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1. Refractory anti-viral resistant CMV retinitis in an immunological nonresponder person living with HIV

Author

Alexandra Serris, Mayda Rahi, Christophe Rioux, Nadhira Fidouh, Veronique Joly, and David Boutolleau

Subjects
Drug resistant cytomegalovirus, HIV, CMV retinitis, HIV immunological non responder, Infectious and parasitic diseases, RC109-216
Abstract

Cytomegalovirus (CMV) retinitis caused by drug-resistant viruses poses a major challenge in immunocompromised patients. We present the case of a patient living with HIV with persistently low CD4+ T cells count despite effective antiretroviral therapy, who experienced multiple episodes of CMV retinitis associated with iterative acquisition of resistance. The failure of ganciclovir and foscarnet treatments led us to implement a combined therapy of intravenous cidofovir, high-dose ganciclovir, and anti-CMV immunoglobulin as well as intravitreal injections of ganciclovir. This triple therapy was successful but resulted in significant myelotoxicity. Furthermore, the relapse of CMV retinitis and/or CMV viremia with each therapeutic de-escalation reflects the high level of immunodeficiency in our patient, despite sustained control of HIV viremia for several months. This case report highlights the need for a particular management of CMV infection in patients living with HIV who are immunological nonresponders.

Published
2024
Full Text
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2. Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

Author

Astrid Marchal, Elizabeth T. Cirulli, Iva Neveux, Evangelos Bellos, Ryan S. Thwaites, Kelly M. Schiabor Barrett, Yu Zhang, Ivana Nemes-Bokun, Mariya Kalinova, Andrew Catchpole, Stuart G. Tangye, András N. Spaan, Justin B. Lack, Jade Ghosn, Charles Burdet, Guy Gorochov, Florence Tubach, Pierre Hausfater, Clifton L. Dalgard, Shen-Ying Zhang, Qian Zhang, Christopher Chiu, Jacques Fellay, Joseph J. Grzymski, Vanessa Sancho-Shimizu, Laurent Abel, Jean-Laurent Casanova, Aurélie Cobat, Alexandre Bolze, Alessandro Aiuti, Saleh Al-Muhsen, Fahd Al-Mulla, Ali Amara, Mark S. Anderson, Evangelos Andreakos, Andrés A. Arias, Lisa M. Arkin, Hagit Baris Feldman, Paul Bastard, Alexandre Belot, Catherine M. Biggs, Dusan Bogunovic, Anastasiia Bondarenko, Alessandro Borghesi, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Manish J. Butte, Giorgio Casari, John Christodoulou, Roger Colobran, Antonio Condino-Neto, Stefan N. Constantinescu, Megan A. Cooper, Murkesh Desai, Beth A. Drolet, Xavier Duval, Jamila El Baghdadi, Philippine Eloy, Sara Espinosa-Padilla, Carlos Flores, José Luis Franco, Antoine Froidure, Peter K. Gregersen, Bodo Grimbacher, Filomeen Haerynck, David Hagin, Rabih Halwani, Lennart Hammarström, James R. Heath, Elena W.Y. Hsieh, Eystein Husebye, Kohsuke Imai, Yuval Itan, Emmanuelle Jouanguy, Elżbieta Kaja, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davood Mansouri, László Maródi, France Mentré, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine H. Mogensen, Tomohiro Morio, Lisa F.P. Ng, Luigi D. Notarangelo, Antonio Novelli, Giuseppe Novelli, Cliona O'Farrelly, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarström, Jean W. Pape, Rebeca Perez de Diego, Jordi Perez-Tur, David S. Perlin, Graziano Pesole, Anna M. Planas, Carolina Prando, Aurora Pujol, Anne Puel, Lluis Quintana-Murci, Sathishkumar Ramaswamy, Laurent Renia, Igor Resnick, Carlos Rodríguez-Gallego, Anna Sediva, Mikko R.J. Seppänen, Mohammad Shahrooei, Anna Shcherbina, Ondrej Slaby, Andrew L. Snow, Pere Soler-Palacín, Vassili Soumelis, Ivan Tancevski, Ahmad Abou Tayoun, Şehime Gülsün Temel, Christian Thorball, Pierre Tiberghien, Sophie Trouillet-Assant, Stuart E. Turvey, K. M. Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Donald C. Vinh, Horst von Bernuth, Joost Wauters, Mayana Zatz, Pawel Zawadzki, Serge Bureau, Yannick Vacher, Anne Gysembergh-Houal, Lauren Demerville, Abla Benleulmi-Chaachoua, Sebastien Abad, Radhiya Abassi, Abdelrafie Abdellaoui, Abdelkrim Abdelmalek, Hendy Abdoul, Helene Abergel, Fariza Abeud, Sophie Abgrall, Noemie Abisror, Marylise Adechian, Nordine Aderdour, Hakeem Farid Admane, Frederic Adnet, Sara Afritt, Helene Agostini, Claire Aguilar, Sophie Agut, Tommaso Francesco Aiello, Marc Ait Kaci, Hafid Ait Oufella, Gokula Ajeenthiravasan, Virginie Alauzy, Fanny Alby-Laurent, Lucie Allard, Marie-Alexandra Alyanakian, Blanca Amador Borrero, Sabrina Amam, Lucile Amrouche, Marc Andronikof, Dany Anglicheau, Nadia Anguel, Djillali Annane, Mohammed Aounzou, Caroline Aparicio, Gladys Aratus, Jean-Benoit Arlet, Jeremy Arzoine, Elisabeth Aslangul, Mona Assefi, Adeline Aubry, Laetitia Audiffred, Etienne Audureau, Christelle Nathalie Auger, Jean-Charles Auregan, Celine Awotar, Sonia Ayllon Milla, Delphine Azan, Laurene Azemar, Billal Azzouguen, Marwa Bachir Elrufaai, Aïda Badsi, Prissile Bakouboula, Coline Balcerowiak, Fanta Balde, Elodie Baldivia, Eliane-Flore Bangamingo, Amandine Baptiste, Fanny Baran-Marszak, Caroline Barau, Nathalie Barget, Flore Baronnet, Romain Barthelemy, Jean-Luc Baudel, Camille Baudry, Elodie Baudry, Laurent Beaugerie, Adel Belamri, Nicolas Belaube, Rhida Belilita, Pierre Bellassen, Rawan Belmokhtar, Isabel Beltran, Ruben Benainous, Mourad Benallaoua, Robert Benamouzig, Amélie Benbara, Jaouad Benhida, Anis Benkhelouf, Jihene Benlagha, Chahinez Benmostafa, Skander Benothmane, Miassa Bentifraouine, Laurence Berard, Quentin Bernier, Enora Berti, Astrid Bertier, Laure Berton, Simon Bessis, Alexandra Beurton, Celine Bianco, Clara Bianquis, Frank Bidar, Philippe Blanche, Clarisse Blayau, Alexandre Bleibtreu, Emmanuelle Blin, Coralie Bloch-Queyrat, Marie-Christophe Boissier, Diane Bollens, Marion Bolzoni, Rudy pierre Bompard, Nicolas Bonnet, Justine Bonnouvrier, Shirmonecrystal Botha, Wissam Boucenna, Fatiha Bouchama, Olivier Bouchaud, Hanane Bouchghoul, Taoueslylia Boudjebla, Noel Boudjema, Catherine Bouffard, Adrien Bougle, Meriem Bouguerra, Leila Bouras, Agnes Bourcier, Anne Bourgarit Durand, Anne Bourrier, Fabrice Bouscarat, Diane Bouvry, Nesrine Bouziri, Ons Bouzrara, Sarah Bribier, Delphine Brugier, Melanie Brunel, Eida Bui, Anne Buisson, Iryna Bukreyeva, Côme Bureau, Jacques Cadranel, Johann Cailhol, Ruxandra Calin, Clara Campos Vega, Pauline Canavaggio, Marta Cancella, Delphine Cantin, Albert Cao, Lionel Carbillon, Nicolas Carlier, Clementine Cassard, Guylaine Castor, Marion Cauchy, Olivier Cha, Benjamin Chaigne, Salima Challal, Karine Champion, Patrick Chariot, Julie Chas, Simon Chauveau, Anthony Chauvin, Clement Chauvin, Nathalie Chavarot, Kamélia Chebbout, Mustapha Cherai, Ilaria Cherubini, Amelie Chevalier, Thibault Chiarabini, Thierry Chinet, Richard Chocron, Pascaline Choinier, Juliette Chommeloux, Christophe Choquet, Laure Choupeaux, Benjamin Chousterman, Dragosmarius Ciocan, Ada Clarke, Gaëlle Clavere, Florian Clavier, Karine Clement, Sebastien Clerc, Yves Cohen, Fleur Cohen, Adrien Cohen, Audrey Coilly, Hester Colboc, Pauline Colin, Magalie Collet, Chloé Comarmond, Emeline Combacon, Alain Combes, Celine Comparon, Jean-Michel Constantin, Hugues Cordel, Anne-Gael Cordier, Adrien Costantini, Nathalie Costedoat Chalumeau, Camille Couffignal, Doriane Coupeau, Alain Creange, Yannie Cuvillier Lamarre, Charlène Da Silveira, Sandrine Dautheville Guibal El Kayani, Nathalie De Castro, Yann De Rycke, Lucie Del Pozo, Quentin Delannoy, Mathieu Delay, Robin Deleris, Juliette Delforge, Laëtitia Delphine, Noemie Demare, Sophie Demeret, Alexandre Demoule, Aurore Deniau, François Depret, Sophie Derolez, Ouda Derradji, Nawal Derridj, Vincent Descamps, Lydia Deschamps, Celine Desconclois, Cyrielle Desnos, Karine Desongins, Robin Dhote, Benjamin Diallo, Morgane Didier, Myriam Diemer, Stephane Diez, Juliette Djadi-Prat, Fatima-Zohra Djamouri Monnory, Siham Djebara, Naoual Djebra, Minette Djietcheu, Hadjer Djillali, Nouara Djouadi, Severine Donneger, Catarina Dos Santos, Nathalie Dournon, Martin Dres, Laura Droctove, Marie Drogrey, Margot Dropy, Elodie Drouet, Valérie Dubosq, Evelyne Dubreucq, Estelle Dubus, Boris Duchemann, Thibault Duchenoy, Emmanuel Dudoignon, Romain Dufau, Florence Dumas, Clara Duran, Emmanuelle Duron, Antoine Durrbach, Claudine Duvivier, Nathan Ebstein, Jihane El Khalifa, Alexandre Elabbadi, Caroline Elie, Gabriel Ernotte, Anne Esling, Martin Etienne, Xavier Eyer, Muriel Sarah Fartoukh, Takoua Fayali, Marion Fermaut, Arianna Fiorentino, Souha Fliss, Marie-Céline Fournier, Benjamin Fournier, Hélène Francois, Olivia Freynet, Yvann Frigout, Isaure Fromont, Axelle Fuentes, Thomas Furet, Joris Galand, Marc Garnier, Agnes Gaubert, Stéphane Gaudry, Samuel Gaugain, Damien Gauthier, Maxime Gautier, Sophie Georgin-Lavialle, Daniela Geromin, Mohamed Ghalayini, Bijan Ghaleh, Myriam Ghezal, Aude Gibelin, Linda Gimeno, Benoit Girard, Bénédicte Giroux Leprieur, Doryan Gomes, Elisabete Gomes-Pires, Anne Gouge, Amel Gouja, Helene Goulet, Sylvain Goupil, Jeanne Goupil De Bouille, Julien Gras, Segolene Greffe, Lamiae Grimaldi, Paul Guedeney, Bertrand Guidet, Matthias Guillo, Mariechristelle Gulczynski, Tassadit Hadjam, Didier Haguenauer, Soumeya Hammal, Nadjib Hammoudi, Olivier Hanon, Anarole Harrois, Coraline Hautem, Guillaume Hekimian, Nicholas Heming, Olivier Hermine, Sylvie Ho, Marie Houllier, Benjamin Huot, Tessa Huscenot, Wafa Ibn Saied, Ghilas Ikherbane, Meriem Imarazene, Patrick Ingiliz, Lina Iratni, Stephane Jaureguiberry, Jean-Francois Jean-Marc, Deleena Jeyarajasingham, Pauline Jouany, Veronique Jouis, Clement Jourdaine, Ouifiya Kafif, Rim Kallala, Sandrine Katsahian, Lilit Kelesyan, Vixra Keo, Flora Ketz, Warda Khamis, Enfel Khelili, Mehdi Khellaf, Christy Gaëlla Kotokpo Youkou, Ilias Kounis, Gaelle Kpalma, Jessica Krause, Vincent Labbe, Karine Lacombe, Jean-Marc Lacorte, Anne Gaelle Lafont, Emmanuel Lafont, Lynda Lagha, Lionel Lamhaut, Aymeric Lancelot, Cecilia Landman, Fanny Lanternier, Cecile Larcheveque, Caroline Lascoux Combe, Ludovic Lassel, Benjamin Laverdant, Christophe Lavergne, Jean-Rémi Lavillegrand, Pompilia Lazureanu, Loïc Le Guennec, Lamia Leberre, Claire Leblanc, Marion Leboyer, Francois Lecomte, Marine Lecorre, Romain Leenhardt, Marylou Lefebvre, Bénédicte Lefebvre, Paul Legendre, Anne Leger, Laurence Legros, Justyna Legrosse, Sébastien Lehuunghia, Julien Lemarec, Jeremie Leporrier-Ext, Manon Lesein, Hubert Lesur, Vincent Levy, Albert Levy, Edwige Lopes, Amanda Lopes, Vanessa Lopez, Julien Lopinto, Olivier Lortholary, Badr Louadah, Bénédicte Loze, Marie-Laure Lucas, Axelle Lucasamichi, Liem Binh Luong, Arouna Magazimama-Ext, David Maingret, Lakhdar Mameri, Philippe Manivet, Cylia Mansouri, Estelle Marcault, Jonathan Marey, Nathalie Marin, Clémence Marois, Olivier Martin, Lou Martineau, Cannelle Martinez-Lopez, Pierre Martyniuck, Pauline Mary De Farcy, Nessrine Marzouk, Rafik Masmoudi, Alexandre Mebazaa, Frédéric Mechai, Fabio Mecozzi, Chamseddine Mediouni, Bruno Megarbane, Mohamed Meghadecha, Élodie Mejean, Arsene Mekinian, Nour Mekki Abdelhadi, Rania Mekni, Thinhinan Sabrina Meliti, Breno Melo Lima, Paris Meng, Soraya Merbah, Fadhila Messani, Yasmine Messaoudi, Baboo-Irwinsingh Mewasing, Lydia Meziane, Carole Michelot-Burger, Françoise Mignot, Fadi Hillary Minka, Makoto Miyara, Pierre Moine, Jean-Michel Molina, Anaïs Montegnies-Boulet, Alexandra Monti, Claire Montlahuc, Anne-Lise Montout, Alexandre Moores, Caroline Morbieu, Helene Mortelette, Stéphane Mouly, Rosita Muzaffar, Cherifa Iness Nacerddine, Marine Nadal, Hajer Nadif, Kladoum Nassarmadji, Pierre Natella, Sandrine Ndingamondze, Stefan Neraal, Caroline Nguyen, Bao N'Guyen, Isabelle Nion Larmurier, Luc Nlomenyengue, Nicolas Noel, Hilario Nunes, Edris Omar, Zineb Ouazene, Elise Ouedraogo, Wassila Ouelaa, Anissa Oukhedouma, Yasmina Ould Amara, Herve Oya, Johanna Oziel, Thomas Padilla, Elena Paillaud, Solenne Paiva, Beatrice Parfait, Perrine Parize, Christophe Parizot, Antoine Parrot, Arthur Pavot, Laetitia Peaudecerf, Frédéric Pene, Marion Pepin, Julie Pernet, Claire Pernin, Mylène Petit, Olivier Peyrony, Marie-Pierre Pietri, Olivia Pietri, Marc Pineton De Chambrun, Michelle Pinson, Claire Pintado, Valentine Piquard, Christine Pires, Benjamin Planquette, Sandrine Poirier, Anne-Laure Pomel, Stéphanie Pons, Diane Ponscarme, Annegaelle Pourcelot, Valérie Pourcher, Anne Pouvaret, Florian Prever, Miresta Previlon, Margot Prevost, Marie-Julie Provoost, Cyril Quemeneur, Cédric Rafat, Agathe Rami, Brigitte Ranque, Maurice Raphael, Jean Herle Raphalen, Anna Rastoin, Mathieu Raux, Amani Rebai, Michael Reby, Alexis Regent, Asma Regrag, Matthieu Resche-Rigon, Quentin Ressaire, Christian Richard, Mariecaroline Richard, Maxence Robert, Benjamin Rohaut, Camille Rolland-Debord, Jacques Ropers, Anne-Marie Roque-Afonso, Charlotte Rosso, Mélanie Rousseaux, Nabila Rousseaux, Swasti Roux, Lorène Roux, Claire Rouzaud, Antoine Rozes, Emma Rubenstein, Jean-Marc Sabate, Sheila Sabet, Sophie-Caroline Sacleux, Nathalie Saidenberg Kermanach, Faouzi Saliba, Dominique Salmon, Laurent Savale, Guillaume Savary, Rebecca Sberro, Anne Scemla, Frederic Schlemmer, Mathieu Schwartz, Saïd Sedfi, Samia Sefir-Kribel, Philippe Seksik, Pierre Sellier, Agathe Selves, Nicole Sembach, Luca Semerano, Marie-Victoire Senat, Damien Sene, Alexandra Serris, Lucile Sese, Naima Sghiouar, Johanna Sigaux, Martin Siguier, Johanne Silvain, Noémie Simon, Tabassome Simon, Lina Innes Skandri, Miassa Slimani, Aurélie Snauwaert, Harry Sokol, Heithem Soliman, Nisrine Soltani, Benjamin Soyer, Gabriel Steg, Lydia Suarez, Tali-Anne Szwebel, Kossi Taffame, Yacine Tandjaoui-Lambiotte, Claire Tantet, Mariagrazia Tateo, Igor Theodose, Pierre clement Thiebaud, Caroline Thomas, Kelly Tiercelet, Julie Tisserand, Carole Tomczak, Krystel Torelino, Fatima Touam-Ext, Lilia Toumi, Gustave Toury, Mireille Toy-Miou, Olivia Tran Dinh Thanh Lien, Alexy Trandinh, Jean-Marc Treluyer, Baptiste Trinque, Jennifer Truchot, Sarah Tubiana, Simone Tunesi, Matthieu Turpin, Agathe Turpin, Tomas Urbina, Rafael Usubillaga Narvaez, Yurdagul Uzunhan, Prabakar Vaittinadaayar, Arnaud Valent, Maelle Valentian, Nadia Valin, Hélène Vallet, Marina Vaz, Miguel-Alejandro Vazquezibarra, Benoit Vedie, Laetitia Velly, Celine Verstuyft, Cedric Viallette, Eric Vicaut, Dorothee Vignes, Damien Vimpere, Myriam Virlouvet, Guillaume Voiriot, Lena Voisot, Emmanuel Weiss, Nicolas Weiss, Anaïs Winchenne, Youri Yordanov, Lara Zafrani, Mohamad Zaidan, Wissem Zaidi, Cathia Zak, Aida Zarhrate-Ghoul, Ouassila Zatout, Suzanne Zeino, Michel Zeitouni, Naïma Zemirli, Lorene Zerah, Ounsa Zia, Marianne Ziol, Oceane Zolario, Julien Zuber, Claire Andrejak, François Angoulvant, Delphine Bachelet, Marie Bartoli, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, Lila Bouadma, Sabelline Bouchez, Maude Bouscambert, Minerva Cervantes-Gonzalez, Anissa Chair, Catherine Chirouze, Alexandra Coelho, Sandrine Couffin-Cadiergues, Eric d’Ortenzio, Marie-Pierre Debray, Laurene Deconinck, Dominique Deplanque, Diane Descamps, Mathilde Desvallée, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Brigitte Elharrar, Vincent Enouf, Hélène Esperou, Marina Esposito-Farese, Manuel Etienne, Eglantine Ferrand Devouge, Nathalie Gault, Alexandre Gaymard, Tristan Gigante, Morgane Gilg, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Ikram Houas, Jean-Sébastien Hulot, Salma Jaafoura, Florentia Kaguelidou, Sabrina Kali, Antoine Khalil, Coralie Khan, Cédric Laouénan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François-Xavier Lescure, Sophie Letrou, Yves Levy, Bruno Lina, Guillaume Lingas, Jean-Christophe Lucet, Denis Malvy, Marina Mambert, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Duc Nguyen, Marion Noret, Saad Nseir, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadja, Thomas Perpoint, Ventzislava Petrov-Sanchez, Gilles Peytavin, Huong Pham, Olivier Picone, Oriane Puéchal, Christian Rabaud, Manuel Rosa-Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Richa Su, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean-François Timsit, Christelle Tual, Sylvie Van Der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanah, Loubna Alavoine, Charlotte Charpentier, Aline Dechanet, Jean-Luc Ecobichon, Wahiba Frezouls, Nadhira Houhou, Jonathan Lehacaut, Pauline Manchon, Mariama Nouroudine, Caroline Quintin, Michael Thy, Sylvie van der Werf, Valérie Vignali, Abir Chahine, Nawal Waucquier, Maria-Claire Migaud, Félix Djossou, Mayka Mergeay-Fabre, Aude Lucarelli, Magalie Demar, Léa Bruneau, Patrick Gérardin, Adrien Maillot, Christine Payet, Bruno Laviolle, Fabrice Laine, Christophe Paris, Mireille Desille-Dugast, Julie Fouchard, Thierry Pistone, Pauline Perreau, Valérie Gissot, Carole L.E. Goas, Samatha Montagne, Lucie Richard, Kévin Bouiller, Maxime Desmarets, Alexandre Meunier, Marilou Bourgeon, Benjamin Lefévre, Hélène Jeulin, Karine Legrand, Sandra Lomazzi, Bernard Tardy, Amandine Gagneux-Brunon, Frédérique Bertholon, Elisabeth Botelho-Nevers, Christelle Kouakam, Leturque Nicolas, Layidé Roufai, Karine Amat, Hélène Espérou, Samia Hendou, Giuseppe Foti, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga, Giacomo Bellani, Jorge Abad, Giulia Accordino, Micol Angelini, Sergio Aguilera-Albesa, Aina Aguiló-Cucurull, Esra Akyüz Özkan, Ilad Alavi Darazam, Jonathan Antonio Roblero Albisures, Juan C. Aldave, Miquel Alfonso Ramos, Taj Ali Khan, Anna Aliberti, Seyed Alireza Nadji, Gulsum Alkan, Suzan A. AlKhater, Jerome Allardet-Servent, Luis M. Allende, Rebeca Alonso-Arias, Mohammed S. Alshahrani, Laia Alsina, Zahir Amoura, Arnau Antolí, Romain Arrestier, Mélodie Aubart, Teresa Auguet, Iryna Avramenko, Gökhan Aytekin, Axelle Azot, Seiamak Bahram, Fanny Bajolle, Fausto Baldanti, Aurélie Baldolli, Maite Ballester, Benoit Barrou, Federica Barzaghi, Sabrina Basso, Gulsum Iclal Bayhan, Liliana Bezrodnik, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blázquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, Elisabeth Botdhlo-Nevers, Aurore Bousquet, David Boutolleau, Claire Bouvattier, Oksana Boyarchuk, Juliette Bravais, M. Luisa Briones, Marie-Eve Brunner, Raffaele Bruno, Maria Rita P. Bueno, Huda Bukhari, Jacinta Bustamante, Juan José Cáceres Agra, Ruggero Capra, Raphael Carapito, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Irene Cassaniti, Martin Castelle, Francesco Castelli, Martín Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Jale Bengi Celik, Alessandro Ceschi, Martin Chalumeau, Bruno Charbit, Cécile Boulanger, Père Clavé, Bonaventura Clotet, Anna Codina, Cloé Comarmond, Patrizia Comoli, Angelo G. Corsico, Taner Coşkuner, Aleksandar Cvetkovski, Cyril Cyrus, David Dalmau, François Danion, David Ross Darley, Vincent Das, Nicolas Dauby, Stéphane Dauger, Paul De Munte, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Isabelle Desguerre, Antonio Di Sabatino, Jean-Luc Diehl, Stephanie Dobbelaere, Elena Domínguez-Garrido, Clément Dubost, Olov Ekwall, Şefika Elmas Bozdemir, Marwa H. Elnagdy, Melike Emiroglu, Akifumi Endo, Emine Hafize Erdeniz, Selma Erol Aytekin, Maria Pilar Etxart Lasa, Romain Euvrard, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Ricard Ferrer, Jose Ferreres, Bruno Francois, Victoria Fumadó, Kitty S.C. Fung, Francesca Fusco, Alenka Gagro, Blanca Garcia Solis, Pierre Garçon, Pascale Gaussem, Zeynep Gayretli, Juana Gil-Herrera, Laurent Gilardin, Audrey Giraud Gatineau, Mònica Girona-Alarcón, Karen Alejandra Cifuentes Godínez, Jean-Christophe Goffard, Nacho Gonzales, Luis I. Gonzalez-Granado, Rafaela González-Montelongo, Antoine Guerder, Belgin Gülhan, Victor Daniel Gumucio, Leif Gunnar Hanitsch, Jan Gunst, Marta Gut, Jérôme Hadjadj, Selda Hancerli, Tetyana Hariyan, Nevin Hatipoglu, Deniz Heppekcan, Elisa Hernandez-Brito, Po-ki Ho, María Soledad Holanda-Peña, Juan P. Horcajada, Sami Hraiech, Linda Humbert, Ivan F.N. Hung, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María Jesús Arranz, Marie-Thérèse Jimeno, Iolanda Jordan, Saliha Kanık-Yüksek, Yalcin Kara, Aydın Karahan, Adem Karbuz, Kadriye Kart Yasar, Ozgur Kasapcopur, Kenichi Kashimada, Sevgi Keles, Yasemin Kendir Demirkol, Yasutoshi Kido, Can Kizil, Ahmet Osman Kılıç, Adam Klocperk, Antonia Koutsoukou, Zbigniew J. Król, Hatem Ksouri, Paul Kuentz, Arthur M.C. Kwan, Yat Wah M. Kwan, Janette S.Y. Kwok, Jean-Christophe Lagier, David S.Y. Lam, Vicky Lampropoulou, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain Lévy, Zhi Li, Daniele Lilleri, Edson Jose Adrian Bolanos Lima, Agnes Linglart, Eduardo López-Collazo, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Kwok-Cheung Lung, Charles-Edouard Luyt, David C. Lye, Cinthia Magnone, Enrico Marchioni, Carola Marioli, Majid Marjani, Laura Marques, Jesus Marquez Pereira, Andrea Martín-Nalda, David Martínez Pueyo, Javier Martinez-Picado, Iciar Marzana, Carmen Mata-Martínez, Alexis Mathian, Larissa R.B. Matos, Gail V. Matthews, Julien Mayaux, Raquel McLaughlin-Garcia, Philippe Meersseman, Jean-Louis Mège, Armand Mekontso-Dessap, Isabelle Melki, Federica Meloni, Jean-François Meritet, Paolo Merlani, Özge Metin Akcan, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Matthieu Million, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Yoko Mizoguchi, Bhavi P. Modi, Francesco Mojoli, Elsa Moncomble, Abián Montesdeoca Melián, Antonio Morales Martinez, Francisco Morandeira, Pierre-Emmanuel Morange, Clémence Mordacq, Guillaume Morelle, Stéphane J. Mouly, Adrián Muñoz-Barrera, Cyril Nafati, Shintaro Nagashima, Yu Nakagama, Bénédicte Neven, João Farela Neves, Yuk-Yung Ng, Hubert Nielly, Yeray Novoa Medina, Esmeralda Nuñez Cuadros, Semsi Nur Karabela, J. Gonzalo Ocejo-Vinyals, Mehdi Oualha, Amani Ouedrani, Tayfun Özçelik, Aslinur Ozkaya-Parlakay, Michele Pagani, Maria Papadaki, Philippe Parola, Tiffany Pascreau, Stéphane Paul, Estela Paz-Artal, Sigifredo Pedraza, Nancy Carolina González Pellecer, Silvia Pellegrini, Rebeca Pérez de Diego, Xosé Luis Pérez-Fernández, Aurélien Philippe, Quentin Philippot, Adrien Picod, Marc Pineton de Chambrun, Antonio Piralla, Laura Planas-Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Garyphallia Poulakou, Marie S. Pouletty, Persia Pourshahnazari, Jia Li Qiu-Chen, Paul Quentric, Thomas Rambaud, Didier Raoult, Violette Raoult, Anne-Sophie Rebillat, Claire Redin, Léa Resmini, Pilar Ricart, Jean-Christophe Richard, Raúl Rigo-Bonnin, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora-Blanch, Mathieu P. Rodero, Carlos Rodrigo, Luis Antonio Rodriguez, Carlos Rodriguez-Gallego, Agustí Rodriguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Damien Roux, Nikoletta Rovina, Flore Rozenberg, Yvon Ruch, Montse Ruiz, Maria Yolanda Ruiz del Prado, Juan Carlos Ruiz-Rodriguez, Joan Sabater-Riera, Kai Saks, Maria Salagianni, Oliver Sanchez, Adrián Sánchez-Montalvá, Silvia Sánchez-Ramón, Laire Schidlowski, Agatha Schluter, Julien Schmidt, Matthieu Schmidt, Catharina Schuetz, Cyril E. Schweitzer, Francesco Scolari, Luis Seijo, Analia Gisela Seminario, Piseth Seng, Sevtap Senoglu, Mikko Seppänen, Alex Serra Llovich, Virginie Siguret, Eleni Siouti, David M. Smadja, Nikaia Smith, Ali Sobh, Xavier Solanich, Jordi Solé-Violán, Catherine Soler, Betül Sözeri, Giulia Maria Stella, Yuriy Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Jean-Luc Taupin, Simon J. Tavernier, Loreto Vidaur Tello, Benjamin Terrier, Guillaume Thiery, Karolina Thorn, Caroline Thumerelle, Imran Tipu, Martin Tolstrup, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Vasiliki Triantafyllia, Jesús Troya, Owen T.Y. Tsang, Liina Tserel, Eugene Y.K. Tso, Alessandra Tucci, Şadiye Kübra Tüter Öz, Matilde Valeria Ursini, Takanori Utsumi, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Valentina Velez-Santamaria, Silvia Patricia Zuniga Veliz, Mateus C. Vidigal, Sébastien Viel, Cédric Villain, Marie E. Vilaire-Meunier, Judit Villar-García, Audrey Vincent, Dimitri Van der Linden, Alla Volokha, Fanny Vuotto, Els Wauters, Alan K.L. Wu, Tak-Chiu Wu, Aysun Yahşi, Osman Yesilbas, Mehmet Yildiz, Barnaby E. Young, Ufuk Yükselmiş, Marco Zecca, Valentina Zuccaro, Jens Van Praet, Bart N. Lambrecht, Eva Van Braeckel, Cédric Bosteels, Levi Hoste, Eric Hoste, Fré Bauters, Jozefien De Clercq, Catherine Heijmans, Hans Slabbynck, Leslie Naesens, Benoit Florkin, Mary-Anne Young, Amanda Willis, Paloma Lapuente-Suanzes, Ana de Andrés-Martín, Matilda Berkell, Valerio Carelli, Alessia Fiorentino, Surbhi Malhotra, Alessandro Mattiaccio, Tommaso Pippucci, Marco Seri, Evelina Tacconelli, Michiel van Agtmael, Anne Geke Algera, Brent Appelman, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Peter Bonta, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve de Bree, Sanne de Bruin, David T.P. Buis, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Mirjam Dijkstra, Dave A. Dongelmans, Romein W.G. Dujardin, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Endry H.T. Lim, Niels van Mourik, Jeaninne Nellen, Esther J. Nossent, Frederique Paulus, Edgar Peters, Dan A.I. Pina-Fuentes, Tom van der Poll, Bennedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Maurits C.F. J. de Rotte, Michiel Schinkel, Marcus J. Schultz, Femke A.P. Schrauwen, Alex Schuurmans, Jaap Schuurmans, Kim Sigaloff, Marleen A. Slim, Patrick Smeele, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa M. Tsonas, Pieter R. Tuinman, Marc van der Valk, Denise P. Veelo, Carolien Volleman, Heder de Vries, Lonneke A. Vught, Michèle van Vugt, Dorien Wouters, A.H. Zwinderman, Matthijs C. Brouwer, W. Joost Wiersinga, Alexander P.J. Vlaar, Miranda F. Tompkins, Camille Alba, Daniel N. Hupalo, John Rosenberger, Gauthaman Sukumar, Matthew D. Wilkerson, Xijun Zhang, Justin Lack, Andrew J. Oler, Kerry Dobbs, Ottavia M. Delmonte, Jeffrey J. Danielson, Andrea Biondi, Laura Rachele Bettini, Mariella D’Angiò, Ilaria Beretta, Luisa Imberti, Alessandra Sottini, Virginia Quaresima, Eugenia Quiros-Roldan, Camillo Rossi, Riccardo Castagnoli, Daniela Montagna, Amelia Licari, and Gian Luigi Marseglia

Subjects
HLA, association, asymptomatic infection, COVID-19, population stratification, Genetics, QH426-470
Abstract

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Published
2024
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3. Herpesviridae lung reactivation and infection in patients with severe COVID-19 or influenza virus pneumonia: a comparative study

Author

Charles-Edouard Luyt, Sonia Burrel, David Mokrani, Marc Pineton de Chambrun, Domitille Luyt, Juliette Chommeloux, Vincent Guiraud, Nicolas Bréchot, Matthieu Schmidt, Guillaume Hekimian, Alain Combes, and David Boutolleau

Subjects
Herpes simplex virus, Cytomegalovirus, COVID-19, Influenza, Acute respiratory distress syndrome, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Lung reactivations of Herpesviridae, herpes simplex virus (HSV) and cytomegalovirus (CMV) have been reported in COVID-19 patients. Whether or not those viral reactivations are more frequent than in other patients is not known. Methods Retrospective monocentric cohort study of 145 patients with severe COVID-19 pneumonia requiring invasive mechanical ventilation and who were tested for HSV and CMV in bronchoalveolar lavage performed during fiberoptic bronchoscopy for ventilator-associated pneumonia suspicion. Rates of HSV and CMV lung reactivations, and HSV bronchopneumonitis were assessed and compared with an historical cohort of 89 patients with severe influenza pneumonia requiring invasive mechanical ventilation. Results Among the 145 COVID-19 patients included, 50% and 42% had HSV and CMV lung reactivations, respectively, whereas among the 89 influenza patients, 63% and 28% had HSV and CMV lung reactivations, respectively. Cumulative incidence of HSV lung reactivation (taking into account extubation and death as competing events) was higher in influenza than in COVID-19 patients (p = 0.03), whereas the rate of HSV bronchopneumonitis was similar in both groups (31% and 25%, respectively). Cumulative incidence of CMV lung reactivation (taking into account extubation and death as competing events) was similar in COVID-19 and influenza patients (p = 0.07). Outcomes of patients with HSV or CMV lung reactivations were similar to that of patients without, whatever the underlying conditions, i.e., in COVID-19 patients, in influenza patients, or when all patients were grouped. Conclusions HSV and CMV lung reactivations are frequent in COVID-19 patients, but not more frequent than in patients with influenza-associated severe pneumonia, despite a higher severity of illness at intensive care unit admission of the latter and a longer duration of mechanical ventilation of the former. Although no impact on outcome of HSV and CMV lung reactivations was detected, the effect of antiviral treatment against these Herpesviridae remains to be determined in these patients.

Published
2022
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4. Phylogeographic analysis reveals an ancient East African origin of human herpes simplex virus 2 dispersal out-of-Africa

Author

Jennifer L. Havens, Sébastien Calvignac-Spencer, Kevin Merkel, Sonia Burrel, David Boutolleau, and Joel O. Wertheim

Subjects
Science
Abstract

There are competing hypotheses for human herpes simplex virus 2’s migration out-of-Africa. Here, the authors sequence 65 new herpes simplex virus 2 genomes with a focus on under-sampled sub-Saharan African countries, suggesting an Eastern African origin for global dispersal the virus between 22-29 thousand years ago.

Published
2022
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5. Cumulative incidence of SARS-CoV-2 infection and associated risk factors among frontline health care workers in Paris: the SEROCOV cohort study

Author

Pierre Hausfater, David Boutolleau, Karine Lacombe, Alexandra Beurton, Margaux Dumont, Jean-Michel Constantin, Jade Ghosn, Alain Combes, Nicolas Cury, Romain Guedj, Michel Djibré, Rudy Bompard, Sandie Mazerand, Valérie Pourcher, Linda Gimeno, Clémence Marois, Elisa Teyssou, Anne-Geneviève Marcelin, David Hajage, and Florence Tubach

Subjects
Medicine, Science
Abstract

Abstract With the COVID-19 pandemic, documenting whether health care workers (HCWs) are at increased risk of SARS-CoV-2 contamination and identifying risk factors is of major concern. In this multicenter prospective cohort study, HCWs from frontline departments were included in March and April 2020 and followed for 3 months. SARS-CoV-2 serology was performed at month 0 (M0), M1, and M3 and RT-PCR in case of symptoms. The primary outcome was laboratory-confirmed SARS-CoV-2 infection at M3. Risk factors of laboratory-confirmed SARS-CoV-2 infection at M3 were identified by multivariate logistic regression. Among 1062 HCWs (median [interquartile range] age, 33 [28–42] years; 758 [71.4%] women; 321 [30.2%] physicians), the cumulative incidence of SARS-CoV-2 infection at M3 was 14.6% (95% confidence interval [CI] [12.5; 16.9]). Risk factors were the working department specialty, with increased risk for intensive care units (odds ratio 1.80, 95% CI [0.38; 8.58]), emergency departments (3.91 [0.83; 18.43]) and infectious diseases departments (4.22 [0.92; 18.28]); current smoking was associated with reduced risk (0.36 [0.21; 0.63]). Age, sex, professional category, number of years of experience in the job or department, and public transportation use were not significantly associated with laboratory-confirmed SARS-CoV-2 infection at M3. The rate of SARS-CoV-2 infection in frontline HCWs was 14.6% at the end of the first COVID-19 wave in Paris and occurred mainly early. The study argues for an origin of professional in addition to private life contamination and therefore including HCWs in the first-line vaccination target population. It also highlights that smokers were at lower risk. Trial registration The study has been registered on ClinicalTrials.gov: NCT04304690 first registered on 11/03/2020.

Published
2022
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6. Prevalence of cervical HPV infection, sexually transmitted infections and associated antimicrobial resistance in women attending cervical cancer screening in Mali

Author

Aude Jary, Ibrahima Teguete, Younoussa Sidibé, Amadou Kodio, Oumar Dolo, Sonia Burrel, David Boutolleau, Laurianne Beauvais-Remigereau, Sophie Sayon, Mamadou Kampo, Fatoumata Tata Traoré, Mariam Sylla, Chad Achenbach, Robert Murphy, Béatrice Berçot, Cécile Bébéar, Vincent Calvez, Anne-Geneviève Marcelin, and Almoustapha I. Maiga

Subjects
HIV, HPV, Cervical lesions, STIs, Antimicrobial resistance, Mali, Infectious and parasitic diseases, RC109-216
Abstract

ABSTRACT: Objectives: To assess the prevalence of sexually transmitted infections (STIs), antimicrobial resistance and cervical lesions among women from Sikasso, Mali. Methods: Women infected with human immunodeficiency virus (HIV) (n=44) and HIV-negative women (n=96) attending cervical cancer screening were included. Screening for human papillomavirus (HPV), Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) was performed using polymerase chain reaction assays, and herpes simplex virus (HSV-1/2) serological status was assessed using enzyme-linked immunosorbent assays. Antibiotic resistance tests were performed for MG- and NG-positive cases. Results: A high prevalence of high-risk HPV (hrHPV) infection (63%) was found. This was associated with cervical lesions in 7.5% of cases. An unusual distribution was found, with HPV31, HPV56 and HPV52 being the most prevalent. The hrHPV distribution differed by HIV status, with HIV-positive cases having HPV35/31/51-52-56 and HIV-negative cases having HPV31/56/52. The seroprevalence of HSV-2 was 49%, and the prevalence of other STIs was as follows: CT, 4%; MG, 9%; NG, 1%; and TV, 7%. Five of nine MG-positive specimens and the NG strains obtained were resistant to fluoroquinolone. Conclusions: These results showed high prevalence of hrHPV and fluoroquinolone resistance in several NG and MG strains. Further studies are required to confirm these data in Mali, and to improve prevention, screening and management of cervical cancer and other STIs in women.

Published
2021
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7. Rapid decline of neutralizing antibodies against SARS-CoV-2 among infected healthcare workers

Author

Stéphane Marot, Isabelle Malet, Valentin Leducq, Karen Zafilaza, Delphine Sterlin, Delphine Planas, Adélie Gothland, Aude Jary, Karim Dorgham, Timothée Bruel, the Sorbonne Université SARS-CoV-2 Neutralizing Antibodies Study Group, Sonia Burrel, David Boutolleau, Olivier Schwartz, Guy Gorochov, Vincent Calvez, and Anne-Geneviève Marcelin

Subjects
Science
Abstract

The humoral immune response to SARS-CoV-2 infection is not yet fully understood. Here, Marot et al. monitor the longitudinal profile and neutralizing activity of IgG, IgA, and IgM among 26 healthcare workers and provide evidence for a short-lasting humoral immune protection due to a decrease of neutralizing antibody titers within 3 months.

Published
2021
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8. Co-infection of SARS-CoV-2 with other respiratory viruses and performance of lower respiratory tract samples for the diagnosis of COVID-19

Author

Sonia Burrel, Pierre Hausfater, Martin Dres, Valérie Pourcher, Charles-Edouard Luyt, Elisa Teyssou, Cathia Soulié, Vincent Calvez, Anne-Geneviève Marcelin, and David Boutolleau

Subjects
SARS-CoV-2, Other respiratory viruses, Co-infection, Lower respiratory tract, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: This study was performed during the early outbreak period of coronavirus disease 2019 (COVID-19) and the seasonal epidemics of other respiratory viral infections, in order to describe the extent of co-infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with other respiratory viruses. It also compared the diagnostic performances of upper respiratory tract (URT) and lower respiratory tract (LRT) samples for SARS-CoV-2 infection. Methods: From 25 January to 29 March 2020, all URT and LRT samples collected from patients with suspected COVID-19 received in the virology laboratory of Pitié-Salpêtrière University Hospital (Paris, France) were simultaneously tested for SARS-CoV-2 and other respiratory viruses. Results: A total of 1423 consecutive patients were tested: 677 (47.6%) males, 746 (52.4%) females, median age 50 (range, 1–103) years. Twenty-one (1.5%) patients were positive for both SARS-CoV-2 and other respiratory viruses. The detection rate of SARS-CoV-2 was significantly higher in LRT than in URT (53.6% vs. 13.4%; p

Published
2021
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9. Fatal Measles Inclusion-Body Encephalitis in Adult with Untreated AIDS, France

Author

Christophe Rodriguez, Meriadeg Ar Gouilh, Nicolas Weiss, Sébastian Stroer, Karima Mokhtari, Danielle Seilhean, Bertrand Mathon, Vanessa Demontant, Melissa N’Debi, Guillaume Gricourt, Paul-Louis Woerther, Jean-Michel Pawlotsky, Karl Stefic, Julien Marlet, Pierre-François Dequin, Antoine Guillon, Valérie Pourcher, David Boutolleau, Astrid Vabret, and Sonia Burrel

Subjects
measles inclusion-body encephalitis, MIBE, HIV/AIDS and other retroviruses, meningitis/encephalitis, viruses, brain biopsy, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

We report a fatal case of measles inclusion-body encephalitis occurring in a woman from Romania with AIDS. After an extensive but unsuccessful diagnostic evaluation, a pan-pathogen shotgun metagenomic approach revealed a measles virus infection. We identified no mutations previously associated with neurovirulence.

Published
2020
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10. Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis

Author

Marie Lecronier, Alexandra Beurton, Sonia Burrel, Luc Haudebourg, Robin Deleris, Julien Le Marec, Sara Virolle, Safaa Nemlaghi, Côme Bureau, Pierre Mora, Martin De Sarcus, Olivier Clovet, Baptiste Duceau, Paul Henri Grisot, Marie Hélène Pari, Jérémy Arzoine, Ulrich Clarac, David Boutolleau, Mathieu Raux, Julie Delemazure, Morgane Faure, Maxens Decavele, Elise Morawiec, Julien Mayaux, Alexandre Demoule, and Martin Dres

Subjects
SARS-CoV-2, Intensive care unit, Hydroxychloroquine, Lopinavir/ritonavir, Standard of care, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients. Methods The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7. Results Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7. Conclusion In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.

Published
2020
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11. Fatal Encephalitis Caused by Cristoli Virus, an Emerging Orthobunyavirus, France

Author

Christophe Rodriguez, Guillaume Gricourt, Melissa Ndebi, Vanessa Demontant, Lila Poiteau, Sonia Burrel, David Boutolleau, Paul-Louis Woerther, Vincent Calvez, Sebastian Stroer, and Jean-Michel Pawlotsky

Subjects
orthobunyavirus, shotgun metagenomics, encephalitis, viruses, Cristoli virus, France, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

We report the discovery of a new orthobunyavirus, Cristoli virus, by means of shotgun metagenomics. The virus was identified in an immunodepressed patient with fatal encephalitis. Full-length genome sequencing revealed high-level expression of a virulence factor, possibly explaining the severity of the infection. The patient’s recent history suggests circulation in France.

Published
2020
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12. Pre-COVID-19 Immunity to Common Cold Human Coronaviruses Induces a Recall-Type IgG Response to SARS-CoV-2 Antigens Without Cross-Neutralisation

Author

Makoto Miyara, Melissa Saichi, Delphine Sterlin, François Anna, Stéphane Marot, Alexis Mathian, Mo Atif, Paul Quentric, Audrey Mohr, Laetitia Claër, Christophe Parizot, Karim Dorgham, Hans Yssel, Jehane Fadlallah, Thibaut Chazal, Julien Haroche, Charles-Edouard Luyt, Julien Mayaux, Alexandra Beurton, Neila Benameur, David Boutolleau, Sonia Burrel, Sophia de Alba, Sasi Mudumba, Rick Hockett, Cary Gunn, Pierre Charneau, Vincent Calvez, Anne-Geneviève Marcelin, Alain Combes, Alexandre Demoule, Zahir Amoura, and Guy Gorochov

Subjects
COVID-19, humoral immune response, coronaviral infection, IgG, IgA, Immunologic diseases. Allergy, RC581-607
Abstract

The capacity of pre-existing immunity to human common coronaviruses (HCoV) to cross-protect against de novo COVID-19is yet unknown. In this work, we studied the sera of 175 COVID-19 patients, 76 healthy donors and 3 intravenous immunoglobulins (IVIG) batches. We found that most COVID-19 patients developed anti-SARS-CoV-2 IgG antibodies before IgM. Moreover, the capacity of their IgGs to react to beta-HCoV, was present in the early sera of most patients before the appearance of anti-SARS-CoV-2 IgG. This implied that a recall-type antibody response was generated. In comparison, the patients that mounted an anti-SARS-COV2 IgM response, prior to IgG responses had lower titres of anti-beta-HCoV IgG antibodies. This indicated that pre-existing immunity to beta-HCoV was conducive to the generation of memory type responses to SARS-COV-2. Finally, we also found that pre-COVID-19-era sera and IVIG cross-reacted with SARS-CoV-2 antigens without neutralising SARS-CoV-2 infectivity in vitro. Put together, these results indicate that whilst pre-existing immunity to HCoV is responsible for recall-type IgG responses to SARS-CoV-2, it does not lead to cross-protection against COVID-19.

Published
2022
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13. Multirecombinant Enterovirus A71 Subgenogroup C1 Isolates Associated with Neurologic Disease, France, 2016–2017

Author

Stéphanie Tomba Ngangas, Alexander Lukashev, Gwendoline Jugie, Olga Ivanova, Jean-Michel Mansuy, Catherine Mengelle, Jacques Izopet, Anne-Sophie L’honneur, Flore Rozenberg, David Leyssene, Denise Hecquet, Stéphanie Marque-Juillet, David Boutolleau, Sonia Burrel, Hélène Peigue-Lafeuille, Christine Archimbaud, Kimberley Benschop, Cécile Henquell, Audrey Mirand, and Jean-Luc Bailly

Subjects
epidemiologic monitoring, whole-genome sequencing, genetic recombination, neurologic manifestations, enterovirus infection, enterovirus, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

In 2016, an upsurge of neurologic disease associated with infection with multirecombinant enterovirus A71 subgenogroup C1 lineage viruses was reported in France. These viruses emerged in the 2000s; 1 recombinant is widespread. This virus lineage has the potential to be associated with a long-term risk for severe disease among children.

Published
2019
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14. Arguments to Support a Viral Origin of Oral Squamous Cell Carcinoma in Non-Smoker and Non-Drinker Patients

Author

Jean-Philippe Foy, Chloé Bertolus, David Boutolleau, Henri Agut, Antoine Gessain, Zdenko Herceg, and Pierre Saintigny

Subjects
herpesvirus, HSV-2, EBV, oral squamous cell carcinoma, non-smoker non-drinker, hit and run, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

In some western countries, an increasing incidence of oral squamous cell carcinoma (OSCC) has been observed in non-smoker non-drinker patients (NSND), mostly in women with HPV-negative OSCC. In the context of the unknown etiology and mechanisms of tumorigenesis of OSCC in NSND, we discuss data supporting the hypothesis of a viral origin not related to HPV. OSCC from NSND are characterized by an antiviral DNA methylation and gene expression signature. Based on the similar increasing incidence of oral tongue SCC (OTSCC) and oropharyngeal SCC (OPSCC) in young women and men respectively, we hypothesize that changes in sexual behaviors may lead to an increasing incidence of herpesvirus in the oral cavity, especially HSV-2, similarly to what has already been described in HPV-positive OPSCC. Because viral genome integration has not been detected in OSCC from NSND, a “hit and run” viral mechanism involving epigenome deregulation could therefore play a key role at early steps of oral carcinogenesis in this population of patients. In conclusion, epidemiological, clinical and molecular data supports a “hit and run” viral origin of OSCC from NSND.

Published
2020
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15. Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling

Author

Prashanth S. Ramachandran, Michael R. Wilson, Gaud Catho, Geraldine Blanchard-Rohner, Nicoline Schiess, Randall J. Cohrs, David Boutolleau, Sonia Burrel, Tetsushi Yoshikawa, Anne Wapniarski, Ethan H. Heusel, John E. Carpenter, Wallen Jackson, Bradley A. Ford, and Charles Grose

Subjects
varicella-zoster virus, Oka strain, human herpesvirus 6, human herpesvirus 7, corticosteroids, serious adverse event, Microbiology, QR1-502
Abstract

Varicella vaccine meningitis is an uncommon delayed adverse event of vaccination. Varicella vaccine meningitis has been diagnosed in 12 children, of whom 3 were immunocompromised. We now report two additional cases of vaccine meningitis in twice-immunized immunocompetent children and we perform further testing on a prior third case. We used three methods to diagnose or investigate cases of varicella vaccine meningitis, none of which have been used previously on this disease. These include metagenomic next-generation sequencing and cytokine multiplex profiling of cerebrospinal fluid and immunology exome analysis of white blood cells. In one new case, the diagnosis was confirmed by metagenomic next-generation sequencing of cerebrospinal fluid. Both varicella vaccine virus and human herpesvirus 7 DNA were detected. We performed cytokine multiplex profiling on the cerebrospinal fluid of two cases and found ten elevated biomarkers: interferon gamma, interleukins IL-1RA, IL-6, IL-8, IL-10, IL-17F, chemokines CXCL-9, CXCL-10, CCL-2, and G-CSF. In a second new case, we performed immunology exome sequencing on a panel of 356 genes, but no errors were found. After a review of all 14 cases, we concluded that (i) there is no common explanation for this adverse event, but (ii) ingestion of an oral corticosteroid burst 3–4 weeks before onset of vaccine meningitis may be a risk factor in some cases.

Published
2021
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17. Author Correction: Rapid decline of neutralizing antibodies against SARS-CoV-2 among infected healthcare workers

Author

Stéphane Marot, Isabelle Malet, Valentin Leducq, Karen Zafilaza, Delphine Sterlin, Delphine Planas, Adélie Gothland, Aude Jary, Karim Dorgham, Timothée Bruel, the Sorbonne Université SARS-CoV-2 Neutralizing Antibodies Study Group, Sonia Burrel, David Boutolleau, Olivier Schwartz, Guy Gorochov, Vincent Calvez, and Anne-Geneviève Marcelin

Subjects
Science
Published
2021
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18. Comparison of Anti-Viral Activity of Frog Skin Anti-Microbial Peptides Temporin-Sha and [K3]SHa to LL-37 and Temporin-Tb against Herpes Simplex Virus Type 1

Author

Maëva Roy, Lucie Lebeau, Céline Chessa, Alexia Damour, Ali Ladram, Bruno Oury, David Boutolleau, Charles Bodet, and Nicolas Lévêque

Subjects
temporin, SHa, [K3]SHa, Tb, LL-37, herpes simplex virus type 1, keratinocyte, cytotoxicity, anti-viral, immunomodulation, Microbiology, QR1-502
Abstract

Temporins are anti-microbial peptides synthesized in the skin of frogs of the Ranidae family. The few studies to date that have examined their anti-viral properties have shown that they have potential as anti-viral therapies. In this work, we evaluated the anti-herpes simplex virus type 1 (HSV-1) activity of the temporin-SHa (SHa) and its synthetic analog [K3]SHa. Human cathelicidin LL-37 and temporin-Tb (Tb), previously demonstrated to have anti-HSV-1 properties, were used as positive controls. We observed that SHa and [K3]SHa significantly inhibit HSV-1 replication in human primary keratinocytes when used at micromolar concentrations. This anti-viral activity was equivalent to that of Tb, but lower than that of LL-37. Transcriptomic analyses revealed that SHa did not act through the modulation of the cell innate immune response, but rather, displayed virucidal properties by reducing infectious titer of HSV-1 in suspension. In contrast, pre-incubation of the virus with LL-37 suggests that this peptide does not act directly on the viral particle at non-cytotoxic concentrations tested. The anti-HSV-1 activity of LL-37 appears to be due to the potentiation of cellular anti-viral defenses through the induction of interferon stimulated gene expression in infected primary keratinocytes. This study demonstrated that SHa and [K3]SHa, in addition to their previously reported antibacterial and antiparasitic activities, are direct-acting anti-HSV-1 peptides. Importantly, this study extends the little studied anti-viral attributes of frog temporins and offers perspectives for the development of new anti-HSV-1 therapies.

Published
2019
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19. Exhausted cytotoxic control of Epstein-Barr virus in human lupus.

Author

Martin Larsen, Delphine Sauce, Claire Deback, Laurent Arnaud, Alexis Mathian, Makoto Miyara, David Boutolleau, Christophe Parizot, Karim Dorgham, Laura Papagno, Victor Appay, Zahir Amoura, and Guy Gorochov

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Systemic Lupus Erythematosus (SLE) pathology has long been associated with an increased Epstein-Barr Virus (EBV) seropositivity, viremia and cross-reactive serum antibodies specific for both virus and self. It has therefore been postulated that EBV triggers SLE immunopathology, although the mechanism remains elusive. Here, we investigate whether frequent peaks of EBV viral load in SLE patients are a consequence of dysfunctional anti-EBV CD8+ T cell responses. Both inactive and active SLE patients (n = 76 and 42, respectively), have significantly elevated EBV viral loads (P = 0.003 and 0.002, respectively) compared to age- and sex-matched healthy controls (n = 29). Interestingly, less EBV-specific CD8+ T cells are able to secrete multiple cytokines (IFN-γ, TNF-α, IL-2 and MIP-1β) in inactive and active SLE patients compared to controls (P = 0.0003 and 0.0084, respectively). Moreover, EBV-specific CD8+ T cells are also less cytotoxic in SLE patients than in controls (CD107a expression: P = 0.0009, Granzyme B release: P = 0.0001). Importantly, cytomegalovirus (CMV)-specific responses were not found significantly altered in SLE patients. Furthermore, we demonstrate that EBV-specific CD8+ T cell impairment is a consequence of their Programmed Death 1 (PD-1) receptor up-regulation, as blocking this pathway reverses the dysfunctional phenotype. Finally, prospective monitoring of lupus patients revealed that disease flares precede EBV reactivation. In conclusion, EBV-specific CD8+ T cell responses in SLE patients are functionally impaired, but EBV reactivation appears to be an aggravating consequence rather than a cause of SLE immunopathology. We therefore propose that autoimmune B cell activation during flares drives frequent EBV reactivation, which contributes in a vicious circle to the perpetuation of immune activation in SLE patients.

Published
2011
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22. Novel mutations in antiviral multiresistant HSV‐2 genital lesion: A case report

Author

Lucas Khellaf, Fabrice Bouscarat, Sonia Burrel, Nadhira Fidouh, Lorry Hachon, Margot Bucau, Sylvie Lariven, David Boutolleau, Véronique Joly, Jade Ghosn, Diane Le Pluart, and Michaël Thy

Subjects
Imiquimod, Herpesvirus 2, Human, Acyclovir, Herpes Simplex, DNA-Directed DNA Polymerase, Antiviral Agents, Thymidine Kinase, Infectious Diseases, Valacyclovir, Virology, Drug Resistance, Viral, Mutation, Humans, Genitalia, Obesity, Cidofovir, Foscarnet
Abstract

HSV-2 antiviral resistance mainly occurs in immunocompromised patients and especially in HIV-positive individuals receiving long-term antiviral treatment. Those situations can be challenging as few alternatives are available for HSV infection management. To describe clinical and virological significance of two novel potential HSV-2 resistance mutations after treating an obese patient with a pseudotumoral genital HSV-related lesion. Consecutive different antiviral treatments were used: valacyclovir (VACV) then foscarnet (FOS) then topical cidofovir (CDV) and finally imiquimod. Under VACV, genotypic resistance testing revealed a novel mutation within viral thymidine kinase (TK, gene UL23) not previously reported but probably accounting for antiviral resistance: W89G, similar to W88R mutation reported in HSV-1 TK, known to be associated with ACV resistance for HSV-1. Under FOS, while initial mutations were still present, a second genotypic resistance testing performed on persisting lesions showed a novel mutation within viral DNA polymerase (DNA pol, gene UL30): C625R. All three antivirals used in this case are small molecules and pharmacokinetics of VACV, FOS, and CDV have not been evaluated in animals and there are very few studies in human. As small molecules are poorly bound to proteins and distribution volume is increased in obese patients, there is risk of underdosage. This mechanism is suspected to be involved in emergence of resistance mutation and further data is needed to adapt, closely to patient profile, antiviral dosage. This report describes a chronic HSV-2 genital lesion, with resistance to current antivirals and novel mutations within viral TK and DNA pol which may confer antiviral resistance.

Published
2022
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23. Acyclovir-Resistant Herpes Simplex Virus 1 Keratitis: A Concerning and Emerging Clinical Challenge

Author

Antoine Rousseau, Sonia Burrel Pharm, Julie Gueudry, Claire Deback, Oscar Haigh, Cédric Schweitzer, David Boutolleau, and Marc Labetoulle

Subjects
Male, Acyclovir, Herpes Simplex, DNA-Directed DNA Polymerase, Herpesvirus 1, Human, Antiviral Agents, Thymidine Kinase, Ophthalmology, Recurrence, Drug Resistance, Viral, Keratitis, Herpetic, Humans, Female, Retrospective Studies
Abstract

To describe the clinical and virological profiles of patients with herpes simplex keratitis (HSK) caused by acyclovir-resistant (ACVMulticenter retrospective case series.HSV-1 resistance to ACV was confirmed using sequencing of genes encoding HSV-1 thymidine kinase (TK) and DNA polymerase (DNA pol). Data were collected on the number of HSK episodes before and after the diagnosis of resistance, ocular findings including the type of HSK, immune status of patients, antiviral treatments, and HSV-1 genotypic resistance profiles.This study evaluated 18 HSK patients (13 male and 5 female, aged 66.8 ± 4.7 years) with ACVHSV-1 resistance to ACV must be suspected in HSK patients with recurrences despite AVP and/or in cases that respond poorly to a suppressive antiviral regimen. Immunocompromised patients and/or those with longstanding disease may be particularly at risk for developing resistance.

Published
2022
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24. 2199. Herpesviridae lung reactivation and infection in patients with severe Covid-19 or influenza virus pneumonia: a comparative study

Author

Charles-Edouard Luyt, Sonia Burrel, Vincent Guiraud, Alain Combes, and David Boutolleau

Subjects
Infectious Diseases, Oncology
Abstract

Background Lung reactivations of Herpesviridae, herpes simplex virus (HSV) and cytomegalovirus (CMV) have been reported in Covid-19 patients. Whether or not those viral reactivations are more frequent than in other patients is not known. Methods Retrospective monocentric cohort study of 145 patients with severe Covid-19 pneumonia requiring invasive mechanical ventilation and who were tested for HSV and CMV in bronchoalveolar lavage performed during fiberoptic bronchoscopy for ventilator-associated pneumonia suspicion. Rates of HSV and CMV lung reactivations, and HSV bronchopneumonitis were assessed and compared with an historical cohort of 89 patients with severe influenza pneumonia requiring invasive mechanical ventilation. Results Among the 145 Covid-19 patients included, 50% and 42 % had HSV and CMV lung reactivations, respectively; whereas among the 89 influenza patients, 63% and 28% had CMV lung reactivations, respectively. Cumulative incidence of HSV lung reactivation (taking into account extubation and death as competing events) was higher in influenza than in Covid-19 patients (p = 0.03, see figure 1), whereas the rate of HSV bronchopneumonitis was similar in both groups (31% and 25%, respectively). Cumulative incidence of CMV lung reactivation (taking into account extubation and death as competing events) was similar in Covid-19 and influenza patients (p=0.07). Outcomes of patients with HSV or CMV lung reactivations were similar to that of patients without, whatever the underlying conditions, i.e., in Covid-19 patients, in influenza patients, or when all patients were grouped. Estimated cumulative incidence of herpes simplex virus (HSV) lung reactivation, extubation or death in Covid-19 and influenza patients, taking into account only the first event that occurred. p values for differences between Covid-19 and influenza patients were 0.03 for HSV reactivation, 0.53 for death and 0.87 for extubation. Conclusion HSV and CMV lung reactivations are frequent in Covid-19 patients, but not more frequent than in patients with influenza-associated severe pneumonia, despite a higher severity of illness at intensive care unit (ICU) admission of the latter and a longer duration of mechanical ventilation of the former. Although no impact on outcome of HSV and CMV lung reactivations was detected, the effect of antiviral treatment against these Herpesviridae remains to be determined in these patients. Disclosures CHARLES-EDOUARD LUYT, MD PhD, AdvanzPharma: Honoraria|Aerogen: Honoraria|Merck: Honoraria.

Published
2022
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25. [BK virus infections in stem cell transplant recipients]

Author

Jérémie, Corneille and David, Boutolleau

Abstract

BK virus (BKV) belongs to the Polyomaviridae family. It is widespread in adults. Primary infection typically occurs during childhood, without specific symptoms, followed by a state of non-replicative infection in various tissues, with the urogenital tract as the principal site. Immunosuppression promotes reactivation and replication of BKV. After kidney allograft, active infections can cause interstitial nephritis up to graft loss. In hematopoietic stem cell transplant (HSCT) recipients,BKVinfections are associated with hemorrhagic cystitis (HC). The pathogenesis of HC after HSCT represents an interplay between urotoxicity of the conditioning regimen, BKV infection and alloimmune reactions from donor lymphocytes targeting the recipient uroepithelial cells. The diagnosis is based on the quantification of BKV DNA by PCR in urine and blood. The current standard of care for HC is symptomatic, since to date no antiviral drug with proven efficacy against BKV replication has been licensed.

Published
2022

27. L’herpès génital

Author

Sonia Burrel and David Boutolleau

Subjects
Gynecology, 03 medical and health sciences, Medical Laboratory Technology, medicine.medical_specialty, 0302 clinical medicine, business.industry, viruses, 030220 oncology & carcinogenesis, Biochemistry (medical), medicine, 030204 cardiovascular system & hematology, business, Analytical Chemistry
Abstract

Resume L’herpes genital constitue la premiere cause d’ulceres genitaux dans le monde. Il est provoque par des virus largement repandus dans la population generale : les virus herpes simplex 1 et 2 (HSV-1 et HSV-2). Cette infection peut affecter la qualite de vie des individus infectes. De plus, l’herpes genital constitue un cofacteur favorisant la transmission du virus de l’immuno-deficience humaine (HIV) par voie sexuelle. La transmission du HSV, au moment de l’accouchement, peut etre responsable de l’herpes neonatal. Le diagnostic de l’herpes genital repose sur deux types de tests biologiques : la detection du genome viral par biologie moleculaire (PCR) dans les ecouvillonnages des voies genitales et la detection d’anticorps specifiques (serologie) pour connaitre le statut immunitaire des patients. La prise en charge therapeutique de l’herpes genital repose essentiellement sur des traitements antiviraux par le valaciclovir, medicament tres actif et tres peu toxique. A ce jour, il n’existe aucun vaccin specifique et l’utilisation du preservatif reste la mesure la plus efficace pour prevenir cette infection virale.

Published
2021
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29. Long-term evolution of humoral immune response after SARS-CoV-2 infection

Author

Elisa, Teyssou, Karen, Zafilaza, Sophie, Sayon, Stéphane, Marot, Margot, Dropy, Cathia, Soulie, Basma, Abdi, Florence, Tubach, Pierre, Hausfater, Anne-Geneviève, Marcelin, David, Boutolleau, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), BIOSFAST [CHU Pitié-Salpêtrière] (GRC 14), 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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), and Centre National de Référence Herpèsvirus [CHU Pitié Salpêtrière]

Subjects
Microbiology (medical), COVID-19 Vaccines, SARS-CoV-2, COVID-19, General Medicine, Antibodies, Viral, Antibodies, Neutralizing, Immunity, Humoral, Immunoglobulin A, Infectious Diseases, Immunoglobulin G, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS
Abstract

We aimed to characterize the evolution of humoral immune response up to 1 year after SARS-CoV-2 infection in healthcare workers (HCWs) during the first wave of COVID-19 in Paris.Serum samples from 92 HCWs were tested at month 0 (M0), M6, and M12 after SARS-CoV-2 infection for IgG targeting the nucleocapsid (N), IgG targeting the receptor-binding domain (RBD) of spike (S) protein, IgA targeting S, and anti-RBD neutralizing antibodies. After M6, 46 HCWs received a single dose of COVID-19 vaccine.We observed a significant decrease in all SARS-CoV-2 immunologic markers at M6 post-infection: median decreases were 0.26 log binding antibody units/mL (M0: 1.9 (interquartile range (IQR) 1.47-2.27); M6: 1.64 (IQR 1.22-1.92)) for anti-RBD IgG; 4.10 (index) (M0: 4.94 (IQR 2.72-6.82); M6: 0.84 (IQR 0.25-1.55)) for anti-N IgG; 0.64 (index) (M0: 2.50 (IQR 1.18-4.62); M6: 1.86 (IQR 0.85-3.54)) for anti-S IgA; and 24.4% (M0: 66.4 (IQR 39.7-82.5); M6: 42.0 (IQR 16.8-68.8)) inhibition activity for the RBD neutralizing antibodies. Between M6 and M12, anti-RBD IgG level, anti-S IgA index, and anti-RBD neutralizing activity significantly increased among COVID-19 vaccinated HCWs, whereas they remained stable among unvaccinated HCWs. Anti-N IgG index significantly decreased between M6 and M12 among both vaccinated (median: 0.73 (IQR 0.23-1.11) at M6 and 0.52 (IQR 0.20-0.73) at M12) and unvaccinated HCWs (median: 0.79 (IQR 0.21-4.67) at M6 and 0.34 (IQR 0.24-2.78) at M12).A steady decline in the anti-N IgG response was observed during the first year after SARS-CoV-2 infection among HCWs, whereas the anti-RBD IgG and the anti-S IgA responses remained stable and could be enhanced by COVID-19 vaccination.

Published
2022
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30. SARS-CoV-2 IGM and IGG rapid serologic test for the diagnosis of COVID-19 in the emergency department

Author

Héloïse Petit, Marta Cancella de Abreu, Pierre Hausfater, Donia Bouzid, David Boutolleau, Nadhira Houdou-Fidouh, Christophe Choquet, Sonia Burrel, Valentine Marie Ferré, Florence Damond, Diane Descamps, Anne-Geneviève Marcelin, and Stéphane Marot

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, 030106 microbiology, Immunoglobulin G, Serology, Betacoronavirus, 03 medical and health sciences, COVID-19 Testing, 0302 clinical medicine, Internal medicine, medicine, Humans, Serologic Tests, 030212 general & internal medicine, skin and connective tissue diseases, Pandemics, biology, Clinical Laboratory Techniques, SARS-CoV-2, business.industry, fungi, COVID-19, Emergency department, medicine.disease, Triage, body regions, Pneumonia, Infectious Diseases, Immunoglobulin M, biology.protein, Coronavirus Infections, Emergency Service, Hospital, business
Abstract

• RT-PCR for SARS-CoV-2′s diagnostic has many false negatives and long turnaround times. • In our study 20% of RT-PCR negative patients had a rapid Sars-CoV2 IgG/IgM positive. • Rapid SARS-CoV2 IgG/IgM may be used as a complementary assay to the RT-PCR. • They can be useful in emergency patient's triage and admission. • They help avoiding to admit a patient infected with SARS-CoV-2 in a COVID-free area.

Published
2020
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31. Fatal Encephalitis Caused by Cristoli Virus, an Emerging Orthobunyavirus, France

Author

Vanessa Démontant, Jean-Michel Pawlotsky, Sonia Burrel, Guillaume Gricourt, Christophe Rodriguez, David Boutolleau, Lila Poiteau, Paul-Louis Woerther, Melissa N'Debi, Vincent Calvez, and Sébastian Ströer

Subjects
Microbiology (medical), Epidemiology, encephalitis, 030231 tropical medicine, lcsh:Medicine, Biology, Virulence factor, DNA sequencing, Orthobunyavirus, Virus, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, orthobunyavirus, 0302 clinical medicine, Meningitis/encephalitis, medicine, Humans, viruses, lcsh:RC109-216, 030212 general & internal medicine, lcsh:R, Dispatch, medicine.disease, biology.organism_classification, Cristoli virus, Virology, Infectious Diseases, Fatal Encephalitis Caused by Cristoli Virus, an Emerging Orthobunyavirus, France, Metagenomics, meningitis/encephalitis, France, Shotgun metagenomics, Encephalitis, shotgun metagenomics
Abstract

We report the discovery of a new orthobunyavirus, Cristoli virus, by means of shotgun metagenomics. The virus was identified in an immunodepressed patient with fatal encephalitis. Full-length genome sequencing revealed high-level expression of a virulence factor, possibly explaining the severity of the infection. The patient’s recent history suggests circulation in France.

Published
2020

34. Phylogeographic analysis reveals an ancient East African origin of the human herpes simplexvirus 2 dispersal out-of-Africa

Author

Jennifer L. Havens, Sébastien Calvignac-Spencer, Kevin Merkel, Sonia Burrel, David Boutolleau, and Joel O. Wertheim

Abstract

Human herpes simplex virus 2 (HSV-2) is a globally ubiquitous, slow evolving DNA virus. HSV-2 genomic diversity can be divided into two main groups: an African lineage and worldwide lineage. Competing hypotheses have been put forth to explain the history of HSV-2. HSV-2 may have originated in Africa and then followed the first wave of human migration out of Africa between 50-100 kya. Alternatively, HSV-2 may have migrated out of Africa via the trans-Atlantic slave trade within the last 150-500 years. The lack of HSV-2 genomes from West and Central Africa, combined with a lack of molecular clock signal in HSV-2 has precluded robust testing of these competing hypotheses. Here, we expand the geographic sampling of HSV-2 genomes in order to resolve the geography and timing of divergence events within HSV-2. We analyze 65 newly sequenced HSV-2 genomes collected from primarily West and Central Africa along with 330 previously published genomes sampled over a 47-year period. Evolutionary simulations confirm that the molecular clock in HSV-2 is too slow to be detected using available data. However, phylogeographic analysis indicates that all biologically plausible evolutionary rates would place the ancestor of the worldwide lineage in East Africa, arguing against the trans-Atlantic slave trade as the source of worldwide diversity. The best supported evolutionary rates between 4.2×10−8 and 5.6×10−8 substitutions/site/year suggest a most recent common ancestor for HSV-2 around 90-120 kya and initial dispersal around 21.9-29.3 kya. These dates suggest HSV-2 left Africa during subsequent waves of human migration out of East Africa.

Published
2022
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35. C-BLUE One : A family of CMOS high speed cameras for wavefront sensing

Author

Jean-Luc Gach, David Boutolleau, Thomas Carmignani, Fabien Clop, Isaure De Kernier, Philippe Feautrier, Matthieu Florentin, Stéphane Lemarchand, Jordan Pettigiani, Theo Romano, Eric Stadler, Julien Tugnoli, and Yann Wanwanscappel

Subjects
Physics - Instrumentation and Detectors, FOS: Physical sciences, Instrumentation and Detectors (physics.ins-det), Astrophysics - Instrumentation and Methods for Astrophysics, Instrumentation and Methods for Astrophysics (astro-ph.IM)
Abstract

We present the evolutions of the C-BLUE One family of cameras (formerly introduced as C-MORE), a laser guide star oriented wavefront sensor camera family. Within the Opticon WP2 european funded project, which has been set to develop LGS cameras, fast path solutions based on existing sensors had to be explored to provide working-proven cameras to ELT projects ready for the first light schedule. Result of this study, C-BLUE One is a CMOS based camera with 1600x1100 pixels (9um pitch) and 481 FPS refresh rate. It has been developed to answer most of the needs of future laser based adaptive optics systems (LGS) to be deployed on 20-40m-class telescopes as well as on smaller ones. We present the main features of the camera and measured performance in terms of noise, dark current, quantum efficiency and image quality which are the key parameters for the application. The camera has been declined also in fast smaller format (800x600x1500FPS) and large format (3200X2200x250FPS) to cover most of the AO applications., Comment: arXiv admin note: substantial text overlap with arXiv:1910.00374

Published
2022
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36. Sub-electron noise infrared camera development using Leonardo large format 2Kx2K SWIR LmAPD array

Author

Philippe Feautrier, Jean-Luc Gach, Dan Owton, Matthew Hicks, Ian Baker, Keith Barnes, and David Boutolleau

Subjects
Physics - Instrumentation and Detectors, FOS: Physical sciences, Instrumentation and Detectors (physics.ins-det), Astrophysics - Instrumentation and Methods for Astrophysics, Instrumentation and Methods for Astrophysics (astro-ph.IM)
Abstract

There have been no significant breakthroughs in infrared imagery since the hybridization of III-V or II-VI narrow-bandgap semiconductors on complementary metal-oxide semiconductor (CMOS) read-out integrated circuits (ROICs). The development of third-generation, linear-mode avalanche photodiode arrays (LmAPDs) using mercury cadmium telluride (MCT) has resulted in a significant sensitivity improvement for short-wave infrared (SWIR) imaging. The first dedicated LmAPD device, called SAPHIRA (320x256/24 microns), was designed by Leonardo UK Ltd specifically for SWIR astronomical applications. In the past decade there has been a significant development effort to make larger LmAPD arrays for low-background astronomy. Larger LmAPD formats for ultra-low noise/flux SWIR imaging, currently under development at Leonardo include a 512 x 512 LmAPD array funded by ESO, MPE and NRC Herzberg, a 1k x 1k array funded by NASA and a 2K x 2K device funded by ESA for general scientific imaging applications. The 2048x2048 pixel ROIC has a pitch of 15 microns, 4/8/16 outputs and a maximum frame rate of 10 Hz. The ROIC characterization is scheduled in the third quarter of 2022, while the first arrays will be fabricated by end-2022. The hybridized arrays will be characterized during end-2022. At this time, First Light Imaging will start the development of an autonomous camera integrating this 2Kx2K LmAPD array, based on the unique experience from the C-RED One camera, the only commercial camera integrating the SAPHIRA SWIR LmAPD array.The detector will be embedded in a compact high vacuum cryostat cooled with low vibration pulse at 50-80K which does not require external pumping. Sub-electron readout noise is expected to be achieved with high multiplication gain. Custom cold filters and beam aperture cold baffling will be integrated in the camera., Comment: 9 pages

Published
2022
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37. Efficacy of Acyclovir to Suppress Herpes Simplex Virus Oropharyngeal Reactivation in Patients Who Are Mechanically Ventilated: An Ancillary Study of the Preemptive Treatment for Herpesviridae (PTH) Trial

Author

Charles-Edouard Luyt, David Hajage, Sonia Burrel, Sami Hraiech, Mamadou Hassimiou Diallo, Laurent Papazian, and David Boutolleau

Subjects
Adult, Male, viruses, Acyclovir, Oropharynx, 01 natural sciences, Antiviral Agents, 03 medical and health sciences, 0302 clinical medicine, Critical Care Medicine, Research Letter, Humans, 030212 general & internal medicine, 0101 mathematics, Aged, Retrospective Studies, Research, 010102 general mathematics, virus diseases, Herpes Simplex, General Medicine, Middle Aged, Respiration, Artificial, Virus Shedding, Online Only, Latent Infection, Female, France
Abstract

This analysis of a randomized clinical trial examines the efficacy of acyclovir for preventing oropharyngeal HSV reactivation among patients who were mechanically ventilated.

Published
2021

38. Immune restoration therapy for multidrug-resistant CMV disease in an allogenic stem cell transplant recipient

Author

Olivier Paccoud, Sophie Alain, Joel Gozlan, Sabrine Jarboui, David Boutolleau, Sébastien Hantz, Giorgia Battipaglia, Annalisa Paviglianiti, Rémy Duléry, Florent Malard, Clémence Médiavilla, Simona Sestili, Béatrice Gaugler, Jean-Luc Meynard, Jérôme Pacanowski, Mohamad Mohty, Eolia Brissot, Paccoud, O., Alain, S., Gozlan, J., Jarboui, S., Boutolleau, D., Hantz, S., Battipaglia, G., Pavaglianiti, A., Dulery, R., Malard, F., Mediavilla, C., Sestili, S., Gaugler, B., Meynard, J. -L., Pacanowski, J., Mohty, M., and Brissot, E.

Subjects
gamma delta T cell, Immune Reconstitution, Cytomegalovirus Infections, Artesunate, Cytomegaloviru, Interleukin-2, Cytomegalovirus, Humans, Hematopoietic stem cell transplantation, General Medicine, General Biochemistry, Genetics and Molecular Biology, Transplant Recipients, Stem Cell Transplantation
Published
2021

39. Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling

Author

Wallen Jackson, Sonia Burrel, Geraldine Blanchard-Rohner, Bradley Ford, Ethan H Heusel, John E. Carpenter, Prashanth S. Ramachandran, Michael R. Wilson, Anne E. Wapniarski, Gaud Catho, Charles Grose, Tetsushi Yoshikawa, David Boutolleau, Nicoline Schiess, Randall J. Cohrs, University of California [San Francisco] (UCSF), University of California, Geneva University Hospitals and Geneva University, Johns Hopkins University School of Medicine [Baltimore], University of Colorado Anschutz [Aurora], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Fujita Health University, University of Iowa [Iowa City], University of California [San Francisco] (UC San Francisco), University of California (UC), and Gestionnaire, HAL Sorbonne Université 5

Subjects
Male, Varicella vaccine, Human herpesvirus 7, Human herpesvirus 6, Herpes zoster, Serious adverse event, serious adverse event, medicine.disease_cause, corticosteroids, 0302 clinical medicine, innate immunity ► Show Figures, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Child, innate immunity, Exome, Exome sequencing, Innate immunity, 0303 health sciences, ddc:618, biology, High-Throughput Nucleotide Sequencing, Meningitis, Viral, QR1-502, 3. Good health, Vaccination, Infectious Diseases, IL-10, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cytokines, human herpesvirus 7, Female, human herpesvirus 6, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Immunocompetence, Meningitis, Adolescent, herpes zoster, Microbiology, Article, Virus, Chickenpox Vaccine, 03 medical and health sciences, Virology, Exome Sequencing, Humans, Corticosteroids, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030304 developmental biology, varicella-zoster virus, IL-6, business.industry, Varicella zoster virus, biology.organism_classification, medicine.disease, Immunology, Oka strain, Varicella-zoster virus, Metagenomics, business, Biomarkers, 030217 neurology & neurosurgery
Abstract

International audience; Varicella vaccine meningitis is an uncommon delayed adverse event of vaccination. Varicella vaccine meningitis has been diagnosed in 12 children, of whom 3 were immunocompromised. We now report two additional cases of vaccine meningitis in twice-immunized immunocompetent children and we perform further testing on a prior third case. We used three methods to diagnose or investigate cases of varicella vaccine meningitis, none of which have been used previously on this disease. These include metagenomic next-generation sequencing and cytokine multiplex profiling of cerebrospinal fluid and immunology exome analysis of white blood cells. In one new case, the diagnosis was confirmed by metagenomic next-generation sequencing of cerebrospinal fluid. Both varicella vaccine virus and human herpesvirus 7 DNA were detected. We performed cytokine multiplex profiling on the cerebrospinal fluid of two cases and found ten elevated biomarkers: interferon gamma, interleukins IL-1RA, IL-6, IL-8, IL-10, IL-17F, chemokines CXCL-9, CXCL-10, CCL-2, and G-CSF. In a second new case, we performed immunology exome sequencing on a panel of 356 genes, but no errors were found. After a review of all 14 cases, we concluded that (i) there is no common explanation for this adverse event, but (ii) ingestion of an oral corticosteroid burst 3–4 weeks before onset of vaccine meningitis may be a risk factor in some cases.

Published
2021
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41. High conservation of varicella-zoster virus helicase-primase complex, the target of the new antiviral drug amenamevir

Author

Sonia Burrel, David Boutolleau, Olivier Bomme, Marie-Liesse Pacreau, Service de Virologie [CHU Pitié-Salpêtrière], 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 Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Gestionnaire, HAL Sorbonne Université 5, Service de virologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Herpesvirus 3, Human, medicine.drug_class, viruses, Natural polymorphism, DNA Primase, medicine.disease_cause, Antiviral Agents, Herpes Zoster, Virus, Immunocompromised Host, 03 medical and health sciences, Helicase–primase complex, Japan, Polymorphism (computer science), Virology, Drug Resistance, Viral, Genotype, medicine, Antiviral resistance testing, Humans, Amenamevir, Polymerase, 030304 developmental biology, Pharmacology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Oxadiazoles, 0303 health sciences, biology, integumentary system, 030306 microbiology, Varicella zoster virus, virus diseases, Middle Aged, biochemical phenomena, metabolism, and nutrition, eye diseases, 3. Good health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, Varicella-zoster virus, Female, Helicase-primase complex, Antiviral drug
Abstract

International audience; Varicella-zoster virus (VZV) resistance to current antiviral drugs, that all target the viral DNA polymerase, represents a growing concern, notably among immunocompromised patients. Amenamevir, a novel antiviral that inhibits the VZV helicase-primase (HP) complex, is approved in Japan for the treatment of herpes zoster. In this study, we describe the low natural polymorphism of VZV HP complex (interstrain identity >99.7% both at nucleotide and amino acid levels) among 44 VZV clinical isolates. This work enabled to settle the maps of natural polymorphisms of VZV HP complex and to provide the genotypic tools for the monitoring of the emergence of VZV resistance to amenamevir in patients.

Published
2021
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42. Cumulative incidence of SARS-CoV-2 infection and associated risk factors among frontline health care workers in Paris: the SEROCOV cohort study

Author

Pierre Hausfater, David Boutolleau, Karine Lacombe, Alexandra Beurton, Margaux Dumont, Jean-Michel Constantin, Jade Ghosn, Alain Combes, Nicolas Cury, Romain Guedj, Michel Djibré, Rudy Bompard, Sandie Mazerand, Valérie Pourcher, Linda Gimeno, Clémence Marois, Elisa Teyssou, Anne-Geneviève Marcelin, David Hajage, and Florence Tubach

Subjects
Adult, Male, Paris, Multidisciplinary, SARS-CoV-2, Health Personnel, Incidence, COVID-19, Cohort Studies, Risk Factors, Humans, Female, Prospective Studies, Melanthiaceae, Pandemics
Abstract

With the COVID-19 pandemic, documenting whether health care workers (HCWs) are at increased risk of SARS-CoV-2 contamination and identifying risk factors is of major concern. In this multicenter prospective cohort study, HCWs from frontline departments were included in March and April 2020 and followed for 3 months. SARS-CoV-2 serology was performed at month 0 (M0), M1, and M3 and RT-PCR in case of symptoms. The primary outcome was laboratory-confirmed SARS-CoV-2 infection at M3. Risk factors of laboratory-confirmed SARS-CoV-2 infection at M3 were identified by multivariate logistic regression. Among 1062 HCWs (median [interquartile range] age, 33 [28–42] years; 758 [71.4%] women; 321 [30.2%] physicians), the cumulative incidence of SARS-CoV-2 infection at M3 was 14.6% (95% confidence interval [CI] [12.5; 16.9]). Risk factors were the working department specialty, with increased risk for intensive care units (odds ratio 1.80, 95% CI [0.38; 8.58]), emergency departments (3.91 [0.83; 18.43]) and infectious diseases departments (4.22 [0.92; 18.28]); current smoking was associated with reduced risk (0.36 [0.21; 0.63]). Age, sex, professional category, number of years of experience in the job or department, and public transportation use were not significantly associated with laboratory-confirmed SARS-CoV-2 infection at M3. The rate of SARS-CoV-2 infection in frontline HCWs was 14.6% at the end of the first COVID-19 wave in Paris and occurred mainly early. The study argues for an origin of professional in addition to private life contamination and therefore including HCWs in the first-line vaccination target population. It also highlights that smokers were at lower risk.Trial registration The study has been registered on ClinicalTrials.gov: NCT04304690 first registered on 11/03/2020.

Published
2021

43. Neutralization heterogeneity of United Kingdom and South-African SARS-CoV-2 variants in BNT162b2-vaccinated or convalescent COVID-19 healthcare workers

Author

Jean-Michel Pawlotsky, Basma Abdi, David Boutolleau, Vincent Calvez, Sonia Burrel, Isabelle Malet, Cathia Soulié, Slim Fourati, Christophe Rodriguez, Stéphane Marot, Marc Wirden, Aude Jary, Valentin Leducq, Elisa Teyssou, Anne-Geneviève Marcelin, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], 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 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), Service de bactériologie, virologie, hygiène [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Service de virologie [CHU Pitié-Salpêtrière]

Subjects
Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), education, Neutralizing antibodies, Neutralization, 03 medical and health sciences, 0302 clinical medicine, Medicine, Potency, 030212 general & internal medicine, 030304 developmental biology, 0303 health sciences, SARS-CoV-2 variants, Viral neutralization test, biology, business.industry, COVID-19, Virology, 3. Good health, Vaccination, Titer, biology.protein, Antibody, business, Vaccine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

There are concerns about neutralizing antibodies (NAb) potency against the newly emerged VOC202012/01 (UK) and 501Y.V2 (SA) SARS-CoV-2 variants in mRNA-vaccinated subjects and in recovered COVID-19 patients. We used a viral neutralization test with a strict 100% neutralizing criterion on UK and SA clinical isolates in comparison with a globally distributed D614G SARS-CoV-2 strain. In two doses BNT162b2-vaccinated healthcare workers (HCW), despite heterogeneity in neutralizing capacity against the three SARS-CoV-2 strains, most of the sera harbored at least a NAb titer ≥ 1:10 suggesting a certain humoral protection activity either on UK or SA variants. However, six months after mild forms of COVID-19, an important proportion of HCW displayed no neutralizing activity against SA strain. This result supports strong recommendations for vaccination of previously infected subjects.

Published
2021
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44. Herpes simplex virus, varicella-zoster virus and cytomegalovirus keratitis: Facts for the clinician

Author

David Boutolleau, Oscar Haigh, Marc Labetoulle, Antoine Rousseau, and Sonia Burrel

Subjects
medicine.medical_specialty, Visual acuity, business.industry, Neurotrophic keratitis, Congenital cytomegalovirus infection, medicine.disease, medicine.disease_cause, Dermatology, eye diseases, Virus, Keratitis, Ophthalmology, medicine.anatomical_structure, Herpes simplex virus, Viral replication, medicine, medicine.symptom, business, Corneal epithelium
Abstract

Keratitis due to Herpes simplex virus (HSK), Varicella-Zoster virus (VZK) and Cytomegalovirus remains a frequent source of concern for many ophthalmologists. They are a frequent cause of emergency consultations at eye care centers and carry the risk of permanent loss of visual acuity or visual quality and/or chronic neurotrophic keratitis, resulting in a significant decrease in the quality of life. HSK and VZK can affect the corneal epithelium, stroma, or endothelium or a combination of layers. In contrast, most cases of CMV keratitis present as isolated endothelitis (CMVE), a clinical entity that has been described within the last 2 decades. These three types of viral keratitis are characterized by a high frequency of recurrences and each new episode increases the risk of sequelae. Hence, ophthalmologists must adapt the treatment to the clinical presentation of each recurrent episode in order to mitigate the immediate consequences of viral replication and the immune response on corneal transparency. In patients with frequent recurrences, preventive long-term antiviral treatment is strongly recommended. However, in some rare cases, continuous exposure to antivirals may promote the emergence of resistant viral strains, which can be difficult to manage. In the future, the introduction of new antiviral drugs, with differing modes of action compared to current medical therapy, could be an alternative until a truly effective preventive solution, such as a vaccine, is available.

Published
2021

45. Cumulative incidence of SARS-CoV-2 infection and associated risk factors among frontline health care workers in Paris, France: the SEROCOV prospective cohort study

Author

Margaux Dumont, Valérie Pourcher, Jean-Michel Constantin, Elisa Teyssou, David Hajage, Karine Lacombe, Romain Guedj, linda gimeno, rudy pierre bompard, Anne-Geneviève Marcelin, Florence Tubach, Michel Djibré, Sandie Mazerand, David Boutolleau, Jade Ghosn, Alexandra Beurton, Clémence Marois, Pierre Hausfater, Alain Combes, and nicolas cury

Subjects
education.field_of_study, medicine.medical_specialty, business.industry, Population, Odds ratio, Lower risk, Confidence interval, Informed consent, Interquartile range, Family medicine, Intensive care, Health care, Emergency medicine, medicine, Cumulative incidence, education, business, Prospective cohort study
Abstract

Background: With the COVID-19 pandemic, documenting whether health care workers (HCWs) are at increased risk of SARS-CoV-2 contamination and identifying risk factors is of major concern. Methods: In this multicenter prospective cohort study, HCWs from COVID-19 frontline departments were included in March and April 2020 and followed for 3 months. SARS-CoV-2 serology was performed at month 0 (M0), M1, and M3 and RT-PCR in case of symptoms. The primary outcome was laboratory-confirmed SARS-CoV-2 infection (positive serology and/or positive RT-PCR result) at M3. Secondary outcomes were positive serology for SARS-CoV-2 at M0, M1 and M3. Risk factors of laboratory-confirmed SARS-CoV-2 infection at M3 were identified by multivariate logistic regression. Findings: Among 1,062 HCWs (median [interquartile range] age, 33 [28-42] years; 758 [71.4%] women; 321 [30.2%] physicians), the cumulative incidence of SARS-CoV-2 infection at M3 was 14.6% (95% confidence interval [CI] [12.5; 16.9]). Seroprevalence at M0, M1, and M3 was 5.9% [4.7; 7.5], 12.9% [10.9; 15.1] and 13.0% [11.1; 15.2], respectively. Risk factors were the working department specialty, with increased risk for intensive care units (odds ratio 1.80, 95%CI [0.38; 8.58]), emergency departments (3.91 [0.83; 18.43]) and infectious diseases departments (4.22 [0.92; 18.28]); active smoking was associated with reduced risk (0.36 [0.21; 0.63]). Age, sex, professional category, number of years of experience in the job or department, and public transportation use were not significantly associated with laboratory-confirmed SARS-CoV-2 infection at M3. Interpretation: The rate of SARS-CoV-2 infection in frontline HCWs was 14.6% at the end of the first COVID-19 wave in Paris and occurred mainly early. Seroprevalence in May was higher than in the general population. The study argues for an origin of professional in addition to private life contamination and therefore including HCWs in the first-line vaccination target population. It also highlights that smokers were at lower risk. Trial Registration: The study is registered on ClinicalTrials.gov: NCT04304690 Funding Statement: The sponsor of the study was Assistance Publique-Hopitaux de Paris (AP-HP), with study management by URC Pitie-Salpetriere. This study was funded by the French Ministry of Health (Programme Hospitalier de Recherche Clinique) and the French Agency for Research (Fond d’amorcage de l’Agence National pour la Recherche). Declaration of Interests: None to declare. Ethics Approval Statement: The SEROCOV study was approved by the ethics committee (CPP Sud-Ouest et Outre-Mer I, approval no. 2-20-023 id7257) and all participants signed informed consent before inclusion.

Published
2021
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46. Neutralization Heterogeneity of UK and South African Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants in BNT162b2-Vaccinated or Convalescent Coronavirus Disease 2019 (COVID-19) Healthcare Workers

Author

Marc Wirden, Valentin Leducq, Isabelle Malet, Sonia Burrel, Christophe Rodriguez, Anne-Geneviève Marcelin, Vincent Calvez, Cathia Soulié, Slim Fourati, Jean-Michel Pawlotsky, Elisa Teyssou, Stéphane Marot, Aude Jary, Basma Abdi, and David Boutolleau

Subjects
0301 basic medicine, Microbiology (medical), 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Health Personnel, education, Antibodies, Viral, Neutralizing antibodies, Neutralization, 03 medical and health sciences, 0302 clinical medicine, Potency, Medicine, Humans, 030212 general & internal medicine, BNT162 Vaccine, SARS-CoV-2 variants, biology, business.industry, SARS-CoV-2, Brief Report, virus diseases, COVID-19, Virology, Antibodies, Neutralizing, United Kingdom, 3. Good health, Titer, 030104 developmental biology, Infectious Diseases, AcademicSubjects/MED00290, biology.protein, Antibody, business, Vaccine
Abstract

There are concerns about neutralizing antibodies’ (NAbs’) potency against severe acute respiratory syndrome coronavirus 2 variants. Despite decreased NAb titers elicited by BNT162b2 vaccine against VOC202012/01 and 501Y.V2 strains, 28/29 healthcare workers (HCWs) had an NAb titer ≥1:10. In contrast, 6 months after coronavirus disease 2019 mild forms, only 9/15 (60%) of HCWs displayed detectable NAbs against 501Y.V2 strain.

Published
2021

47. Use of a Multiplex PCR Assay To Assess the Presence of Treponema pallidum in Mucocutaneous Ulcerations in Patients with Suspected Syphilis

Author

Jean-Luc Robert, Christiane Bébéar, Nicolas Dupin, Arabella Touati, Julie Saule, Sonia Burrel, A. Vermersch-Langlin, Dominique Moulene, Nadjet Benhaddou, Pervenche Martinet, Philippe Grange, Aude Jary, Michel Janier, C. Isnard, and David Boutolleau

Subjects
Microbiology (medical), Paris, Context (language use), urologic and male genital diseases, medicine.disease_cause, Serology, Multiplex polymerase chain reaction, Humans, Medicine, Syphilis, Treponema pallidum, Ulcer, Treponema, biology, business.industry, Lymphogranuloma venereum, Bacteriology, bacterial infections and mycoses, medicine.disease, biology.organism_classification, Virology, female genital diseases and pregnancy complications, Genital ulcer, France, medicine.symptom, business, Chlamydia trachomatis, Multiplex Polymerase Chain Reaction
Abstract

We evaluated the utility of the commercial Allplex genital ulcer real-time PCR multiplex assay for detecting Treponema pallidum, herpes simplex virus 1 (HSV-1) and 2 (HSV-2), and Chlamydia trachomatis serovar L (lymphogranuloma venereum [LGV]) DNA in mucosal and genital ulcers in the context of suspected syphilis. In total, 374 documented genital and mucosal ulcers from patients with and without syphilis presenting at several sexually transmitted infection (STI) centers in France from October 2010 to December 2016 were analyzed at the National Reference Center (CNR) for Bacterial STIs at Cochin Hospital in Paris. T. pallidum subsp. pallidum detection results were compared with the final diagnosis based on a combination of clinical examination, serological results, and in-house nested PCR (nPCR). Detections of HSV and LGV were validated against reference methods. We found that 44.6% of the 374 samples tested were positive for T. pallidum subsp. pallidum, 21% for HSV, and 0.8% for LGV. No positive results were obtained for 30.7% of samples, and 4.8% presented coinfections. For T. pallidum subsp. pallidum detection, the overall sensitivity was 80% (95% confidence interval [CI], 76.1 to 84.1%), specificity was 98.8% (95% CI, 97.7 to 99.9%), positive predictive value was 98.8% (95% CI, 97.7 to 99.9%) and negative predictive value was 80.2% (95% CI, 76.2 to 84.2%), with a rate of concordance with the reference method of 92.5% (k = 0.85). This PCR multiplex assay is suitable for T. pallidum subsp. pallidum detection in routine use and facilitates the simultaneous rapid detection of a broad panel of pathogens relevant in a context of suspected syphilis lesions.

Published
2021
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48. The Delta SARS-CoV-2 variant has a higher viral load than the Beta and the historical variants in nasopharyngeal samples from newly diagnosed COVID-19 patients

Author

Emna Ghidaoui, Stéphane Marot, Sidonie Lambert-Niclot, Basma Abdi, David Boutolleau, Héloise Delagrèverie, Charlotte Charpentier, Elisa Teyssou, Ségolène Brichler, Aude Jary, Laurence Morand-Joubert, Diane Descamps, Vincent Calvez, Anne-Geneviève Marcelin, Cathia Soulié, Sepideh Akhavan, Aurélie Schnuriger, Valentine Marie Ferré, Eve Todesco, Nadhira Houhou-Fidouh, Benoit Visseaux, TEYSSOU, Elisa, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], 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), CHU Strasbourg, 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, Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Hôpital Avicenne [AP-HP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Laboratoire de virologie [APHP Claude Bernard Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Herpèsvirus [CHU Pitié Salpêtrière], and 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]

Subjects
Microbiology (medical), Delta, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Alpha (ethology), Newly diagnosed, Biology, Nasopharynx, Humans, Beta (finance), Letter to the Editor, ComputingMilieux_MISCELLANEOUS, Alpha, SARS-CoV-2, Variants, Beta, COVID-19, Viral Load, Virology, United Kingdom, [SDV] Life Sciences [q-bio], Infectious Diseases, Spike Glycoprotein, Coronavirus, Viral load
Abstract

International audience; The Delta SARS-CoV-2 variant has a higher viral load than the Beta and the historical variants in nasopharyngeal samples from newly diagnosed COVID-19 patients

Published
2021
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49. 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
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50. 359. Ventilator-associated pneumonia in patients with SARS-CoV-2–associated acute respiratory failure requiring mechanical ventilation: a retrospective cohort study

Author

Nicolas Bréchot, Matthieu Schmidt, Alain Combes, Jean Chastre, Sonia Burrel, Charles-Edouard Luyt, Pauline Vidal, Guillaume Hékimian, David Boutolleau, and Jérôme Robert

Subjects
Mechanical ventilation, First episode, medicine.medical_specialty, ARDS, business.industry, medicine.medical_treatment, Ventilator-associated pneumonia, Retrospective cohort study, medicine.disease, Intensive care unit, law.invention, respiratory tract diseases, Pneumonia, AcademicSubjects/MED00290, Infectious Diseases, Respiratory failure, Oncology, law, Internal medicine, Poster Abstracts, Medicine, business
Abstract

Background Data on incidence, clinical presentation and outcomes of ventilator-associated pneumonia (VAP) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia requiring mechanical ventilation (MV) are limited. Methods Case series of patients with COVID-19 pneumonia admitted to a single ICU in France. All consecutive patients requiring MV with RT-PCR–confirmed SARS-CoV-2 infection between March 12th and April 24th, 2020 were included. Frequency, clinical characteristics, responsible pathogens and outcomes of VAP were assessed, and compared to an historical cohort of patients with severe influenza-associated pneumonia requiring MV admitted to the same ICU during the preceding three winter seasons. Results Fifty-four consecutive patients with COVID-19–associated respiratory failure requiring MV were included (median (IQR) age 48 (42–58) years; 74% male; 93% requiring veno-venous ECMO). VAP occurred in 46 (85%) of them (median (IQR) prior MV duration before the first episode, 11 (8–16) days) (Table 1). Pathogens responsible for VAP were predominantly Enterobacteriaceae (72%), and particularly inducible AmpC-cephalosporinase producers (41%), followed by Pseudomonas aeruginosa (35%) (Table 2). Pulmonary infection recurrence and death were observed in 46 (85%) and 17 (31%) patients, respectively. Details on recurrent episodes and pathogens responsible for recurrences are given in Table 3. Most recurrences were relapse (i.e. infection with the same pathogen), with a high proportion occurring during antimicrobial treatment despite its adequacy. Despite a high rate of P. aeruginosa VAP in patients with influenza-associated ARDS, pulmonary infection recurrence rate was significantly lower than in patients with COVID-19. Overall mortality was similar in the two groups. Baseline characteristics of patients Characteristics of first ventilator-associated pneumonia episode Characteristics of recurrent VAP episodes in Covid-19 and influenza patients. Conclusion Patients with severe COVID-19–associated respiratory failure requiring MV had a very high late-onset VAP rate. Inducible AmpC cephalosporinase–producing Enterobacteriaceae and Pseudomonas aeruginosa appeared to be frequently responsible for VAP, with multiple subsequent episodes and difficulties to eradicate the pathogen from the lung. Disclosures All Authors: No reported disclosures

Published
2020
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