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1. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trials

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Hermine, Olivier, Mariette, Xavier, Ravaud, Philippe, Bureau, Serge, Dougados, Maxime, Resche-Rigon, Matthieu, Tharaux, Pierre-Louis, Tibi, Annick, Azoulay, Elie, Cadranel, Jacques, Emmerich, Joseph, Fartoukh, Muriel, Guidet, Bertrand, Humbert, Marc, Lacombe, Karine, Mahevas, Matthieu, Pene, Frédéric, Porcher, Raphaël, Pourchet-Martinez, Valerie, Schlemmer, Frédéric, Yazdanpanah, Yazdan, Baron, Gabriel, Perrodeau, Elodie, Vanhoye, Damien, Kedzia, Cécile, Demerville, Lauren, Gysembergh-Houal, Anne, Bourgoin, Alexandre, Raked, Nabil, Mameri, Lakhdar, Montlahuc, Claire, Biard, Lucie, Alary, St.phanie, Hamiria, Samir, Bariz, Thinhinane, Semri, Hala, Hai, Dhiaa Meriem, Benafla, Moustafa, Belloul, Mohamed, Vauboin, Pernelle, Flamand, Saskia, Pacheco, Claire, Walter-Petrich, Anouk, Stan, Emilia, Benarab, Souad, Nyanou, Corine, Charreteur, Robin, Dupre, Céline, Cardet, Kévin, Lehmann, Blandine, Baghli, Kamyl, Madelaine, Claire, D'Ortenzio, Eric, Puéchal, Oriane, Semaille, Caroline, Savale, Laurent, Harrois, Anatole, Figueiredo, Samy, Duranteau, Jacques, Anguel, Nadia, Pavot, Arthur, Monnet, Xavier, Richard, Christian, Teboul, Jean-Louis, Durand, Philippe, Tissieres, Pierre, Jevnikar, Mitja, Montani, David, Pavy, Stephan, Nocturne, Gaétane, Bitoun, Samuel, Noel, Nicolas, Lambotte, Olivier, Escaut, Lelia, Jauréguiberry, Stephane, Baudry, Elodie, Verny, Christiane, Lefevre, Edouard, Zaidan, Mohamad, Molinari, Domitille, Leprun, Gaël, Fourreau, Alain, Cylly, Laurent, Grimaldi, Lamiae, Virlouvet, Myriam, Meftali, Ramdane, Fabre, Soléne, Licois, Marion, Mamoune, Asmaa, Boudali, Yacine, Le Tiec, Clotilde, Verstuyft, Céline, Roques, Anne-Marie, Georgin-Lavialle, Sophie, Senet, Patricia, Pialoux, Gilles, Soria, Angele, Parrot, Antoine, François, Helene, Rozensztajn, Nathalie, Blin, Emmanuelle, Choinier, Pascaline, Camuset, Juliette, Rech, Jean-Simon, Canellas, Antony, Rolland-Debord, Camille, Lemarié, Nadege, Belaube, Nicolas, Nadal, Marine, Siguier, Martin, Petit-Hoang, Camille, Chas, Julie, Drouet, Elodie, Lemoine, Matthieu, Phibel, Audrey, Aunay, Lucie, Bertrand, Eliane, Ravato, Sylviane, Vayssettes, Marie, Adda, Anne, Wilpotte, Celine, Thibaut, Pélagie, Fillon, Julie, Debrix, Isabelle, Fellahi, Soraya, Bastard, Jean-Philippe, Lefévre, Guillaume, Gottenberg, Jacques-Eric, Hansmann, Yves, Blanc, Frédéric, Ohlmann-Caillard, Sophie, Castelain, Vincent, Chatelus, Emmanuel, Chatron, Eva, Collange, Olivier, Danion, François, De Blay, Frédéric, Diemunsch, Pierre, Diemunsch, Sophie, Felten, Renaud, Goichot, Bernard, Greigert, Valentin, Guffroy, Aurelien, Heger, Bob, Kaeuffer, Charlotte, Kassegne, Loic, Korganow, Anne Sophie, Le Borgne, Pierrick, Lefebvre, Nicolas, Mertes, Paul-Michel, Noll, Eric, Oberlin, Mathieu, Poindron, Vincent, Pottecher, Julien, Ruch, Yvon, Weill, François, Meyer, Nicolas, Andres, Emmanuel, Demonsant, Eric, Tayebi, Hakim, Nisand, Gabriel, Brin, Stéphane, Sublon, Cédric, Becker, Guillaume, Hutt, Anne, Martin, Tristan, Bayer, Sophie, Metzger, Catherine, Mekinian, Arsene, Abisror, Noémie, Adedjouma, Amir, Bollens, Diane, Bonneton, Marion, Bourcicaux, Nathalie, Bourrier, Anne, Thibault Chiarabiani, Maria Chauchard, Chopin, Doroth.e, Cohen, Jonathan, Devred, Ines, Donadille, Bruno, Fain, Olivier, Hariri, Geoffrey, Jachiet, Vincent, Ingliz, Patrick, Garnier, Marc, Gatfosse, Marc, Ghrenassia, Etienne, Gobert, Delphine, Krause le Garrec, Jessica, Landman, Cecilia, Lavillegrand, Jean Remy, Lefebvre, Benedicte, Mahevas, Thibault, Mazerand, Sandie, Meynard, Jean Luc, Morgand, Marjolaine, Ouaz.ne, Zineb, Pacanowski, Jerome, Riviere, S.bastien, Seksik, Philippe, Sokol, Harry, Soliman, Heithem, Valin, Nadia, Urbina, Thomas, McAvoy, Chloé, Miranda, Maria Pereira, Aratus, Gladys, Berard, Laurence, Simon, Tabassome, Nguyen, Anne Daguenel, Girault, Elise, Mayala-Kanda, Cl.mentine, Antignac, Marie, Leplay, Céline, Arlet, Jean-Benoit, Diehl, Jean-Luc, Bellenfant, Florence, Blanchard, Anne, Buffet, Alexandre, Cholley, Bernard, Fayol, Antoine, Flamarion, Edouard, Godier, Anne, Gorget, Thomas, Hamada, Sophie-Rym, Hauw-Berlemont, Caroline, Hulot, Jean-Sébastien, Lebeaux, David, Livrozet, Marine, Michon, Adrien, Neuschwander, Arthur, Pennet, Marie-Aude, Planquette, Benjamin, Ranque, Brigitte, Sanchez, Olivier, Volle, Geoffroy, Briois, Sandrine, Cornic, Mathias, Elisee, Virginie, Denis, Jesuthasan, Djadi-Prat, Juliette, Jouany, Pauline, Junquera, Ramon, Henriques, Mickael, Kebir, Amina, Lehir, Isabelle, Meunier, Jeanne, Patin, Florence, Paquet, Val.rie, Tréhan, Anne, Vigna, Véronique, Sabatier, Brigitte, Bergerot, Damien, Jouve, Charléne, Knosp, Camille, Lenoir, Olivia, Mahtal, Nassim, Resmini, Léa, Lescure, Xavier, Ghosn, Jade, Bachelard, Antoine, Rachline, Anne, Isernia, Valentina, Bao-chau, Phung, Vallois, Dorothée, Sautereau, Aurelie, Neukrich, Catherine, Dossier, Antoine, Borie, Raphaël, Crestani, Bruno, Ducrocq, Gregory, Steg, Philippe Gabriel, Dieude, Philippe, Papo, Thomas, Marcault, Estelle, Chaudhry, Marhaba, Da Silveira, Charléne, Metois, Annabelle, Mahenni, Ismahan, Meziani, Meriam, Nilusmas, Cyndie, Le Gac, Sylvie, Ndiaye, Awa, Louni, Fran.oise, Chansombat, Malikhone, Julia, Zelie, Chalal, Solaya, Chalal, Lynda, Kramer, Laura, Le Grand, Jeniffer, Ouifiya, Kafif, Piquard, Valentine, Tubiana, Sarah, Nguyen, Yann, Honsel, Vasco, Weiss, Emmanuel, Codorniu, Anais, Zarrouk, Virginie, de Lastours, Victoire, Uzzan, Matthieu, Gamany, Naura, Claveirole, Agathe, Navid, Alexandre, Fouque, Tiffanie, Cohen, Yonathan, Lupo, Maya, Gilles, Constance, Rahli, Roza, Louis, Zeina, Boutboul, David, Galicier, Lionel, Amara, Yaël, Archer, Gabrielle, Benattia, Amira, Bergeron, Anne, Bondeelle, Louise, de Castro, Nathalie, Clément, Melissa, Darmon, Michaël, Denis, Blandine, Dupin, Clairelyne, Feredj, Elsa, Feyeux, Delphine, Joseph, Adrien, Lenglin, Etienne, Le Guen, Pierre, Liégeon, Geoffroy, Lorillon, Gwenaël, Mabrouki, Asma, Mariotte, Eric, Martin de Frémont, Grégoire, Mirouse, Adrien, Molina, Jean-Michel, Peffault de Latour, Régis, Oksenhendler, Eric, Saussereau, Julien, Tazi, Abdellatif, Tudesq, Jean-Jacques, Zafrani, Lara, Brindele, Isabelle, Bugnet, Emmanuelle, Lebras, Karine Celli, Chabert, Julien, Djaghout, Lamia, Fauvaux, Catherine, Jegu, Anne Lise, Kozakiewicz, Ewa, Meunier, Martine, Tremorin, Marie-Thérèse, Davoine, Claire, Madelaine, Isabelle, Caillat-Zucman, Sophie, Delaugerre, Constance, Morin, Florence, Sène, Damien, Burlacu, Ruxandra, Chousterman, Benjamin, Mégarbanne, Bruno, Richette, Pascal, Riveline, Jean-Pierre, Frazier, Aline, Vicaut, Eric, Berton, Laure, Hadjam, Tassadit, Vazquez-Ibarra, Miguel Alejandro, Jourdaine, Clément, Tran, Olivia, Jouis, Véronique, Jacob, Aude, Smati, Julie, Renaud, Stéphane, Pernin, Claire, Suarez, Lydia, Semerano, Luca, Abad, Sébastien, nainous, Ruben B., Bonnet, Nicolas, Comparon, Celine, Cohen, Yves, Cordel, Hugues, Dhote, Robin, Dournon, Nathalie, Duchemann, Boris, Ebstein, Nathan, Gille, Thomas, Giroux-Leprieur, Benedicte, Goupil de Bouille, Jeanne, Nunes, Hilario, Oziel, Johanna, Roulot, Dominique, Sese, Lucile, ClaireTantet, Uzunhan, Yurdagul, Bloch-Queyrat, Coralie, Levy, Vincent, Messani, Fadhila, Rahaoui, Mohammed, Petit, Myléne, Brahmi, Sabrina, Rathoin, Vanessa, Rigal, Marthe, Costedoat-Chalumeau, Nathalie, Luong, Liem Binh, Hamou, Zakaria Ait, Benghanem, Sarah, Blanche, Philippe, Carlier, Nicolas, Chaigne, Benjamin, Gauzit, Remy, Joumaa, Hassan, Jozwiak, Mathieu, Lachétre, Marie, Lafoeste, Hélène, Launay, Odie, Legendre, Paul, Marey, Jonathan, Morbieu, Caroline, Palmieri, Lola-Jade, Szwebel, Tali-Anne, Abdoul, Hendy, Bruneau, Alexandra, Beclin-Clabaux, Audrey, Larrieu, Charly, Montanari, Pierre, Dufour, Eric, Clarke, Ada, Le Bourlout, Catherine, Marin, Nathalie, Menage, Nathalie, Saleh-Mghir, Samira, Cisse, Mamadou Salif, Cheref, Kahina, Guerin, Corinne, Zerbit, Jérémie, Michel, Marc, Gallien, Sébastien, Crickx, Etienne, Le Vavasseur, Benjamin, Kempf, Emmanuelle, Jaffal, Karim, Vindrios, William, Oniszczuk, Julie, Guillaud, Constance, Lim, Pascal, Fois, Elena, Melica, Giovanna, Matignon, Marie, Jalabert, Maud, Lelièvre, Jean-Daniel, Schmitz, David, Bourhis, Marion, Belazouz, Sylia, Languille, Laetitia, Boucle, Caroline, Cita, Nelly, Didier, Agnés, Froura, Fahem, Ledudal, Katia, Sadaoui, Thiziri, Thiemele, Alaki, Le Febvre De Bailly, Delphine, Verlinde, Muriel Carvhalo, Mayaux, Julien, Cacoub, Patrice, Saadoun, David, Vautier, Mathieu, Bugaut, Héléne, Benveniste, Olivier, Allenbach, Yves, Leroux, Gaëlle, Rigolet, Aude, Guillaume-Jugnot, Perrine, Domont, Fanny, Desbois, Anne Claire, Comarmond, Chloé, Champtiaux, Nicolas, Toquet, Segolene, Ghembaza, Amine, Vieira, Matheus, Maalouf, Georgina, Boleto, Goncalo, Ferfar, Yasmina, Corvol, Jean-Christophe, Louapre, C.line, Sambin, Sara, Mariani, Louise-Laure, Karachi, Carine, Tubach, Florence, Estellat, Candice, Gimeno, Linda, Martin, Karine, Bah, Aicha, Keo, Vixra, Ouamri, Sabrine, Messaoudi, Yasmine, Yelles, Nessima, Faye, Pierre, Cavelot, Sebastien, Larcheveque, Cecile, Annonay, Laurence, Benhida, Jaouad, Zahrate-Ghoul, Aida, Hammal, Soumeya, Belilita, Ridha, Charbonnier, Fanny, Aguilar, Claire, Alby-Laurent, Fanny, Burger, Carole, Campos-Vega, Clara, Chavarot, Nathalie, Fournier, Benjamin, Rouzaud, Claire, Vimpére, Damien, Elie, Caroline, Bakouboula, Prissile, Choupeaux, Laure, Granville, Sophie, Issorat, Elodie, Broissand, Christine, Alyanakian, Marie-Alexandra, Geri, Guillaume, Derridj, Nawal, Sguiouar, Naima, Meddah, Hakim, Djadel, Mourad, Chambrin-Lauvray, Héléne, Duclos-vallée, Jean-Charles, Saliba, Faouzi, Sacleux, Sophie-Caroline, Kounis, Ilias, Tamazirt, Sonia, Rudant, Eric, Michot, Jean-Marie, Stoclin, Annabelle, Colomba, Emeline, Pommeret, Fanny, Willekens, Christophe, Da Silva, Rosa, Dejean, Valérie, Mekid, Yasmina, Ben-Mabrouk, Ines, Netzer, Florence, Pradon, Caroline, Drouard, Laurence, Camara-Clayette, Valérie, Morel, Alexandre, Garcia, Gilles, Mohebbi, Abolfazl, Berbour, Férial, Dehais, Mélanie, Pouliquen, Anne-Lise, Klasen, Alison, Soyez-Herkert, Loren, London, Jonathan, Keroumi, Younes, Guillot, Emmanuelle, Grailles, Guillaume, El amine, Younes, Defrancq, Fanny, Fodil, Hanane, Bouras, Chaouki, Dautel, Dominique, Gambier, Nicolas, Dieye, Thierno, Bienvenu, Boris, Lancon, Victor, Lecomte, Laurence, Beziriganyan, Kristina, Asselate, Belkacem, Allanic, Laure, Kiouris, Elena, Legros, Marie-Héléne, Lemagner, Christine, Martel, Pascal, Provitolo, Vincent, Ackermann, Félix, Le Marchand, Mathilde, Chan Hew Wai, Aurélie, Fremont, Dimitri, Coupez, Elisabeth, Adda, Mireille, Duée, Frédéric, Bernard, Lise, Gros, Antoine, Henry, Estelle, Courtin, Claire, Pattyn, Anne, Guinot, Pierre-Grégoire, Bardou, Marc, Maurer, Agnes, Jambon, Julie, Cransac, Amélie, Pernot, Corinne, Mourvillier, Bruno, Marquis, Eric, Benoit, Philippe, Roux, Damien, Gernez, Coralie, Yelnik, Cécile, Poissy, Julien, Nizard, Mandy, Denies, Fanette, Gros, Helene, Mourad, Jean-Jacques, Sacco, Emmanuelle, Renet, Sophie, Ader, F., Yazdanpanah, Y., Mentre, F., Peiffer-Smadja, N., Lescure, F.X., Poissy, J., Bouadma, L., Timsit, J.F., Lina, B., Morfin-Sherpa, F., Bouscambert, M., Gaymard, A., Peytavin, G., Abel, L., Guedj, J., Andrejak, C., Burdet, C., Laouenan, C., Belhadi, D., Dupont, A., Alfaiate, T., Basli, B., Chair, A., Laribi, S., Level, J., Schneider, M., Tellier, M.C., Dechanet, A., Costagliola, D., Terrier, B., Ohana, M., Couffin-Cadiergues, S., Esperou, H., Delmas, C., Saillard, J., Fougerou, C., Moinot, L., Wittkop, L., Cagnot, C., Le Mestre, S., Lebrasseur-Longuet, D., Petrov-Sanchez, V., Diallo, A., Mercier, N., Icard, V., Leveau, B., Tubiana, S., Hamze, B., Gelley, A., Noret, M., D’Ortenzio, E., Puechal, O., Semaille, C., Welte, T., Paiva, J.A., Halanova, M., Kieny, M.P., Balssa, E., Birkle, C., Gibowski, S., Landry, E., Le Goff, A., Moachon, L., Moins, C., Wadouachi, L., Paul, C., Levier, A., Bougon, D., Djossou, F., Epelboin, L., Dellamonica, J., Marquette, C.H., Robert, C., Gibot, S., Senneville, E., Jean-Michel, V., Zerbib, Y., Chirouze, C., Boyer, A., Cazanave, C., Gruson, D., Malvy, D., Andreu, P., Quenot, J.P., Terzi, N., Faure, K., Chabartier, C., Le Moing, V., Klouche, K., Ferry, T., F, Valour, Gaborit, B., Canet, E., Le Turnier, P., Boutoille, D., Bani-Sadr, F., Benezit, F., Revest, M., Cameli, C., Caro, A., Um Tegue, MJ Ngo, Le Tulzo, Y., Laviolle, B., Laine, F., Thiery, G., Meziani, F., Hansmann, Y., Oulehri, W., Tacquard, C., Vardon-Bounes, F., Riu-Poulenc, B., Murris-Espin, M., Bernard, L., Garot, D., Hinschberger, O., Martinot, M., Bruel, C., Pilmis, B., Bouchaud, O., Loubet, P., Roger, C., Monnet, X., Figueiredo, S., Godard, V., Mira, J.P., Lachatre, M., Kerneis, S., Aboab, J., Sayre, N., Crockett, F., Lebeaux, D., Buffet, A., Diehl, J.L., Fayol, A., Hulot, J.S., Livrozet, M., Dessap, A Mekontso, Ficko, C., Stefan, F., Le Pavec, J., Mayaux, J., Ait-Oufella, H., Molina, J.M., Pialoux, G., Fartoukh, M., Textoris, J., Brossard, M., Essat, A., Netzer, E., Riault, Y., Ghislain, M., Beniguel, L., Genin, M., Gouichiche, L., Betard, C., Belkhir, L., Altdorfer, A., Centro, V Fraipont, Braz, S., Ribeiro, JM Ferreira, Alburqueque, R Roncon, Berna, M., Alexandre, M., Lamprecht, B., Egle, A., Greil, R., Joannidis, M., Patterson, Thomas F., Ponce, Philip O., Taylor, Barbara S., Patterson, Jan E., Bowling, Jason E., Javeri, Heta, Kalil, Andre C., Larson, LuAnn, Hewlett, Angela, Mehta, Aneesh K., Rouphael, Nadine G., Saklawi, Youssef, Scanlon, Nicholas, Traenkner, Jessica J., Trible, Ronald P., Jr., Walter, Emmanuel B., Ivey, Noel, Holland, Thomas L., Ruiz-Palacios, Guillermo M., Ponce de León, Alfredo, Rajme, Sandra, Hsieh, Lanny, Amin, Alpesh N., Watanabe, Miki, Lee, Helen S., Kline, Susan, Billings, Joanne, Noren, Brooke, Kim, Hyun, Bold, Tyler D., Tapson, Victor, Grein, Jonathan, Sutterwala, Fayyaz, Iovine, Nicole, Beattie, Lars K., Wakeman, Rebecca Murray, Shaw, Matthew, Jain, Mamta K., Mocherla, Satish, Meisner, Jessica, Luque, Amneris, Sweeney, Daniel A., Benson, Constance A., Ali, Farhana, Atmar, Robert L., El Sahly, Hana M., Whitaker, Jennifer, Falsey, Ann R., Branche, Angela R., Rozario, Cheryl, Pineda, Justino Regalado, Martinez-Orozco, José Arturo, Lye, David Chien, Ong, Sean WX., Chia, Po Ying, Young, Barnaby E., Sandkovsky, Uriel, Berhe, Mezgebe, Haley, Clinton, Dishner, Emma, Cantos, Valeria D., Kelley, Colleen F., Rebolledo Esteinou, Paulina A., Kandiah, Sheetal, Doernberg, Sarah B., Crouch, Pierre-Cedric B., Jang, Hannah, Luetkemeyer, Anne F., Dwyer, Jay, Cohen, Stuart H., Thompson, George R., 3rd, Nguyen, Hien H., Finberg, Robert W., Wang, Jennifer P., Perez-Velazquez, Juan, Wessolossky, Mireya, Jackson, Patrick E.H., Bell, Taison D., West, Miranda J., Taiwo, Babafemi, Krueger, Karen, Perez, Johnny, Pearson, Triniece, Paules, Catharine I., Julian, Kathleen G., Ahmad, Danish, Hajduczok, Alexander G., Arguinchona, Henry, Arguinchona, Christa, Erdmann, Nathaniel, Goepfert, Paul, Ahuja, Neera, Frank, Maria G., Wyles, David, Young, Heather, Oh, Myoung-don, Park, Wan Beom, Kang, Chang Kyung, Marconi, Vincent, Moanna, Abeer, Cribbs, Sushma, Harrison, Telisha, Kim, Eu Suk, Jung, Jongtak, Song, Kyoung-Ho, Kim, Hong Bin, Tan, Seow Yen, Shafi, Humaira, Chien, Jaime, Fong, Raymond KC., Murray, Daniel D., Lundgren, Jens, Nielsen, Henrik, Jensen, Tomas, Zingman, Barry S., Grossberg, Robert, Riska, Paul F., Yang, Otto O., Ahn, Jenny, Arias, Rubi, Rapaka, Rekha R., Hauser, Naomi, Campbell, James D., Short, William R., Tebas, Pablo, Baron, Jillian T., McLellan, Susan L.F., Blanton, Lucas S., Seashore, Justin B., Creech, C. Buddy, Rice, Todd W., Walker, Shannon, Thomsen, Isaac P., Lopez de Castilla, Diego, Van Winkle, Jason W., Riedo, Francis X., Pada, Surinder Kaur, Wang, Alvin DY., Lin, Li, Harkins, Michelle, Mertz, Gregory, Sosa, Nestor, Ann Chai, Louis Yi, Tambyah, Paul Anantharajah, Tham, Sai Meng, Archuleta, Sophia, Yan, Gabriel, Lindholm, David A., Markelz, Ana Elizabeth, Mende, Katrin, Mularski, Richard, Hohmann, Elizabeth, Torres-Soto, Mariam, Jilg, Nikolaus, Maves, Ryan C., Utz, Gregory C., George, Sarah L., Hoft, Daniel F., Brien, James D., Paredes, Roger, Mateu, Lourdes, Loste, Cora, Kumar, Princy, Thornton, Sarah, Mohanraj, Sharmila, Hynes, Noreen A., Sauer, Lauren M., Colombo, Christopher J., Schofield, Christina, Colombo, Rhonda E., Chambers, Susan E., Novak, Richard M., Wendrow, Andrea, Gupta, Samir K., Lee, Tida, Lalani, Tahaniyat, Holodniy, Mark, Chary, Aarthi, Huprikar, Nikhil, Ganesan, Anuradha, Ohmagari, Norio, Mikami, Ayako, Price, D. Ashley, Duncan, Christopher J.A., Dierberg, Kerry, Neumann, Henry J., Taylor, Stephanie N., Lacour, Alisha, Masri, Najy, Swiatlo, Edwin, Widmer, Kyle, Neaton, James D., Bessesen, Mary, Stephens, David S., Burgess, Timothy H., Uyeki, Timothy M., Walker, Robert, Marks, G. Lynn, Osinusi, Anu, Cao, Huyen, Cardoso, Anabela, de Bono, Stephanie, Schlichting, Douglas E., Chung, Kevin K., Ferreira, Jennifer L., Green, Michelle, Makowski, Mat, Wierzbicki, Michael R., Conrad, Tom M., El-Khorazaty, Jill Ann, Hill, Heather, Bonnett, Tyler, Gettinger, Nikki, Engel, Theresa, Lewis, Teri, Wang, Jing, Beigel, John H., Tomashek, Kay M., Ghazaryan, Varduhi, Beresnev, Tatiana, Nayak, Seema, Dodd, Lori E., Dempsey, Walla, Nomicos, Effie, Lee, Marina, Pikaart-Tautges, Rhonda, Elsafy, Mohamed, Jurao, Robert, Koo, Hyung, Proschan, Michael, Yokum, Tammy, Arega, Janice, Florese, Ruth, Voell, Jocelyn D., Davey, Richard, Serrano, Ruth C., Wiley, Zanthia, Phadke, Varun K., Goepfert, Paul A., Gomez, Carlos A., Sofarelli, Theresa A., Certain, Laura, Imlay, Hannah N., Wolfe, Cameron R., Ko, Emily R., Engemann, John J., Felix, Nora Bautista, Wan, Claire R., Elmor, Sammy T., Bristow, Laurel R., Harkins, Michelle S., Iovine, Nicole M., Elie-Turenne, Marie-Carmelle, Tapson, Victor F., Choe, Pyoeng Gyun, Mularski, Richard A., Rhie, Kevin S., Hussein, Rezhan H., Ince, Dilek, Winokur, Patricia L., Takasaki, Jin, Saito, Sho, McConnell, Kimberly, Wyles, David L., Sarcone, Ellen, Grimes, Kevin A., Perez, Katherine, Janak, Charles, Whitaker, Jennifer A., Rebolledo, Paulina A., Gharbin, John, Lambert, Allison A., Zea, Diego F., Bainbridge, Emma, Hostler, David C., Hostler, Jordanna M., Shahan, Brian T., Ling, Evelyn, Go, Minjoung, Hubbard, Fleesie A., Chakrabarty, Melony, Laguio-Vila, Maryrose, Walsh, Edward E., Guirgis, Faheem, Marconi, Vincent C., Madar, Christian, Borgetti, Scott A., Levine, Corri, Nock, Joy, Candiotti, Keith, Rozman, Julia, Dangond, Fernando, Hyvert, Yann, Seitzinger, Andrea, Cross, Kaitlyn, Pettibone, Stephanie, Nayak, Seema U., Deye, Gregory A., Siempos, Ilias I., Belhadi, Drifa, Veiga, Viviane Cordeiro, Cavalcanti, Alexandre Biasi, Branch-Elliman, Westyn, Papoutsi, Eleni, Gkirgkiris, Konstantinos, Xixi, Nikoleta A., and Kotanidou, Anastasia

Published
2024
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2. Outbreak of Invasive Wound Mucormycosis in a Burn Unit Due to Multiple Strains of Mucor circinelloides f. circinelloides Resolved by Whole-Genome Sequencing

Author

Garcia-Hermoso, Dea, Criscuolo, Alexis, Lee, Soo Chan, Legrand, Matthieu, Chaouat, Marc, Denis, Blandine, Lafaurie, Matthieu, Rouveau, Martine, Soler, Charles, Schaal, Jean-Vivien, Mimoun, Maurice, Mebazaa, Alexandre, Heitman, Joseph, Dromer, Françoise, Brisse, Sylvain, Bretagne, Stéphane, Alanio, Alexandre, Lockhart, Shawn, and Voigt, Kerstin

Subjects
Infectious Diseases, Emerging Infectious Diseases, Biotechnology, Aetiology, 2.2 Factors relating to the physical environment, Infection, Burn Units, Burns, Cluster Analysis, Cross Infection, Disease Outbreaks, France, Genetic Variation, Genotype, Humans, Molecular Epidemiology, Molecular Typing, Mucor, Mucormycosis, Phylogeny, Whole Genome Sequencing, Wound Infection, Wounds and Injuries, Mucor circinelloides, Mucorales, burn, clade, genome, genotype, mixed infection, mucormycosis, outbreak, strains, whole-genome sequencing, wound, Microbiology
Abstract

Mucorales are ubiquitous environmental molds responsible for mucormycosis in diabetic, immunocompromised, and severely burned patients. Small outbreaks of invasive wound mucormycosis (IWM) have already been reported in burn units without extensive microbiological investigations. We faced an outbreak of IWM in our center and investigated the clinical isolates with whole-genome sequencing (WGS) analysis. We analyzed M. circinelloides isolates from patients in our burn unit (BU1, Hôpital Saint-Louis, Paris, France) together with nonoutbreak isolates from Burn Unit 2 (BU2, Paris area) and from France over a 2-year period (2013 to 2015). A total of 21 isolates, including 14 isolates from six BU1 patients, were analyzed by whole-genome sequencing (WGS). Phylogenetic classification based on de novo assembly and assembly free approaches showed that the clinical isolates clustered in four highly divergent clades. Clade 1 contained at least one of the strains from the six epidemiologically linked BU1 patients. The clinical isolates were specific to each patient. Two patients were infected with more than two strains from different clades, suggesting that an environmental reservoir of clonally unrelated isolates was the source of contamination. Only two patients from BU1 shared one strain, which could correspond to direct transmission or contamination with the same environmental source. In conclusion, WGS of several isolates per patients coupled with precise epidemiological data revealed a complex situation combining potential cross-transmission between patients and multiple contaminations with a heterogeneous pool of strains from a cryptic environmental reservoir.IMPORTANCE Invasive wound mucormycosis (IWM) is a severe infection due to environmental molds belonging to the order Mucorales. Severely burned patients are particularly at risk for IWM. Here, we used whole-genome sequencing (WGS) analysis to resolve an outbreak of IWM due to Mucor circinelloides that occurred in our hospital (BU1). We sequenced 21 clinical isolates, including 14 from BU1 and 7 unrelated isolates, and compared them to the reference genome (1006PhL). This analysis revealed that the outbreak was mainly due to multiple strains that seemed patient specific, suggesting that the patients were more likely infected from a pool of diverse strains from the environment rather than from direct transmission among them. This study revealed the complexity of a Mucorales outbreak in the settings of IWM in burn patients, which has been highlighted based on WGS combined with careful sampling.

Published
2018

4. Invasive Infections with Nannizziopsis obscura Species Complex in 9 Patients from West Africa, France, 2004-2020

Author

Garcia-Hermoso, Dea, Hamane, Samia, Fekkar, Arnaud, Jabet, Arnaud, Denis, Blandine, Siguier, Martin, Galeazzi, Guy, Haddad, Elie, Brun, Sophie, Vidal, Valerie, Nevez, Gilles, Berre, Rozenn Le, Gits-Muselli, Maud, Lanternier, Fanny, and Bretagne, Stephane

Subjects
Posaconazole -- Health aspects, Fungi -- Health aspects, Metronidazole -- Health aspects, Immunotherapy -- Health aspects, T cells -- Health aspects, Health
Abstract

Nannizziopsis spp. are described as keratinophilic ascomycetous fungi that cause dermal infections with frequently fatal outcomes in various reptiles (e.g., lizards, geckos, chameleons, iguanas, snakes, and crocodiles), mainly in captivity [...]

Published
2020
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8. First Patient-to-Patient Intrahospital Transmission of Clade I Candida auris in France Revealed after a Two-Month Incubation Period

Author

Alanio, Alexandre, primary, Snell, Hannah Marie, additional, Cordier, Camille, additional, Desnos-Olivier, Marie, additional, Dellière, Sarah, additional, Aissaoui, Nesrine, additional, Sturny-Leclère, Aude, additional, Da Silva, Elodie, additional, Eblé, Cyril, additional, Rouveau, Martine, additional, Thégat, Micheline, additional, Zebiche, Widad, additional, Lafaurie, Matthieu, additional, Denis, Blandine, additional, Touratier, Sophie, additional, Benyamina, Mourad, additional, Dudoignon, Emmanuel, additional, Hamane, Samia, additional, Cuomo, Christina A., additional, and Dépret, François, additional

Published
2022
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9. Active Surveillance Program to Increase Awareness on Invasive Fungal Diseases: the French RESSIF Network (2012 to 2018)

Author

Bretagne, Stéphane, Sitbon, Karine, Desnos-Ollivier, Marie, Garcia-Hermoso, Dea, Letscher-Bru, Valérie, Cassaing, Sophie, Millon, Laurence, Morio, Florent, Gangneux, Jean-Pierre, Hasseine, Lilia, Favennec, Loïc, Cateau, Estelle, Bailly, Eric, Moniot, Maxime, Bonhomme, Julie, Desbois-Nogard, Nicole, Chouaki, Taieb, Paugam, André, Bouteille, Bernard, Pihet, Marc, Dalle, Frédéric, Eloy, Odile, Sasso, Milène, Demar, Magalie, Mariani-Kurkdjian, Patricia, Robert, Vincent, Lortholary, Olivier, Dromer, Françoise, French Mycoses Study Group, The, Damiani, Céline, Dupont, Hervé, Maizel, Julien, Totet, Anne, Bouchara, Jean-Philippe, Bellanger, Anne Pauline, Berceanu, Ana, Navellou, Jean Christophe, Scherer, Emeline, Abboud, Philippe, Aznar, Christine, Blanchet, Denis, Djossou, Félix, Cayot, Sophie, Garrouste, Cyril, Lesens, Olivier, Moluçon, Cécile, Nourrisson, Céline, Poirier, Philippe, Bailly, Éloïse, Basmaciyan, Louise, Belaid, Bouhemad, Blot, Mathieu, Caillot, Denis, Charles, Pierre-Emmanuel, Quenot, Jean Pierre, Amazan, Emmanuelle, Baubion, Emilie, Cabie, André, Chabartier, Cyrille, Deligny, Christophe, Emal, Violaine, Flechelle, Olivier, Hatchuel, Yves, Le Govic, Yohann, Merle, Harold, Miossec, Charline, Turmel, Jean-Marie, Valentino, Ruddy, Durieux, Marie-Fleur, Turlure, Pascal, Mercier, Victor, Gari-Toussaint, Martine, Risso, Karine, Simon, Loïc, Bretonnière, Cedric, Boutoille, David, Gastinne, Thomas, Lakhal, Karim, Launay, Elise, Lepoivre, Thierry, Peterlin, Pierre, Rialland, Fanny, Le Pape, Patrice, Canoui, Etienne, Dahane, Naima, Kerneis, Solène, Angebault, Cécile, Bougnoux, Marie-Elisabethh, Guennouni, Nadia, Lanternier, Fanny, Neven, Bennedicte, Oualha, Mehdi, Scemla, Anne, Sitterlé, Emilie, Suarez, Felipe, Toubiana, Julie, Bonacorci, Stéphane, Alanio, Alexandre, Bergeron, Anne, Denis, Blandine, Gits-Muselli, Maud, Hamane, Samia, Touratier, Sophie, Chaumeil, Christine, Merabet, Lilia, Claudéon, Joelle, Curlier, Elodie, Galantine, Valérie, Gallois, Jean Claude, Markowicz, Samuel, Nicolas, Muriel, Musson, Pascal, Schepers, Kinda, Minoza, Alida, Kauffmann-Lacroix, Catherine, Guégan, Hélène, Costa, Damien, Dehais, Marion, Gargala, Gilles, Bajolet, Odile, Banisadr, Firouze, Cousson, Joel, Himberlin, Chantal, Huguenin, Antoine, Toubas, Dominique, Flori, Pierre, Mahinc, Caroline, Raberin, Hélène, Denis, Julie, Herbrecht, Raoul, Mertes, Paul-Michel, Meziani, Fehrat, Sabou, Marcela, Schneider, Francis, Bertozzi, Anne-Isabelle, Chauvin, Pamela, Charpentier, Elena, Cointault, Olivier, Cottrel, Claire, Delavigne, Karen, Faguer, Stanislas, Fillaux, Judith, Guemas, Emilie, Iriart, Xavier, Lelièvre, Lucie, Ruiz, Jean, Bastides, Frédéric, Chesnay, Adélaïde, Desoubeaux, Guillaume, Therby, Audrey, Chachaty, Elisabeth, Gachot, Bertrand, Westerdijk Fungal Biodiversity Institute, Westerdijk Fungal Biodiversity Institute - Software and Databasing, Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Dynamique des interactions hôte pathogène (DIHP), Université de Strasbourg (UNISTRA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Nantes Université (Nantes Univ), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Rouen, Normandie Université (NU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Clermont-Ferrand, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU de la Martinique [Fort de France], CHU Amiens-Picardie, Hôpital Cochin [AP-HP], CHU Limoges, SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), Laboratoire de Parasitologie-Mycologie (CHU d'Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Infections Respiratoires Fongiques (IRF), Université d'Angers (UA)-Université de Brest (UBO), Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre Hospitalier de Versailles André Mignot (CHV), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Hôpital Robert Debré Paris, Hôpital Robert Debré, Westerdijk Fungal Biodiversity Institute [Utrecht] (WI), Royal Netherlands Academy of Arts and Sciences (KNAW), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Laboratoire de Parasitologie-Mycologie [CHU Angers], Hôpital Bretonneau, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by recurrent financial support from Santé Publique France and Institut Pasteur. The funders had no role in study design, data collection, analysis, interpretation of data, or the decision to submit the work for publication., We thank Didier Che (Direction des Maladies Infectieuses, Santé Publique France) for his continuous support and interest in invasive fungal infections and Etienne Sevin (EpiConcept, Paris, France) for his contribution in the development of the RESSIF website using the VOOZANOO platform. We are thankful for the technical help of Catherine Blanc, Anne Boullié, Cécile Gautier, Virginie Geolier, and Damien Hoinard (Institut Pasteur) for the characterization of the isolates received at the NRCMA., The French Mycoses Study Group includes collaborators who contributed to these data by their involvement in the management of patients, expertise in diagnostic tools, and/or characterization of fungal isolates. They are listed in alphabetical order of a city in France and for each center, in alphabetical order of the last names: in Amiens, Céline Damiani, Hervé Dupont, Julien Maizel, and Anne Totet, in Angers, Jean-Philippe Bouchara, in Besançon, Anne Pauline Bellanger, Ana Berceanu, Jean Christophe Navellou, and Emeline Scherer, in Cayenne, Philippe Abboud, Christine Aznar, Denis Blanchet, and Félix Djossou, in Clermont-Ferrand, Sophie Cayot, Cyril Garrouste, Olivier Lesens, Cécile Moluçon, Céline Nourrisson, and Philippe Poirier, in Dijon, Éloïse Bailly, Louise Basmaciyan, Bouhemad Belaid, Mathieu Blot, Denis Caillot, Pierre-Emmanuel Charles, and Jean Pierre Quenot, in Fort de France, Emmanuelle Amazan, Emilie Baubion, André Cabie, Cyrille Chabartier, Christophe Deligny, Violaine Emal, Olivier Flechelle, Yves Hatchuel, Yohann Le Govic, Harold Merle, Charline Miossec, Jean-Marie Turmel, and Ruddy Valentino, in Limoges, Marie-Fleur Durieux and Pascal Turlure, in Nîmes, Victor Mercier, in Nice, Martine Gari-Toussaint, Karine Risso, and Loïc Simon, in Nantes, Cedric Bretonnière, David Boutoille, Thomas Gastinne, Karim Lakhal, Elise Launay, Thierry Lepoivre, Pierre Peterlin, Fanny Rialland, and Patrice Le Pape, in Paris, in Hôpital Cochin, Etienne Canoui, Naima Dahane, and Solène Kerneis, in Hôpital Necker-Enfants Malades, Cécile Angebault, Marie-Elisabethh Bougnoux, Nadia Guennouni, Fanny Lanternier, Bennedicte Neven, Mehdi Oualha, Anne Scemla, Emilie Sitterlé, Felipe Suarez, and Julie Toubiana, in Hôpital Robert-Debré, Stéphane Bonacorci, in Hôpital Saint-Louis, Alexandre Alanio, Anne Bergeron, Blandine Denis, Maud Gits-Muselli, Samia Hamane, and Sophie Touratier, in hôpital des XV-XX, Christine Chaumeil and Lilia Merabet, in Pointe-à-Pitre, Joelle Claudéon, Elodie Curlier, Valérie Galantine, Jean Claude Gallois, Samuel Markowicz, Muriel Nicolas, Pascal Musson, and Kinda Schepers, in Poitiers, Alida Minoza and Catherine Kauffmann-Lacroix, in Rennes, Hélène Guégan, in Rouen, Damien Costa, Marion Dehais, and Gilles Gargala, in Reims, Odile Bajolet, Firouze Banisadr, Joel Cousson, Chantal Himberlin, Antoine Huguenin, and Dominique Toubas, in Saint Etienne, Pierre Flori, Caroline Mahinc, and Hélène Raberin, in Strabourg, Julie Denis, Raoul Herbrecht, Paul-Michel Mertes, Fehrat Meziani, Marcela Sabou, and Francis Schneider, in Toulouse, Anne-Isabelle Bertozzi, Pamela Chauvin, Elena Charpentier, Olivier Cointault, Claire Cottrel, Karen Delavigne, Stanislas Faguer, Judith Fillaux, Emilie Guemas, Xavier Iriart, Lucie Lelièvre, and Jean Ruiz, in Tours, Frédéric Bastides, Adélaïde Chesnay, and Guillaume Desoubeaux, in Versailles, Audrey Therby, and in Villejuif, Elisabeth Chachaty and Bertrand Gachot., and CLEMENT, Nathalie

Subjects
Antifungal Agents, pneumocytosis, invasive fungal infections, Pneumonia, Pneumocystis, [SDV]Life Sciences [q-bio], candidemia, Microbiology, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, mucormycosis, [SDV] Life Sciences [q-bio], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Virology, Humans, aspergillosis, epidemiology, Watchful Waiting, Fungemia, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged
Abstract

International audience; The French National Reference Center for Invasive Mycoses and Antifungals leads an active and sustained nationwide surveillance program on probable and proven invasive fungal diseases (IFDs) to determine their epidemiology in France. Between 2012 and 2018, a total of 10,886 IFDs were recorded. The incidence increased slightly over time (2.16 to 2.36/10,000 hospitalization days, P = 0.0562) in relation with an increase of fungemia incidence (1.03 to 1.19/10,000, P = 0.0023), while that of other IFDs remained stable. The proportion of ≥65-year-old patients increased from 38.4% to 45.3% (P < 0.0001). Yeast fungemia (n = 5,444) was due mainly to Candida albicans (55.6%) with stable proportions of species over time. Echinocandins became the main drug prescribed (46.7% to 61.8%), but global mortality rate remained unchanged (36.3% at 1 month). Pneumocystis jirovecii pneumonia (n = 2,106) was diagnosed mostly in HIV-negative patients (80.7%) with a significantly higher mortality than in HIV-positive patients (21.9% versus 5.4% at 1 month, P < 0.0001). Invasive aspergillosis (n = 1,661) and mucormycosis (n = 314) were diagnosed mostly in hematology (>60% of the cases) with a global mortality rate of 42.5% and 59.3%, respectively, at 3 months and significant changes in diagnosis procedure over time. More concurrent infections were also diagnosed over time (from 5.4% to 9.4% for mold IFDs, P = 0.0115). In conclusion, we observed an aging of patients with IFD with a significant increase in incidence only for yeast fungemia, a trend toward more concurrent infections, which raises diagnostic and therapeutic issues. Overall, global survival associated with IFDs has not improved despite updated guidelines and new diagnostic tools.IMPORTANCE The epidemiology of invasive fungal diseases (IFDs) is hard to delineate given the difficulties in ascertaining the diagnosis that is often based on the confrontation of clinical and microbiological criteria. The present report underlines the interest of active surveillance involving mycologists and clinicians to describe the global incidence and that of the main IFDs. Globally, although the incidence of Pneumocystis pneumonia, invasive aspergillosis, and mucormycosis remained stable over the study period (2012 to 2018), that of yeast fungemia increased slightly. We also show here that IFDs seem to affect older people more frequently. The most worrisome observation is the lack of improvement in the global survival rate associated with IFDs despite the increasing use of more sensitive diagnostic tools, the availability of new antifungal drugs very active in clinical trials, and a still low/marginal rate of acquired in vitro resistance in France. Therefore, other tracks of improvement should be investigated actively.

Published
2022

10. Hepatosplenic Candidiasis in Patients With Hematological Malignancies: A 13-Year Retrospective Cohort Study

Author

Boussen, Inès, primary, Lisan, Quentin, additional, Raffoux, Emmanuel, additional, Di Blasi, Roberta, additional, Boissel, Nicolas, additional, Oksenhendler, Eric, additional, Adès, Lionel, additional, Xhaard, Aliénor, additional, Bretagne, Stéphane, additional, Alanio, Alexandre, additional, Molina, Jean-Michel, additional, and Denis, Blandine, additional

Published
2022
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13. Azole resistance of Aspergillus fumigatus in immunocompromised patients with invasive Aspergillosis

Author

Alanio, Alexandre, Denis, Blandine, Hamane, Samia, Raffoux, Emmanuel, de Latour, Regis Peffault, Menotti, Jean, Amorim, Sandy, Touratier, Sophie, Bergeron, Anne, and Bretagne, Stephane

Subjects
Aspergillus -- Physiological aspects -- Research, Microbial drug resistance -- Research, Aspergillosis -- Drug therapy -- Research, Health
Abstract

To the Editor: First-line antifungal therapy for invasive aspergillosis (IA) is voriconazole, which is challenged by the emergence of azole resistance (1). A recent article reported a 3.2% prevalence of [...]

Published
2016

14. Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia

Author

Hermine, Olivier, Mariette, Xavier, Tharaux, Pierre-Louis, Resche-Rigon, Matthieu, Porcher, Raphaël, Ravaud, Philippe, Bureau, Serge, Dougados, Maxime, Tibi, Annick, Azoulay, Elie, Cadranel, Jacques, Emmerich, Joseph, Fartoukh, Muriel, Guidet, Bertrand, Humbert, Marc, Lacombe, Karine, Mahevas, Matthieu, Pene, Frédéric, Pourchet-Martinez, Valérie, Schlemmer, Frédéric, Yazdanpanah, Yazdan, Baron, Gabriel, Perrodeau, Elodie, Vanhoye, Damien, Kedzia, Cécile, Demerville, Lauren, Gysembergh-Houal, Anne, Bourgoin, Alexandre, Dalibey, Sarah, Raked, Nabil, Mameri, Lakhdar, Alary, Stéphanie, Hamiria, Samir, Bariz, Thinhinane, Semri, Hala, Hai, Dhiaa Meriem, Benafla, Moustafa, Belloul, Mohamed, Vauboin, Pernelle, Flamand, Saskia, Pacheco, Claire, Walter-Petrich, Anouk, Stan, Emilia, Benarab, Souad, Nyanou, Corine, Montlahuc, Claire, Biard, Lucie, Charreteur, Robin, Dupré, Celine, Cardet, Kévin, Lehmann, Blandine, Baghli, Kamyl, Madeleine, Claire, DOrtenzio, Eric, Puéchal, Oriane, Semaille, Caroline, Savale, Laurent, Harrois, Anatole, Figueiredo, Samy, Duranteau, Jacques, Anguel, Nadia, Monnet, Xavier, Richard, Christian, Teboul, Jean-Louis, Durand, Philippe, Tissieres, Pierre, Jevnikar, Mitja, Montani, David, Pavy, Stéphan, Noel, Nicolas, Lambotte, Olivier, Escaut, Lelia, Jauréguiberry, Stéphane, Baudry, Elodie, Verny, Christiane, Lefèvre, Edouard, Zaidan, Mohamad, Le Tiec, Clotilde Le Tiec, Verstuyft, Céline Verstuyft, Roques, Anne-Marie, Grimaldi, Lamiae, Molinari, Domitille, Leprun, Gaël, Fourreau, Alain, Cylly, Laurent, Virlouvet, Myriam, Meftali, Ramdane, Fabre, Solène, Licois, Marion, Mamoune, Asmaa, Boudali, Yacine, Georgin-Lavialle, Sophie, Senet, Patricia, Soria, Angèle, Parrot, Antoine, François, Hélène, Rozensztajn, Nathalie, Blin, Emmanuelle, Choinier, Pascaline, Camuset, Juliette, Rech, Jean-Simon, Canellas, Antony, Rolland-Debord, Camille, Lemarié, Nadège, Belaube, Nicolas, Nadal, Marine, Siguier, Martin, Petit-Hoang, Camille, Chas, Julie, Drouet, Elodie, Lemoine, Matthieu, Phibel, Audrey, Aunay, Lucie, Bertrand, Eliane, Ravato, Sylviane, Vayssettes, Marie, Adda, Anne, Wilpotte, Celine, Thibaut, Pélagie, Fillon, Julie, Debrix, Isabelle, Fellahi, Soraya, Bastard, Jean-Philippe, Lefèvre, Guillaume, Fallet, Vincent, Gottenberg, Jacques-Eric, Hansmann, Yves, Andres, Emmanuel, Bayer, Sophie, Becker, Guillaume, Blanc, Frédéric, Brin, Stéphane, Castelain, Vincent, Chatelus, Emmanuel, Chatron, Eva, Collange, Olivier, Danion, François, De Blay, Frédéric, Demonsant, Eric, Diemunsch, Pierre, Diemunsch, Sophie, Felten, Renaud, Goichot, Bernard, Greigert, Valentin, Guffroy, Aurélien, Heger, Bob, Hutt, Anne, Kaeuffer, Charlotte, Kassegne, Loic, Korganow, Anne Sophie, Le Borgne, Pierrick, Lefebvre, Nicolas, Martin, Tristan, Mertes, Paul Michel, Metzger, Catherine, Meyer, Nicolas, Nisand, Gabriel, Noll, Eric, Oberlin, Mathieu, Ohlmann-Caillard, Sophie, Poindron, Vincent, Pottecher, Julien, Ruch, Yvon, Sublon, Cédric, Tayebi, Hakim, Weill, François, Mekinian, Arsène, Chopin, Dorothée, Fain, Olivier, Garnier, Marc, Krause Le Garrec, Jessica, Morgand, Marjolaine, Pacanowski, Jerome, Urbina, Tomas, Mcavoy, Chloe, Pereira, Maria, Aratus, Gladys, Berard, Laurence, Simon, Tabassome, Daguenel Nguyen, Anne, Antignac, Marie, Leplay, Céline, Arlet, Jean-Benoit, Diehl, Jean-Luc, Bellenfant, Florence, Blanchard, Anne, Buffet, Alexandre, Cholley, Bernard, Fayol, Antoine, Flamarion, Edouard, Godier, Anne, Gorget, Thomas, Hamada, Sophie-Rym, Hauw-Berlemont, Caroline, Hulot, Jean- Se´bastien, Lebeaux, David, Livrozet, Marine, Michon, Adrien, Neuschwander, Arthur, Penet, Marie-Aude, Planquette, Benjamin, Ranque, Brigitte, Sanchez, Olivier, Volle, Geoffroy, Briois, Sandrine, Cornic, Mathias, Elisee, Virginie, Jesuthasan, Denis, Djadi-Prat, Juliette, Jouany, Pauline, Junquera, Ramon, Henriques, Mickael, Kebir, Amina, Lehir, Isabelle, Meunier, Jeanne, Patin, Florence, Paquet, Vale´rie, Tre´Han, Anne, Vigna, Ve´ronique, Sabatier, Brigitte, Bergerot, Damien, Jouve, Charle`ne, Knosp, Camille, Lenoir, Olivia, Mahtal, Nassim, Resmini, Léa, Lescure, Xavier, Ghosn, Jade, Bachelard, Antoine, Bironne, Timothee, Borie, Raphael, Bounhiol, Agathe, Boussard, Catherine, Chauffier, Jeanne, Chalal, Solaya, Chalal, Lynda, Chansombat, Malikhone, Crespin, Paul, Crestani, Bruno, Daconceicao, Olivia, Deconinck, Laurene, Dieude, hilippe, Dossier, Antoine, Dubert, Marie, Ducrocq, Greggory, Fuentes, Axelle, Gervais, Anne, Gilbert, Marie, Isernia, Valentina, Ismael, Sophie, Joly, Veronique, Julia, Zelie, Lariven, Sylvie, Le Gac, Sylvie, Le Pluart, Diane, Louni, Francoise, Ndiaye, Awa, Papo, Thomas, Parisey, Marion, Phung, Bao, Pourbaix, Annabelle, Rachline, Anne, Rioux, Christophe, Sautereau, Aurelie, Steg, Gabriel, Tharini, Hassan, Valayer, Simon, Vallois, Dorothee, Vermes, Paul, Volpe, Thomas, Nguyen, Yann, Honsel, Vasco, Weiss, Emmanuel, Codorniu, Anaïs, Zarrouk, Virginie, De Lastours, Victoire, Uzzan, Matthieu, Gamany, Naura, Rahli, Roza, Louis, Zeina, Boutboul, David, Galicier, Lionel, Amara, Yaël, Archer, Gabrielle, Benattia, Amira, Bergeron, Anne, Bondeelle, Louise, De Castro, Nathalie, Clément, Melissa, Darmont, Michaël, Denis, Blandine, Dupin, Clairelyne, Feredj, Elsa, Feyeux, Delphine, Joseph, Adrien, Lengliné, Etienne, Le Guen, Pierre, Liégeon, Geoffroy, Lorillon, Gwenaël, Mabrouki, Asmaa, Mariotte, Eric, Martin De Frémont, Grégoire, Mirouse, Adrien, Molina, Jean-Michel, Peffault De Latour, Régis, Oksenhendler, Eric, Saussereau, Julien, Tazi, Abdellatif, Tudesq, Jean-Jacques, Zafrani, Lara, Brindele, Isabelle, Bugnet, Emmanuelle, Celli Lebras, Karine, Chabert, Julien, Djaghout, Lalia, Fauvaux, Catherine, Jegu, Anne Lise, Kozaliewicz, Ewa, Meunier, Martine, Tremorin, Marie-Thérèse, Davoine, Claire, Madeleine, Isabelle, Caillat-Zucman, Sophie, Delaugerre, Constance, Morin, Florence, Sene, Damien, Burlacu, Ruxandra, Chousterman, Benjamin, Megarbane, Bruno, Richette, Pascal, Riveline, Jean-Pierre, Frazier, Aline, Vicaut, Eric, Berton, Laure, Hadjam, Tassadit, Vasquez-Ibarra, Miguel Alejandro, Jourdaine, Clément, Jacob, Aude, Smati, Julie, Renaud, Stéphane, Manivet, Philippe, Pernin, Claire, Suarez, Lydia, Semerano, Luca, Abad, Sebastien, Benainous, Ruben, Bloch Queyrat, Coralie, Bonnet, Nicolas, Brahmi, Sabrina, Cailhol, johann, Cohen, Yves, Comparon, Celine, Cordel, Hugues, Dhote, Robin, Dournon, Nathalie, Duchemann, Boris, Ebstein, Nathan, Giroux-Leprieur, Benedicte, Goupil De Bouille, Jeanne, Jacolot, Anne, Nunes, Hilario, Oziel, Johanna, Rathouin, Vanessa, Rigal, Marthe, Roulot, Dominique, Tantet, Claire, Uzunhan, Yurdagul, Costedoat-Chalumeau, Nathalie, Ait Hamou, Zakaria, Benghanem, Sarah, Blanche, Philippe, Canoui, Etienne, Carlier, Nicolas, Chaigne, Benjamin, Contejean, Adrien, Dunogue, Bertrand, Dupland, Pierre, Durel - Maurisse, Aurélie, Gauzit, Remy, Jaubert, Paul, Joumaa, Hassan, Jozwiak, Mathieu, Kerneis, Solen, Lachatre, Marie, Lafoeste, Hélène, Legendre, Paul, Luong Nguyen, Liem Binh, Marey, Jonathan, Morbieu, Caroline, Mouthon, Luc, Nguyen, Lee, Palmieri, Lola-Jade, Regent, Alexis, Szwebel, Tali-Anne, Terrier, Benjamin, Guerin, Corinne, Zerbit, Jérémie, Cheref, Kahina, Chitour, Kamil, Cisse, Mamadou Salif, Clarke, Ada, Clavere, Gaelle, Dusanter, Isabelle, Gaudefroy, Caroline, Jallouli, Moez, Kolta, Sami, Le Bourlout, Catherine, Marin, Nathalie, Menage, Nathalie, Moores, Alexandre, Peigney, Isabelle, Pierron, Cédric, Saleh-Mghir, Samira, Vallet, Mathilde, Michel, Marc, Melica, Giovanna, Lelievre, Jean-Daniel, Fois, Elena, Lim, Pascal, Matignon, Marie, Guillaud, Constance, Thiemele, Alaki, Schmitz, David, Bouhris, Marion, Belazouz, Syllia, Languille, Laetitia, Mekontso-Dessaps, Armand, Sadaoui, Thiziri, Mayaux, Julien, Cacoub, Patrice, Corvol, Jean-Christophe, Louapre, Céline, Sambin, Sara, Mariani, Louise-Laure, Karachi, Carine, Tubach, Florence, Estellat, Candice, Gimeno, Linda, Martin, Karine, Bah, Aïcha, Keo, Vixra, Ouamri, Sabrine, Messaoudi, Yasmine, Yelles, Nessima, Faye, Pierre, Cavelot, Sébastien, Larcheveque, Cecile, Annonay, Laurence, Benhida, Jaouad, Zahrate-Ghoul, Aida, Hammal, Soumeya, Belilita, Ridha, Lecronier, Marie, Beurton, Alexandra, Haudebourg, Luc, Deleris, Robin, Le Marec, Julien, Virolle, Sara, Nemlaghi, Safaa, Bureau, Côme, Mora, Pierre, De Sarcus, Martin, Clovet, Olivier, Duceau, Baptiste, Grisot, Paul Henri, Pari, Marie hélène, Arzoine, Jérémy, Clarac, Ulrich, Faure, Morgane, Delemazure, Julie, Decavele, Maxence, Morawiec, Elise, Demoule, Alexandre, Dres, Martin, Vautier, Mathieu, Allenbach, Yves, Benveniste, Olivier, Leroux, Gaelle, Rigolet, Aude, Guillaume-Jugnot, Perrine, Domont, Fanny, Desbois, Anne Claire, Comarmond, Cloé, Champtiaux, Nicolas, Toquet, Segolene, Ghembaza, Amine, Vieira, Matheus, Maalouf, Georgina, Boleto, Gonçalo, Ferfar, Yasmina, Charbonnier, Fanny, Aguilar, Claire, Alby-Laurent, Fanny, Alyanakian, Marie-Alexandra, Bakouboula, Prissile, Broissand, Christine, Burger, Carole, Campos-Vega, Clara, Chavarot, Nathalie, Choupeaux, Laure, Elie, Caroline, Fournier, Benjamin, Granville, Sophie, Issorat, Elodie, Rouzaud, Claire, Vimpere, Damien, Geri, Guillaume, Derridj, Nawal, Sguiouar, Naima, Meddah, Hakim, Djadel, Mourad, Chambrin-Lauvray, Helene, Duclos-Vallée, Jean-Charles, Saliba, Faouzi, Sacleux, Sophie-Caroline, Koumis, Ilias, Michot, Jean-Marie, Stoclin, Annabelle, Colomba, Emeline, Pommeret, Fanny, Willekens, Chistophe, Da Silva, Rosa, Dejean, Valérie, Mekid, Yasmina, Ben-Mabrouk, Ines, Pradon, Caroline, Drouard, Laurence, Camara-Clayette, Valérie, Morel, Alexandre, Garcia, Gilles, Mohebbi, Abolfazl, Berbour, Férial, Dehais, Mélanie, Pouliquen, Anne-Lise, Klasen, Alison, Soyez-Herkert, Loren, London, Jonathan, Keroumi, Younes, Guillot, Emmanuelle, Grailles, Guillaume, El Amine, Younes, Defrancq, Fanny, Fodil, Hanane, Bouras, Chaouki, Dautel, Dominique, Gambier, Nicolas, Dieye, Thierno, Bienvenu, Boris, Lancon, Victor, Lecomte, Laurence, Beziriganyan, Kristina, Asselate, Belkacem, Allanic, Laure, Kiouris, Elena, Legros, Marie-Hélène, Lemagner, Christine, Martel, Pascal, Provitolo, Vincent, Ackermann, Félix, Le Marchand, Mathilde, Clan Hew Wai, Aurélie, Fremont, Dimitri, Coupez, Elisabeth, Adda, Mireille, Duée, Frédéric, Bernard, Lise, Gros, Antoine, Henry, Estelle, Courtin, Claire, Pattyn, Anne, Guinot, Pierre-Grégoire, Bardou, Marc, Maurer, Agnes, Jambon, Julie, Cransac, Amélie, Pernot, Corinne, Mourvillier, Bruno, Servettaz, Amélie, Deslée, Gaetan, Wynckel, Alain, Benoit, Philippe, Marquis, Eric, Roux, Damien, Gernez, Coralie, Yelnik, Cécile, Poissy, Julien, Nizard, Mandy, Denies, Fanette, Gros, Hélène, Mourad, Jean-Jacques, Sacco, Emmanuelle, Renet, Sophie, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), 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), 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 Paris Cité (UPCité), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hopital Saint-Louis [AP-HP] (AP-HP), Centre d'épidémiologie Clinique [Hôtel-Dieu], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Hôtel Dieu, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Centre de recherche en Myologie – U974 SU-INSERM, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CORIMUNO-19 Collaborative Group, Porcher, Raphaël, Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), and ANR-21-COVR-0024,ACT-LONG-COVID,Caractérisation clinique et biologique du syndrome d'activation mastocytaire dans le COVID long et prédisposition génétique(2021)

Subjects
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal Medicine
Abstract

International audience; Importance Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19).Objective To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia.Design, Setting, and Particpants This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes.Interventions Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants.Main Outcomes and Measures Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events.Results Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21).Conclusions and Relevance In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care unit, TCZ did not reduce WHO-CPS scores lower than 5 at day 4 but might have reduced the risk of NIV, MV, or death by day 14. No difference on day 28 mortality was found. Further studies are necessary for confirming these preliminary results.Trial Registration ClinicalTrials.gov Identifier: NCT04331808

Published
2021
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15. Hepatitis Rebound after Infection with Yellow Fever Virus

Author

Denis, Blandine, Chirio, David, Ponscarme, Diane, Brichler, Segolene, de Verdiere, Nathalie Colin, Simon, Francois, and Molina, Jean-Michel

Subjects
Yellow fever -- Diagnosis -- Health aspects, Travelers -- Health aspects, Hepatitis -- Diagnosis -- Health aspects, Enzymes -- Health aspects, Liver -- Health aspects, HIV, Immune response, Pathogenic microorganisms, RNA, Vaccination, Health
Abstract

Although most cases of yellow fever are asymptomatic, some lead to severe liver disease, caused by liver cell cytolysis. In February 2018, yellow fever with hepatitis was diagnosed for 2 [...]

Published
2019
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16. Variable Correlation between Bronchoalveolar Lavage Fluid Fungal Load and Serum-(1,3)-β-d-Glucan in Patients with Pneumocystosis—A Multicenter ECMM Excellence Center Study

Author

Mercier, Toine, primary, Aissaoui, Nesrine, additional, Gits-Muselli, Maud, additional, Hamane, Samia, additional, Prattes, Juergen, additional, Kessler, Harald H., additional, Mareković, Ivana, additional, Pleško, Sanja, additional, Steinmann, Jörg, additional, Scharmann, Ulrike, additional, Maertens, Johan, additional, Lagrou, Katrien, additional, Denis, Blandine, additional, Bretagne, Stéphane, additional, and Alanio, Alexandre, additional

Published
2020
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18. COVID‐19–Related IgA Vasculitis

Author

Allez, Matthieu, primary, Denis, Blandine, additional, Bouaziz, Jean‐David, additional, Battistella, Maxime, additional, Zagdanski, Anne‐Marie, additional, Bayart, Jules, additional, Lazaridou, Ingrid, additional, Gatey, Caroline, additional, Pillebout, Evangeline, additional, Chaix Baudier, Marie‐Laure, additional, Delaugerre, Constance, additional, Molina, Jean‐Michel, additional, and Le Goff, Jérôme, additional

Published
2020
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19. COVID-19 Infection in Kidney Transplant Recipients: Disease Incidence and Clinical Outcomes

Author

Elias, Michelle, primary, Pievani, Daniele, additional, Randoux, Christine, additional, Louis, Kevin, additional, Denis, Blandine, additional, Delion, Alexandra, additional, Le Goff, Océane, additional, Antoine, Corinne, additional, Greze, Clarisse, additional, Pillebout, Evangeline, additional, Abboud, Imad, additional, Glotz, Denis, additional, Daugas, Eric, additional, and Lefaucheur, Carmen, additional

Published
2020
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20. Profiles and outcomes in patients with COVID-19 admitted to wards of a French oncohematological hospital: A clustering approach.

Author

Bondeelle, Louise, Chevret, Sylvie, Cassonnet, Stéphane, Harel, Stéphanie, Denis, Blandine, de Castro, Nathalie, and Bergeron, Anne

Subjects
COVID-19, SURVIVAL rate, PROGNOSIS, OLDER patients, PHYSICIANS
Abstract

Objectives: Although some prognostic factors for COVID-19 were consistently identified across the studies, differences were found for other factors that could be due to the characteristics of the study populations and the variables incorporated into the statistical model. We aimed to a priori identify specific patient profiles and then assess their association with the outcomes in COVID-19 patients with respiratory symptoms admitted specifically to hospital wards. Methods: We conducted a retrospective single-center study from February 2020 to April 2020. A non-supervised cluster analysis was first used to detect patient profiles based on characteristics at admission of 220 consecutive patients admitted to our institution. Then, we assessed the prognostic value using Cox regression analyses to predict survival. Results: Three clusters were identified, with 47 patients in cluster 1, 87 in cluster 2, and 86 in cluster 3; the presentation of the patients differed among the clusters. Cluster 1 mostly included sexagenarian patients with active malignancies who were admitted early after the onset of COVID-19. Cluster 2 included the oldest patients, who were generally overweight and had hypertension and renal insufficiency, while cluster 3 included the youngest patients, who had gastrointestinal symptoms and delayed admission. Sixty-day survival rates were 74.3%, 50.6% and 96.5% in clusters 1, 2, and 3, respectively. This was confirmed by the multivariable Cox analyses that showed the prognostic value of these patterns. Conclusion: The cluster approach seems appropriate and pragmatic for the early identification of patient profiles that could help physicians segregate patients according to their prognosis. [ABSTRACT FROM AUTHOR]

Published
2021
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21. Variable Correlation between Bronchoalveolar Lavage Fluid Fungal Load and Serum-(1,3)-βD-Glucan in Patients with Pneumocystosis--A Multicenter ECMM Excellence Center Study.

Author

Mercier, Toine, Aissaoui, Nesrine, Gits-Muselli, Maud, Hamane, Samia, Prattes, Juergen, Kessler, Harald H., Mareković, Ivana, Pleško, Sanja, Steinmann, Jörg, Scharmann, Ulrike, Maertens, Johan, Lagrou, Katrien, Denis, Blandine, Bretagne, Stéphane, and Alanio, Alexandre

Subjects
BRONCHOALVEOLAR lavage, SERUM, PNEUMOCYSTIS pneumonia, BACTERIAL diseases, BIOMARKERS
Abstract

Pneumocystis jirovecii pneumonia is a difficult invasive infection to diagnose. Apart from microscopy of respiratory specimens, two diagnostic tests are increasingly used including real-time quantitative PCR (qPCR) of respiratory specimens, mainly in bronchoalveolar lavage fluids (BAL), and serum β-1,3-D-glucan (BDG). It is still unclear how these two biomarkers can be used and interpreted in various patient populations. Here we analyzed retrospectively and multicentrically the correlation between BAL qPCR and serum BDG in various patient population, including mainly non-HIV patients. It appeared that a good correlation can be obtained in HIV patients and solid organ transplant recipients but no correlation can be observed in patients with hematologic malignancies, solid cancer, and systemic diseases. This observation reinforces recent data suggesting that BDG is not the best marker of PCP in non-HIV patients, with potential false positives due to other IFI or bacterial infections and false-negatives due to low fungal load and low BDG release. [ABSTRACT FROM AUTHOR]

Published
2020
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22. Invasive Infections with Nannizziopsis obscura Species Complex in 9 Patients from West Africa, France, 2004-20201.

Author

Garcia-Hermoso, Dea, Hamane, Samia, Fekkar, Arnaud, Jabet, Arnaud, Denis, Blandine, Siguier, Martin, Galeazzi, Guy, Haddad, Elie, Brun, Sophie, Vidal, Valérie, Nevez, Gilles, Le Berre, Rozenn, Gits-Muselli, Maud, Lanternier, Fanny, and Bretagne, Stéphane

Subjects
SEQUENCE analysis, CLINICAL drug trials, INFECTION, ETIOLOGY of diseases, REPTILES, ANTIFUNGAL agents, RESEARCH, ANIMAL experimentation, RESEARCH methodology, FUNGI, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies, MICROBIAL sensitivity tests, PHARMACODYNAMICS
Abstract

Nine new human invasive infections caused by the keratinophilic fungi Nannizziopsis obscura have been reported in France since 2004. The patients had variable clinical manifestations, had frequent dissemination, were mainly T-cell immunocompromised, and all originated from sub-Saharan West Africa. Before collection of the isolates, the etiologies of these infections were often misidentified, underscoring the extent of microscopic and cultural polymorphisms. All isolates but 1 had low MICs for the 8 antifungal drugs tested. When treated, patients received mainly azole therapy. Two of 7 patients with a known outcome died. We performed multilocus sequence analysis of N. obscura clinical strains and several strains of Nannizziopsis spp. isolated from reptiles. The human strains were clearly differentiated from the animal strains. N. obscura might be endemic to West Africa and responsible for undetected infections, which might become reactivated when immunosuppression occurs. N. obscura infection is probably underestimated because only sequencing enables proper identification. [ABSTRACT FROM AUTHOR]

Published
2020
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25. Infections fongiques chez les patients infectés par le VIH à l'ère des combinaisons antirétrovirales (cART) : étude des pneumocystoses et aspergilloses invasives sur la base FHDH

Author

Denis, Blandine, STAR, ABES, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris VI, Dominique Costagliola, and Olivier Lortholary

Subjects
Épidémiologie, Fungal infections, SIDA, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Pneumocystose, Aspergillose invasive, HIV, VIH, Évolution, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pneumocystis jirovecii pneumonia, Invasive aspergillosis (IA)
Abstract

The advent of combined antiretroviral therapy (cART) in 1996 resulted in a dramatic fall in the incidence of AIDS-defining illness (ADI), including Pneumocystis jirovecii pneumonia (PCP). Nevertheless, PCP was the second most frequent ADI in France in 2001-2003 and fungal infections remain a major threat for HIV-infected individuals worldwide. Epidemiological data on fungal infections in the late cART period in resource-rich settings are scarce. The purpose of our work was to study changes in the epidemiology of fungal infections among HIV-infected individuals in France in the late cART period, focusing on PCP and invasive aspergillosis (IA) in the French Hospital Database on HIV ANRS CO4 (FHDH). In the FHDH, during the 2004-2011 period, half of the 1259 PCP cases occurred among HIV-infected individuals who had waning adherence to care, and for those who had a prior ADI before PCP the 3-year mortality rate was 25%. For the second study on IA, a review committee validated IA cases among all the cases that included a diagnostic code for aspergillosis (ICD-9 or ICD-10) in the FHDH over a 20-year period. Our study demonstrated that only half of validated IA cases among HIV-infected individuals met EORTC criteria. The 3-months survival rate after IA diagnosis improved after the advent of cART and a protective role of voriconazole was observed in the period after 2001., Depuis la disponibilité des combinaisons antirétrovirales (cART) en 1996, l’incidence des infections opportunistes classantes SIDA (IO), dont la pneumocystose (PCP) a très fortement diminué. Malgré tout, chez les patients infectés par le VIH, la PCP était la 2ème IO la + fréquente en France en 2001-2003 et les infections fongiques, avec 1 million de nouveaux cas/an de cryptococcose, restent un problème de santé publique majeur au niveau mondial. Cependant, depuis l’ère des cART, très peu de recherches épidémiologiques sur les infections fongiques dans les pays industrialisés ont été entreprises. C’est dans ce contexte que nous avons mené une étude épidémiologique de 2 infections fongiques chez les patients infectés par le VIH en France sur la French Hospital Database on HIV ANRS CO4 (FHDH) : la pneumocystose et l’aspergillose invasive. Concernant la pneumocystose, sur la période 2004-2011, dans la base FHDH, la moitié des 1259 cas de PCP étaient survenus chez des patients qui avaient interrompus leur suivi, et, pour ceux qui avaient déjà eu une IO avant la PCP, leur mortalité était de 25% à 3 ans. Pour l’aspergillose invasive (AI), après un retour national aux dossiers des cas déclarés sur 20 ans sur la base FHDH, un comité d’experts a validé 242 cas d’AI. Les données montrent que, chez les patients infectés par le VIH, seulement la moitié des AI validées répondaient aux critères EORTC. La mortalité à 3 mois après une AI s’est améliorée après l’ère des cART et un rôle protecteur du voriconazole sur la survie à 3 mois a également été démontré pour la 1ère fois chez les patients infectés par le VIH.

Published
2016

26. Inherited CARD9 deficiency in otherwise healthy children and adults with meningo-encephalitis and/or colitis caused by Candida

Author

Lanternier, Fanny, Mahdaviani, Seyed Alireza, Barbati, Elisa, Chaussade, Hélène, Koumar, Yatrika, Levy, Romain, Denis, Blandine, Brunel, Anne-Sophie, Martin, Sophie, Loop, Michèle, Peeters, Julie, de Selys, Ariel, Vanclaire, Jean, Vermylen, Christiane, Nassogne, Marie-Cécile, Chatzis, Olga, Liu, Luyan, Migaud, Mélanie, Pedergnana, Vincent, Desoubeaux, Guillaume, Jouvion, Gregory, Chretien, Fabrice, Darazam, Ilad Alavi, Schäffer, Alejandro A., Netea, Mihai G., De Bruycker, Jean-Jacques, Bernard, Louis, Reynes, Jacques, Amazrine, Noureddine, Abel, Laurent, Van der Linden, Dimitri, Harrison, Tom, Picard, Capucine, Lortholary, Olivier, Mansouri, Davood, Casanova, Jean-Laurent, and Puel, Anne

Subjects
Adult, Central Nervous System, Male, Adolescent, Homozygote, Gene Expression, Sequence Analysis, DNA, Colitis, Article, Pedigree, CARD Signaling Adaptor Proteins, Gastrointestinal Tract, Consanguinity, Genetic Loci, Meningoencephalitis, Humans, Candidiasis, Invasive, Female, Child, Candida, Genome-Wide Association Study
Abstract

Invasive infections of the central nervous system (CNS) or digestive tract caused by commensal fungi of the genus Candida are rare and life-threatening. The known risk factors include acquired and inherited immunodeficiencies, with patients often displaying a history of multiple infections. Cases of meningoencephalitis, colitis, or both caused by Candida species remain unexplained.We studied 5 previously healthy children and adults with unexplained invasive disease of the CNS, digestive tract, or both caused by Candida species. The patients were aged 39, 7, 17, 37, and 26 years at the time of infection and were unrelated, but each was born to consanguineous parents of Turkish (2 patients), Iranian, Moroccan, or Pakistani origin. Meningoencephalitis was reported in 3 patients, meningoencephalitis associated with colitis was reported in a fourth patient, and the fifth patient had colitis only.Inherited caspase recruitment domain family, member 9 (CARD9) deficiency was recently reported in otherwise healthy patients with other forms of severe disease caused by Candida, Trichophyton, Phialophora, and Exophiala species, including meningoencephalitis but not colitis caused by Candida and Exophiala species. Therefore we sequenced CARD9 in the 5 patients.All patients were found to be homozygous for rare and deleterious mutant CARD9 alleles: R70W and Q289* for the 3 patients with Candida albicans-induced meningoencephalitis, R35Q for the patient with meningoencephalitis and colitis caused by Candida glabrata, and Q295* for the patient with Candida albicans-induced colitis. Regardless of their levels of mutant CARD9 protein, the patients' monocyte-derived dendritic cells responded poorly to CARD9-dependent fungal agonists (curdlan, heat-killed C albicans, Saccharomyces cerevisiae, and Exophiala dermatitidis).Invasive infections of the CNS or digestive tract caused by Candida species in previously healthy children and even adults might be caused by inherited CARD9 deficiency.

Published
2015

28. Dual Invasive Infection with Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides in a Renal Transplant Recipient: Case Report and Comprehensive Review of the Literature of Phaeoacremonium Phaeohyphomycosis

Author

Colombier, Marie-Alice, primary, Alanio, Alexandre, additional, Denis, Blandine, additional, Melica, Giovanna, additional, Garcia-Hermoso, Dea, additional, Levy, Bénédicte, additional, Peraldi, Marie-Noëlle, additional, Glotz, Denis, additional, Bretagne, Stéphane, additional, and Gallien, Sébastien, additional

Published
2015
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29. Critical Importance of Long-Term Adherence to Care in HIV Infected Patients in the cART Era: New Insights from Pneumocystis jirovecii Pneumonia Cases over 2004–2011 in the FHDH-ANRS CO4 Cohort

Author

Denis, Blandine, primary, Guiguet, Marguerite, additional, de Castro, Nathalie, additional, Mechaï, Frédéric, additional, Revest, Matthieu, additional, Mahamat, Aba, additional, Gregoire, Giovanna Melica, additional, Lortholary, Olivier, additional, and Costagliola, Dominique, additional

Published
2014
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32. Critical Importance of Long-Term Adherence to Care in HIV Infected Patients in the cART Era: New Insights from Pneumocystis jirovecii Pneumonia Cases over 2004–2011 in the FHDH-ANRS CO4 Cohort.

Author

Denis, Blandine, Guiguet, Marguerite, de Castro, Nathalie, Mechaï, Frédéric, Revest, Matthieu, Mahamat, Aba, Gregoire, Giovanna Melica, Lortholary, Olivier, and Costagliola, Dominique

Subjects
*MEDICAL care of HIV-positive persons, *PNEUMONIA, *CD4 antigen, *KAPLAN-Meier estimator, *VIROLOGY, HOSPITAL information systems
Abstract

Objective: To describe characteristics and outcomes of HIV-infected patients with Pneumocystis jirovecii pneumonia (PCP) over 2004–2011 in France, in particular in those previously enrolled (PE) in the French Hospital Database on HIV (FHDH). Methods: PE patients with an incident PCP were compared with patients with an inaugural PCP revealing HIV infection (reference). Adequate adherence to care was defined as a CD4 measurement at least every 6 months. Immune reconstitution (CD4≥200/mm3) and risk of death were studied using Kaplan-Meier estimates and multivariable Cox proportional hazards models. Results: In a context of a decreasing incidence of PCP, 1259 HIV-infected patients had a PCP diagnosis, and 593 (47%) were PE patients of whom 161 (27%) have had a prior history of AIDS-defining clinical illness (prior ADI). Median time since enrolment was 8 years for PE patients; 74% had received cART. Median proportion of time with adequate adherence to care was 85% (IQR, 66–96) for all FHDH enrollees, but only 45% (IQR, 1–81) for PE patients during the 2 years before PCP. Median CD4 cell count (38/mm3) and HIV viral load (5.2 log10 copies/ml) at PCP diagnosis did not differ between PE patients and the reference group. Three year mortality rate of 25% was observed for PE prior ADI group, higher than in PE non-prior ADI group (8%) and the reference group (9%) (p<0.0001). In the PE prior ADI group, poor prognosis remained even after adjustment for virological control and immune reconstitution (HR, 2.4 [95%CI, 1.5–3.7]). Conclusion: Almost 50% of PCP diagnoses in HIV-infected patients occurred presently in patients already in care, mainly with a previous cART prescription but with waning adherence to care. Having repeated ADI is contributing to the risk of death beyond its impact on immune reconstitution and viral suppression: special efforts must be undertaken to maintain those patients in care. [ABSTRACT FROM AUTHOR]

Published
2014
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33. Dual Invasive Infection with Phaeoacremonium parasiticumand Paraconiothyrium cyclothyrioidesin a Renal Transplant Recipient: Case Report and Comprehensive Review of the Literature of PhaeoacremoniumPhaeohyphomycosis

Author

Colombier, Marie-Alice, Alanio, Alexandre, Denis, Blandine, Melica, Giovanna, Garcia-Hermoso, Dea, Levy, Bénédicte, Peraldi, Marie-Noëlle, Glotz, Denis, Bretagne, Stéphane, and Gallien, Sébastien

Abstract

ABSTRACTDespite increasing reports of human infection, data about the optimal care of Phaeoacremoniuminfections are missing. We report a case of an infection due to Phaeoacremonium parasiticumand Paraconiothyrium cyclothyrioides, initially localized to skin and soft tissue, in a kidney transplant patient. Despite surgical drainage and excision of the lesion and combination antifungal therapy with voriconazole and liposomal amphotericin B, a disseminated infection involving the lungs and brain developed and led to death. We performed a systematic literature review to assess the general features and outcome of human infections due to Phaeoacremoniumspecies. Thirty-six articles were selected, and 42 patients, including ours, were reviewed. Thirty-one patients (74%) were immunocompromised because of organ or bone marrow transplantation (n= 17), diabetes or glucose intolerance (n= 10), rheumatoid arthritis or Still's disease (n= 4), chronic hematological diseases (n= 3), or chronic granulomatous disease (n= 3). Ten patients (24%) reported initial cutaneous trauma. Skin and soft tissue infections represented 57% of infections (n= 24), and disseminated infections, all occurring in immunocompromised patients, represented 14% of infections (n= 6). The main antifungal drugs used were azoles (n= 41) and amphotericin B (n= 16). Surgical excision or drainage was performed in 64% of cases (n= 27). The cure rate was 67% (n= 28). There were 10% cases of treatment failure or partial response (n= 4), 19% relapses (n= 8), and 7% losses to follow-up (n= 3). The death rate was 19% (n= 8). Management of Phaeoacremoniuminfections is complex because of slow laboratory identification and limited clinical data, and treatment relies on a combination of surgery and systemic antifungal therapy.

Published
2015
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35. Evaluation of a New Histoplasmaspp. Quantitative RT-PCR Assay

Author

Alanio, Alexandre, Gits-Muselli, Maud, Lanternier, Fanny, Sturny-Leclère, Aude, Benazra, Marion, Hamane, Samia, Rodrigues, Anderson Messias, Garcia-Hermoso, Dea, Lortholary, Olivier, Dromer, Françoise, Bretagne, Stéphane, Woimant, Marine Gosset, blanchard, Geneviève, Silhadi, Souad, Vignier, Nicolas, Pitsch, Aurelia, Jidar, Kaoutar, Traversier, Nicolas, Poisson, Didier, Lecointre, Claire, Foulet, Françoise, Botterel, Françoise, Ammar, Nawel Ait, Amsellem, Gabriel, Frederic, Poirier, Philipe, Cornu, Marjorie, Loridant, Severine, Morio, Florent, Boutoille, David, Jeddi, Fakhri, Hasseine, Lilia, Ouissa, Rachida, Toubas, Dominique, Bailly, Eric, Désoubeaux, Guillaume, Ronez, Emily, Foulon, Guillaume, Lefrançois, Sebastien, Bonnal, Christine, Paugam, André, Dougados, Maxime, Desroches, Marine, Barazzutti, Hélène, Paleiron, Nicolas, rabodonirina, Meja, Catherinot, Emilie, Cardot-Martin, Emilie, Hiesse, Chrisian, Salvator, Hélène, Aguilar, Claire, Gigandon, Anne, de Montpreville, Thomas, Bougnoux, Marie-Elisabeth, Sitterlé, Emilie, Fekkar, Arnaud, Imbert, Sébastien, Bleibtreu, Alexandre, Senghor, Yaye, Denis, Blandine, Molina, Jean-Michel, Liegeon, Geoffroy, Munnier, Anne-Lise, Malphettes, Marion, Denis, Julie, Berlioz-Arthaud, Alain, Lange, Franciska, Chiaruzzi, Myriam, and Epelboin, Loic

Abstract

Laboratory diagnosis of histoplasmosis is based on various methods, including microscopy, culture, antigen, and DNA detection of Histoplasma capsulatumvar. capsulatumor Histoplasma capsulatumvar. duboisii. To improve sensitivity of existing real-time quantitative PCR (qPCR) assays, we developed a new RT-qPCR assay that allows amplification of whole nucleic acids of Histoplasmaspp. validated on suspected cases. The limit of detection was 20 copies, and the specificity against 114 fungal isolates/species was restricted to Histoplasmaspp.. Whole nucleic acids of 1319 prospectively collected consecutive samples from 907 patients suspected of having histoplasmosis were tested routinely between May 2015 and May 2019 in parallel with standard diagnostic procedures performed in parallel. Forty-four had proven histoplasmosis attributable to H. capsulatumvar. capsulatum(n= 40) or H. capsulatumvar. duboisii(n= 4) infections. The results of RT-qPCR were positive in 43 of 44 patients (97.7% sensitivity) in at least one specimen. Nine of 863 cases (99% specificity) were RT-qPCR positive and therefore classified as possible cases. RT-qPCR was positive in 13 of 30 (43.3%) blood samples tested in proven cases. A positive RT-qPCR result in blood was significantly associated with H. capsulatumvar. capsulatumprogressively disseminated histoplasmosis with a positive RT-qPCR result in 92.3% of the immunocompromised patients with disseminated disease. This new HistoplasmaRT-qPCR assay enabling amplification of H. capsulatumvar. capsulatumand H. capsulatumvar. duboisiiis highly sensitive and allows the diagnosis of histoplasmosis advantageously from blood and bronchoalveolar lavage.

Published
2021
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36. Entamoeba histolyticaDNA Detection in Serum from Patients with Suspected Amoebic Liver Abscess

Author

Ghelfenstein-Ferreira, Théo, Gits-Muselli, Maud, Dellière, Sarah, Denis, Blandine, Guigue, Nicolas, Hamane, Samia, Alanio, Alexandre, and Bretagne, Stéphane

Abstract

Amoebic liver abscess (ALA) is regularly seen in travelers or immigrants from tropical countries. The diagnosis relies on liver imaging that is not specific and on the detection of anti-Entamoeba histolyticaantibodies, which cannot distinguish an acute from a former infection. We tested whether E. histolyticaDNA detection in serum can improve the diagnosis of ALA. We retrospectively tested available serum samples taken from patients with ALA and non-ALA space-occupying lesions of the liver between 1 January 2010 and 30 November 2019.

Published
2020
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37. Outbreak of Invasive Wound Mucormycosis in a Burn Unit Due to Multiple Strains of Mucor circinelloidesf. circinelloidesResolved by Whole-Genome Sequencing

Author

Garcia-Hermoso, Dea, Criscuolo, Alexis, Lee, Soo Chan, Legrand, Matthieu, Chaouat, Marc, Denis, Blandine, Lafaurie, Matthieu, Rouveau, Martine, Soler, Charles, Schaal, Jean-Vivien, Mimoun, Maurice, Mebazaa, Alexandre, Heitman, Joseph, Dromer, Françoise, Brisse, Sylvain, Bretagne, Stéphane, and Alanio, Alexandre

Abstract

ABSTRACTMucorales are ubiquitous environmental molds responsible for mucormycosis in diabetic, immunocompromised, and severely burned patients. Small outbreaks of invasive wound mucormycosis (IWM) have already been reported in burn units without extensive microbiological investigations. We faced an outbreak of IWM in our center and investigated the clinical isolates with whole-genome sequencing (WGS) analysis. We analyzed M. circinelloidesisolates from patients in our burn unit (BU1, Hôpital Saint-Louis, Paris, France) together with nonoutbreak isolates from Burn Unit 2 (BU2, Paris area) and from France over a 2-year period (2013 to 2015). A total of 21 isolates, including 14 isolates from six BU1 patients, were analyzed by whole-genome sequencing (WGS). Phylogenetic classification based on de novoassembly and assembly free approaches showed that the clinical isolates clustered in four highly divergent clades. Clade 1 contained at least one of the strains from the six epidemiologically linked BU1 patients. The clinical isolates were specific to each patient. Two patients were infected with more than two strains from different clades, suggesting that an environmental reservoir of clonally unrelated isolates was the source of contamination. Only two patients from BU1 shared one strain, which could correspond to direct transmission or contamination with the same environmental source. In conclusion, WGS of several isolates per patients coupled with precise epidemiological data revealed a complex situation combining potential cross-transmission between patients and multiple contaminations with a heterogeneous pool of strains from a cryptic environmental reservoir.IMPORTANCEInvasive wound mucormycosis (IWM) is a severe infection due to environmental molds belonging to the order Mucorales. Severely burned patients are particularly at risk for IWM. Here, we used whole-genome sequencing (WGS) analysis to resolve an outbreak of IWM due to Mucor circinelloidesthat occurred in our hospital (BU1). We sequenced 21 clinical isolates, including 14 from BU1 and 7 unrelated isolates, and compared them to the reference genome (1006PhL). This analysis revealed that the outbreak was mainly due to multiple strains that seemed patient specific, suggesting that the patients were more likely infected from a pool of diverse strains from the environment rather than from direct transmission among them. This study revealed the complexity of a Mucorales outbreak in the settings of IWM in burn patients, which has been highlighted based on WGS combined with careful sampling.

Published
2018
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38. Invasive Infections with Nannizziopsis obscura Species Complex in 9 Patients from West Africa, France, 2004-20201.

Author

Garcia-Hermoso, Dea, Hamane, Samia, Fekkar, Arnaud, Jabet, Arnaud, Denis, Blandine, Siguier, Martin, Galeazzi, Guy, Haddad, Elie, Brun, Sophie, Vidal, Valérie, Nevez, Gilles, Le Berre, Rozenn, Gits-Muselli, Maud, Lanternier, Fanny, and Bretagne, Stéphane

Subjects
*SEQUENCE analysis, *CLINICAL drug trials, *INFECTION, *ETIOLOGY of diseases, *REPTILES, *ANTIFUNGAL agents, *RESEARCH, *ANIMAL experimentation, *RESEARCH methodology, *FUNGI, *MEDICAL cooperation, *EVALUATION research, *COMPARATIVE studies, *MICROBIAL sensitivity tests, *PHARMACODYNAMICS
Abstract

Nine new human invasive infections caused by the keratinophilic fungi Nannizziopsis obscura have been reported in France since 2004. The patients had variable clinical manifestations, had frequent dissemination, were mainly T-cell immunocompromised, and all originated from sub-Saharan West Africa. Before collection of the isolates, the etiologies of these infections were often misidentified, underscoring the extent of microscopic and cultural polymorphisms. All isolates but 1 had low MICs for the 8 antifungal drugs tested. When treated, patients received mainly azole therapy. Two of 7 patients with a known outcome died. We performed multilocus sequence analysis of N. obscura clinical strains and several strains of Nannizziopsis spp. isolated from reptiles. The human strains were clearly differentiated from the animal strains. N. obscura might be endemic to West Africa and responsible for undetected infections, which might become reactivated when immunosuppression occurs. N. obscura infection is probably underestimated because only sequencing enables proper identification. [ABSTRACT FROM AUTHOR]

Published
2020
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