Vincent, Aurélien Zhu-Soubise, Lisa King, Olivier Catelinois, Colin Deschanvres, Olivier Glass, Vincent Enouf, Mounira Smati-Lafarge, Marilyne Gojon, Delphine Barataud, Jacques Izopet, Florence Daubresse, Valérie Lebaillif, Sylvie Behillil, Anne Guinard, Valérie Garrait, Sylvie van der Werf, Guillaume Spaccaferri, Etienne Simon-Loriere, Amine Si Ali, Sibylle Bernard-Stoecklin, Simon Ribes, Blandine De Kerros, Esra Morvan, Muriel Beliah-Nappez, Karine Vilhes, Clémentine Calba, Alexandra Mailles, Sarah Mahdjoub-Assaad, Damien Mouly, Aurélie Misme, Berenice Villegas-Ramirez, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Agence Régionale de Santé Ile-de-France [Paris] (ARS IDF), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Prévention et contrôle des infections (PCI ), Hôpitaux Universitaires de Genève (HUG), Centre Hospitalier Intercommunal de Créteil (CHIC), Hôpital Lariboisière-Fernand-Widal [APHP], Agence régionale de Santé Pays de la Loire [Nantes], Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Agence Régionale de Santé Occitanie (ARS Occitanie), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP), Pasteur International Bioresources network (PIBNet), and Plateforme de Microbiologie Mutualisée (PIBnet) - Mutualized Platform for Microbiology (P2M)
Subjects: Adult, Male, Adolescent, Epidemiology, [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Black People, law.invention, Young Adult, law, Communicable Diseases, Imported, Virology, Humans, Child, SARS-CoV-2 variants 20H/501Y.V2, Mozambique, Aged, Travel, SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, Middle Aged, Geography, Transmission (mechanics), Cluster, COVID-19 Nucleic Acid Testing, Mainland, Incubation, Female, France, Rapid Communication
Abstract: International audience; Two cases of confirmed SARS-CoV-2 infection with the B.1.351 variant were reported in France in mid-January, 2020. These cases attended a gathering in Mozambique in mid-December 2020. Investigations led to the identification of five imported cases responsible for 14 transmission chains and a total 36 cases. Epidemiological characteristics seemed comparable to those described before the emergence of the South African variant B.1.351. The lack of tertiary transmission outside of the personal sphere suggests that distancing and barrier measures were effective.
Published: 2021

56. Early phylodynamics analysis of the COVID-19 epidemic in France

Author: Jean-Christophe Plantier, Antonin Bal, Gonché Danesh, Anne-Geneviève Marcelin, Laurence Josset, Sonia Burrel, Sylvie Behillil, Sylvie van der Werf, Etienne Simon-Loriere, Samuel Alizon, Grégory Destras, Yannis Michalakis, Vincent Enouf, Vincent Thibault, Bruno Lina, Baptiste Elie, David Boutolleau, Mircea T. Sofonea, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Hôpital de la Croix-Rousse [CHU - HCL], Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Charles Nicolle [Rouen], CHU Pontchaillou [Rennes], Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris], Pasteur International Bioresources network (PIBNet), Evolution Théorique et Expérimentale (MIVEGEC-ETE), Perturbations, Evolution, Virulence (PEV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), ANR-20-COVI-0098,PHYEPI,Intégration de données de séquences et d'incidence pour analyser et contrôler les épidémies virales(2020), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université de Paris (UP), Génétique et évolution des maladies infectieuses (GEMI), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Génétique et évolution des maladies infectieuses (GEMI), Alizon, Samuel, and Intégration de données de séquences et d'incidence pour analyser et contrôler les épidémies virales - - PHYEPI2020 - ANR-20-COVI-0098 - COVID-19 - VALID
Subjects: 0106 biological sciences, Coronavirus disease 2019 (COVID-19), Genomic data, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Context (language use), [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, 010603 evolutionary biology, 01 natural sciences, 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Incidence data, Pandemic, [SDV.BID.SPT] Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], [SDV.EE.ECO] Life Sciences [q-bio]/Ecology, environment/Ecosystems, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], [SDV.EE.IEO] Life Sciences [q-bio]/Ecology, environment/Symbiosis, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, Geography, Viral phylodynamics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.GEN.GPO] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Contact tracing, Demography, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: France was one of the first countries to be reached by the COVID-19 pandemic. Here, we analyse 196 SARS-Cov-2 genomes collected between Jan 24 and Mar 24 2020, and perform a phylodynamics analysis. In particular, we analyse the doubling time, reproduction number (ℛt) and infection duration associated with the epidemic wave that was detected in incidence data starting from Feb 27. Different models suggest a slowing down of the epidemic in Mar, which would be consistent with the implementation of the national lock-down on Mar 17. The inferred distributions for the effective infection duration andℛtare in line with those estimated from contact tracing data. Finally, based on the available sequence data, we estimate that the French epidemic wave originated between mid-Jan and early Feb. Overall, this analysis shows the potential to use sequence genomic data to inform public health decisions in an epidemic crisis context and calls for further analyses with denser sampling.
Published: 2021

57. First Cases of Coronavirus Disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020

Author: Gianfranco Spiteri, James Fielding, Michaela Diercke, Christine Campese, Vincent Enouf, Alexandre Gaymard, Antonino Bella, Paola Sognamiglio, Maria José Sierra Moros, Antonio Nicolau Riutort, Yulia V. Demina, Romain Mahieu, Markku Broas, Malin Bengnér, Silke Buda, Julia Schilling, Laurent Filleul, Agnès Lepoutre, Christine Saura, Alexandra Mailles, Daniel Levy-Bruhl, Bruno Coignard, Sibylle Bernard-Stoecklin, Sylvie Behillil, Sylvie van der Werf, Martine Valette, Bruno Lina, Flavia Riccardo, Emanuele Nicastri, Inmaculada Casas, Amparo Larrauri, Magdalena Salom Castell, Francisco Pozo, Rinat A. Maksyutov, Charlotte Martin, Marc Van Ranst, Nathalie Bossuyt, Lotta Siira, Jussi Sane, Karin Tegmark-Wisell, Maria Palmérus, Eeva K. Broberg, Julien Beauté, Pernille Jorgensen, Nick Bundle, Dmitriy Pereyaslov, Cornelia Adlhoch, Jukka Pukkila, Richard Pebody, Sonja Olsen, and Bruno Christian Ciancio
Published: 2020

58. Lessons learned from the investigation of a COVID-19 cluster in Creil, France: effectiveness of targeting symptomatic cases and conducting contact tracing around them

Author: Vincent Pommier de Santi, Anaïs Grosset-Janin, Françoise Raynaud, Franck de Laval, Marc Antoine Sanchez, Anne Couderc, Vincent Enouf, Emilie Javelle, César Destanque, Etienne Simon-Loriere, Fabrice Biot, Christelle Tong, Dinaherisoa Andriamanantena, Flavie Letois, Audrey Mérens, Olivier Ferraris, François Delon, Alexandre Allonneau, Christine Bigaillon, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'épidémiologie et de santé publique des armées [Marseille] (CESPA), Service de Santé des Armées, Direction Générale de l'Armement, Direction Generale de l'Armement, Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris], Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Pasteur International Bioresources network (PIBNet), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), COMBE, Isabelle, and Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID
Subjects: 0301 basic medicine, Male, Pediatrics, Attack rate, Infectious and parasitic diseases, RC109-216, Serology, Disease Outbreaks, 0302 clinical medicine, COVID-19 Testing, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Reverse Transcriptase Polymerase Chain Reaction, Medicine, MESH: COVID-19, 030212 general & internal medicine, Young adult, MESH: Disease Outbreaks, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Middle Aged, Reverse Transcriptase Polymerase Chain Reaction, Respiratory infection, Middle Aged, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Asymptomatic, Infectious Diseases, MESH: Young Adult, MESH: RNA, Viral, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, RNA, Viral, France, medicine.symptom, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Serial interval, Adult, medicine.medical_specialty, RT-PCR, Disease cluster, MESH: Contact Tracing, 03 medical and health sciences, Young Adult, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Humans, MESH: SARS-CoV-2, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, MESH: Humans, business.industry, SARS-CoV-2, Research, COVID-19, MESH: Adult, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, MESH: France, 030104 developmental biology, Cluster, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Contact Tracing, business, Contact tracing
Abstract: Background This study presents the methods and results of the investigation into a SARS-CoV-2 outbreak in a professional community. Due to the limited testing capacity available in France at the time, we elaborated a testing strategy according to pre-test probability. Methods The investigation design combined active case finding and contact tracing around each confirmed case with testing of at-risk contact persons who had any evocative symptoms (n = 88). One month later, we performed serology testing to test and screen symptomatic and asymptomatic cases again (n = 79). Results Twenty-four patients were confirmed (14 with RT-PCR and 10 with serology). The attack rate was 29% (24/83). Median age was 40 (24 to 59), and the sex ratio was 15/12. Only three cases were asymptomatic (= no symptoms at all, 13%, 95% CI, 3–32). Nineteen symptomatic cases (79%, 95% CI, 63–95) presented a respiratory infection, two of which were severe. All the RT-PCR confirmed cases acquired protective antibodies. Median incubation was 4 days (from 1 to 13 days), and the median serial interval was 3 days (0 to 15). We identified pre-symptomatic transmission in 40% of this cluster, but no transmission from asymptomatic to symptomatic cases. Conclusion We report the effective use of targeted testing according to pre-test probability, specifically prioritizing symptomatic COVID-19 diagnosis and contact tracing. The asymptomatic rate raises questions about the real role of asymptomatic infected people in transmission. Conversely, pre-symptomatic contamination occurred frequently in this cluster, highlighting the need to identify, test, and quarantine asymptomatic at-risk contact persons (= contact tracing). The local lockdown imposed helped reduce transmission during the investigation period.
Published: 2020

59. Dissemination of Extended-Spectrum-β-Lactamase-Producing

Author: Matthieu, Pot, Stéphanie, Guyomard-Rabenirina, David, Couvin, Célia, Ducat, Vincent, Enouf, Séverine, Ferdinand, Gaëlle, Gruel, Edith, Malpote, Antoine, Talarmin, Sébastien, Breurec, and Yann, Reynaud
Subjects: West Indies, wildlife, fungi, Enterobacteriaceae Infections, Enterobacter cloacae complex, Microbial Sensitivity Tests, ST114, Hospitals, beta-Lactamases, Anti-Bacterial Agents, Epidemiology and Surveillance, bla CTX-M-15, one health, Enterobacter cloacae, Animals, Humans, IncHI2, Guadeloupe, wastewater treatment plant, Plasmids
Abstract: Wastewater treatment plants are considered hot spots for antibiotic resistance. Most studies have addressed the impact on the aquatic environment, as water is an important source of anthropogenic pollutants., Wastewater treatment plants are considered hot spots for antibiotic resistance. Most studies have addressed the impact on the aquatic environment, as water is an important source of anthropogenic pollutants. Few investigations have been conducted on terrestrial animals living near treatment ponds. We isolated extended-spectrum-β-lactamase Enterobacter cloacae complex-producing strains from 35 clinical isolates, 29 samples of wastewater, 19 wild animals, and 10 domestic animals living in the hospital sewers and at or near a wastewater treatment plant to study the dissemination of clinically relevant resistance through hospital and urban effluents. After comparison of the antibiotic-resistant profiles of E. cloacae complex strains, a more detailed analysis of 41 whole-genome-sequenced strains demonstrated that the most common sequence type, ST114 (n = 20), was present in human (n = 9) and nonhuman (n = 11) samples, with a close genetic relatedness. Whole-genome sequencing confirmed local circulation of this pathogenic lineage in diverse animal species. In addition, nanopore sequencing and specific synteny of an IncHI2/ST1/blaCTX-M-15 plasmid recovered on the majority of these ST114 clones (n = 18) indicated successful worldwide diffusion of this mobile genetic element.
Published: 2020

60. No evidence of SARS-CoV-2 transfusion transmission despite RNA detection in blood donors showing symptoms after donation

Author: Laure Boizeau, Pascal Morel, Vincent Enouf, Virginie Sauvage, Quentin Lucas, Lila Chabli, Daniel Candotti, Josiane Pillonel, Pierre Cappy, Syria Laperche, Johanna Gomez, Pierre Tiberghien, Institut National de la Transfusion Sanguine [Paris] (INTS), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Direction des maladies infectieuses - Infectious Diseases Division [Saint-Maurice], Santé publique France - French National Public Health Agency [Saint-Maurice, France], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), and Candotti, Daniel
Subjects: Blood transfusion, medicine.medical_treatment, Blood Donors, 030204 cardiovascular system & hematology, Letter to BLOOD, Biochemistry, 0302 clinical medicine, Medicine, 030212 general & internal medicine, Young adult, Child, health care economics and organizations, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Sleep disorder, Hematology, Middle Aged, 3. Good health, Chronic mountain sickness, Child, Preschool, Donation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, France, medicine.symptom, Coronavirus Infections, Adult, medicine.medical_specialty, Adolescent, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, Immunology, Betacoronavirus, Young Adult, 03 medical and health sciences, Internal medicine, health services administration, Humans, Blood Transfusion, Pandemics, Aged, SARS-CoV-2, business.industry, COVID-19, Cell Biology, medicine.disease, Pneumonia, business, Tinnitus
Abstract: International audience; The diagnosis of chronic mountain sickness (CMS) is based on a score including 7 clinical features (breathlessness, sleep disturbance, cyanosis, venous dilatation, paresthesia, headache, and tinnitus) in the setting of extreme erythrocytosis. Examining individuals in La Rinconada, Peru, the highest city in the world, the authors demonstrated that CMS at extreme altitude is not linked to elevation of hemoglobin, since CMS+ and CMS− individuals had similar levels of erythrocytosis.
Published: 2020

61. A new SARS-CoV-2 variant with high lethality poorly detected by RT-PCR on nasopharyngeal samples: an observational study

Author: Sylvie van der Werf, Anna Zhukova, Etienne Simon-Loriere, Elena Guillotel, Pierre Fillâtre, Alice Gabellec, Artem Baidaliuk, François-Xavier Lescure, Rodolphe Buzelé, Dominique Costagliola, Bertrand Gagnière, Vincent Enouf, Vincent Thibault, Pascale Reusse, Véronique Merour, Marion Valence, Sylvie Behillil, Catherine Montagne, Marie-José Dufour, Claire Grolhier, Charlotte Pronier, Pierre Tattevin, Mathieu Tourdjman, Rémi Vatan, Nicolas Velmans, Edith Droumaguet, Sophie Geffroy Du Coudret, and Nicolas Massart
Subjects: Microbiology (medical), 0303 health sciences, medicine.medical_specialty, business.industry, Outbreak, General Medicine, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Real-time polymerase chain reaction, medicine.anatomical_structure, Interquartile range, Internal medicine, Severity of illness, medicine, Observational study, 030212 general & internal medicine, Seroconversion, Respiratory system, 10. No inequality, business, 030304 developmental biology, Respiratory tract
Abstract: 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 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.
Published: 2022

62. Viral dynamic modeling of SARS-CoV-2 in non-human primates

Author: Antonio Gonçalves, Pauline Maisonnasse, Flora Donati, Mélanie Albert, Sylvie Behillil, Vanessa Contreras, Thibaut Naninck, Romain Marlin, Caroline Solas, Andres Pizzorno, Julien Lemaitre, Nidhal Kahlaoui, Olivier Terrier, Raphael Ho Tsong Fang, Vincent Enouf, Nathalie Dereuddre-Bosquet, Angela Brisbarre, Franck Touret, Catherine Chapon, Bruno Hoen, Bruno Lina, Manuel Rosa-Calatrava, Xavier de Lamballerie, France Mentré, Roger Le Grand, Sylvie van der Werf, and Jeremie Guedj
Subjects: business.industry, viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Medicine, business, Virology
Abstract: Non-human primates infected with SARS-CoV-2 exhibit mild clinical signs. Here we used a mathematical model to characterize in detail the viral dynamics in 31 cynomolgus macaques infected with 106 pfu of SARS-CoV-2 for which nasopharyngeal and tracheal viral load were frequently assessed. We identified that infected cells had a large daily viral production (>104 virus) and a within-host reproductive basic number of 6 and 4 in nasopharyngeal and tracheal compartment, respectively. After peak viral load, infected cells were rapidly cleared with a half-life of 9 hours, with no significant association between cytokine elevation and clearance. Translating our model to the context of human-to-human infection, human mild infection may be characterized by a peak occurring 4 days after infection, a viral shedding of ~11 days and a generation time of 4 days. These results improve the understanding of SARS-CoV-2 viral replication and better understand the infection to SARS-CoV-2 in humans.
Published: 2020

63. Introductions and early spread of SARS-CoV-2 in France, 24 January to 23 March 2020

Author: Mélanie Albert, Fawzi Derrar, Sylvie Behillil, Flora Donati, Sylvie van der Werf, Marion Barbet, Andreea Alexandru, Etienne Simon-Loriere, Fabiana Gámbaro, Angela Brisebarre, Maud Vanpeene, Artem Baidaliuk, Meline Bizard, Vincent Enouf, Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Plateforme de Microbiologie Mutualisée (PIBnet) - Mutualized Platform for Microbiology (P2M), National Influenza Center, Viral Respiratory Laboratory [Alger], This study has received funding from Institut Pasteur, CNRS, Université de Paris, Santé publique France, the French Government's Investissement d'Avenir programme, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant n°ANR-10-LABX-62-IBEID), REACTing (Research & Action Emerging Infectious Diseases), France Génomique (ANR-10-INBS-09-09), IBISA, and the RECOVER project funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 101003589. ESL acknowledges funding from the INCEPTION programme (Investissements d’Avenir grant ANR-16-CONV-0005)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Institut Pasteur [Paris], Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: 0301 basic medicine, MESH: Coronavirus Infections, Epidemiology, [SDV]Life Sciences [q-bio], phylogeny, Disease Outbreaks, 0302 clinical medicine, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Coronavirus, outbreak surveillance, MESH: COVID-19, 030212 general & internal medicine, MESH: Disease Outbreaks, MESH: Phylogeny, Clade, virus genomics, Phylogenetic tree, biology, Reverse Transcriptase Polymerase Chain Reaction, Transmission (medicine), 3. Good health, Geography, MESH: RNA, Viral, MESH: Sentinel Surveillance, RNA, Viral, MESH: Betacoronavirus, France, MESH: Genome, Viral, Coronavirus Infections, Sequence Analysis, Rapid Communication, MESH: Pandemics, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, Zoology, Genome, Viral, Betacoronavirus, Viral Proteins, MESH: Sequence Analysis, 03 medical and health sciences, Virology, Humans, MESH: SARS-CoV-2, Pandemics, MESH: Humans, SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, biology.organism_classification, MESH: Viral Proteins, Coronavirus, MESH: France, 030104 developmental biology, MESH: Pneumonia, Viral, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Sentinel Surveillance
Abstract: 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.
Published: 2020

64. Prior infection by seasonal coronaviruses does not prevent SARS-CoV-2 infection and associated Multisystem Inflammatory Syndrome in children

Author: Isabelle Sermet-Gaudelus, Sarah Temmam, Christèle Huon, Sylvie Behillil, Vincent Gajdos, Thomas Bigot, Thibaut Lurier, Delphine Chrétien, Marija Backovic, Agnès Moisan-Delaunay, Flora Donati, Mélanie Albert, Elsa Foucaud, Bettina Mesplées, Grégoire Benoist, Albert Faye, Marc Duval-Arnould, Célia Cretolle, Marina Charbit, Mélodie Aubart, Johanne Auriau, Mathie Lorrot, Dulanjalee Kariyawasam, Laura Fertitta, Gilles Orliaguet, Bénédicte Pigneur, Brigitte Bader-Meunier, Coralie Briand, Vincent Enouf, Julie Toubiana, Tiffany Guilleminot, Sylvie van der Werf, Marianne Leruez-Ville, and Marc Eloit
Subjects: biology, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viruses, Prevalence, Antigen specificity, virus diseases, medicine.disease_cause, Asymptomatic, CTL, Immunity, Immunology, biology.protein, Medicine, Antibody, medicine.symptom, business, Coronavirus
Abstract: BackgroundChildren have a lower rate of COVID-19, potentially related to cross-protective immunity conferred by seasonal coronaviruses (HCoVs). We tested if prior infections with seasonal coronaviruses impacted SARS-CoV-2 infections and related Multisystem Inflammatory Syndrome (MIS).MethodsThis cross-sectional observational study in Paris hospitals enrolled 739 pauci or asymptomatic children (HOS group) plus 36 children with suspected MIS (MIS group). Prevalence, antigen specificity and neutralizing capability of SARS-CoV-2 antibodies were tested. Antibody frequency and titres against Nucleocapsid (N) and Spike (S) of the four seasonal coronaviruses (NL63, HKU1, 229E, OC43) were measured in a subset of seropositive patients (54 SARS-CoV-2 (HOS-P subgroup) and 15 MIS (MIS-P subgroup)), and in 118 matched SARS-CoV-2 seronegative patients (CTL subgroup).FindingsSARS-CoV-2 mean prevalence rate in HOSP children was 11.7% from April 1 to June 1. Neutralizing antibodies were found in 55·6% of seropositive children, and their relative frequency increased with time (up to 100 % by mid-May). A majority of MIS children (25/36) were SARS-CoV-2 seropositive, of which all tested (n=15) had neutralizing antibodies. On average, seropositive MIS children had higher N and S1 SARS-CoV-2 titres as compared to HOS children. Patients from HOS-P, MIS-P, and CTL subgroups had a similar prevalence of antibodies against the four seasonal HCoVs (66·9 −100%). The level of anti-SARS-CoV-2 antibodies was not significantly different in children who had prior seasonal coronavirus infection.InterpretationPrior infection with HCoVs does not prevent SARS-CoV-2 infection and related MIS in children. Children develop neutralizing antibodies after SARS-CoV-2 infection.Evidence before this studyChildren seem to be less likely affected by SARS-CoV-2 infection and clinical course of COVID-19 is less severe than in adults. As those asymptomatic or mildly symptomatic children are underdiagnosed and their viral loads are comparable to those of adults, they may act as an asymptomatic reservoir for the spread of the virus. One explanation of the difference between the adult and the pediatric infectious profile might be that infection with seasonal human coronaviruses, which is very frequent from a very young age, could lead to cross protective immunity. We searched in PubMed, MedRxiv and BioRxiv for publications from inception to June 15, 2020, using the terms “COVID-19, SARS-CoV-2, children, serology, Kawasaki, Corona Virus”.Added value of this studySARS-CoV-2 mean prevalence rate was 11.7% from April 1 to June 1 and neutralizing antibodies were found in 55% of the tested seropositive children. Among patients with a Multisystem Inflammatory Syndrome, Kawasaki-like disease, 70% were SARS-CoV-2 seropositive and had neutralizing antibodies. COVID-19 and MIS attack rates, and anti-SARS-CoV-2 antibodies titres were not significantly impacted by prior seasonal coronavirus infection.Implications of all the available evidencePrior infection by seasonal coronaviruses does not prevent SARS-CoV-2 infection and associated Multisystem Inflammatory Syndrome in children As antibodies against seasonal coronaviruses are very frequent and as these viruses circulate efficiently in human populations every winter, our results question to what extent the concept of herd immunity based on circulating antibodies can be applied to seasonal coronaviruses and possibly SARS-CoV-2.
Published: 2020
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65. Detection and Quantification of Influenza Virus Defective Viral Genomes from NGS Datasets Obtained after RT or RT-PCR Product Sequencing

Author: Sylvie van der Werf, Sylvie Behillil, Jeremy Boussier, Bernadette Crescenzo-Chaigne, Vincent Enouf, Nadia Naffakh, and Sandie Munier
Subjects: biology, RNA, RNA-Seq, lcsh:A, Computational biology, Virus, law.invention, Real-time polymerase chain reaction, Viral replication, law, biology.protein, defective viral genomes, RNA-seq, lcsh:General Works, influenza, Polymerase chain reaction, Polymerase, Illumina dye sequencing
Abstract: Like most RNA viruses, influenza viruses (IAV) generate defective viral genomes (DVGs) during viral replication. Although there is accumulating evidence of a biological impact of DVGs, the molecular mechanisms leading to their production remain to be unveiled. Various next-generation sequencing (NGS) technologies and detection methods can be used to characterize DVGs. Here, we developed a bioinformatics pipeline called DG-seq to quickly identify and quantify DVGs in influenza viral stocks and compared two processing methods for NGS, with or without PCR amplification. To evaluate the performance of the DG-seq pipeline, we used either synthetic in-vitro-transcribed DVGs mixed with the full set of synthetic full-length genomic RNAs, or biological RNA samples extracted in duplicate from three IAV stocks: mutant viruses with a K635A or a R638A mutation in the PA subunit of the polymerase that impairs viral transcription, and their wild-type (WT) counterpart. Viral genomic RNAs were reverse-transcribed and either directly subjected to Illumina sequencing (RT-seq) or PCR-amplified prior to sequencing (RT-PCR-seq). Both methods displayed a good reproducibility between batches, with a lower detection rate but a more accurate quantification of DVGs in RT-seq samples. The PA mutants produced more DVGs than the WT virus, derived mostly from the polymerase gene segments, but also from the NA and HA segments, suggesting that an imbalance between transcription and replication can promote DVG production. Breakpoints occurred near the segment extremities, with no hotspot identified. Interestingly, we observed short direct A/T-rich repeats adjacent to the breakpoint ends at a significantly higher frequency than in the random case. This work provides the first comparison of DVG detection and quantification from NGS data obtained in the presence or absence of PCR amplification and gives novel insight into the mechanisms of influenza virus DVG production.
Published: 2020

66. Hydroxychloroquine in the treatment and prophylaxis of SARS-CoV-2 infection in non- human primates

Author: Angela Brisebarre, Jeremie Guedj, Manuel Rosa Calatrava, Bruno Lina, Julien Lemaitre, Romain Marlin, Raphael Ho Tsong Fan, Vanessa Contreras, Catherine Chapon, Roger Le Grand, Antonio Gonçalves, Caroline Solas, Thibaut Naninck, Nathalie Bosquet, Bruno Hoen, Sylvie van der Werf, Sylvie Behillil, Nidhal Kahlaoui, Olivier Terrier, Vincent Enouf, Pauline Maisonnasse, Andrés Pizzorno, Xavier de Lamballerie, and Franck Toure
Subjects: business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Medicine, Hydroxychloroquine, business, Virology, medicine.drug
Abstract: COVID-19 has become a pandemic that has caused over 200,000 deaths worldwide, with no antiviral drug or vaccine yet available. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals worldwide but definitive evidence for HCQ efficacy in treatment of COVID-19 is still missing.We evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in monkey African green monkey kidney (VeroE6) cells but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to placebo, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor HCQ+AZTH showed a significant effect on the viral load levels in any of the tested compartments. When the drug was used as a pre-exposure prophylaxis (PrEP), HCQ did not confer protection against acquisition of infection.Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral treatment for COVID-19 in humans.
Published: 2020

67. Introductions and early spread of SARS-CoV-2 in France

Author: Meline Bizard, Etienne Simon-Loriere, Andreea Alexandru, Sylvie van der Werf, Vincent Enouf, Flora Donati, Marion Barbet, Maud Vanpeene, Artem Baidaliuk, Fabiana Gámbaro, Angela Brisebarre, Fawzi Derrar, Sylvie Behillil, and Mélanie Albert
Subjects: 0303 health sciences, Coronavirus disease 2019 (COVID-19), 030306 microbiology, Transmission (medicine), Genomic data, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Disease, Biology, medicine.disease_cause, Virology, Virus, 3. Good health, 03 medical and health sciences, medicine, Clade, 030304 developmental biology, Coronavirus
Abstract: Following the emergence of coronavirus disease (COVID-19) in Wuhan, China in December 2019, specific COVID-19 surveillance was launched in France on January 10, 2020. Two weeks later, the first three imported cases of COVID-19 into Europe were diagnosed in France. We sequenced 97 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from samples collected between January 24 and March 24, 2020 from infected patients in France. Phylogenetic analysis identified several early independent SARS-CoV-2 introductions without local transmission, highlighting the efficacy of the measures taken to prevent virus spread from symptomatic cases. In parallel, our genomic data reveals the later predominant circulation of a major clade in many French regions, and implies local circulation of the virus in undocumented infections prior to the wave of COVID-19 cases. This study emphasizes the importance of continuous and geographically broad genomic sequencing and calls for further efforts with inclusion of asymptomatic infections.
Published: 2020

68. SARS-CoV-2 serological analysis of COVID-19 hospitalized patients, pauci-symptomatic individuals and blood donors

Author: Lucie Le Fevre, Diane Descamps, Sylvie van der Werf, Nicolas Escriou, Delphine Planas, Olivier Schwartz, Flora Donati, Cyril Planchais, Rémy Robinot, Isabelle Staropoli, Bernadette Crescenzo, Bruno Hoen, Mireille Nowakowski, Marion Gransagne, Mélanie Albert, Jérémy Dufloo, Marc Eloit, Stéphane Petres, Camille Besombes, Ludivine Grzelak, Yazdan Yazdanpanah, Hugo Mouquet, Sarah Temmam, Arnaud Fontanet, Pierre Charneau, Marija Backovic, Vincent Enouf, Pascal Morel, Françoise Porrot, Quentin Le Hingrat, Audrey Lemaitre, Timothée Bruel, Philippe Souque, Maxime Chazal, Guillaume Mellon, Laura Tondeur, Anabelle Pourbaix, Simon Rolland, Félix A. Rey, Christèle Huon, Julian Buchrieser, Sylvie Behillil, Marie-Noëlle Ungeheuer, François Anna, Maaran Michael Rajah, Lila Bouadma, Florence Guivel, Jacques Bellalou, Marie-Aude Creach, Caroline Demeret, and Kuang-Yu Chen
Subjects: 0303 health sciences, education.field_of_study, biology, 030306 microbiology, business.industry, Population, Antibody titer, Virology, Asymptomatic, 3. Good health, Serology, 03 medical and health sciences, Antigen, biology.protein, Medicine, Seroprevalence, Antibody, Seroconversion, medicine.symptom, education, business, 030304 developmental biology
Abstract: It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their antibody response profile. Here, we performed a pilot study to assess the levels of anti-SARS-CoV-2 antibodies in samples taken from 491 pre-epidemic individuals, 51 patients from Hôpital Bichat (Paris), 209 pauci-symptomatic individuals in the French Oise region and 200 contemporary Oise blood donors. Two in-house ELISA assays, that recognize the full-length nucleoprotein (N) or trimeric Spike (S) ectodomain were implemented. We also developed two novel assays: the S-Flow assay, which is based on the recognition of S at the cell surface by flow-cytometry, and the LIPS assay that recognizes diverse antigens (including S1 or N C-terminal domain) by immunoprecipitation. Overall, the results obtained with the four assays were similar, with differences in sensitivity that can be attributed to the technique and the antigen in use. High antibody titers were associated with neutralisation activity, assessed using infectious SARS-CoV-2 or lentiviral-S pseudotypes. In hospitalized patients, seroconversion and neutralisation occurred on 5-14 days post symptom onset, confirming previous studies. Seropositivity was detected in 29% of pauci-symptomatic individuals within 15 days post-symptoms and 3 % of blood of healthy donors collected in the area of a cluster of COVID cases. Altogether, our assays allow for a broad evaluation of SARS-CoV2 seroprevalence and antibody profiling in different population subsets.
Published: 2020

69. Excess cases of influenza-like illnesses synchronous with coronavirus disease (COVID-19) epidemic, France, March 2020

Author: Thomas Hanslik, Bruno Lina, Sylvie Behillil, Clément Turbelin, Caroline Guerrisi, Sylvie van der Werf, Thierry Blanchon, Daniel Lévy-Bruhl, Titouan Launay, Chiara Poletto, Pierre-Yves Boëlle, Vincent Enouf, Cécile Souty, Vittoria Colizza, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Lyon], Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Santé Publique France., Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Bodescot, Myriam
Subjects: Surveillance Sentinel Network, Pediatrics, Epidemiology, Disease, medicine.disease_cause, Disease Outbreaks, Pandemic, Coronavirus, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, education.field_of_study, biology, virus diseases, 3. Good health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, France, Coronavirus Infections, Rapid Communication, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, Population, influenza-like illness, Betacoronavirus, 03 medical and health sciences, Virology, Influenza, Human, medicine, Humans, education, Pandemics, 030304 developmental biology, Influenza-like illness, SARS-CoV-2, 030306 microbiology, business.industry, Public Health, Environmental and Occupational Health, COVID-19, biology.organism_classification, Surveillance Sentinel Network, influenza-like illness, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Sentinel Surveillance
Abstract: Several French regions where coronavirus disease (COVID-19) has been reported currently show a renewed increase in ILI cases in the general practice-based Sentinelles network. We computed the number of excess cases by region from 24 February to 8 March 2020 and found a correlation with the number of reported COVID-19 cases so far. The data suggest larger circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the French population than apparent from confirmed cases.
Published: 2020

70. First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020

Author: Laurent Filleul, C. Saura, Gianfranco Spiteri, Alexandra Mailles, Paola Sognamiglio, Magdalena Salom Castell, Rinat A. Maksyutov, Inmaculada Casas, Lotta Siira, Yulia V. Demina, Amparo Larrauri, Agnes Lepoutre, Sonja J. Olsen, Michaela Diercke, Flavia Riccardo, Alexandre Gaymard, Sylvie van der Werf, Jussi Sane, Bruno Christian Ciancio, Nick Bundle, Romain Mahieu, Cornelia Adlhoch, Julia Schilling, Silke Buda, María José Sierra Moros, Francisco Pozo, Eeva Broberg, Richard Pebody, Maria Palmérus, Markku Broas, Nathalie Bossuyt, Charlotte Martin, Bruno Lina, Martine Valette, Malin Bengnér, Antonio Nicolau Riutort, Sylvie Behillil, Pernille Jorgensen, Karin Tegmark-Wisell, C Campese, Jukka Pukkila, Antonino Bella, Daniel Lévy-Bruhl, Bruno Coignard, James E Fielding, Dmitriy Pereyaslov, Sibylle Bernard-Stoecklin, Julien Beauté, Vincent Enouf, Emanuele Nicastri, Marc Van Ranst, European Centre for Disease Prevention and Control [Stockholm, Sweden] (ECDC), WHO Regional Office for Europe [Copenhagen], Robert Koch Institute [Berlin] (RKI), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Istituto Superiore di Sanità (ISS), Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), Centro de Coordinacion de Alertas y Emergencias Sanitarias - Coordination Centre for Health Alerts and Emergencies [Madrid, Spain] (CCAES), Ministerio de Sanidad / Ministry of Health [Madrid, Spain], Rospotrebnadzor - Federal Service for Surveillance on Consumer Rights Protection and Human Well-being [Moscow, Russia], Santé publique France Nouvelle-Aquitaine [Bordeaux], Santé publique France Auvergne‑Rhône‑Alpes, Partenaires INRAE, Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Sciensano [Bruxelles], Réseau International des Instituts Pasteur (RIIP), and Finnish Institute for Health and Welfare [Helsinki, Finland] (FIHW)
Subjects: 0301 basic medicine, Male, Viral Envelope Proteins -- analysis, Epidemiology, [SDV]Life Sciences [q-bio], Betacoronavirus -- genetics -- isolation & purification, Health services, 0302 clinical medicine, Viral Envelope Proteins, Risk Factors, 030212 general & internal medicine, Child, Aged, 80 and over, Travel, Europe -- epidemiology, Novel coronavirus, Sciences bio-médicales et agricoles, Middle Aged, European region, Europe, Hospitalization, Child, Preschool, Population Surveillance, Female, Coronavirus Infections, Rapid Communication, Adult, COVID-19, coronavirus disease 2019, SARS, SARS-COV-2, medicine.medical_specialty, 2019-20 coronavirus outbreak, China, Coronavirus disease 2019 (COVID-19), Adolescent, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, Library science, Coronavirus Infections -- diagnosis -- epidemiology, Real-Time Polymerase Chain Reaction, World Health Organization, 03 medical and health sciences, Betacoronavirus, Young Adult, Virology, Political science, medicine, Humans, ddc:610, Aged, Public health, Public Health, Environmental and Occupational Health, China -- epidemiology, Pneumonia, Viral -- diagnosis -- epidemiology, 030104 developmental biology, 610 Medizin und Gesundheit, Reporting system
Abstract: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases., info:eu-repo/semantics/published
Published: 2020

71. Genome-based insights into the resistomes and mobilomes of two Providencia rettgeri strains isolated from wound infections in Madagascar

Author: Jean-Marc Collard, Lovasoa Ramparany, Pierrette Landrie Simo Tchuinte, Elisoa Ratsima, Frédérique Randrianirina, Mamitina Alain Noah Rabenandrasana, Vincent Enouf, Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Pasteur International Bioresources network (PIBNet), Institut Pasteur [Paris] (IP), This study was conducted during a postdoctoral internship supported by a Postdoctoral Grant CALMETTE and YERSIN from the Institute Pasteur Department of International Affairs., and Institut Pasteur [Paris]
Subjects: 0301 basic medicine, Antimicrobial resistance, MESH: Genome, Bacterial, Genome, MESH: Madagascar, 0302 clinical medicine, Plasmid, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Resistance, Multiple, Bacterial, Providencia rettgeri, Immunology and Allergy, MESH: Genomic Islands, 030212 general & internal medicine, Insertion sequence, MESH: Phylogeny, MESH: High-Throughput Nucleotide Sequencing, Phylogeny, Wound infections, Genetics, MESH: Microbial Sensitivity Tests, biology, High-Throughput Nucleotide Sequencing, QR1-502, Anti-Bacterial Agents, Gene cassette, Horizontal gene transfer, MESH: Whole Genome Sequencing, Plasmids, Microbiology (medical), MESH: Interspersed Repetitive Sequences, Gene Transfer, Horizontal, Genomic Islands, 030106 microbiology, Immunology, Microbial Sensitivity Tests, Providencia, MESH: Providencia, Microbiology, 03 medical and health sciences, MESH: Plasmids, Intensive care, MESH: Anti-Bacterial Agents, Madagascar, MESH: Spain, MESH: United States, MESH: Wound Infection, Humans, Intensive care unit, MESH: Humans, Whole Genome Sequencing, MESH: Drug Resistance, Multiple, Bacterial, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, United States, MESH: Gene Transfer, Horizontal, Interspersed Repetitive Sequences, Spain, Wound Infection, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Mobile genetic elements, Genome, Bacterial
Abstract: Objectives A molecular analysis was performed of two Providencia rettgeri (P. rettgeri) strains (Pr 297 and Pr 269) collected in 2007 and 2009 from wound swabs of patients admitted to the intensive care units at Joseph Ravoangy Andrianavalona hospital and the Military Hospital in Antananarivo, Madagascar. Methods The two P. rettgeri isolates were subjected to susceptibility testing. Whole genome sequencing was performed to characterise the antibiotic resistance genes, genomic islands and mobilomes (integrons, plasmids and insertion sequences). Results All isolates were found to be multidrug-resistant. Antibiotic-resistant genes described were amongst eight different classes of antimicrobial agents. Thirty insertion sequences and twelve genomic islands were predicted in each genome. Class 1 and class 2 integrons were found in both genomes, with gene cassette regions encompassing arr-2 - cmlA5 - blaOXA-10 - ant (3”)-Ia and dfrA1 - sat2 - ant (3”)-Ia – orfX, respectively. IncA/C2, ColM and ColE1-like plasmids were described harbouring blaCMY-30, qnrD and aac(6’)-Ib-cr4 genes, respectively. Phylogenetic analysis showed that Pr 297 and Pr 269 isolates were genetically identical and clustered with P. rettgeri strains described in the USA and Spain. Conclusions It is believed that this is the first molecular characterisation of wound infection pathogens from Madagascan patients and the first description of P. rettgeri co-producing CMY-30, OXA-10 and AAC(6’)-Ib-cr4 enzymes. The diversity of the resistance determinants and mobile genetic elements was probably due to extensive horizontal gene transfer events, highlighting the need to conduct further molecular monitoring studies to understand the genomic plasticity of resistant bacteria in Madagascan hospitals.
Published: 2020

72. First cases of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures, January 2020

Author: Daniel Lévy-Bruhl, Sylvie Behillil, Clément Bassi, Alexandra Mailles, Anne Simondon, Yassoungo Silue, P. Rolland, François Xavier Lescure, Matthieu Mechain, Morgane Stempfelet, Anouk Tabaï, Clément Lazarus, Bruno Coignard, C Campese, Investigation team, Sophie Ismael, Sibylle Bernard Stoecklin, Denis Malvy, Vincent Enouf, Mathieu Nguyen, Laure Meurice, Estelle Yamani, Duc Minh Nguyen, Scarlett Georges, Santé publique France - French National Public Health Agency, Agence Régionale de Santé Ile-de-France [Paris] (ARS IDF), Agence Régionale de la Santé (ARS), Centre National de Référence des virus des infections respiratoires (dont la grippe) [Paris] (CNR), Institut Pasteur [Paris], Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Bordeaux GeoSentinel Site [Bordeaux], Service des maladies infectieuses et tropicales [Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Direction Générale de la Santé [Paris] (DGS), Ministère des Solidarités et de la Santé [Paris, France], Santé publique France [Saint-Maurice, France] (French National Public Health Agency), parent-French National Public Health Agency, Investigation Team: Laurent Filleul, Stéphanie Vandentorren, Guillaume Spaccaferri, Hélène Prouvost, Mélanie Albert, Marion Barbet, Angela Brisebarre, Flora Donati, Sylvie van der Werf, Alexis Ardoin, Marion Dreyer, Karim Tararbit, Matthieu Amodeo, Elodie Couaillier, Pascal Fabre, Daniel Habold, Didier Che, Gisèle Bendjelloul, Marine Billaudelle Lallemant, Valentine Charachon, Laurène Deconinck, Diane Descamps, Sandrine Gérard, Nadirha Houhou, Quentin Le Hingrat, Isabelle Lolom, Jean-Christophe Lucet, Annabelle Pourbaix, Simon Valayer, Yazdan Yazdanpanah, Alexandre Boyer, Benjamin Clouzeau, Xavier Combes, Arnaud Desclaux, Jean-Michel Dindart, Alexandre Duvignaud, Isabelle Garrigue, Didier Gruson, Marie-Edith Lafon, Pauline Perreau, Thierry Pistone, Maxime Poteau, Eric Tentillier, Pauline Mathieu., Direction des maladies infectieuses - Infectious Diseases Division [Saint-Maurice], Santé publique France - French National Public Health Agency [Saint-Maurice, France], Direction des régions [Saint-Maurice], Cellule Régionale Ile-de-France [Paris], Santé publique France - French National Public Health Agency [Saint-Maurice, France]-Santé publique France - French National Public Health Agency [Saint-Maurice, France], Agence Régionale de Santé Nouvelle-Aquitaine [Bordeaux] (ARS NA), Cellule Régionale Nouvelle-Aquitaine [Bordeaux], Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre opérationnel de réception et de régulation des urgences sanitaires et sociales [Paris], Ministère des Solidarités et de la Santé [Paris, France]-Ministère des Solidarités et de la Santé [Paris, France], Direction alerte et crise [Saint-Maurice], Investigation Team : Laurent Filleul, Stéphanie Vandentorren, Guillaume Spaccaferri, Hélène Prouvost, Mélanie Albert, Marion Barbet, Angela Brisebarre, Flora Donati, Sylvie van der Werf, Alexis Ardoin, Marion Dreyer, Karim Tararbit, Matthieu Amodeo, Elodie Couaillier, Pascal Fabre, Daniel Habold, Didier Che, Gisèle Bendjelloul, Marine Billaudelle Lallemant, Valentine Charachon, Laurène Deconinck, Diane Descamps, Sandrine Gérard, Nadirha Houhou, Quentin Le Hingrat, Isabelle Lolom, Jean-Christophe Lucet, Annabelle Pourbaix, Simon Valayer, Yazdan Yazdanpanah, Alexandre Boyer, Benjamin Clouzeau, Xavier Combes, Arnaud Desclaux, Jean-Michel Dindart, Alexandre Duvignaud, Isabelle Garrigue, Didier Gruson, Marie-Edith Lafon, Pauline Perreau, Thierry Pistone, Maxime Poteau, Eric Tentillier, Pauline Mathieu, Bodescot, Myriam, and Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR)
Subjects: 0301 basic medicine, Male, Epidemiology, MESH: Coronavirus Infections, [SDV]Life Sciences [q-bio], coronavirus, medicine.disease_cause, MESH: Risk Assessment, contact tracing, containment, MESH: Infection Control, 0302 clinical medicine, COVID-19, France, 2019-nCov, Surveillance, SARS-CoV-2, Coronavirus, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infection control, MESH: COVID-19, 030212 general & internal medicine, MESH: Travel, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Travel, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Middle Aged, biology, Transmission (medicine), Middle Aged, MESH: China, 3. Good health, Population Surveillance, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Betacoronavirus, Risk assessment, Coronavirus Infections, Adult, medicine.medical_specialty, China, Pneumonia, Viral, Disease cluster, Risk Assessment, MESH: Population Surveillance, MESH: Contact Tracing, 03 medical and health sciences, Betacoronavirus, Virology, medicine, Humans, MESH: SARS-CoV-2, Infection Control, MESH: Humans, business.industry, Public Health, Environmental and Occupational Health, MESH: Adult, biology.organism_classification, medicine.disease, MESH: Male, MESH: France, Pneumonia, 030104 developmental biology, MESH: Pneumonia, Viral, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Emergency medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Contact tracing
Abstract: Investigation Team : Santé publique France, Direction des régions, Cellule Régionale Nouvelle Aquitaine, Bordeaux, France: Laurent Filleul, Stéphanie Vandentorren.Santé publique France, Direction des régions, Cellule Régionale Auvergne-Rhône-Alpes, Lyon, France: Guillaume Spaccaferri.Santé publique France, Direction des régions, Cellule Régionale Hauts-de-France, Lille, France: Hélène Prouvost.Centre national de référence Virus des infections respiratoires, dont la grippe, Institut Pasteur, Paris, France: Mélanie Albert, Marion Barbet, Angela Brisebarre, Flora Donati, Sylvie van der Werf.Agence Régionale de Santé Ile-de-France, Paris, France: Alexis Ardoin, Marion Dreyer, Karim Tararbit.Agence Régionale de Santé Nouvelle-Aquitaine, Bordeaux, France: Matthieu Amodeo, Elodie Couaillier, Pascal Fabre, Daniel Habold.Santé publique France, Direction des maladies infectieuses, Saint-Maurice, France: Didier Che.AP-HP, Hôpital Bichat, Service des maladies infectieuses et tropicales, Paris, France: Gisèle Bendjelloul, Marine Billaudelle Lallemant, Valentine Charachon, Laurène Deconinck, Diane Descamps, Sandrine Gérard, Nadirha Houhou, Quentin Le Hingrat, Isabelle Lolom, Jean-Christophe Lucet, Annabelle Pourbaix, Simon Valayer, Yazdan Yazdanpanah.Centre Hospitalier Universitaire de Bordeaux, Bordeaux GeoSentinel Site, Bordeaux, France: Alexandre Boyer, Benjamin Clouzeau, Xavier Combes, Arnaud Desclaux, Jean-Michel Dindart, Alexandre Duvignaud, Isabelle Garrigue, Didier Gruson, Marie-Edith Lafon, Pauline Perreau, Thierry Pistone, Maxime Poteau, Eric Tentillier.Direction Générale de la Santé, Ministère des solidarités et de la santé, Centre opérationnel de réception et de régulation des urgences sanitaires et sociales, Paris, France: Pauline Mathieu; International audience; A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) causing a cluster of respiratory infections (coronavirus disease 2019, COVID-19) in Wuhan, China, was identified on 7 January 2020. The epidemic quickly disseminated from Wuhan and as at 12 February 2020, 45,179 cases have been confirmed in 25 countries, including 1,116 deaths. Strengthened surveillance was implemented in France on 10 January 2020 in order to identify imported cases early and prevent secondary transmission. Three categories of risk exposure and follow-up procedure were defined for contacts. Three cases of COVID-19 were confirmed on 24 January, the first cases in Europe. Contact tracing was immediately initiated. Five contacts were evaluated as at low risk of exposure and 18 at moderate/high risk. As at 12 February 2020, two cases have been discharged and the third one remains symptomatic with a persistent cough, and no secondary transmission has been identified. Effective collaboration between all parties involved in the surveillance and response to emerging threats is required to detect imported cases early and to implement adequate control measures.
Published: 2020

73. Un nouveau coronavirus venu du Moyen-Orient

Author: Astrid, Vabret, Sylvie, Pillet, and Vincent, Enouf
Published: 2020

74. Absence of SARS-CoV-2 infection in cats and dogs in close contact with a cluster of COVID-19 patients in a veterinary campus

Author: Sylvie Behillil, Lucie Chevallier, Laurent Tiret, Ambre Jaraud, Christèle Huon, Djérène Maso, Sarah Temmam, Vincent Enouf, Alix Barbarino, Sylvie van der Werf, Philippe Pérot, Marc Eloit, Marija Backovic, Patrick Verwaerde, Découverte de pathogènes – Pathogen discovery, Institut Pasteur [Paris], Centre Collaborateur de l'OIE de Détection et identification chez l’homme des pathogènes animaux émergents et développement d’outils pour leur diagnostic / Collaborating Center for the Detection and identification in humans of emerging animal pathogens and development of tools for their diagnoses (CCOIE-OIECC), Institut Pasteur [Paris]-Organisation Mondiale de la Santé Animale / World Animal Health Information System (OIE-WAHIS), École nationale vétérinaire - Alfort (ENVA), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Virologie Structurale - Structural Virology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), We also thank funding from Institut Pasteur, Labex IBEID (ANR-10-LABX-62-IBEID), REACTing (Research & Action Emerging Infectious Diseases), Cani-DNA BRC that is part of the CRB-Anim infra-structure, ANR-11-INBS-0003 and EU Grant 101003589 RECoVER., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-11-INBS-0003,CRB-Anim,Réseau de Centres de Ressources Biologiques pour les animaux domestiques(2011), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), École nationale vétérinaire d'Alfort (ENVA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé Animale / World Organisation Animal Health [Paris] (OIE), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé Animale / World Animal Health Information System (OIE-WAHIS), Tiret, Laurent, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Infrastructures - Réseau de Centres de Ressources Biologiques pour les animaux domestiques - - CRB-Anim2011 - ANR-11-INBS-0003 - INBS - VALID, and Rapid European COVID-19 Emergency Response research - RECOVER - - H2020-SC1-PHE-CORONAVIRUS-20202020-02-14 - 2022-02-13 - 101003589 - VALID
Subjects: Veterinary medicine, COVID-19 epidemiology, viruses, 030231 tropical medicine, Anosmia, Disease, medicine.disease_cause, Disease cluster, Article, Virus, Canine, Feline, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pandemic, medicine, 030212 general & internal medicine, Index case, 030304 developmental biology, Coronavirus, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, lcsh:R5-920, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, CATS, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, biology, 030306 microbiology, business.industry, Luciferase immunoprecipitation system, fungi, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Public Health, Environmental and Occupational Health, Outbreak, 3. Good health, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, Antibody, lcsh:Medicine (General), business, Self-isolation, LIPS
Abstract: International audience; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China, in 2019, is responsible for the COVID-19 pandemic. It is now accepted that the wild fauna, probably bats, constitute the initial reservoir of the virus, but little is known about the role pets can play in the spread of the disease in human communities, knowing the ability of SARS-CoV-2 to infect some domestic animals. In this cross-sectional study, we tested the antibody response in a cluster of 21 domestic pets (9 cats and 12 dogs) living in close contact with their owners (belonging to a veterinary community of 20 students) in which two students tested positive for COVID-19 and several others (n = 11/18) consecutively showed clinical signs (fever, cough, anosmia, etc.) compatible with COVID-19 infection. Although a few pets presented many clinical signs indicative for a coronavirus infection, no antibodies against SARS-CoV-2 were detectable in their blood one month after the index case was reported, using an immunoprecipitation assay. These original data can serve a better evaluation of the host range of SARS-CoV-2 in natural environment exposure conditions.
Published: 2020

75. Incidence of H1N1 2009 virus infection through the analysis of paired plasma specimens among blood donors, France.

Author: Angie Bone, Jean-Paul Guthmann, Azzedine Assal, Dominique Rousset, Armelle Degeorges, Pascal Morel, Martine Valette, Vincent Enouf, Eric Jacquot, Bertrand Pelletier, Yann Le Strat, Josiane Pillonel, Laure Fonteneau, Sylvie van der Werf, Bruno Lina, Pierre Tiberghien, and Daniel Lévy-Bruhl
Subjects: Medicine, Science
Abstract: BackgroundKnowledge of the age-specific prevalence of seroprotection and incidence of seroconversion infection is necessary to complement clinical surveillance data and statistical models. It provides the basis for estimating the future impact of influenza A (H1N1pdm09) and implementing appropriate prevention and response strategies.MethodsUsing a cross-sectional design, two-stage stratified sampling and paired plasma samples, we estimated the age-specific prevalence of a protective level of H1N1pdm09 antibodies in the French adult population before and after the 2009/10 pandemic, and the proportion of those susceptible that seroconverted due to infection, from a single sample of 1,936 blood donors aged 20-70 years in mainland France in June 2010. Samples with a haemagglutination inhibition (HI) titre ≥1∶40 were considered seropositive, and seroconversion due to infection was defined as a 4-fold increase in titre in the absence of H1N1pdm09 vaccination or pre-pandemic seropositivity.ResultsOut of the 1,936 donors, 1,708 were included in the analysis. Seroprevalence before the pandemic was 6.7% (95% CI 5.0, 8.9) with no significant differences by age-group (p = 0.3). Seroprevalence afterwards was 23.0% (95% CI 17.7, 29.3) with 20-29 year olds having a higher level than older groups (pConclusionsBefore the 2009/2010 winter influenza season, only 6.7% of the French mainland population aged 20-70 had a level of antibodies usually considered protective. During the first pandemic wave, 12.2% of the population seroconverted due to infection and the seroprevalence after the wave rose to 23%, either due to prepandemic seropositivity, infection or vaccination. This relatively low latter figure contributed to an extension of target groups for influenza vaccination for the 2010/2011 season.
Published: 2012
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76. I223R mutation in influenza A(H1N1)pdm09 neuraminidase confers reduced susceptibility to oseltamivir and zanamivir and enhanced resistance with H275Y.

Author: Jérome LeGoff, Dominique Rousset, Georges Abou-Jaoudé, Anne Scemla, Patricia Ribaud, Séverine Mercier-Delarue, Valérie Caro, Vincent Enouf, François Simon, Jean-Michel Molina, and Sylvie van der Werf
Subjects: Medicine, Science
Abstract: BackgroundResistance of pandemic A(H1N1)2009 (H1N1pdm09) virus to neuraminidase inhibitors (NAIs) has remained limited. A new mutation I223R in the neuraminidase (NA) of H1N1pdm09 virus has been reported along with H275Y in immunocompromised patients. The aim of this study was to determine the impact of I223R on oseltamivir and zanamivir susceptibility.MethodsThe NA enzymatic characteristics and susceptibility to NAIs of viruses harbouring the mutations I223R and H275Y alone or in combination were analyzed on viruses produced by reverse genetics and on clinical isolates collected from an immunocompromised patient with sustained influenza H1N1pdm09 virus shedding and treated by oseltamivir (days 0-15) and zanamivir (days 15-25 and 70-80).ResultsCompared with the wild type, the NA of recombinant viruses and clinical isolates with H275Y or I223R mutations had about two-fold reduced affinity for the substrate. The H275Y and I223R isolates showed decreased susceptibility to oseltamivir (246-fold) and oseltamivir and zanamivir (8.9- and 4.9-fold), respectively. Reverse genetics assays confirmed these results and further showed that the double mutation H275Y and I223R conferred enhanced levels of resistance to oseltamivir and zanamivir (6195- and 15.2-fold). In the patient, six days after initiation of oseltamivir therapy, the mutation H275Y conferring oseltamivir resistance and the I223R mutation were detected in the NA. Mutations were detected concomitantly from day 6-69 but molecular cloning did not show any variant harbouring both mutations. Despite cessation of NAI treatment, the mutation I223R persisted along with additional mutations in the NA and the hemagglutinin.ConclusionsReduced susceptibility to both oseltamivir and zanamivir was conferred by the I223R mutation which potentiated resistance to both NAIs when associated with the H275Y mutation in the NA. Concomitant emergence of the I223R and H275Y mutations under oseltamivir treatment underlines the importance of close monitoring of treated patients especially those immunocompromised.
Published: 2012
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77. Influenza virus polymerase subunits co-evolve to ensure proper levels of dimerization of the heterotrimer

Author: Emmanuel Dos Santos Afonso, Nadia Naffakh, Catherine Isel, Vincent Enouf, Kuang-Yu Chen, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Pasteur International Bioresources network (PIBNet), Institut Pasteur [Paris], Génétique moléculaire des virus à ARN ((U-Pasteur_ 2 / UMR_3569)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris]
Subjects: RNA viruses, Protein Conformation, viruses, Reassortment, Virus Replication, medicine.disease_cause, Physical Chemistry, Biochemistry, Polymerases, Transcription (biology), [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Influenza A virus, Biology (General), Pathology and laboratory medicine, Polymerase, Genetics, 0303 health sciences, biology, Microbial Mutation, 030302 biochemistry & molecular biology, virus diseases, Medical microbiology, Enzymes, 3. Good health, Chemistry, Physical Sciences, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Pathogens, Oxidoreductases, Dimerization, Luciferase, Network Analysis, Reassortant Viruses, Research Article, Computer and Information Sciences, QH301-705.5, Protein subunit, Immunology, RNA polymerase complex, Microbiology, Virus, Viral Proteins, 03 medical and health sciences, Virology, DNA-binding proteins, Influenza, Human, medicine, Influenza viruses, Humans, Molecular Biology, 030304 developmental biology, Medicine and health sciences, Organisms, Viral pathogens, Biology and Life Sciences, Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, RC581-607, biochemical phenomena, metabolism, and nutrition, RNA-Dependent RNA Polymerase, Viral Replication, Microbial pathogens, Signaling Networks, Protein Subunits, HEK293 Cells, Chemical Properties, Viral replication, A549 Cells, Mutation, Enzymology, biology.protein, Parasitology, Immunologic diseases. Allergy, Wireless Sensor Networks, Protein Multimerization, Orthomyxoviruses
Abstract: The influenza A virus RNA-dependent RNA polymerase complex consists in three subunits, PB2, PB1 and PA, that perform transcription and replication of the viral genome through very distinct mechanisms. Biochemical and structural studies have revealed that the polymerase can adopt multiple conformations and form oligomers. However so far it remained unclear whether the available oligomeric crystal structures represent a functional state of the polymerase. Here we gained new insights into this question, by investigating the incompatibility between non-cognate subunits of influenza polymerase brought together through genetic reassortment. We observed that a 7:1 reassortant virus whose PB2 segment derives from the A/WSN/33 (WSN) virus in an otherwise A/PR/8/34 (PR8) backbone is attenuated, despite a 97% identity between the PR8-PB2 and WSN-PB2 proteins. Independent serial passages led to the selection of phenotypic revertants bearing distinct second-site mutations on PA, PB1 and/or PB2. The constellation of mutations present on one revertant virus was studied extensively using reverse genetics and cell-based reconstitution of the viral polymerase. The PA-E349K mutation appeared to play a major role in correcting the initial defect in replication (cRNA -> vRNA) of the PR8xWSN-PB2 reassortant. Strikingly the PA-E349K mutation, and also the PB2-G74R and PB1-K577G mutations present on other revertants, are located at a dimerization interface of the polymerase. All three restore wild-type-like polymerase activity in a minigenome assay while decreasing the level of polymerase dimerization. Overall, our data show that the polymerase subunits co-evolve to ensure not only optimal inter-subunit interactions within the heterotrimer, but also proper levels of dimerization of the heterotrimer which appears to be essential for efficient viral RNA replication. Our findings point to influenza polymerase dimerization as a feature that is controlled by a complex interplay of genetic determinants, can restrict genetic reassortment, and could become a target for antiviral drug development., Author summary Influenza viruses, because of their yearly recurrence and the occasional emergence of pandemics, represent a worldwide major public health threat. Enhancing the fundamental knowledge on the influenza RNA-dependent RNA-polymerase, a PB1-PB2-PA heterotrimer which ensures transcription and replication of the viral genome, is essential to reach the goal of better prevention and treatment of the disease. Here we gained new insights into the viral polymerase function by investigating the incompatibility between polymerase subunits derived from distinct parental influenza viruses and brought together through genetic reassortment. Our data show that the polymerase subunits co-evolve to ensure not only optimal inter-subunit cooperation within the heterotrimer, but also proper levels of dimerization of the heterotrimer which appears to be essential for efficient viral RNA replication. Our findings point to influenza polymerase dimerization as a feature that can restrict genetic reassortment, a major evolutionary mechanism for influenza viruses, and could become an attractive target for antiviral drug development.
Published: 2019

78. Prospective evaluation of ID NOW COVID-19 assay used as point-of-care test in an emergency department

Author: Assaf Mizrahi, Olivier Ganansia, Benoit Pilmis, Alban Le Monnier, Jean-Claude Nguyen Van, Vincent Enouf, Amir khaterchi, Camille Gerlier, Gauthier Péan de Ponfilly, Groupe Hospitalier Paris Saint-Joseph (hpsj), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), and Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Point-of-care testing, Sensitivity and Specificity, Article, Prospective evaluation, Isothermal amplification, COVID-19 Testing, Nasopharynx, Virology, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Point-of-care test, SARS-CoV-2, Emergency department, business.industry, COVID-19, Clinical microbiology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Direct assay, Point-of-Care Testing, ID NOW COVID-19, Viral Transport medium, Emergency Service, Hospital, business
Abstract: BackgroundRapid testing for COVID-19 has been clearly identified as an essential component of the strategy to control the SARS-CoV-2 epidemic, worldwide. The ID NOW COVID-19 assay is a simple, user-friendly, rapid molecular biology test based on nicking and extension amplification reaction (NEAR).ObjectivesThe aim of this study was to evaluate the ID NOW COVID-19 assay when used as a point-of-care test (POCT) in our Emergency Department (ED).Type of studyThis prospective study enrolled 395 consecutive patients; paired nasopharyngeal swabs were collected from each study participant. The first swab was tested with the ID NOW COVID-19 assay at the point-of-care by ED nurses. The second swab was diluted in viral transport medium (VTM) and sent to the clinical microbiology department for analysis by both the RT-PCR Simplexa test COVID-19 Direct assay as the study reference method, and the ID NOW COVID-19 assay performed in the laboratory.ResultsNasopharyngeal swabs directly tested with the ID NOW COVID-19 assay yielded a sensitivity, specificity, PPV and NPV of 98.0%, 97.5%, 96.2% and 98.7%, respectively, in comparison with the RT-PCR study reference assay. When the ID NOW COVID-19 assay was performed in the laboratory using the VTM samples, the sensitivity decreased to 62.5% and the NPV to 79.7%. Three false negative test results were reported with the ID NOW COVID-19 assay when performed using undiluted swabs directly in the ED; these results were obtained from patients with elevated CT values (>30).ConclusionWe demonstrated that the ID NOW COVID-19 assay, performed as a point of care test in the ED using dry swabs, provides a rapid and reliable alternative to laboratory-based RT-PCR methods
Published: 2021

79. Correction: Efficacy of Oseltamivir-Zanamivir Combination Compared to Each Monotherapy for Seasonal Influenza: A Randomized Placebo-Controlled Trial.

Author: Xavier Duval, Sylvie van der Werf, Thierry Blanchon, Anne Mosnier, Maude Bouscambert-Duchamp, Annick Tibi, Vincent Enouf, Cécile Charlois-Ou, Corine Vincent, Laurent Andreoletti, Florence Tubach, Bruno Lina, France Mentré, and Catherine Leport
Subjects: Medicine
Published: 2010
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80. Efficacy of oseltamivir-zanamivir combination compared to each monotherapy for seasonal influenza: a randomized placebo-controlled trial.

Author: Xavier Duval, Sylvie van der Werf, Thierry Blanchon, Anne Mosnier, Maude Bouscambert-Duchamp, Annick Tibi, Vincent Enouf, Cécile Charlois-Ou, Corine Vincent, Laurent Andreoletti, Florence Tubach, Bruno Lina, France Mentré, Catherine Leport, and Bivir Study Group
Subjects: Medicine
Abstract: BackgroundNeuraminidase inhibitors are thought to be efficacious in reducing the time to alleviation of symptoms in outpatients with seasonal influenza. The objective of this study was to compare the short-term virological efficacy of oseltamivir-zanamivir combination versus each monotherapy plus placebo.Methods and findingsWe conducted a randomized placebo-controlled trial with 145 general practitioners throughout France during the 2008-2009 seasonal influenza epidemic. Patients, general practitioners, and outcome assessors were all blinded to treatment assignment. Adult outpatients presenting influenza-like illness for less than 36 hours and a positive influenza A rapid test diagnosis were randomized to oseltamivir 75 mg orally twice daily plus zanamivir 10 mg by inhalation twice daily (OZ), oseltamivir plus inhaled placebo (O), or zanamivir plus oral placebo (Z). Treatment efficacy was assessed virologically according to the proportion of patients with nasal influenza reverse transcription (RT)-PCR below 200 copies genome equivalent (cgeq)/µl at day 2 (primary outcome), and clinically to the time to alleviation of symptoms until day 14. Overall 541 patients (of the 900 planned) were included (OZ, =192; O, n=176; Z, n=173), 49% male, mean age 39 years. In the intention-to-treat analysis conducted in the 447 patients with RT-PCR-confirmed influenza A, 46%, 59%, and 34% in OZ (n=157), O (n=141), and Z (n=149) arms had RT-PCRConclusionsIn adults with seasonal influenza A mainly H3N2 virus infection, the oseltamivir-zanamivir combination appeared less effective than oseltamivir monotherapy, and not significantly more effective than zanamivir monotherapy. Despite the theoretical potential for the reduction of the emergence of antiviral resistance, the lower effectiveness of this combination calls for caution in its use in clinical practice.Trial registrationwww.ClinicalTrials.govNCT00799760.
Published: 2010
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81. Enzymatic properties of the neuraminidase of seasonal H1N1 influenza viruses provide insights for the emergence of natural resistance to oseltamivir.

Author: Marie-Anne Rameix-Welti, Vincent Enouf, Frédérique Cuvelier, Patricia Jeannin, and Sylvie van der Werf
Subjects: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Published: 2008
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82. Oseltamivir Resistance in Severe Influenza A(H1N1)pdm09 Pneumonia and Acute Respiratory Distress Syndrome: A French Multicenter Observational Cohort Study

Author: Guillaume Voiriot, Sylvie Behillil, Thomas Chicheportiche, Romain Sonneville, Yacine Tandjaoui-Lambiotte, Damien Roux, Armand Mekontso Dessap, Slim Fourati, Nicolas de Prost, Faten May, Julien Mayaux, Sylvie van der Werf, Vincent Enouf, Laurent Guérin, Alexis Ferré, Eric Maury, Charles-Edouard Luyt, Jean-François Georger, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], Université Sorbonne Paris Cité (USPC), Université Paris Diderot - Paris 7 (UPD7), Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation Médico-Chirurgicale [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Service de Réanimation Médico-Chirurgicale [Hôpital Louis Mourier], Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Intercommunal de Villeneuve-Saint-Georges (CHIV), Service de Réanimation et USC Médico-Chirurgicale = Médecine intensive réanimation [CHU Tenon], CHU Tenon [AP-HP], Génétique moléculaire des virus à ARN ((U-Pasteur_ 2 / UMR_3569)), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Réanimation et USC Médico-Chirurgicale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), and CHU Saint-Antoine [AP-HP]
Subjects: Microbiology (medical), Adult, Oseltamivir, medicine.medical_specialty, viruses, [SDV]Life Sciences [q-bio], Neuraminidase, Acute respiratory distress, Severe influenza, medicine.disease_cause, Antiviral Agents, Virus, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Influenza A Virus, H1N1 Subtype, Internal medicine, Drug Resistance, Viral, Influenza, Human, Influenza A virus, medicine, Influenza A Virus, Humans, H1N1 Subtype, 030212 general & internal medicine, Viral, 0303 health sciences, Respiratory Distress Syndrome, biology, 030306 microbiology, business.industry, virus diseases, Pneumonia, medicine.disease, 3. Good health, respiratory tract diseases, Infectious Diseases, chemistry, biology.protein, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cohort study
Abstract: In a multicenter cohort study including 22 oseltamivir-treated patients with influenza A(H1N1)pdm09 acute respiratory distress syndrome, prevalence of the H275Y substitution in the neuraminidase, responsible for highly reduced sensitivity to oseltamivir, was 23%. Patients infected with the H275Y mutant virus had higher day 28 mortality than others (80% vs 12%; P = .011).
Published: 2019

83. The risk of a swine influenza pandemic: still a concern?

Author: Odile Launay, Vincent Enouf, and Paul Loubet
Subjects: Pulmonary and Respiratory Medicine, business.industry, Environmental health, Public Health, Environmental and Occupational Health, Pandemic influenza, Immunology and Allergy, Medicine, Influenza pandemic, business
Published: 2019

84. Clonal transmission and new mechanism of resistance to trimethoprim-sulfamethoxazole in Stenotrophomonas maltophilia strains isolated in a neonatology unit at Antananarivo, Madagascar, deciphered by whole genome sequence analysis

Author: Mamitina Alain Noah Rabenandrasana, Mélanie Bonneault, Benoit Garin, Elisabeth Delarocque-Astagneau, Sébastien Breurec, Lulla Opatowski, Zafitsara Zo Andrianirina, Volasoa Herilalaina Andrianoelina, Perlinot Herindrainy, Vincent Enouf, Jean-Marc Collard, and Bich-Tram Huynh
Subjects: Whole genome sequencing, medicine.drug_class, Sulfamethoxazole, Antibiotics, Biology, bacterial infections and mycoses, Integron, biology.organism_classification, Antimicrobial, Trimethoprim, Microbiology, Stenotrophomonas maltophilia, medicine, Trimethoprim Resistance, biology.protein, medicine.drug
Abstract: Stenotrophomonas maltophilia has been recognized as an emerging multidrug resistant organism in hospital settings due to its resistance to a broad range of antimicrobial agents. These include β-lactams and aminoglycosides, afforded by the existence of intrinsic and acquired resistance mechanisms. Trimethoprim/sulfamethoxazole (SXT) is recommended as one of the best treatment choices against S. maltophilia infections; however increasing resistance to SXT has complicated the treatment. From July 2014 to March 2015, individuals and surfaces from a neonatology ward in Antananarivo, Madagascar, were longitudinally followed to assess the transmission of bacteria resistant to antibiotics between neonates, individuals (parents and nurses) and ward environments. Four S. maltophilia strains were successively isolated from a water-tap (N=1), from feces obtained from a newborn (N=1), and nursing staff (N=2). Antimicrobial susceptibility testing and whole genome sequencing were performed on each isolate. Based on coregenome alignment, all strains were identical and belonged to the new sequence type ST-288. They were resistant to trimethoprim-sulfamethoxazole, carbapenems and intermediate to levofloxacin. Each isolate carried the aadB, strA, strB and sul1 genes located in a class I integron but variants of the dfrA gene were absent. We assessed by PROVEAN analysis the single nucleotide mutations found in folA, folC and folM genes and only the mutation in folA (A114T:GCC→ACC) has an effect on the activity of trimethoprim. Our findings demonstrated the prolonged presence of SXT-resistant S. maltophilia in a clinical setting with consecutive transfers from the environment to a newborn and staff based on the isolation dates. We also hypothesized that single nucleotide mutations in folA could be responsible for trimethoprim resistance.
Published: 2019

85. Phenotypic and molecular characterisations of carbapenem-resistant Acinetobacter baumannii strains isolated in Madagascar

Author: Jean-Marc Collard, Carole Kowalewicz, Frédérique Randrianirina, Andriniaina Rakotondrasoa, Elisoa Hariniaina Ratsima, Pierrette Landrie Simo Tchuinte, Mamitiana Alain Noah Rabenandrasana, Zafitsara Zo Andrianirina, Vincent Enouf, Volasoa Herilalaina Andrianoelina, Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier de Soavinandriana (CENHOSOA), Pasteur International Bioresources network (PIBNet), Institut Pasteur [Paris], This study is based upon a postdoctoral internship supported by Postdoctoral Grant CALMETTE and YERSIN from Institut Pasteur Department of International Affairs., and Institut Pasteur [Paris] (IP)
Subjects: Acinetobacter baumannii, Drug resistance, Antimicrobial resistance, MESH: Carbapenems, MESH: Madagascar, Plasmid, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genotype, polycyclic compounds, Medicine, MESH: Genomic Islands, Pharmacology (medical), Insertion sequence, MESH: Bacterial Proteins, 0303 health sciences, MESH: Microbial Sensitivity Tests, biology, 3. Good health, MESH: Integrons, Infectious Diseases, MESH: DNA Transposable Elements, MESH: Acinetobacter Infections, Microbiology (medical), Virulence, MESH: Phenotype, lcsh:Infectious and parasitic diseases, Microbiology, 03 medical and health sciences, Antibiotic resistance, MESH: Plasmids, Intensive care, MESH: Anti-Bacterial Agents, lcsh:RC109-216, 030304 developmental biology, MESH: Virulence Factors, MESH: Humans, 030306 microbiology, business.industry, MESH: Acinetobacter baumannii, Public Health, Environmental and Occupational Health, MESH: Drug Resistance, Multiple, Bacterial, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, biology.organism_classification, Carbapenem-resistance, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, bacteria, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Background The present study aimed to perform a deep phenotypic and genotypic analysis of 15 clinical carbapenem-resistant Acinetobacter baumannii (CRAb) strains isolated in Madagascar between 2008 and 2016 from diverse sources. Methods CRAb isolates collected from the Clinical Biology Centre of the Institut Pasteur of Madagascar, from the neonatal unit of Antananarivo military hospital, and from intensive care units of Mahajanga Androva and Antananarivo Joseph Ravoahangy Andrianavalona (HJRA) hospitals were subjected to susceptibility testing. Whole-genome sequencing allowed us to assess the presence of antibiotic-resistance determinants, insertion sequences, integrons, genomic islands and potential virulence factors in all strains. The structure of the carO porin gene and deduced protein (CarO) were also assessed in CRAb isolates. Results All isolates were found to be multidrug-resistant strains. Antibiotic-resistance genes against six classes of antimicrobial agents were described. The four carbapenem-resistance genes: bla OXA-51 like , bla OXA-23 , bla OXA-24 , and bla OXA-58 genes were detected in 100, 53.3, 13.3, and 6.6% of the isolates, respectively. Additionally, an ISAba1 located upstream of bla OXA-23 and bla ADC-like genes was observed in 53.3 and 66.7% of isolates, respectively. Further, Tn2006 and Tn2008 were found associated to the ISAba1-bla OXA-23 structure. An 8051-bp mobilizable plasmid harbouring the bla OXA-24 gene was isolated in two strains. In addition, 46.7% of isolates were positive for class 1 integrons. Overall, five sequences types (STs), with predominantly ST2, were detected. Several virulence genes were found in the CRAb isolates, among which two genes, epsA and ptk, responsible for the capsule-positive phenotype, were involved in A. baumannii pathogenesis. Conclusions This study revealed the presence of high-level carbapenem resistance in A. baumannii with the first description of OXA-24 and OXA-58 carbapenemases in Madagascar. This highlights the importance of better monitoring and controlling CRAb in Madagascan hospitals to avoid their spread.
Published: 2019

86. Detection of human bocavirus-1 in both nasal and stool specimens from children under 5 years old with influenza-like illnesses or diarrhea in Gabon

Author: Eric M. Leroy, Vincent Enouf, Sylvie Behillil, Sonia Etenna Lekana-Douki, Nicolas Berthet, Centre International de Recherches Médicales de Franceville (CIRMF), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris] (IP), None., and We acknowledge Carolyn Engel-Gautier and and Heïdi Lançon for editing the English usage and style. We thank all hospital staff of the health centers.
Subjects: 0301 basic medicine, Male, [SDV]Life Sciences [q-bio], Prevalence, lcsh:Medicine, Influenza A Virus, H1N1 Subtype, Human bocavirus, Epidemiology, Influenza-like illness, Medicine, Respiratory Tract Infections, lcsh:QH301-705.5, Children, biology, MESH: Influenza, Human, General Medicine, MESH: Infant, Diarrhea, Research Note, MESH: Diarrhea, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Child, Preschool, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Respiratory virus, Female, medicine.symptom, medicine.medical_specialty, MESH: Gabon, MESH: Parvoviridae Infections, General Biochemistry, Genetics and Molecular Biology, Parvoviridae Infections, MESH: Influenza A Virus, H1N1 Subtype, 03 medical and health sciences, Internal medicine, Influenza, Human, parasitic diseases, Humans, Gabon, lcsh:Science (General), Feces, MESH: Prevalence, Retrospective Studies, MESH: Humans, business.industry, HBoV-1, lcsh:R, MESH: Child, Preschool, Infant, MESH: Retrospective Studies, biology.organism_classification, MESH: Male, respiratory tract diseases, 030104 developmental biology, lcsh:Biology (General), MESH: Human bocavirus, MESH: Respiratory Tract Infections, Etiology, business, MESH: Female, lcsh:Q1-390
Abstract: Objective Human bocavirus (HBoV) is a viral pathogen which causes respiratory tract diseases and acute gastroenteritis worldwide. This virus mainly affected children under 5 years old. There is little information on HBoV in Gabon. Two first studies was conducted to determine the prevalence of respiratory and enteric viruses in children under 5 years old who visited health centers for influenza-like illness (ILI) or diarrhea in Gabon from March 2010 to June 2011. However, HBoV was not included in the screening. The aim of this retrospective study was to evaluate the prevalence and the HBoV genotype in children under 5 years old with ILI or diarrhea in Gabon. Results A total of 810 nasal swabs and 317 feces samples collected during the two first study were analyzed among which 32 (4.4%) and 7 (2.2%) were positive for HBoV respectively. While there were no significant differences in prevalence between age groups in children with ILI, all children with diarrhea were under 12 months of age. Moreover, 84.4 and 42.8% were diagnosed in co-infections with at least one other respiratory virus, or enteric viruses respectively. Finally, HBoV subtype 1 has been detected in both respiratory and gastrointestinal tracts with very low variability.
Published: 2018

87. Phenotypic and molecular characterisations of carbapenem-resistant

Author: Pierrette Landrie, Simo Tchuinte, Mamitiana Alain Noah, Rabenandrasana, Carole, Kowalewicz, Volasoa Herilalaina, Andrianoelina, Andriniaina, Rakotondrasoa, Zafitsara Zo, Andrianirina, Vincent, Enouf, Elisoa Hariniaina, Ratsima, Frédérique, Randrianirina, and Jean-Marc, Collard
Subjects: Acinetobacter baumannii, Genomic Islands, Virulence Factors, Research, Microbial Sensitivity Tests, Carbapenem-resistance, Antimicrobial resistance, Anti-Bacterial Agents, Integrons, Phenotype, Bacterial Proteins, Carbapenems, Drug Resistance, Multiple, Bacterial, DNA Transposable Elements, Madagascar, Humans, Acinetobacter Infections, Plasmids
Abstract: Background The present study aimed to perform a deep phenotypic and genotypic analysis of 15 clinical carbapenem-resistant Acinetobacter baumannii (CRAb) strains isolated in Madagascar between 2008 and 2016 from diverse sources. Methods CRAb isolates collected from the Clinical Biology Centre of the Institut Pasteur of Madagascar, from the neonatal unit of Antananarivo military hospital, and from intensive care units of Mahajanga Androva and Antananarivo Joseph Ravoahangy Andrianavalona (HJRA) hospitals were subjected to susceptibility testing. Whole-genome sequencing allowed us to assess the presence of antibiotic-resistance determinants, insertion sequences, integrons, genomic islands and potential virulence factors in all strains. The structure of the carO porin gene and deduced protein (CarO) were also assessed in CRAb isolates. Results All isolates were found to be multidrug-resistant strains. Antibiotic-resistance genes against six classes of antimicrobial agents were described. The four carbapenem-resistance genes: blaOXA-51 like, blaOXA-23, blaOXA-24, and blaOXA-58 genes were detected in 100, 53.3, 13.3, and 6.6% of the isolates, respectively. Additionally, an ISAba1 located upstream of blaOXA-23 and blaADC-like genes was observed in 53.3 and 66.7% of isolates, respectively. Further, Tn2006 and Tn2008 were found associated to the ISAba1-blaOXA-23 structure. An 8051-bp mobilizable plasmid harbouring the blaOXA-24 gene was isolated in two strains. In addition, 46.7% of isolates were positive for class 1 integrons. Overall, five sequences types (STs), with predominantly ST2, were detected. Several virulence genes were found in the CRAb isolates, among which two genes, epsA and ptk, responsible for the capsule-positive phenotype, were involved in A. baumannii pathogenesis. Conclusions This study revealed the presence of high-level carbapenem resistance in A. baumannii with the first description of OXA-24 and OXA-58 carbapenemases in Madagascar. This highlights the importance of better monitoring and controlling CRAb in Madagascan hospitals to avoid their spread. Electronic supplementary material The online version of this article (10.1186/s13756-019-0491-9) contains supplementary material, which is available to authorized users.
Published: 2018

88. Déterminants de la charge virale nasopharyngée chez les patients infectés par un virus grippal, consultant en soins primaire : 2010–2018

Author: Shirley Masse, R. Gueneau, Sylvie Behillil, Ana-Maria Vilcu, Vincent Enouf, Yoann Madec, and S. van der Werf
Subjects: Infectious Diseases, viruses
Abstract: Introduction La grippe est un probleme de sante publique persistant compte tenu d’epidemies saisonnieres recurrentes qui justifient une surveillance epidemique et virologique. La detection de virus par RT-qPCR, largement utilisee pour la surveillance, est principalement un outil diagnostique qualitatif, mais permet egalement une estimation de la charge virale. Nous avons analyse les facteurs associes au niveau estime de charge virale nasopharyngee de patients consultant en soins primaires avec un diagnostic d’infection par un virus grippal confirme. Materiels et methodes Les patients recrutes par le reseau de surveillance en soins primaires durant les saisons 2010–2011 a 2017–2018 pour lesquels un ecouvillonnage nasopharynge etait positif pour un virus de type A ou de type B, diagnostique par RT-qPCR, etaient inclus. Pour chaque patient, des donnees epidemiologiques et cliniques etaient collectees. Les analyses par RT-qPCR, permettaient l’identification du virus et l’estimation de la charge virale. Les facteurs associes au niveau de charge virale etaient identifies par regression lineaire et ceux associes a la severite (presence d’une dyspnee ou hospitalisation) par regression logistique. Resultats Sur l’ensemble des saisons, 6297 patients ont ete inclus dans l’analyse. La proportion d’hommes etait de 50,7 %, l’âge median (intervalle inter quartile) au diagnostic etait de 20 ans (6–43). Le virus grippal etait A(H1N1)pdm09 chez 1722 (27,4 %) patients, A(H3N2) chez 2184 (34,7 %) patients et B chez 2345 (37,2 %) patients. En analyse multivariee, les patients infectes par des virus de type A(H3N2) et B presentaient des charges virales significativement plus elevees que les patients infectes par des virus de type A(H1N1)pdm09 (p Conclusion Apres ajustement pour les facteurs confondants parmi lesquels le type de virus, des fluctuations persistaient d’une saison a l’autre, sans explications pertinente a ce jour. On remarque cependant que les saisons associees aux plus faibles charges virales sont les saisons pendant lesquelles les 3 virus co-circulaient.
Published: 2020

89. Fatal Myopericarditis Following an Influenza A (H3N2) Infection

Author: Caroline Lefeuvre, Françoise Lunel-Fabiani, Antonio Monteiro-Rodrigues, Alexandra Ducancelle, Stéphane Triau, Hélène Le Guillou-Guillemette, François Templier, Cong Tri Tran, Vincent Enouf, Sylvie Behillil, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université Bretagne Loire (UBL), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Génomique virale et vaccination, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Pediatrics, medicine.medical_specialty, Myocarditis, Adolescent, Fulminant, [SDV]Life Sciences [q-bio], Orthomyxoviridae, medicine.disease_cause, Pericardial effusion, Pericardial Effusion, 03 medical and health sciences, Lethargy, Fatal Outcome, Cardiac tamponade, Influenza, Human, medicine, Influenza A virus, Humans, Phylogeny, biology, Sequence Analysis, RNA, business.industry, Influenza A Virus, H3N2 Subtype, Articles, General Medicine, medicine.disease, biology.organism_classification, 030112 virology, Heart Arrest, 3. Good health, Cardiac Tamponade, RNA, Female, business, Sequence Analysis, Myopericarditis
Abstract: Patient: Female, 14 Final Diagnosis: Myopericarditis Symptoms: Cardiac tamponade • dyspnea • pericardial effusion • tachycardia Medication: — Clinical Procedure: Cardiopulmonary resuscitation Specialty: Infectious Diseases Objective: Unusual clinical course Background: Influenza viruses induce uncomplicated infections in most cases in individuals with no known predisposing factors. Acute febrile illness is generally limited to upper respiratory symptoms and several constitutional symptoms, including headache, lethargy, and myalgia. However, influenza A virus is a cause of severe morbidity and mortality worldwide. Some patients are at risk for serious and fatal complications. Cardiac involvement is a well-known condition, but, clinically apparent influenza myocarditis is not common. Few reports exist regarding recurrent fulminant influenza myocarditis. Case Report: We report here a fatal case of heart failure following myocarditis in a 14-year-old female who had seasonal flu symptoms but was otherwise healthy. H3N2 influenza virus infection was detected by molecular analyses of throat and nasal swabs, suggesting damage to myocardial cells caused directly by the virus. Conclusions: Pericardial effusion myopericarditis may occur during influenza virus infection in young individuals, even those with no known predisposing factors. Physicians need to be aware that acute myopericarditis can be a fatal complication of recent influenza virus infection in all patients with instable hemodynamics. Early diagnosis and treatment could reduce, in some cases, the risk of severe cardiac events. However, this sudden and fatal outcome was difficult to predict in a healthy young female with no known risk factors.
Published: 2018

90. Estimation of seasonal influenza vaccine effectiveness using data collected in primary care in France: comparison of the test-negative design and the screening method

Author: Alessandra Falchi, Shirley Masse, M. Valette, Clément Turbelin, Vincent Enouf, Lisandru Capai, Sylvie Behillil, Thomas Hanslik, Thierry Blanchon, Louise Rossignol, Bruno Lina, Caroline Guerrisi, Cécile Souty, Ana-Maria Vilcu, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Génétique moléculaire des virus à ARN ((U-Pasteur_ 2 / UMR_3569)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), EA Bioscope Corse Méditerranée : Dynamique des infections virales en milieu insulaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pascal Paoli (UPP), Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [UNIV Corse-Inserm] (EA7310), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Centre National de Référence Virus Influenza (Région Sud), Hospices Civils de Lyon (HCL), Laboratory of Virology East, Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Pascal Paoli (UPP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), VILCU, Ana-Maria, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses, Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des virus influenzae (Grippe)-Génétique moléculaire des virus à ARN (CNR), Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Corse-Inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [GH Nord HCL, Lyon] (CNR des virus influenza), Institut des Agents Infectieux [GH Nord HCL, Lyon]-Groupement Hospitalier Nord des HCL [Lyon], Service de Médecine Interne [AP-HP Hôpital Ambroise Paré], and AP-HP, Hôpital Ambroise Paré
Subjects: 0301 basic medicine, Male, Primary health care, Seasonal influenza, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Screening method, Medicine, Mass Screening, 030212 general & internal medicine, Child, Aged, 80 and over, education.field_of_study, General Medicine, Middle Aged, 3. Good health, virology, Infectious Diseases, Treatment Outcome, Influenza Vaccines, Child, Preschool, Epidemiological Monitoring, surveillance, Female, France, Microbiology (medical), Adult, Adolescent, 030106 microbiology, Population, Primary care, 03 medical and health sciences, Young Adult, primary care, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, Influenza, Human, Humans, education, Aged, Estimation, Primary Health Care, vaccine effectiveness, business.industry, Infant, Newborn, Infant, Confidence interval, Influenza, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography
Abstract: International audience; Objectives: We discussed which method between the test-negative design (TND) and the screening method (SM) could provide more robust real-time and end-of-season vaccine effectiveness (VE) estimates using data collected from routine influenza surveillance in primary care. Methods: We used data collected during two influenza seasons, 2014e15 and 2015e16. Using the SM, we estimated end-of-season VE in preventing medically attended influenza-like illness and laboratory-confirmed influenza among the population at risk. Using the TND, we estimated end-of-season VE in preventing influenza among both the general and the at-risk population. We estimated real-time VE using both methods. Results: For the SM, the overall adjusted end-of-season VE was 24% (95% confidence interval (CI), 16 to 32) and 12% (95% CI, À16 to 33) during season 2014e15, and 53% (95% CI, 44 to 60) and 47% (95% CI, 23 to 64) during season 2015e16, in preventing influenza-like illness and laboratory-confirmed influenza, respectively. For the TND, the overall adjusted end-of-season VE was À17% (95% CI, À79 to 24) and À38% (95% CI, À199 to 13) in 2014e15, and 10% (95% CI, À31 to 39) and 18% (95% CI, À33 to 50) in 2015e16, among the general and at-risk population, respectively. Real-time VE estimates obtained through the TND showed more variability across each season and lower precision than those estimated with the SM. Conclusions: Although the worldwide use of the TND allows for comparison of overall VE estimates among countries, the SM performs better in providing robust real-time VE estimates among the population at risk. A.M. Vilcu, Clin Microbiol Infect 2018;24:431.e5e431.e12
Published: 2018

91. Evolutionary dynamics and genomic features of the Elizabethkingia anophelis 2015 to 2016 Wisconsin outbreak strain

Author: Gwen Borlaug, Eduardo P. C. Rocha, Matthew B. Crist, Phalasy Juieng, Maroya Spalding Walters, Lina I Elbadawi, Elise Larsonneur, Kathryn E. Holt, Jeffrey P. Davis, Marie Touchon, Anne M. Whitney, David J. Edwards, John R. McQuiston, Alexis Criscuolo, Kristin M. Gundlach, Dominique Clermont, Timothy A. Monson, Vincent Enouf, Melissa Bell, David M. Warshauer, Perrine Hugon, Ainsley C. Nicholson, Vladimir N. Loparev, Olaya Rendueles, Amandine Perrin, Christopher A. Gulvik, Sylvain Brisse, Jean Cury, Judith Noble-Wang, Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, University of Melbourne, Wisconsin State Laboratory of Hygiene [Madison] (WSLH), University of Wisconsin-Madison, Collection de l'Institut Pasteur (CIP), Institut Pasteur [Paris], Pasteur International Bioresources network (PIBNet), Plateforme de Microbiologie Mutualisée (PIBnet) - Mutualized Platform for Microbiology (P2M), Prévention et Thérapie Moléculaires des Maladies humaines, This work was supported by Institut Pasteur, French government’s Investissement d’Avenir program Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant ANR-10-LABX-62-IBEID), and the Advanced Molecular Detection (AMD) initiative at CDC. O.R. was supported by a fellowship from Fondation pour la Recherche Médicale (grant number ARF20150934077). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention., We thank D. Mornico of Institut Pasteur and V. Nyak of CDC for assistance with submission of sequence data to public repositories. We would also like to thank the State Health Departments of Michigan and Illinois for contributing strains and information for the cases outside of the State of Wisconsin. The efforts of laboratory staff in both DHQP and DHCPP are greatly appreciated., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Rendueles, Olaya, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Bioinformatics and Sequence Analysis (BONSAI), Laboratoire d'Informatique Fondamentale de Lille (LIFL), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS)-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria), Institut Français de Bioinformatique - UMS CNRS 3601 (IFB-CORE), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Forest research, Northern research station, Forestry Commission, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des virus influenzae (Grippe)-Génétique moléculaire des virus à ARN (CNR), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), and Génotypage des Pathogènes et Santé Publique (Plate-forme) (PF8)
Subjects: 0301 basic medicine, Most recent common ancestor, MESH: Sequence Analysis, DNA, MESH: Mutation Rate, Elizabethkingia, General Physics and Astronomy, medicine.disease_cause, DNA Glycosylases, Disease Outbreaks, Mutation Rate, Flavobacteriaceae Infections, Bacterial genetics, MESH: Disease Outbreaks, MESH: Phylogeny, MESH: Flavobacteriaceae Infections / epidemiology, ComputingMilieux_MISCELLANEOUS, Phylogeny, Genetics, MESH: Bacterial Proteins / genetics, Multidisciplinary, MESH: Flavobacteriaceae / pathogenicity, Phylogenetic tree, Virulence, 3. Good health, MESH: Wisconsin / epidemiology, MESH: Flavobacteriaceae / genetics, Elizabethkingia anophelis, Pathogens, Flavobacteriaceae, food.ingredient, Science, 030106 microbiology, Bacterial genome size, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, food, Wisconsin, Bacterial Proteins, Phylogenetics, MESH: Virulence / genetics, medicine, Humans, MESH: Genome, Bacterial / genetics, Evolutionary dynamics, MESH: DNA Glycosylases / genetics, MESH: Humans, Outbreak, General Chemistry, Sequence Analysis, DNA, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, 030104 developmental biology, Bacterial genes, Evolutionary biology, MESH: Flavobacteriaceae Infections / microbiology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bacterial infection, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Genome, Bacterial
Abstract: An atypically large outbreak of Elizabethkingia anophelis infections occurred in Wisconsin. Here we show that it was caused by a single strain with thirteen characteristic genomic regions. Strikingly, the outbreak isolates show an accelerated evolutionary rate and an atypical mutational spectrum. Six phylogenetic sub-clusters with distinctive temporal and geographic dynamics are revealed, and their last common ancestor existed approximately one year before the first recognized human infection. Unlike other E. anophelis, the outbreak strain had a disrupted DNA repair mutY gene caused by insertion of an integrative and conjugative element. This genomic change probably contributed to the high evolutionary rate of the outbreak strain and may have increased its adaptability, as many mutations in protein-coding genes occurred during the outbreak. This unique discovery of an outbreak caused by a naturally occurring mutator bacterial pathogen provides a dramatic example of the potential impact of pathogen evolutionary dynamics on infectious disease epidemiology., Elizabethkingia anophelis is an emerging pathogen of high antimicrobial resistance. Perrin and colleagues sequenced isolates of a 2015/2016 E. anophelis outbreak in Wisconsin and found substantial genetic diversity, accelerated evolutionary rate and a disruptive mutation in the DNA repair gene mutY.
Published: 2017

92. Temporal Association Between Rhinovirus Activity and Kingella kingae Osteoarticular Infections

Author: Nina Droz, Philippe Bidet, Romain Basmaci, Sylvie Behillil, A L Simon, Manon Bachy, Marion Caseris, Vincent Enouf, Damir Mohamed, and Stéphane Bonacorsi
Subjects: 0301 basic medicine, medicine.medical_specialty, Seasonal distribution, Rhinovirus, Neisseriaceae Infections, 030106 microbiology, Kingella kingae, medicine.disease_cause, Real-Time Polymerase Chain Reaction, Tertiary care, Virus, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Respiratory system, Arthritis, Infectious, Picornaviridae Infections, biology, business.industry, Infant, biology.organism_classification, Pathophysiology, 3. Good health, Child, Preschool, Pediatrics, Perinatology and Child Health, Respiratory virus, France, Seasons, business
Abstract: OBJECTIVE: To determine whether the seasonal distribution of Kingella kingae osteoarticular infections is similar to that of common respiratory viruses. STUDY DESIGN: Between October 2009 and September 2016, we extracted the results of K kingae-specific real-time polymerase chain reaction analyses performed for bone or joint specimens in patients from 2 pediatric tertiary care centers in Paris. We used data of respiratory virus detection from the Réseau National des Laboratoires network with coordination with the National Influenza Center of France. The Spearman rank correlation was used to assess a correlation between weekly distributions, with P
Published: 2017

93. Performance of influenza case definitions for influenza community surveillance: based on the French influenza surveillance network GROG, 2009-2014

Author: Bruno Lina, Mehdi Benchaib, Jean-Sébastien Casalegno, Isabelle Daviaud, Anne Mosnier, Astrid Vabret, Sylvie van der Werf, Martine Valette, Daniel Eibach, Jean Claude Soulary, Jean Cohen, Vincent Enouf, Sylvie Behillil, Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Bernhard Nocht Institute for Tropical Medicine - Bernhard-Nocht-Institut für Tropenmedizin [Hamburg, Germany] (BNITM), Génétique moléculaire des virus à ARN ((U-Pasteur_ 2 / UMR_3569)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Réseau des Groupes Régionaux d'Observation de la Grippe (GROG), Coordination nationale, Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Parcours santé systémique (P2S), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre national de référence influenza (France sud), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Département de Médecine et Biologie de la Reproduction, Faculté de médecine-CECOS, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, myalgia, Male, Pediatrics, Databases, Factual, Epidemiology, Common Cold, Surveillance and Outbreak Report, 0302 clinical medicine, 030212 general & internal medicine, Child, Respiratory Tract Infections, Fatigue, case definitions, ComputingMilieux_MISCELLANEOUS, Headache, Respiratory infection, virus diseases, Pharyngitis, Middle Aged, 3. Good health, Europe, Child, Preschool, Epidemiological Monitoring, surveillance, Bronchitis, Female, France, Public Health, medicine.symptom, influenza, Adult, medicine.medical_specialty, Adolescent, Fever, 030106 microbiology, Sensitivity and Specificity, World health, 03 medical and health sciences, Young Adult, Virology, Influenza, Human, medicine, Humans, Influenza like illness, Intensive care medicine, Aged, Influenza-like illness, business.industry, Public Health, Environmental and Occupational Health, Infant, Newborn, Infant, medicine.disease, United States, Otitis, Dyspnea, Cough, Bronchiolitis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Centers for Disease Control and Prevention, U.S, business, Sentinel Surveillance
Abstract: International case definitions recommended by the Centers for Disease Control and Prevention (CDC), the European Centre for Disease Prevention and Control (ECDC), and the World Health Organization (WHO) are commonly used for influenza surveillance. We evaluated clinical factors associated with the laboratory-confirmed diagnosis of influenza and the performance of these influenza case definitions by using a complete dataset of 14,994 patients with acute respiratory infection (ARI) from whom a specimen was collected between August 2009 and April 2014 by the Groupes Régionaux d’Observation de la Grippe (GROG), a French national influenza surveillance network. Cough and fever ≥ 39 °C most accurately predicted an influenza infection in all age groups. Several other symptoms were associated with an increased risk of influenza (headache, weakness, myalgia, coryza) or decreased risk (adenopathy, pharyngitis, shortness of breath, otitis/otalgia, bronchitis/ bronchiolitis), but not throughout all age groups. The WHO case definition for influenza-like illness (ILI) had the highest specificity with 21.4%, while the ECDC ILI case definition had the highest sensitivity with 96.1%. The diagnosis among children younger than 5 years remains challenging. The study compared the performance of clinical influenza definitions based on outpatient surveillance and will contribute to improving the comparability of data shared at international level.
Published: 2017

94. Real-Time Whole-Genome Sequencing for Surveillance of Listeria monocytogenes , France

Author: Emmanuel Quevillon, Mathieu Tourdjman, Andreea Alexandru, Hélène Bracq-Dieye, Sylvain Brisse, Alexandre Leclercq, Henriette de Valk, Marie Pierre Donguy, Mylène M. Maury, Vincent Enouf, Edith Laurent, Nathalie Tessaud-Rita, Guillaume Vales, Alexis Criscuolo, Alexandra Moura, Nathalie Fredriksen, Dieter Van Cauteren, Pierre Thouvenot, Marc Lecuit, Estelle Hamelin, Institut Pasteur [Paris], Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Ministère de l'agriculture, de l'agroalimentaire et de la forêt, Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This study was supported by the Institut Pasteur, including the PIBnet program, the Institut National de la Santé et de la Recherche Médicale, Santé Publique France, the Investissement d’Avenir Program, Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (ANR-10-LABX-62-IBEID) of the French Government, and the European Research Council. A.M. was supported by the Swiss National Science Foundation (Project SINERGIA, grant no. CRSII3_147692) and the Institut Pasteur., We thank the Mutualized Platform for Microbiology, Institut Pasteur, Paris, France, for genome sequencing, Laura Viñas, Maud Vanpeene, and Wilhame Sobhy for optimization of sequencing pipelines, Keith Jolley for constant development of BIGSdb software, and participating laboratories for referring Listeria strains and their contributions to surveillance., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), DIAKITE, andrée, and Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID
Subjects: 0301 basic medicine, Epidemiology, lcsh:Medicine, high-throughput DNA sequencing, medicine.disease_cause, Genome, Disease Outbreaks, listeriosis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Real-Time Whole-Genome Sequencing for Surveillance of Listeria monocytogenes, France, bacteria, Genetics, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, public health, Epidemiologic Surveillance, PFGE, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, whole-genome sequencing, pulsed-field gel electrophoresis, Epidemiological Monitoring, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, surveillance, France, prospective study, Microbiology (medical), 030106 microbiology, Biology, lcsh:Infectious and parasitic diseases, Microbiology, 03 medical and health sciences, Listeria monocytogenes, Pulsed-field gel electrophoresis, medicine, Humans, lcsh:RC109-216, Typing, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Whole genome sequencing, Whole Genome Sequencing, Research, lcsh:R, molecular typing, Outbreak, bacterial infections and mycoses, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Food Microbiology, Multilocus sequence typing, core genome multilocus sequence typing, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, cgMLST, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genome, Bacterial, WGS
Abstract: International audience; During 2015-2016, we evaluated the performance of whole-genome sequencing (WGS) as a routine typing tool. Its added value for microbiological and epidemiologic surveillance of listeriosis was compared with that for pulsed-field gel electrophoresis (PFGE), the current standard method. A total of 2,743 Listeria monocytogenes isolates collected as part of routine surveillance were characterized in parallel by PFGE and core genome multilocus sequence typing (cgMLST) extracted from WGS. We investigated PFGE and cgMLST clusters containing human isolates. Discrimination of isolates was significantly higher by cgMLST than by PFGE (p
Published: 2017
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95. Impaired humoral and cellular immune responses to influenza vaccination in chronic obstructive pulmonary disease patients

Author: Laurent Margarit, Bruno Housset, Jean-Daniel Lelièvre, Laurent Boyer, Serge Adnot, Philippe Le Corvoisier, Vincent Enouf, Christos Chouaid, Aurélie Wiedemann, Christine Lacabaratz, Aurélien Parpaleix, Yves Levy, Anne Lino, Bernard Maitre, and Ala Covali-Noroc
Subjects: 0301 basic medicine, Male, T-Lymphocytes, Immunology, Pulmonary disease, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Immune system, Text mining, Influenza A Virus, H1N1 Subtype, Influenza, Human, Immunology and Allergy, Medicine, Humans, 030212 general & internal medicine, B-Lymphocytes, Immunity, Cellular, business.industry, Influenza A Virus, H3N2 Subtype, Vaccination, Middle Aged, Immunity, Humoral, Influenza B virus, 030104 developmental biology, Influenza Vaccines, Female, business
Published: 2016

96. Erratum to 'Predominance of influenza A(H3N2) virus genetic subclade 3C.2a1 during an early 2016/17 influenza season in Europe – Contribution of surveillance data from World Health Organization (WHO) European region to the WHO vaccine composition consultation for northern hemisphere 2017/18' [Vaccine 35 (2017) 4828–4835]

Author: Angeliki Melidou, Eeva Broberg, Cornelia Adlhoch, René Snacken, Pasi Penttinen, Dmitriy Pereyaslov, Caroline Brown, Monika Redlberger-Fritz, Therese Popow-Kraupp, Isabelle Thomas, Cyril Barbezange, Nathalie Bossuyt, Helena Jirincova, Alexander Nagy, Ramona Trebbien, Thea K. Fischer, Niina Ikonen, Anu Haveri, Outi Lyytikäinen, Satu Murtopuro, Sylvie Behillil, Vincent Enouf, Sylvie van der Werf, Alessandra Falchi, Martine Valette, Bruno Lina, Brunhilde Schweiger, Barbara Biere, Susanne Duwe, Marianne Wedde, Silke Buda, Andreas Mentis, Athanasios Kossyvakis, Vasiliki Pogka, Anna Papa-Konidari, Georgia Gioula, Maria Exindari, Linda Dunford, Jeff Connell, Grainne Tuite, Margaret Duffy, Joanne Moran, Bridget Hogg, Allison Waters, Cillian de Gascun, Lisa Domegan, Joan O'Donnell, Michael Joyce, Maria Rita Castrucci, Simona Puzelli, Caterina Rizzo, Antonino Bella, Francesco Maraglino, Dinagul Otorbaeva, Gulbarchyn Saparova, Natalija Zamjatina, Gatis Pakarna, Raina Nikiforova, Joël Mossong, Matthias Opp, Adam Meijer, Pieter Overduin, Marit de Lange, Anne Teirlinck, Guus Rimmelzwaan, Ruud van Beek, Marion Koopmans, Gé Donker, Olav Hungnes, Karoline Bragstad, Raquel Guiomar, Pedro Pechirra, Paula Cristóvão, Inês Costa, Patricia Conde, Ana Paula Rodrigues, Alina Elena Ivanciuc, Elena Burtseva, Elena Kirillova, Evgeniya Mukasheva, Elena Tichá, Katarina Prosenc, Nataša Berginc, Francisco Pozo, Inmaculada Casas, Amparo Larrauri, Jesús Oliva, Concha Delgado, Raúl Ortiz de Lejarazu Leonardo, Mia Brytting, Åsa Wiman, Samuel Cordey, Ana Rita Goncalves, Damir Perisa, Rita Born, Joanna Ellis, Monica Galiano, Catherine Thompson, Maria Zambon, Richard Pebody, Rory Gunson, Arlene Reynolds, Jim McMenamin, Conall McCaughey, and Cathriona Kearns
Subjects: Surveillance data, General Veterinary, General Immunology and Microbiology, Public Health, Environmental and Occupational Health, Northern Hemisphere, Influenza a, Subclade, Influenza season, 010501 environmental sciences, European region, 01 natural sciences, World health, Virus, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Geography, Molecular Medicine, 030212 general & internal medicine, 0105 earth and related environmental sciences, Demography
Abstract: The publisher regrets that the co-authors in the “European region influenza surveillance network” were not tagged correctly. The full and complete list of authors and their affiliations for this article is given above. The publisher would like to apologise for any inconvenience caused.
Published: 2018

97. Complications and factors associated with severity of influenza in hospitalized children and adults during the pandemic wave of A(H1N1)pdm2009 infections—The Fluco French cohort

Author: Sylvie Van der WERF, Vincent ENOUF, Bruno Lina, Thierry BLANCHON, Soraya Boucherit, Michael Schwarzinger, Patrice André, Monique ROTHAN-TONDEUR, Fabrice Carrat, Florent Valour, Hala Zahreddine Fahs, and Dominique Ploin
Subjects: Adult, Male, ARDS, Pediatrics, medicine.medical_specialty, Oseltamivir, Adolescent, Disease, Antiviral Agents, Severity of Illness Index, Young Adult, chemistry.chemical_compound, Influenza A Virus, H1N1 Subtype, Risk Factors, Virology, Influenza, Human, Pandemic, medicine, Humans, Prospective Studies, Child, Aged, business.industry, Infant, Newborn, Infant, Middle Aged, medicine.disease, Hospitalization, Infectious Diseases, Respiratory failure, Multicenter study, chemistry, Child, Preschool, Cohort, Female, France, Complication, business
Abstract: Background The emergence of novel A(H1N1)pdm2009 virus threatened to lead to frequent severe manifestations. Objectives To describe the clinical, virological, and biological characteristics of the disease and identify the factors associated with severe presentations. Study design This prospective multicenter study recruited consecutive hospitalized patients with confirmed A(H1N1)pdm2009 disease. Clinical, virological and biological assessments were carried out at inclusion and 30 days post-inclusion. Disease manifestations were assessed by an adjudication committee using pre-identified definitions of complications and severity scores. Results The study analyzed from November 30th, 2009 to February 8th, 2010, 40 hospitalized patients, 21 children and 19 adults. Eighteen (45%) were considered to have severe presentations. Except age, main characteristics in children and adults did not differ. The majority (18/21) of children and all adults had a respiratory presentation; extra-respiratory manifestations tended to be more frequent in children (12 vs. 6, P = 0.10). Two children against 5 adults presented acute respiratory distress syndrome (ARDS, P = 0.23), but more children suffered respiratory failure (7 vs. 1, P = 0.046) without ARDS. At day 30, one death had occurred in each group. The main factor associated with non-severe presentation was an early ( P = 0.038). Conclusions Although the study failed to achieve its main objective, due mainly to the difficulty of carrying a study of this nature in the midst of a pandemic, it allowed the description of a panel of unusual and complicated forms and confirmed the added value of early oseltamivir treatment in limiting severity in hospitalized children and adults.
Published: 2013

98. Guidance for clinical and public health laboratories testing for influenza virus antiviral drug susceptibility in Europe

Author: Angie Lackenby, Francisco Pozo, Eeva Broberg, Rod S. Daniels, Athanasios Kossyvakis, Adam Meijer, Vincent Enouf, Helena Rebelo de Andrade, and Bruno Lina
Subjects: Antiviral Drugs, Oseltamivir, Quality Assurance, Health Care, Rimantadine, medicine.drug_class, viruses, Microbial Sensitivity Tests, Biology, Antiviral Agents, chemistry.chemical_compound, Influenza A Virus, H1N1 Subtype, Zanamivir, Susceptibility Testing, Virology, Drug Resistance, Viral, Influenza, Human, medicine, Humans, media_common.cataloged_instance, European union, media_common, Neuraminidase inhibitor, Resistência aos Antimicrobianos, Influenza A Virus, H3N2 Subtype, Amantadine, Orthomyxoviridae, Influenza, Infectious Diseases, chemistry, Immunology, biology.protein, Guidance, Antiviral drug, Neuraminidase, medicine.drug
Abstract: Two classes of antiviral drugs are licensed in Europe for treatment and prophylaxis of influenza; the M2 ion-channel blockers amantadine and rimantadine acting against type A influenza viruses only and the neuraminidase enzyme inhibitors zanamivir and oseltamivir acting against type A and type B influenza viruses. This guidance document was developed for but not limited to the European Union (EU) and other European Economic Area (EEA) countries on how and when to test for influenza virus antiviral drug susceptibility. It is aimed at clinical and influenza surveillance laboratories carrying out antiviral drug susceptibility testing on influenza viruses from patients suspected of harbouring viruses with reduced susceptibility or for the monitoring of the emergence of such among circulating viruses, respectively. Therefore, the guidance should not be read as a directive or an algorithm for treatment. Monitoring for emergence of influenza viruses with reduced drug susceptibility in hospitalized cases is crucial for decision making on possible changes to antiviral treatment. Therefore, it is important to test for antiviral susceptibility in certain patient groups, such as patients treated with influenza antiviral drugs. It is also important to determine the frequency of viruses with natural (not related to drug use) reduced susceptibility among community and hospitalized cases, as this knowledge is essential for making empirical antiviral treatment decisions. Furthermore, testing of specimens from community influenza patients is needed to determine the frequency of viruses with reduced susceptibility and good viral fitness that are readily transmissible, as they may become dominant among circulating viruses. Phenotypic neuraminidase enzyme inhibition assays are recommended to determine the level of inhibition of the neuraminidase enzyme by antiviral drugs as a measure of drug susceptibility of the virus. Genotypic assays are recommended to identify amino acid substitutions in the neuraminidase and M2 ion-channel proteins that have been associated with reduced antiviral susceptibility previously. By 2012 all circulating seasonal influenza A(H1N1)pdm09 and A(H3N2) viruses were naturally resistant to the M2 ion-channel blockers, so priority should be given to testing for neuraminidase inhibitor susceptibility. RD and AM are partners in a consortium that received and receives funding from the European Centre for Disease Prevention and Control(ECDC), framework service contracts ECDC/08/013 (September 2008–August 2011) “Coordination of the Community Network of Reference Laboratories for Human Influenza in Europe (CNRL)” and ECDC/2012/009 (June 2012–July 2015) “Laboratory Supportfor the Surveillance ofInfluenza at EuropeanLevel”, respectively.
Published: 2013

99. Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission

Author: Anne Goffard, Sylvie Behillil, Caroline Séjourné, Fanny Vuotto, Vincent Enouf, Valérie Caro, Julien Poissy, Daniel Mathieu, Benoit Guery, Jean Claude Manuguerra, Didier Che, Xavier Lemaire, Nicolas Ettahar, Alexandra Mailles, Loubna El Mansouf, Sylvie van der Werf, Arnaud Fontanet, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier [Douai, Nord], Centre hospitalier [Valenciennes, Nord], Centre National de Référence des virus influenzae (Grippe) (CNR), Institut Pasteur [Paris] (IP), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Cellule d'Intervention Biologique d'Urgence - Laboratory for Urgent Response to Biological Threats (CIBU), Institut de Veille Sanitaire (INVS), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), The National Reference Center for Influenza Viruses and the CIBU are supported in part by funds from the French Institute for Public Health Surveillance (Institut de veille sanitaire, InVS). Work related to collection of data, implementation of the assays, and sequencing was done with funds from ANR grant Labex Integrative Biology of Emerging Infectious Diseases (IBEID, grant number ANR-10-LABX-62-IBEID from the French Government's Investissement d'Avenir programme) and from the European Community's Seventh Framework Programme (FP7/2007–2013) under the project EMPERIE (European Community grant agreement number 223498) and under the project PREDEMICS (grant agreement number 278433), We thank the nurses and all health-care workers from the hospitals in Valenciennes, Douai, and Lille who, in this crisis situation, took care of the patients and controlled the spread of this disease. We thank P Despres, S Paulous, and M P Frenkiel (Unit of Flavivirus-Host Molecular Interactions, Institut Pasteur) for preliminary serological analyses. We thank Eric Kipnis for editing of the report., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 223498,EC:FP7:HEALTH,FP7-HEALTH-2007-B,EMPERIE(2009), European Project: 278433,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,PREDEMICS(2011), Institut Pasteur [Paris], and Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)
Subjects: Male, medicine.medical_specialty, Middle East respiratory syndrome coronavirus, medicine.medical_treatment, [SDV]Life Sciences [q-bio], medicine.disease_cause, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Extracorporeal membrane oxygenation, Humans, 030212 general & internal medicine, Intensive care medicine, 030304 developmental biology, Coronavirus, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Cross Infection, medicine.diagnostic_test, business.industry, General Medicine, 3. Good health, Bronchoalveolar lavage, medicine.anatomical_structure, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Sputum, Chills, medicine.symptom, business, Coronavirus Infections, Viral load, Respiratory tract
Abstract: Summary Background Human infection with a novel coronavirus named Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia and the Middle East in September, 2012, with 44 laboratory-confirmed cases as of May 23, 2013. We report detailed clinical and virological data for two related cases of MERS-CoV disease, after nosocomial transmission of the virus from one patient to another in a French hospital. Methods Patient 1 visited Dubai in April, 2013; patient 2 lives in France and did not travel abroad. Both patients had underlying immunosuppressive disorders. We tested specimens from the upper (nasopharyngeal swabs) or the lower (bronchoalveolar lavage, sputum) respiratory tract and whole blood, plasma, and serum specimens for MERS-CoV by real-time RT-PCR targeting the upE and Orf1A genes of MERS-CoV. Findings Initial clinical presentation included fever, chills, and myalgia in both patients, and for patient 1, diarrhoea. Respiratory symptoms rapidly became predominant with acute respiratory failure leading to mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Both patients developed acute renal failure. MERS-CoV was detected in lower respiratory tract specimens with high viral load (eg, cycle threshold [Ct] values of 22·9 for upE and 24 for Orf1a for a bronchoalveolar lavage sample from patient 1; Ct values of 22·5 for upE and 23·9 for Orf1a for an induced sputum sample from patient 2), whereas nasopharyngeal specimens were weakly positive or inconclusive. The two patients shared the same room for 3 days. The incubation period was estimated at 9–12 days for the second case. No secondary transmission was documented in hospital staff despite the absence of specific protective measures before the diagnosis of MERS-CoV was suspected. Patient 1 died on May 28, due to refractory multiple organ failure. Interpretation Patients with respiratory symptoms returning from the Middle East or exposed to a confirmed case should be isolated and investigated for MERS-CoV with lower respiratory tract sample analysis and an assumed incubation period of 12 days. Immunosuppression should also be taken into account as a risk factor. Funding French Institute for Public Health Surveillance, ANR grant Labex Integrative Biology of Emerging Infectious Diseases, and the European Community's Seventh Framework Programme projects EMPERIE and PREDEMICS.
Published: 2013

100. Oseltamivir–zanamivir bitherapy compared to oseltamivir monotherapy in the treatment of pandemic 2009 influenza A(H1N1) virus infections

Author: François Gueyffier, Anne Mosnier, Xavier Duval, Bruno Lina, Thierry Blanchon, Ségolène Gaillard, Sylvie van der Werf, Catherine Cornu, Vanessa Escuret, Florent Boutitie, M. Bouscambert-Duchamp, Catherine Leport, Vincent Enouf, Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Oseltamivir, [SDV]Life Sciences [q-bio], viruses, Drug resistance, medicine.disease_cause, Antiviral Agents, Virus, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, Influenza A Virus, H1N1 Subtype, 0302 clinical medicine, Zanamivir, Virology, Drug Resistance, Viral, Influenza, Human, medicine, Influenza A virus, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Pharmacology, 0303 health sciences, 030306 microbiology, business.industry, Amantadine, virus diseases, Middle Aged, Virus Shedding, respiratory tract diseases, 3. Good health, Nasal Mucosa, Treatment Outcome, Tolerability, chemistry, Drug Therapy, Combination, Female, France, business, Viral load, medicine.drug
Abstract: Background The emergence of oseltamivir resistance in 2007 highlighted the need for alternative strategies against influenza. To limit the putative emergence of resistant viruses this clinical trial aimed to evaluate the antiviral efficacy and tolerability of oseltamivir–zanamivir (O + Z) bitherapy compared to oseltamivir monotherapy (O). This clinical trial was designed in 2008–2009 and was conducted during the A(H1N1) influenza virus pandemic in 2009–2010. The A(H1N1)pdm09 viruses were reported to be sensitive to oseltamivir and zanamivir but resistant to amantadine. Methods During the pandemic phase in France, adults with influenza-like illness for less than 42 h and who tested positive to influenza A were randomised into treatment groups: (O + Z) or (O). Patients had a nasal wash at day 0, before the beginning of treatment and daily at days 1 to 4. They also had a nasal swab at days 5 and 7 to check for the negativation of viral excretion. Virological response was assessed using the GAPDH adjusted M gene quantification. Results Analysis was possible for 24 patients, 12 in the (O + Z) arm and 12 in the (O) arm. The mean viral load decreased at around 1 log10 cgeq/μl per day regardless of allocated treatment group. We could not detect any significant difference between treatment groups in the duration needed to alleviate symptoms. All treatments were well tolerated. No oseltamivir-resistant H275Y NA mutated virus has been detected in patients of both treatment groups. Conclusions The sample size of our study is too limited to be fully informative and we could not detect whether combination therapy (O + Z) improves or reduces the effectiveness of oseltamivir in the treatment of influenza A(H1N1)pdm09 virus infection in community patients. Additional studies are needed to improve the antiviral treatment of patients infected with influenza virus.
Published: 2012

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