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19 results on '"Sabrina Kali"'

1. Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

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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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2. Experiences and challenges with the new European Clinical Trials Regulation

Author

Thale D. J. H. Patrick-Brown, Josephine Bourner, Sabrina Kali, Marius Trøseid, Yazdan Yazdanpanah, Piero Olliaro, and Inge Christoffer Olsen

Subjects
Clinical trial, Government regulation, Pandemics, Epidemics, Multicenter trials, Medicine (General), R5-920
Abstract

Abstract Background The new European Medicines Agency (EMA) Clinical Trials Information System (CTIS), based on the Clinical Trials Regulation (CTR EU 536/2014), came into full effect on 31 January 2022 and was intended to provide an easier, more streamlined approach to the registration of clinical trials taking place in Europe. Using the experience gained on the new regulatory framework from three multi-national European clinical research studies of outbreak-prone infectious diseases, this article describes the advantages and shortcomings of the new clinical trial submission procedure. Methods We report the time to approval, size of the application dossier, and number of requests for information (RFIs) for each study. We also explore the experience of each study within the regulatory framework and its use of CTIS to document the real-world, practical consequences of the system on individual studies. The study assesses the experience of three multi-country studies conducted in Europe working within the EU and non-EU regulatory environments. Results While the time to regulatory and ethical approval has improved since the implementation of the new regulation, the timelines for approvals are still unacceptably slow, particularly for studies being conducted in the context of an evolving outbreak. Within the new regulatory approval procedure, there is evidence of conflicting application requirements, increased document burden, barriers to submitting important modifications, and debilitating technical hurdles. Conclusions CTIS promised to lower the administrative bar, but unfortunately this has not been achieved. There are challenges that need to be urgently confronted and addressed for international research collaborators to effectively manage health crises in the future. While the value of multi-national outbreak research is clear, the limitations and delays imposed by the system, which raise challenging ethical questions about the regulation, are prejudicial to all clinical research, especially publicly funded academic studies. This report is relevant to both regulators and clinical researchers. It is hoped that these findings can help improve pan-European clinical trials, especially for the purpose of epidemic preparedness and response. Trial registration This paper references experiences gained during management of three pan-European trials: EU-SolidAct’s Bari-SolidAct (CT No. 2022-500385-99-00 - 15 March 2022) and AXL-SolidAct (CT No. 2022-500363-12-00 - 19 April 2022), and MOSAIC (CT No. 2022-501132-42-00 - 22 June 2022).

Published
2024
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3. MOSAIC: A cohort study of human mpox virus disease [version 3; peer review: 2 approved]

Author

Yazdan Yazdanpanah, Laura Merson, F-Xavier Lescure, Amanda Rojek, Alexandra Calmy, Piero Olliaro, Josephine Bourner, Isabelle Hoffmann, Peter Horby, Elise Pesonel, Alpha Diallo, Laetitia Guiraud, Sabrina Kali, Jake Dunning, France Mentré, Cédric Laouénan, Romain Palich, Diana Molino, Coralie Tardivon, and Evelina Tacconelli

Subjects
Mpox, observational study, low-intervention clinical trial, tecovirimat, eng, Medicine, Science
Abstract

Background Human mpox is a viral disease caused by an Orthopoxvirus, human mpox virus (hMPXV), typically causing fever and a rash. Mpox has historically been endemic to parts of Central and West Africa, with small numbers of imported cases reported elsewhere, but starting May 2022 an unprecedented global outbreak caused by clade IIb hMPXV was reported outside traditionally endemic countries. This prompted the initiation of MOSAIC, a cohort study implemented in Europe and Asia that aims to describe clinical and virologic outcomes of PCR-confirmed hMPXV disease, including those who receive antiviral therapy. The focus of this article, however, is on describing the study protocol itself with implementation process and operational challenges. Methods MOSAIC recruits participants of any age with laboratory-confirmed mpox disease who provide informed consent. Participants enrol in the cohort for a total of six months. Blood, lesion and throat samples are collected at several timepoints from the day of diagnosis or the first day of treatment (Day 1) until Day 28 for PCR detection of hMPXV. Clinical data are collected by clinicians and participants (via a self-completion questionnaire) for six months to characterize the signs and symptoms associated with the illness, as well as short- and more long-term outcomes. Discussion The design and prompt implementation of clinical research response is key in addressing emerging outbreaks. MOSAIC began enrolment within two months of the start of the international mpox epidemic. Enrolment has been stopped and the last follow-up visits are expected in January 2024. ICTRP registration EU CT number: 2022-501132-42-00 (22/06/2022)

Published
2023
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4. MOSAIC: A cohort study of human mpox virus disease [version 2; peer review: 2 approved]

Author

Yazdan Yazdanpanah, Laura Merson, F-Xavier Lescure, Amanda Rojek, Alexandra Calmy, Piero Olliaro, Josephine Bourner, Isabelle Hoffmann, Peter Horby, Elise Pesonel, Alpha Diallo, Laetitia Guiraud, Sabrina Kali, Jake Dunning, France Mentré, Cédric Laouénan, Romain Palich, Diana Molino, Coralie Tardivon, and Evelina Tacconelli

Subjects
Mpox, observational study, low-intervention clinical trial, tecovirimat, eng, Medicine, Science
Abstract

Background Human mpox is a viral disease caused by an Orthopoxvirus, human mpox virus (hMPXV), typically causing fever and a rash. Mpox has historically been endemic to parts of Central and West Africa, with small numbers of imported cases reported elsewhere, but starting May 2022 an unprecedented global outbreak caused by clade IIb hMPXV was reported outside traditionally endemic countries. This prompted the initiation of MOSAIC, a cohort study implemented in Europe and Asia that aims to describe clinical and virologic outcomes of PCR-confirmed hMPXV disease, including those who receive antiviral therapy. The study is ongoing. Methods MOSAIC recruits participants of any age with laboratory-confirmed mpox disease who provide informed consent. Participants enrol in the cohort for a total of six months. Blood, lesion and throat samples are collected at several timepoints from the day of diagnosis or the first day of treatment (Day 1) until Day 28 for PCR detection of hMPXV. Clinical data are collected by clinicians and participants (via a self-completion questionnaire) for six months to characterize the signs and symptoms associated with the illness, as well as short- and more long-term outcomes. Discussion The design and prompt implementation of clinical research response is key in addressing emerging outbreaks. MOSAIC began enrolment within two months of the start of the international mpox epidemic. While the number of cases is now low, the study remains open for inclusion. ICTRP registration EU CT number: 2022-501132-42-00 (22/06/2022)

Published
2023
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5. Arbidol (Umifenovir): A Broad-Spectrum Antiviral Drug That Inhibits Medically Important Arthropod-Borne Flaviviruses

Author

Jan Haviernik, Michal Štefánik, Martina Fojtíková, Sabrina Kali, Noël Tordo, Ivo Rudolf, Zdeněk Hubálek, Luděk Eyer, and Daniel Ruzek

Subjects
flavivirus, arbidol, umifenovir, antiviral activity, cytotoxicity, cell-type dependent antiviral effect, Microbiology, QR1-502
Abstract

Arthropod-borne flaviviruses are human pathogens of global medical importance, against which no effective small molecule-based antiviral therapy has currently been reported. Arbidol (umifenovir) is a broad-spectrum antiviral compound approved in Russia and China for prophylaxis and treatment of influenza. This compound shows activities against numerous DNA and RNA viruses. The mode of action is based predominantly on impairment of critical steps in virus-cell interactions. Here we demonstrate that arbidol possesses micromolar-level anti-viral effects (EC50 values ranging from 10.57 ± 0.74 to 19.16 ± 0.29 µM) in Vero cells infected with Zika virus, West Nile virus, and tick-borne encephalitis virus, three medically important representatives of the arthropod-borne flaviviruses. Interestingly, no antiviral effects of arbidol are observed in virus infected porcine stable kidney cells (PS), human neuroblastoma cells (UKF-NB-4), and human hepatoma cells (Huh-7 cells) indicating that the antiviral effect of arbidol is strongly cell-type dependent. Arbidol shows increasing cytotoxicity when tested in various cell lines, in the order: Huh-7 < HBCA < PS < UKF-NB-4 < Vero with CC50 values ranging from 18.69 ± 0.1 to 89.72 ± 0.19 µM. Antiviral activities and acceptable cytotoxicity profiles suggest that arbidol could be a promising candidate for further investigation as a potential therapeutic agent in selective treatment of flaviviral infections.

Published
2018
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6. Low to undetectable Omicron BQ.1.1 neutralization by patient’s sera a month after initiation of AZD7442 600 mg

Author

Franck Touret, Guillaume Martin-Blondel, Xavier de Lamballerie, Axelle Dupont, Jacques Izopet, France Mentré, Nassim Kamar, Brigitte Autran, Gilles Paintaud, Sophie Caillard, Christophe Richez, Lionel Couzi, Aliénor Xhaard, Zora Marjanovic, Jerome Avouac, Caroline Jacquet, Dany Anglicheau, Morgane Cheminant, Yazdan Yazdanpanah, Stéphanie N’Guyen, Benjamin Terrier, Jacques Eric Gottenberg, Caroline Besson, Sophie Letrou, Sabrina Kali, Denis Angoulvant, Karine Barthélémy, Stéphane Priet, Elif Nurtop, Ventzislava Petrov Sanchez, Coralie Tardivon, Gilles Blancho, Amandine Le Bourgeois, and Vincent Lévy

Subjects
Microbiology (medical), Infectious Diseases
Published
2023

7. Low serum neutralization of Omicron variants a month after AZD7442 prophylaxis initiation

Author

Xavier de Lamballerie, Guillaume Martin-Blondel, Axelle Dupont, Jacques Izopet, France Mentré, Nassim Kamar, Brigitte Autran, Gilles Paintaud, Sophie Caillard, Amandine le Bourgeois, Christophe Richez, Lionel Couzi, Aliénor Xhaard, Zora Marjanovic, Jerome Avouac, Caroline Jacquet, Denis Anglicheau, Morgane Cheminant, Yazdan Yazdanpanah, Stéphanie N Guyen, Benjamin Terrier, Jacques Eric Gottenberg, Caroline Besson, Sophie Letrou, Sabrina Kali, Denis Angoulvant, Ventzislava Petrov Sanchez, Coralie Tardivon, Gilles Blancho, Vincent Lévy, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'Epidemiologie, Biostatistique et Recherche Clinique (DEBRC), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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, Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), CHU Strasbourg, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hematologie [CHU Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie [CHU Pellegrin], Groupe hospitalier Pellegrin, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares de l'Est et du Sud-Ouest (RESO), CHU Bordeaux [Bordeaux], Hopital Saint-Louis [AP-HP] (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP]

Subjects
Microbiology (medical), Infectious Diseases, [SDV]Life Sciences [q-bio]
Published
2023

8. Experiences and challenges with the new European Clinical Trials Regulation

Author

Thale D.J.H. Patrick-Brown, Josephine Bourner, Sabrina Kali, Marius Trøseid, Yazdan Yazdanpanah, Piero Olliaro, and Inge Christoffer Olsen

Abstract

Background The new European Medicines Agency (EMA) Clinical Trials Information System (CTIS), based on the Clinical Trials Regulation (CTR EU 536/2014), came into full effect on 31 January 2022 and was intended to provide an easier, more streamlined approach to the registration of clinical trials taking place in Europe. Using the experience gained on the new regulatory framework from three multi-national European clinical research studies of outbreak-prone infectious diseases, this article describes the advantages and shortcomings of the new clinical trial submission procedure. Methods We report the time to approval, size of the application dossier, and number of Requests for Information (RFIs) for each study. We also explore the experience of each study within the regulatory framework and its use of CTIS to document the real-world, practical consequences of the system on individual studies. The study assesses the experience of three multi-country studies conducted in Europe working within the EU and non-EU regulatory environments. Results While the time to regulatory and ethical approval has improved since the implementation of the new regulation, the timelines for approvals are still unacceptably slow, particularly for studies being conducted in the context of an evolving outbreak. Within the new regulatory approval procedure, there is evidence of conflicting application requirements, increased document burden, barriers to submitting important modifications, and debilitating technical hurdles. Conclusions CTIS promised to lower the regulatory administrative bar, but unfortunately this has not been achieved. There are challenges that need to be urgently confronted and addressed for international research collaborators to effectively manage health crises in the future. While the impact on multi-national outbreak research is clear, the limitations and delays imposed by the system, which raise challenging ethical questions about the regulation, are prejudicial to all clinical research, especially publicly funded academic studies. The objective of this work is to help improve pan-European clinical trials. Trial Registration This paper references experiences gained during management of three pan-European trials: EU-SolidAct’s Bari-SolidAct (CT No. 2022-500395-99-00) and AXL-SolidAct (CT No. 2022-500363-12-00), and MOSAIC (CT No. 2022-501132-42-00).

Published
2023

9. Early humoral response to COVID-19 vaccination in patients living with obesity and diabetes in France. The COVPOP OBEDIAB study with results from the ANRS0001S COV-POPART cohort

Author

Bénédicte Gaborit, Sara Fernandes, Paul Loubet, Laetitia Ninove, Anne Dutour, Bertrand Cariou, Muriel Coupaye, Karine Clement, Sébastien Czernichow, Claire Carette, Noémie Resseguier, Laure Esterle, Sabrina Kali, Marie Houssays, Xavier de Lamballerie, Linda Wittkop, Odile Launay, and Martine Laville

Subjects
Endocrinology, Endocrinology, Diabetes and Metabolism
Published
2023

10. Detection of SARS-CoV-2 N-antigen in blood during acute COVID-19 provides a sensitive new marker and new testing alternatives

Author

Marcoul Emmanuelle, Benoit Visseaux, Minh Patrick Lê, Alphonsine Diouf, Mergeay-Fabre Mayka, Kasprzyk Emmanuelle, Hazevis Beatrice, Houhou Nadhira, Christophe Choquet, Laviolle Bruno, Benedicte Rossignol, Verdon Renaud, Aqourras Khadija, Bourgeon Marilou, Lehur Claire, Ikram Houas, Ventzislava Petrov-Sanchez, Jeremie Guedj, Aurelie Veislinger, Amina Meziane, Brick Lysiane, Salma Jaafoura, Alexandre Hoctin, Visseaux Benoit, Oriane Puéchal, Alavoine Loubna, Denis Malvy, Gautier Celine, Letienne Estelle, Djossou Felix, Amiel-Taieb Karline, Esperou Helene, Thy Michael, Alpha Diallo, Bertholon Frederique, Sow Khaly, Boutrou Mathilde, Somers Stephanie, Tardy Bernard, Descamps Dianes, Rose Thierry, Morgane Gilg, Lucarelli Aude, Kikoine John, Charles Burdet, Barbet Marion, Kafif Ouifiya, Yazdan Yazdanpanah, Perez Lucas, Justine Pages, Laurent Abel, Florence Damond, Kouakam Christelle, Guillemin Francis, Dominique Deplanque, Marie Pierre Debray, Camille Couffignal, Botelho-Nevers Elisabeth, Jean Sebastien Hulot, Desmarets Maxime, Meunier Alexandre, Legrand Amelie, Maillot Adrien, Marine Beluze, Hartard Cedric, Bansard Helene, Legoas Carole, Gantier Emilie, Ledru Eric, Noemie Mercier, Sylvie van der Werf, Philippine Eloy, Guillaume Lingas, Coralie Tardivon, Fouchard Julie, Dewitte Marie, Bruno Lina, Alexandra Coelho, Boissel Nolwenn, Demeret Caroline, Marty-Quinternet Solene, Cédric Laouénan, Nassima Si Mohammed, Meghadecha Mohamed, Reminiac Cecile, Isabelle Gorenne, Chabouis Agnes, Paris Adeline, Sabrina Kali, Pierrez Nathalie, Mathilde Desvallee, Cracowski Jean Luc, Nathan Peiffer-Smadja, Tournier Anne, Abry Dominique, Marina Esposito-Farese, Lucet Jean-Christophe, Tristan Gigante, Abad Fanny, Olivier Picone, Lefevre Benjamin, Soizic Le Mestre, Ecobichon Jean-Luc, Manuel Rosa-Calatrava, Morel Bruno, Leturque Nicolas, Nguyen Duc, Nathalie Gault, Simon Sandrine, Jade Ghosn, Letrou Sophie, Elrezzi Elise, Ilic-Habensus Emila, Hodaj Enkelejda, Quintin Caroline, Doute Jean Michel, Schoemaecker Betty, Escriou Nicolas, Francois Dubos, A. Jeudy, Gilles Peytavin, Nadhira Houhou-Fidouh, Aurelie Papadopoulos, Noemie Vanel, Aurélie Wiedemann, Vincent Enouf, Rasoamanana Patrick, Behillil Sylvie, Le Hingrat Quentin, Vernet Pauline, Eric D'Ortenzio, Couffin-Cadiergues Sandrine, Damond Florence, Rousseau Alexandra, Jimmy Mullaert, Lemestre Soizic, Cracowski Claire, Malapate Catherine, Hocquet Didier, Francois Teoule, Hervé Le Nagard, Krishna Bhavsar, Mandic Milica, Postolache Andreea, Yves Levy, Caroline Semaille, Perreau Pauline, Frezouls Wahiba, Malvy Denis, Bouscambert Maud, Nadège Néant, Soler Catherine, Dreyere Marion, Nabil Benmalek, Diane Descamps, Allain Jean-Sebastien, Gerardin Patrick, Lila Bouadma, Charlotte Charpentier, Roufai Layide, Caillat-Zucman Sophie, Sandrine Couffin-Cardiergues, Sylvie Behilill, François Angoulvant, Coignard Bruno, Marina Mambert, Petres Stephane, Jean-François Timsit, Dehbia Benkerrou, Coralie Khan, Goyard Sophie, Motiejunaite Justina, Le Meut Guillaume, Burdet Charles, Christelle Paul, Catherine Chirouze, Pagadoy Maider, Hugo Mouquet, Hendou Samia, Fortuna Viviane, Dechanet Aline, Claire Andrejak, Marion Schneider, Claire Levy-Marchal, Christelle Tual, Olivier Terrier, Gerset Sandrine, J.-C. Lucet, Ammour Douae, Quentin Le Hingrat, Madeline Isabelle, Piquard Valentine, Costenoble Virginie, Paris Christophe, Lepiller Quentin, Manuel Etienne, Vignali Valerie, Oubbea Soumaya, Kane Maty, Hélène Espérou, François-Xavier Lescure, Desan Vristi, Vauchy Charline, Francois Bompart, Simondon Anne, Xavier Duval, Delphine Bachelet, Tyrode Sandrine, Rexah Jade, Bruneau Lea, Carine Roy, Gilbert Marie, Amat Karine, Augustin Shana, Gissot Valerie, Lehacaut Jonathan, Do Thi Thu Huong, Antoine Khalil, Marie Capucine Tellier, Pauline Manchon, Ouifiya Kafif, Bouiller Kevin, Jeulin Helene, Faurous William, Tubiana Sarah, Cour Sylvie, Detoc Maelle, Van Der Werf Sylvie, Mailles Alexandra, Audoin Pierre, Nguefang Solange, Mespoulhe Pauline, Caumes Eric, Alexandre Gaymard, Pistone Thierry, Laouenan Cedric, Delmas Christelle, Lepuil Severine, Ayala Sandrine, Lemouche Dalila, Dequand Stephane, Céline Dorival, Lina Bruno, Minerva Cervantes-Gonzalez, Duval Xavier, Costa Yolande, Leclercq Anne, Vabret Astrid, Theo Trioux, Samira Laribi, Roche-Gouanvic Elise, Houria Ichou, Deplanque Dominique, Isabelle Hoffmann, Marion Noret, Benmalek Nabil, Gaillanne Laurence, Mélanie Bertine, Lysa Tagherset, Peiffer-Smadja Nathan, Migaud Maria-Claire, Waucquier Nawal, Desille-Dugast Mireille, Nadia Ettalhaoui, Sarah Tubiana, Payet Christine, Romain Basmaci, Laine Fabrice, Attia Mikael, Patrick Rossignol, Charlene Da Silveira, Legrand Karine, Florentia Kaguelidou, Chirouze Catherine, Chan Thien Eric, Lebeaux David, Maude Bouscambert, Vesval Thiphaine, Charpentier Charlotte, Terzian Zaven, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Qiagen, BioMérieux, Gilead, Theratechnologie, Hologic, ViiV Healthcare, Abbvie, BMS, J&J, Pfizer, Beckton Dickinson, REACTing, 20-0424, Ministry of Health, ANRS, AAZ, Inserm, Sanofi Pasteur, Da Volterra, Biomerieux, Mylan, MSD, Medimune, Gilead Sciences, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent

Subjects
0301 basic medicine, Microbiology (medical), Serum, medicine.medical_specialty, Saliva, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], 030106 microbiology, Antigenemia, Gastroenterology, 03 medical and health sciences, Plasma, 0302 clinical medicine, Antigen, Internal medicine, Medicine, Sampling (medicine), 030212 general & internal medicine, Symptom onset, Diagnostic, business.industry, SARS-CoV-2, COVID-19, General Medicine, Serum samples, 3. Good health, [SDV] Life Sciences [q-bio], Research Note, Infectious Diseases, Blood, business, Viral load
Abstract

Objectives Molecular assays on nasopharyngeal swabs remain the cornerstone of COVID-19 diagnostics. The high technicalities of nasopharyngeal sampling and molecular assays, as well as scarce resources of reagents, limit our testing capabilities. Several strategies failed, to date, to fully alleviate this testing process (e.g. saliva sampling or antigen testing on nasopharyngeal samples). We assessed the clinical performances of SARS-CoV-2 nucleocapsid antigen (N-antigen) ELISA detection in serum or plasma using the COVID-19 Quantigene® (AAZ, France) assay. Methods Performances were determined on 63 serum samples from 63 non-COVID patients and 227 serum samples (165 patients) from the French COVID and CoV-CONTACT cohorts with RT-PCR-confirmed SARS-CoV-2 infection, including 142 serum samples (114 patients) obtained within 14 days after symptom onset. Results Specificity was 98.4% (95% CI 95.3–100). Sensitivity was 79.3% overall (180/227, 95% CI, 74.0–84.6) and 93.0% (132/142, 95% CI, 88.7–97.2) within 14 days after symptom onset. Ninety-one of the included patients had serum samples and nasopharyngeal swabs collected in the same 24 hr. Among those with high nasopharyngeal viral loads, i.e. Ct value below 30 and 33, only 1/50 and 4/67 tested negative for N-antigenaemia, respectively. Among those with a negative nasopharyngeal RT-PCR, 8/12 presented positive N-antigenaemia; the lower respiratory tract was explored for six of these eight patients, showing positive RT-PCR in five cases. Discussion This is the first evaluation of a commercially available serum N-antigen detection assay. It presents a robust specificity and sensitivity within the first 14 days after symptoms onset. This approach provides a valuable new option for COVID-19 diagnosis, only requiring a blood draw and easily scalable in all clinical laboratories.

Published
2021

11. DABMA: A Derivative of ABMA with Improved Broad-Spectrum Inhibitory Activity of Toxins and Viruses

Author

Valérie Pons, Robert A. Davey, Olena Shtanko, Julien Barbier, Noël Tordo, Sabrina Kali, Daniel Gillet, Yu Wu, Michel R. Popoff, Jean-Christophe Cintrat, Romain Noel, Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO) (SIMoS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Chimie Bio-Organique et de Marquage (SCBM), Stratégies antivirales, Institut Pasteur [Paris] (IP), Texas Biomedical Research Institute [San Antonio, TX], National Emerging Infectious Diseases Laboratories (NEIDL), Boston University [Boston] (BU), Bactéries anaérobies et Toxines, This work has been funded by the joint ministerial program of R&D against CBRNE risks, CEA and under Contract ANR-18-CE18-0016. This work was also supported by U.S. National Institutes of Health and National Institute of Allergy and Infectious Diseases grant R01AI063513. SIMOPRO and SCBM are members of the Laboratory of Excellence LERMIT supported by a grant from the Agence Nationale de la Recherche (ANR-10-LABX-33) and RetroLeishma project R3., ANR-10-LABX-0033,LERMIT,Research Laboratory on Drugs and Therapeutic Innovation(2010), ANR-18-CE18-0016,LeishmaStop,Agents anti-leishmaniose ciblant le trafic intracellulaire de la cellule hôte(2018), and Institut Pasteur [Paris]

Subjects
[SDV]Life Sciences [q-bio], virus, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Inhibitory postsynaptic potential, medicine.disease_cause, 01 natural sciences, Biochemistry, Structure−activity relationship study, Virus, chemistry.chemical_compound, Drug Discovery, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, Parasite hosting, toxin, 010405 organic chemistry, Toxin, Intracellular parasite, Organic Chemistry, broad-spectrum inhibitor, Small molecule, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Mechanism of action, medicine.symptom, endolysosomal pathway, Derivative (chemistry)
Abstract

International audience; The small molecule ABMA has been previously shown to protect cells against multiple toxins and pathogens including virus, intracellular bacteria, and parasite. Its mechanism of action is directly associated with host endolysosomal pathway rather than targeting toxin or pathogen itself. However, the relationship of its broad-spectrum anti-infection activity and chemical structure is not yet resolved. Here, we synthesized a series of derivatives and compared their activities against diphtheria toxin (DT). Dimethyl-ABMA (DABMA), one of the most potent analogs with about 20-fold improvement in protection efficacy against DT, was identified with a similar mechanism of action to ABMA. Moreover, DABMA exhibited enhanced efficacy against Clostridium difficile toxin B (TcdB), Clostridium sordellii lethal toxin (TcsL), Pseudomonas Exotoxin A (PE) as well as Rabies and Ebola viruses. The results revealed a structure-activity relationship of ABMA, which is a starting point for its clinical development as broad-spectrum drug against existing and emerging infectious diseases.

Published
2019

12. Broad spectrum compounds targeting early stages of rabies virus (RABV) infection

Author

Sabrina Kali, Saliha Azebi, Corinne Jallet, Juliana Pipoli Da Fonseca, Daniel Gillet, Jean-Christophe Cintrat, Noël Tordo, Thomas Cokelaer, Yu Wu, Julien Barbier, Stratégies antivirales, Institut Pasteur [Paris], Institut Pasteur d'Algérie, Réseau International des Instituts Pasteur (RIIP), Biomics (plateforme technologique), Neuro-Immunologie Virale - Viral Neuro-immunology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO) (SIMoS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Chimie Bio-Organique et de Marquage (SCBM), Institut Pasteur de Guinée, The following programs contributed to fund the current research, both for material and fellowships: the joint ministerial program of R&D against CBRNE risks and Centre d’Energie Atomique (CEA - P/NRBC n°I1.1.8 'Large Spectrum Antivirals'), the European program ASKLEPIOS « Advanced Studies towards Knowledge on Lyssavirus Encephalitis Pathogenesis Improving Options for Survival » (FP7 - 602825 - Neglected infectious diseases of Central and Eastern Europe). In addition, the project benefited from the core facilities of the « Centre de Ressources et Recherches Technologiques » at the Institut Pasteur for imaging and bioinformatics., European Project: 602825,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,ASKLEPIOS(2013), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Benzylamines, Indoles, Endosome, G protein, [SDV]Life Sciences [q-bio], 030106 microbiology, Adamantane, Endosomes, Biology, medicine.disease_cause, Antiviral Agents, Late endosome, Cell Line, Viral Proteins, 03 medical and health sciences, Virology, Drug Resistance, Viral, Ribavirin, Rabies glycoprotein, medicine, Animals, Endosomal pathway inhibitors, Pharmacology, Rabies virus, RNA, Drug Synergism, Virus Internalization, Umifenovir, medicine.disease, Drug synergy, 3. Good health, 030104 developmental biology, RAB7A, Mutation, Rabies, medicine.drug
Abstract

International audience; ABMA and its analogue DABMA are two molecules of the adamantane family known to perturbate the endosomal pathway and to inhibit cell infection of several RNA and DNA viruses. Their activity against Rabies Virus (RABV) infection has already been demonstrated in vitro. (Wu et al., 2017, 2019). Here, we describe in more details their mechanism of action by comparison to Arbidol (umifenovir) and Ribavirin, two broad spectrum antivirals against emerging viruses such as Lassa, Ebola, influenza and Hantaan viruses. ABMA and DABMA, delivered 2 h pre-infection, inhibit RABV infection in vitro with an EC50 of 7.8 μM and 14 μM, respectively. They act at post-entry, by causing RABV accumulation within the endosomal compartment and DABMA specifically diminishes the expression of the GTPase Rab7a controlling the fusion of early endosomes to late endosomes or lysosomes. This may suggest that ABMA and DABMA act at different stages of the late endosomal pathway as supported by their different profile of synergy/antagonism with the fusion inhibitor Arbidol. This difference is further confirmed by the RABV mutants induced by successive passages under increasing selective pressure showing a particular involvement of the viral G protein in the DABMA inhibition while ABMA inhibition induces less mutations dispersed in the M, G and L viral proteins. These results suggest new therapeutic perspectives against rabies.

Published
2021

13. ABMA, a small molecule that inhibits intracellular toxins and pathogens by interfering with late endosomal compartments

Author

Didier Sauvaire, Philippe M. Loiseau, Sabrina Kali, Rahima Yousfi, Pascal Clayette, Daniel Gillet, Céline Bouclier, Noël Tordo, Jérôme Laporte, Amélie Goudet, Goulven Merer, Roman Lopez, Michel R. Popoff, Sandrine Cojean, Valérie Pons, Céline Aubenque, Claire Boulogne, Emmanuel Lemichez, Annette Fischer, Jean-Christophe Cintrat, Laetitia Panigai, Yu Wu, Cynthia Gillet, Roger Le Grand, Thomas Rudel, Robert A. Davey, Julien Barbier, Jo-Ana Herweg, Emilie Gobbo, Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO) (SIMoS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Chimie Bio-Organique et de Marquage (SCBM), Agence nationale de sécurité du médicament et des produits de santé [Saint-Denis] (ANSM), Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Stratégies antivirales, Institut Pasteur [Paris], Texas Biomedical Research Institute, CEA [Fontenay-aux-Roses] (UGRA / SETA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Molécules bioactives, conception, isolement et synthèse (MBCIS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Bactéries anaérobies et Toxines, Pharmacologie des rétrovirus, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work has been funded by the joint ministerial program of R&D against CBRNE risks and CEA, and benefited from the core facilities of Imagerie-Gif (http://www.i2bc.paris-saclay.fr), member of IBiSA (http://www.ibisa.net), supported by 'France-BioImaging' (ANR-10-INBS-04–01) and the Labex 'Saclay Plant Science' (ANR-11-IDEX-0003–02). This work was also supported by U.S. National Institutes of Health and National Institute of Allergy and Infectious Diseases grant R01AI063513, Defense Threat Reduction Agency grant HDTRA1–12–1–0002, and the Douglass and Ewing Halsell Foundations. Work on Simkania and Chlamydia was supported by the Deutsche Forschungsgemeinschaft (DFG) Priority programme 1580 to T.R. SIMOPRO and SCBM are members of the Laboratory of Excellence LERMIT supported by a grant from the Agence Nationale de la Recherche (ANR-10-LABX-33) and RetroLeishma project R3, We greatfully thank Anne Doye (Université de Nice Sophia-Antipolis) for technical assistance and Bruno Beaumelle for providing ricin, ANR-11-IDEX-0002,UNITI,Université Fédérale de Toulouse(2011), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Julius-Maximilians-Universität Würzburg (JMU), Institut Pasteur [Paris] (IP), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Popoff, Michel, Initiative d'excellence - Université Fédérale de Toulouse - - UNITI2011 - ANR-11-IDEX-0002 - IDEX - VALID, Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, and Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID

Subjects
0301 basic medicine, Benzylamines, Endosome, 030106 microbiology, Cell, Golgi Apparatus, lcsh:Medicine, Adamantane, Endosomes, Ricin, Endoplasmic Reticulum, Article, Mice, 03 medical and health sciences, symbols.namesake, ddc:570, Benzyl Compounds, Organelle, medicine, Animals, Humans, lcsh:Science, Pathogen, Toxins, Biological, Multidisciplinary, Chemistry, Antimicrobials, Endoplasmic reticulum, Intracellular parasite, lcsh:R, High-throughput screening, Golgi apparatus, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Cell Compartmentation, 3. Good health, Cell biology, 030104 developmental biology, medicine.anatomical_structure, symbols, Infectious diseases, lcsh:Q, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Lysosomes, Intracellular, HeLa Cells
Abstract

Intracellular pathogenic microorganisms and toxins exploit host cell mechanisms to enter, exert their deleterious effects as well as hijack host nutrition for their development. A potential approach to treat multiple pathogen infections and that should not induce drug resistance is the use of small molecules that target host components. We identified the compound 1-adamantyl (5-bromo-2-methoxybenzyl) amine (ABMA) from a cell-based high throughput screening for its capacity to protect human cells and mice against ricin toxin without toxicity. This compound efficiently protects cells against various toxins and pathogens including viruses, intracellular bacteria and parasite. ABMA provokes Rab7-positive late endosomal compartment accumulation in mammalian cells without affecting other organelles (early endosomes, lysosomes, the Golgi apparatus, the endoplasmic reticulum or the nucleus). As the mechanism of action of ABMA is restricted to host-endosomal compartments, it reduces cell infection by pathogens that depend on this pathway to invade cells. ABMA may represent a novel class of broad-spectrum compounds with therapeutic potential against diverse severe infectious diseases.

Published
2017

14. Bulgarian contribution to the economics of the European Union

Author

Sabrina Kalinkova

Subjects
bulgarian contribution, total product, european union’s economy, Economic growth, development, planning, HD72-88, Economics as a science, HB71-74
Abstract

Bulgaria, as one of the youngest members of the European Union (EU), has made significant contributions to the economic development of the Union. Since joining the European Union in 2007, Bulgaria has undergone a series of economic reforms and has shown impressive growth rates, which have had positive effects on the European Union's economy. The country's strategic location, low-cost labour force, and relatively low corporate tax rates have made it an attractive destination for foreign investors, leading to increased trade and investment flows between Bulgaria and other European Union member states. Bulgaria has also played an active role in the European Union's efforts to deepen economic integration and promote the digital single market. However, the country still faces challenges related to corruption, governance, and demographic trends that need to be addressed to ensure sustainable growth and to fully realize its potential in the European Union's economy.

Published
2023
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15. Bulgarian economy as a producer of intermediate goods for the European Union

Author

Sabrina Kalinkova

Subjects
bulgarian economy, european union, intermediate products, export, import, sectors of the economy, Economic growth, development, planning, HD72-88, Economics as a science, HB71-74
Abstract

Relevance of research topic. In conditions of globalization, the economic development of a country depends a lot on its relations with the rest of the world. When using economic indicators, including the "foreign trade balance" one, their correct interpretation is of particular importance. Formulation of the problem. The research interest should be focused not only on the volume of exports and imports in monetary terms, but also on its structure. It is a question of what production (goods and services) the Bulgarian economy exports (respectively imports), as well as where it exports (from where the Bulgarian economy imports). Setting the task, the purpose of the study. This report aims to present the Bulgarian economy in its role of producer and supplier of intermediate products for the countries of the European Union. Method or methodology for conducting research. The study is based on the use of the input-output model and in particular the symmetric input-output tables provided by the World Input-Output Database. Presentation of the main material (results of work). This report presents the results of the study of volume and structure of exports of the Bulgarian economy as a producer and supplier of intermediate goods, directed to the countries of the European Union. The interactions with the following countries were analyzed: Austria, Belgium, Germany, Denmark, Spain, France, Great Britain, Greece, Italy, the Netherlands, Poland, and Romania. Some of the member states of the European Union are not included. The reason for this is the lack of interactions between them and the Bulgarian economy, based on the provision of intermediate products. Conclusions according to the article. The study presents only one aspect of the foreign economic relations that take place between Bulgaria and the European Union. For the most part, the relations between Bulgaria and the other economies in the European Union are based mainly on industries related to the supply of resources. Services and products with a final degree of readiness are provided to a much lesser extent.

Published
2021
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16. Karaganov V. S. Leontief – is there a misunderstanding of Leontief’s model?

Author

Sabrina Kalinkova

Subjects
leontief, balance of inter-branch relations, input-output model, branches of national economy, producers, consumers, Economic growth, development, planning, HD72-88, Economics as a science, HB71-74
Abstract

Relevance of research topic: Cross-sectoral balance is a tool with unique qualities for analyzing and designing economic development. The evolution of economic systems also affects the very balance and attitude of researchers to it. Formulation of the problem: For this reason, the opinion of one of the famous economists – Prof. Karaganov regarding the basic assumptions of Leontief's model is of interest. These are the baseline indicators examined with the model whose nature is not subject to change. The purpose of this study is to substantiate the inconsistency of criticism of Leontief's cross-sectoral balance model by Professor Sergei Karaganov. Method or methodology for conducting research. Scientific literature analysis method and the method of comparison were used. Presentation of the main material (results of work). At the very beginning of the article by Prof. Karaganov an incorrect presentation of the structure of the model of Leontief is made. The balance of inter-branch connections simultaneously reflects each of the branches in a dual role – a producer of production and a supplier of own manufactured products for other industries to meet their production needs. Prof. Karaganov demonstrates a clear lack of knowledge of the balance of cross-sectoral links (input-output model) by misrepresenting each of the branches of a national economic system. According to him, the branches of the national economy are divided into producing and consuming industries. It is beyond the view of Prof. Karaganov that in the balance of inter-sectoral links, the industries are not divided into producing and consuming products. At each point in time, each industry is represented both in its role as a producer of production and in its role as a recipient of production from other industries in connection with the production of its own production. Conclusions according to the article. At present, Leontiev's model is used solely from its analytical capabilities. And the main reason for this is the presence of many methodological and informational problems. But it is particularly important to make it clear that these problems, existing outside and independently of the model, do not make the model itself wrong or inadequate to use. The circumstances presented by Prof. Sergey Karaganov are just some of the examples of misunderstanding the capabilities of the model, leading it to impute problems that do not actually exist.

Published
2020
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17. Measuring the competitiveness of post-socialist countries

Author

Sabrina Kalinkova

Subjects
competitiveness, economic development, competitive advantages, post-socialist countries, Economic growth, development, planning, HD72-88, Economics as a science, HB71-74
Abstract

Relevance of research topic. The development of a country (economic, social and environmental) is mostly determined by the political system within which this country is developing. As a direct reflection of the level of development of a nation, its competitiveness is considered. Formulation of the problem. For this reason, the present study is focused at examining and analyzing the national competitiveness of countries that have transformed their governance system from socialism to democracy. Method or methodology for conducting research. Speaking of competitiveness, despite the many studies, there is still no uniform definition that best describes the concept. The starting point for the study is the disclosure of the methodology used to measure the competitiveness of the countries - the methodology of the World Economic Forum. The clarified methodology based on which the index used is constructed is the basis for directing the study to present and analyze the results achieved by the post-socialist countries surveyed over the last 10 years. Presentation of the main material (results of work). The focus is on the following countries: Armenia, Albania, Bulgaria, Estonia, Latvia, Lithuania, Romania, Russia, Slovak Republic, Ukraine, and the Czech Republic. The index of global competitiveness of a nation is estimated by indicators in 12 areas, grouped into 3 sub-indexes. Sub-index "basic (fundamental) requirements" includes indicators in groups: institutions; infrastructure; macroeconomic environment; health and primary education. Sub-index "performance accelerators" includes groups of indicators: higher education and training; goods markets efficiency; labor market efficiency; financial market development; technological readiness and market size. The sub-index "Innovation and Complexity of Factors" includes indicators in groups of "business and strategy complexity" and "innovation". Conclusions according to the article. Different countries achieve their development at different rates, depending on the advantages they have for achieving competitiveness. As a result of the study, it can be concluded that the post-socialist countries today have a positive tendency in the area of competitiveness.

Published
2019
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18. The new paradigm for managing the post-socialist countries in a market economy

Author

Sabrina Kalinkova

Subjects
paradigm, management, economic systems, Economic growth, development, planning, HD72-88, Economics as a science, HB71-74
Abstract

The results of the applied management paradigm at all economic levels showed its inadequacy and the need of a new management paradigm. In the paper are presented the reasons that justify this need and the distinguishing features of the new management paradigm, especially in the post-socialist countries. The challenges and prospects of the new management logic are also presented in the paper. The main subject of research in the article is the need for a new paradigm of economic systems management (at all levels). From here comes the purpose of the study, which is to prove this need, as well as the specific dimensions of the so called "a new paradigm". The methodology of the study is based on historical analysis of past economic performance. And also the scientific achievements in the field of planning, created by the Bulgarian economists - Academic Evgeni Mateev, Member of the correspondence for the Academy of Science Ivan Iliev and Full professor Vassil Manov. As a result of the studies, in the article are presented aspects of the new paradigm that can be applied in the management of various economic levels.

Published
2018
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19. Sera neutralizing activities against SARS-CoV-2 and multiple variants six month after hospitalization for COVID-19

Author

Blandine Monel, David Veyer, Benoit Visseaux, Anne Blanchard, Antoine Fayol, David Lebeaux, Benoit Vedie, Maureen Betton, Hélène Péré, Jade Ghosn, Delphine Planas, Timothée Bruel, Marine Livrozet, Jean-Sébastien Hulot, Jean-Claude Manuguerra, Olivier Schwartz, Nicolas Robillard, Eric Tartour, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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 biochimie [AP-HP Hôpital Européen Georges Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire d’immunologie [Hôpital Européen Georges Pompidou - APHP], Service de Microbiologie [CHU GeorgesPompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Cellule d'Intervention Biologique d'Urgence (Centre National de Référence) - Laboratory for Urgent Response to Biological Threats (National Reference Center) (CIBU), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris]-Institut Pasteur [Paris], Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, 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), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), The French COVID cohort is funding by the REACTing (REsearch & ACtion emergING infectious diseases) consortium and by a grant of the French Ministry of Health (PHRC n°20-0424). Work in OS lab is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR. Outside the submitted work, JSH is supported by AP-HP, INSERM, the French National Research Agency (NADHeart ANR-17-CE17-0015-02, PACIFIC ANR-18-CE14-0032-01, CORRECT_LMNA ANR-19-CE17-0013-02), the ERA-Net-CVD (ANR-16-ECVD-0011-03, Clarify project), Fédération Française de Cardiologie, the Fondation pour la Recherche Médicale, and by a grant from the Leducq Foundation (18CVD05), and is coordinating a French PIA Project (2018-PSPC-07, PACIFIC-preserved, BPIFrance) and a University Research Federation against heart failure (FHU2019, PREVENT_Heart Failure)., The French COVID cohort study group : Laurent ABEL (Inserm UMR 1163, Paris, France), Claire ANDREJAK (CHU Amiens, France), François ANGOULVANT (Hôpital Necker, Paris, France), Delphine BACHELET, Krishna BHAVSAR, Lila BOUADMA, Anissa CHAIR, Camille COUFFIGNAL, Charlene DA SILVEIRA, Marie-Pierre DEBRAY, Diane DESCAMPS, Xavier DUVAL, Philippine ELOY, Marina ESPOSITO-FARESE, Nadia ETTALHAOUI, Nathalie GAULT, Jade GHOSN, Isabelle GORENNE, Isabelle HOFFMANN, Ouifiya KAFIF, Sabrina KALI, Antoine KHALIL, Cédric LAOUÉNAN, Samira LARIBI, Minh LE, Quentin LE HINGRAT, François-Xavier LESCURE, Jean Christophe LUCET, France MENTRÉ, Jimmy Mullaert, Nathan PEIFFER-SMADJA, Gilles PEYTAVIN, Carine ROY, Marion SCHNEIDER, Nassima SI MOHAMMED, Lysa TAGHERSET, Coralie TARDIVON, Marie-Capucine TELLIER, Jean-François TIMSIT, Théo TRIOUX, Sarah TUBIANA, Benoit VISSEAUX, Yazdan YAZDANPANAH (Hôpital Bichat, Paris, France), Romain BASMACI, Olivier PICONE (Hôpital Louis Mourier, Colombes, France), Sylvie BEHILILL, Sylvie VAN DER WERF, Vincent ENOUF, Hugo MOUQUET (Pasteur Institute, Paris, France), Marine BELUZE (F-CRIN Partners Platform, Paris, France), Dehbia BENKERROU, Céline DORIVAL, François TÉOULÉ, Amina MEZIANE (Inserm UMR 1136, Paris, France), François BOMPART (Drugs for Neglected Diseases initiative, Geneva, Switzerland), Maude BOUSCAMBERT (Inserm UMR 1111, Lyon, France), Minerva CERVANTES-GONZALEZ, Eric d’ORTENZIO, Oriane PUÉCHAL, Caroline SEMAILLE (REACTing, Paris, France), Catherine CHIROUZE (CHRU Jean Minjoz, Besançon, France), Alexandra COELHO (Inserm UMR 1018, Paris, France), Sandrine COUFFIN-CADIERGUES, Hélène ESPEROU, Ikram HOUAS, Salma JAAFOURA, Aurélie PAPADOPOULOS (Inserm sponsor, Paris, France), Dominique DEPLANQUE (Hôpital Calmette, Lille, France), Mathilde DESVALLÉE, Coralie KHAN (Inserm UMR 1219, Bordeaux, France), Alpha DIALLO, Marie BARTOLI, Soizic LE MESTRE, Noémie MERCIER, Christelle PAUL, Ventzislava PETROV-SANCHEZ (ANRS, Paris, France), Alphonsine DIOUF, Alexandre HOCTIN, Marina MAMBERT (Inserm UMR 1018, Paris, France), François DUBOS (CHU Lille, France), Manuel ETIENNE (CHU Rouen, France), Alexandre GAYMARD (Inserm UMR 1111, Lyon, France), Tristan GIGANTE, Morgane GILG, Bénédicte ROSSIGNOL (F-CRIN INI-CRCT, Nancy, France), Jérémie GUEDJ, Hervé LE NAGARD, Guillaume LINGAS, Nadège NEANT (Inserm UMR 1137, Paris, France), Jean-Sébastien HULOT (Hôpital Européen Georges Pompidou, Paris, France), Florentia KAGUELIDOU, Justine PAGES (Hôpital Robert Debré, Paris, France), Yves LEVY, Aurélie WIEDEMANN (Vaccine Research Insitute (VRI), Inserm UMR 955, Créteil, France), Claire LEVY-MARCHAL (F-CRIN INI-CRCT, Paris, France), Bruno LINA, Manuel ROSA-CALATRAVA, Olivier TERRIER (Inserm UMR 1111, Lyon, France), Denis MALVY (CHU Bordeaux, France), Marion NORET (RENARCI, Annecy, France), Patrick ROSSIGNOL (CHU Nancy, France), Christelle TUAL, Aurélie VEISLINGER (Inserm CIC-1414, Rennes, France), Noémie VANEL (Hôpital la Timone, Marseille, France), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-17-CE17-0015,NAD-HEART,Supplémentation en précurseur du NAD+ pour le traitement de l'insuffisance cardiaque(2017), ANR-18-CE14-0032,PACIFIC,Cellules PW1+ dans la fibrose cardiaque(2018), ANR-19-CE17-0013,Correct-LMNA,Édition génomique par CRISPR/Cas9 pour traiter les cardiomyopathies liées aux mutations du gène LMNA(2019), ANR-16-ECVD-0011,CLARIFY,Communication between cardiomyocytes and innate immune cells in failing hearts(2016), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), Institut Pasteur [Paris] (IP)-Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, and French COVID cohort study group

Subjects
0301 basic medicine, Microbiology (medical), [SDV]Life Sciences [q-bio], 030106 microbiology, Antibodies, Viral, medicine.disease_cause, Severity of Illness Index, Immunoglobulin G, Neutralization, law.invention, Serology, 03 medical and health sciences, 0302 clinical medicine, law, Intensive care, Major Article, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Pandemics, Coronavirus, biology, SARS-CoV-2, business.industry, COVID-19, Antibodies, Neutralizing, Intensive care unit, 3. Good health, Hospitalization, Editorial Commentary, AcademicSubjects/MED00290, Infectious Diseases, Spike Glycoprotein, Coronavirus, Immunology, biology.protein, Antibody, business
Abstract

Background Humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs within the first weeks after coronavirus disease 2019 (COVID-19). Those antibodies exert a neutralizing activity against SARS-CoV-2, whose evolution over time after COVID-19 as well as efficiency against novel variants are poorly characterized. Methods In this prospective study, sera of 107 patients hospitalized with COVID-19 were collected at 3 and 6 months postinfection. We performed quantitative neutralization experiments on top of high-throughput serological assays evaluating anti-spike (S) and anti-nucleocapsid (NP) immunoglobulin G (IgG). Results Levels of seroneutralization and IgG rates against the ancestral strain decreased significantly over time. After 6 months, 2.8% of the patients had a negative serological status for both anti-S and anti-NP IgG. However, all sera had a persistent and effective neutralizing effect against SARS-CoV-2. IgG levels correlated with seroneutralization, and this correlation was stronger for anti-S than for anti-NP antibodies. The level of seroneutralization quantified at 6 months correlated with markers of initial severity, notably admission to intensive care units and the need for mechanical invasive ventilation. In addition, sera collected at 6 months were tested against multiple SARS-CoV-2 variants and showed efficient neutralizing effects against the D614G, B.1.1.7, and P.1 variants but significantly weaker activity against the B.1.351 variant. Conclusions Decrease in IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7, and P.1 variants for at least 6 months in patients previously hospitalized for COVID-19. A weaker protection was, however, observed for the B.1.351 variant.

Published
2021

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