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1. Biomarkers in pulmonary infections: a clinical approach

Author: Pedro Póvoa, Luís Coelho, José Pedro Cidade, Adrian Ceccato, Andrew Conway Morris, Jorge Salluh, Vandack Nobre, Saad Nseir, Ignacio Martin-Loeches, Thiago Lisboa, Paula Ramirez, Anahita Rouzé, Daniel A. Sweeney, and Andre C. Kalil
Subjects: Pulmonary infections, Pathogen-specific biomarkers, Host-response biomarkers, C-reactive protein, Procalcitonin, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Severe acute respiratory infections, such as community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia, constitute frequent and lethal pulmonary infections in the intensive care unit (ICU). Despite optimal management with early appropriate empiric antimicrobial therapy and adequate supportive care, mortality remains high, in part attributable to the aging, growing number of comorbidities, and rising rates of multidrug resistance pathogens. Biomarkers have the potential to offer additional information that may further improve the management and outcome of pulmonary infections. Available pathogen-specific biomarkers, for example, Streptococcus pneumoniae urinary antigen test and galactomannan, can be helpful in the microbiologic diagnosis of pulmonary infection in ICU patients, improving the timing and appropriateness of empiric antimicrobial therapy since these tests have a short turnaround time in comparison to classic microbiology. On the other hand, host-response biomarkers, for example, C-reactive protein and procalcitonin, used in conjunction with the clinical data, may be useful in the diagnosis and prediction of pulmonary infections, monitoring the response to treatment, and guiding duration of antimicrobial therapy. The assessment of serial measurements overtime, kinetics of biomarkers, is more informative than a single value. The appropriate utilization of accurate pathogen-specific and host-response biomarkers may benefit clinical decision-making at the bedside and optimize antimicrobial stewardship.
Published: 2024
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2. Immunosuppression at ICU admission is not associated with a higher incidence of ICU-acquired bacterial bloodstream infections: the COCONUT study

Author: Ghadi Zebian, Louis Kreitmann, Marion Houard, Antoine Piantoni, Gaetan Piga, Sarah Ruffier des Aimes, Bérénice Holik, Frédéric Wallet, Julien Labreuche, and Saad Nseir
Subjects: Intensive care units, Critical illness, Immunocompromised hosts, Neoplasms, Bloodstream infections, Bacteremia, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Immunosuppression at intensive care unit (ICU) admission has been associated with a higher incidence of ICU-acquired infections, some of them related to opportunistic pathogens. However, the association of immunosuppression with the incidence, microbiology and outcomes of ICU-acquired bacterial bloodstream infections (BSI) has not been thoroughly investigated. Methods Retrospective single-centered cohort study in France. All adult patients hospitalized in the ICU of Lille University-affiliated hospital for > 48 h between January 1st and December 31st, 2020, were included, regardless of their immune status. Immunosuppression was defined as active cancer or hematologic malignancy, neutropenia, hematopoietic stem cell and solid organ transplants, use of steroids or immunosuppressive drugs, human immunodeficiency virus infection and genetic immune deficiency. The primary objective was to compare the 28-day cumulative incidence of ICU-acquired bacterial BSI between immunocompromised and non-immunocompromised patients. Secondary objectives were to assess the microbiology and outcomes of ICU-acquired bacterial BSI in the two groups. Results A total of 1313 patients (66.9% males, median age 62 years) were included. Among them, 271 (20.6%) were immunocompromised at ICU admission. Severity scores at admission, the use of invasive devices and antibiotic exposure during ICU stay were comparable between groups. Both prior to and after adjustment for pre‐specified baseline confounders, the 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between immunocompromised and non-immunocompromised patients. The distribution of bacteria was comparable between groups, with a majority of Gram-negative bacilli (~ 64.1%). The proportion of multidrug-resistant bacteria was also similar between groups. Occurrence of ICU-acquired bacterial BSI was associated with a longer ICU length-of-stay and a longer duration of invasive mechanical ventilation, with no significant association with mortality. Immune status did not modify the association between occurrence of ICU-acquired bacterial BSI and these outcomes. Conclusion The 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between patients with and without immunosuppression at ICU admission.
Published: 2024
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3. Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

Author: Astrid Marchal, Elizabeth T. Cirulli, Iva Neveux, Evangelos Bellos, Ryan S. Thwaites, Kelly M. Schiabor Barrett, Yu Zhang, Ivana Nemes-Bokun, Mariya Kalinova, Andrew Catchpole, Stuart G. Tangye, András N. Spaan, Justin B. Lack, Jade Ghosn, Charles Burdet, Guy Gorochov, Florence Tubach, Pierre Hausfater, Clifton L. Dalgard, Shen-Ying Zhang, Qian Zhang, Christopher Chiu, Jacques Fellay, Joseph J. Grzymski, Vanessa Sancho-Shimizu, Laurent Abel, Jean-Laurent Casanova, Aurélie Cobat, Alexandre Bolze, Alessandro Aiuti, Saleh Al-Muhsen, Fahd Al-Mulla, Ali Amara, Mark S. Anderson, Evangelos Andreakos, Andrés A. Arias, Lisa M. Arkin, Hagit Baris Feldman, Paul Bastard, Alexandre Belot, Catherine M. Biggs, Dusan Bogunovic, Anastasiia Bondarenko, Alessandro Borghesi, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Manish J. Butte, Giorgio Casari, John Christodoulou, Roger Colobran, Antonio Condino-Neto, Stefan N. Constantinescu, Megan A. Cooper, Murkesh Desai, Beth A. Drolet, Xavier Duval, Jamila El Baghdadi, Philippine Eloy, Sara Espinosa-Padilla, Carlos Flores, José Luis Franco, Antoine Froidure, Peter K. Gregersen, Bodo Grimbacher, Filomeen Haerynck, David Hagin, Rabih Halwani, Lennart Hammarström, James R. Heath, Elena W.Y. Hsieh, Eystein Husebye, Kohsuke Imai, Yuval Itan, Emmanuelle Jouanguy, Elżbieta Kaja, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davood Mansouri, László Maródi, France Mentré, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine H. Mogensen, Tomohiro Morio, Lisa F.P. Ng, Luigi D. Notarangelo, Antonio Novelli, Giuseppe Novelli, Cliona O'Farrelly, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarström, Jean W. Pape, Rebeca Perez de Diego, Jordi Perez-Tur, David S. Perlin, Graziano Pesole, Anna M. Planas, Carolina Prando, Aurora Pujol, Anne Puel, Lluis Quintana-Murci, Sathishkumar Ramaswamy, Laurent Renia, Igor Resnick, Carlos Rodríguez-Gallego, Anna Sediva, Mikko R.J. Seppänen, Mohammad Shahrooei, Anna Shcherbina, Ondrej Slaby, Andrew L. Snow, Pere Soler-Palacín, Vassili Soumelis, Ivan Tancevski, Ahmad Abou Tayoun, Şehime Gülsün Temel, Christian Thorball, Pierre Tiberghien, Sophie Trouillet-Assant, Stuart E. Turvey, K. M. Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Donald C. Vinh, Horst von Bernuth, Joost Wauters, Mayana Zatz, Pawel Zawadzki, Serge Bureau, Yannick Vacher, Anne Gysembergh-Houal, Lauren Demerville, Abla Benleulmi-Chaachoua, Sebastien Abad, Radhiya Abassi, Abdelrafie Abdellaoui, Abdelkrim Abdelmalek, Hendy Abdoul, Helene Abergel, Fariza Abeud, Sophie Abgrall, Noemie Abisror, Marylise Adechian, Nordine Aderdour, Hakeem Farid Admane, Frederic Adnet, Sara Afritt, Helene Agostini, Claire Aguilar, Sophie Agut, Tommaso Francesco Aiello, Marc Ait Kaci, Hafid Ait Oufella, Gokula Ajeenthiravasan, Virginie Alauzy, Fanny Alby-Laurent, Lucie Allard, Marie-Alexandra Alyanakian, Blanca Amador Borrero, Sabrina Amam, Lucile Amrouche, Marc Andronikof, Dany Anglicheau, Nadia Anguel, Djillali Annane, Mohammed Aounzou, Caroline Aparicio, Gladys Aratus, Jean-Benoit Arlet, Jeremy Arzoine, Elisabeth Aslangul, Mona Assefi, Adeline Aubry, Laetitia Audiffred, Etienne Audureau, Christelle Nathalie Auger, Jean-Charles Auregan, Celine Awotar, Sonia Ayllon Milla, Delphine Azan, Laurene Azemar, Billal Azzouguen, Marwa Bachir Elrufaai, Aïda Badsi, Prissile Bakouboula, Coline Balcerowiak, Fanta Balde, Elodie Baldivia, Eliane-Flore Bangamingo, Amandine Baptiste, Fanny Baran-Marszak, Caroline Barau, Nathalie Barget, Flore Baronnet, Romain Barthelemy, Jean-Luc Baudel, Camille Baudry, Elodie Baudry, Laurent Beaugerie, Adel Belamri, Nicolas Belaube, Rhida Belilita, Pierre Bellassen, Rawan Belmokhtar, Isabel Beltran, Ruben Benainous, Mourad Benallaoua, Robert Benamouzig, Amélie Benbara, Jaouad Benhida, Anis Benkhelouf, Jihene Benlagha, Chahinez Benmostafa, Skander Benothmane, Miassa Bentifraouine, Laurence Berard, Quentin Bernier, Enora Berti, Astrid Bertier, Laure Berton, Simon Bessis, Alexandra Beurton, Celine Bianco, Clara Bianquis, Frank Bidar, Philippe Blanche, Clarisse Blayau, Alexandre Bleibtreu, Emmanuelle Blin, Coralie Bloch-Queyrat, Marie-Christophe Boissier, Diane Bollens, Marion Bolzoni, Rudy pierre Bompard, Nicolas Bonnet, Justine Bonnouvrier, Shirmonecrystal Botha, Wissam Boucenna, Fatiha Bouchama, Olivier Bouchaud, Hanane Bouchghoul, Taoueslylia Boudjebla, Noel Boudjema, Catherine Bouffard, Adrien Bougle, Meriem Bouguerra, Leila Bouras, Agnes Bourcier, Anne Bourgarit Durand, Anne Bourrier, Fabrice Bouscarat, Diane Bouvry, Nesrine Bouziri, Ons Bouzrara, Sarah Bribier, Delphine Brugier, Melanie Brunel, Eida Bui, Anne Buisson, Iryna Bukreyeva, Côme Bureau, Jacques Cadranel, Johann Cailhol, Ruxandra Calin, Clara Campos Vega, Pauline Canavaggio, Marta Cancella, Delphine Cantin, Albert Cao, Lionel Carbillon, Nicolas Carlier, Clementine Cassard, Guylaine Castor, Marion Cauchy, Olivier Cha, Benjamin Chaigne, Salima Challal, Karine Champion, Patrick Chariot, Julie Chas, Simon Chauveau, Anthony Chauvin, Clement Chauvin, Nathalie Chavarot, Kamélia Chebbout, Mustapha Cherai, Ilaria Cherubini, Amelie Chevalier, Thibault Chiarabini, Thierry Chinet, Richard Chocron, Pascaline Choinier, Juliette Chommeloux, Christophe Choquet, Laure Choupeaux, Benjamin Chousterman, Dragosmarius Ciocan, Ada Clarke, Gaëlle Clavere, Florian Clavier, Karine Clement, Sebastien Clerc, Yves Cohen, Fleur Cohen, Adrien Cohen, Audrey Coilly, Hester Colboc, Pauline Colin, Magalie Collet, Chloé Comarmond, Emeline Combacon, Alain Combes, Celine Comparon, Jean-Michel Constantin, Hugues Cordel, Anne-Gael Cordier, Adrien Costantini, Nathalie Costedoat Chalumeau, Camille Couffignal, Doriane Coupeau, Alain Creange, Yannie Cuvillier Lamarre, Charlène Da Silveira, Sandrine Dautheville Guibal El Kayani, Nathalie De Castro, Yann De Rycke, Lucie Del Pozo, Quentin Delannoy, Mathieu Delay, Robin Deleris, Juliette Delforge, Laëtitia Delphine, Noemie Demare, Sophie Demeret, Alexandre Demoule, Aurore Deniau, François Depret, Sophie Derolez, Ouda Derradji, Nawal Derridj, Vincent Descamps, Lydia Deschamps, Celine Desconclois, Cyrielle Desnos, Karine Desongins, Robin Dhote, Benjamin Diallo, Morgane Didier, Myriam Diemer, Stephane Diez, Juliette Djadi-Prat, Fatima-Zohra Djamouri Monnory, Siham Djebara, Naoual Djebra, Minette Djietcheu, Hadjer Djillali, Nouara Djouadi, Severine Donneger, Catarina Dos Santos, Nathalie Dournon, Martin Dres, Laura Droctove, Marie Drogrey, Margot Dropy, Elodie Drouet, Valérie Dubosq, Evelyne Dubreucq, Estelle Dubus, Boris Duchemann, Thibault Duchenoy, Emmanuel Dudoignon, Romain Dufau, Florence Dumas, Clara Duran, Emmanuelle Duron, Antoine Durrbach, Claudine Duvivier, Nathan Ebstein, Jihane El Khalifa, Alexandre Elabbadi, Caroline Elie, Gabriel Ernotte, Anne Esling, Martin Etienne, Xavier Eyer, Muriel Sarah Fartoukh, Takoua Fayali, Marion Fermaut, Arianna Fiorentino, Souha Fliss, Marie-Céline Fournier, Benjamin Fournier, Hélène Francois, Olivia Freynet, Yvann Frigout, Isaure Fromont, Axelle Fuentes, Thomas Furet, Joris Galand, Marc Garnier, Agnes Gaubert, Stéphane Gaudry, Samuel Gaugain, Damien Gauthier, Maxime Gautier, Sophie Georgin-Lavialle, Daniela Geromin, Mohamed Ghalayini, Bijan Ghaleh, Myriam Ghezal, Aude Gibelin, Linda Gimeno, Benoit Girard, Bénédicte Giroux Leprieur, Doryan Gomes, Elisabete Gomes-Pires, Anne Gouge, Amel Gouja, Helene Goulet, Sylvain Goupil, Jeanne Goupil De Bouille, Julien Gras, Segolene Greffe, Lamiae Grimaldi, Paul Guedeney, Bertrand Guidet, Matthias Guillo, Mariechristelle Gulczynski, Tassadit Hadjam, Didier Haguenauer, Soumeya Hammal, Nadjib Hammoudi, Olivier Hanon, Anarole Harrois, Coraline Hautem, Guillaume Hekimian, Nicholas Heming, Olivier Hermine, Sylvie Ho, Marie Houllier, Benjamin Huot, Tessa Huscenot, Wafa Ibn Saied, Ghilas Ikherbane, Meriem Imarazene, Patrick Ingiliz, Lina Iratni, Stephane Jaureguiberry, Jean-Francois Jean-Marc, Deleena Jeyarajasingham, Pauline Jouany, Veronique Jouis, Clement Jourdaine, Ouifiya Kafif, Rim Kallala, Sandrine Katsahian, Lilit Kelesyan, Vixra Keo, Flora Ketz, Warda Khamis, Enfel Khelili, Mehdi Khellaf, Christy Gaëlla Kotokpo Youkou, Ilias Kounis, Gaelle Kpalma, Jessica Krause, Vincent Labbe, Karine Lacombe, Jean-Marc Lacorte, Anne Gaelle Lafont, Emmanuel Lafont, Lynda Lagha, Lionel Lamhaut, Aymeric Lancelot, Cecilia Landman, Fanny Lanternier, Cecile Larcheveque, Caroline Lascoux Combe, Ludovic Lassel, Benjamin Laverdant, Christophe Lavergne, Jean-Rémi Lavillegrand, Pompilia Lazureanu, Loïc Le Guennec, Lamia Leberre, Claire Leblanc, Marion Leboyer, Francois Lecomte, Marine Lecorre, Romain Leenhardt, Marylou Lefebvre, Bénédicte Lefebvre, Paul Legendre, Anne Leger, Laurence Legros, Justyna Legrosse, Sébastien Lehuunghia, Julien Lemarec, Jeremie Leporrier-Ext, Manon Lesein, Hubert Lesur, Vincent Levy, Albert Levy, Edwige Lopes, Amanda Lopes, Vanessa Lopez, Julien Lopinto, Olivier Lortholary, Badr Louadah, Bénédicte Loze, Marie-Laure Lucas, Axelle Lucasamichi, Liem Binh Luong, Arouna Magazimama-Ext, David Maingret, Lakhdar Mameri, Philippe Manivet, Cylia Mansouri, Estelle Marcault, Jonathan Marey, Nathalie Marin, Clémence Marois, Olivier Martin, Lou Martineau, Cannelle Martinez-Lopez, Pierre Martyniuck, Pauline Mary De Farcy, Nessrine Marzouk, Rafik Masmoudi, Alexandre Mebazaa, Frédéric Mechai, Fabio Mecozzi, Chamseddine Mediouni, Bruno Megarbane, Mohamed Meghadecha, Élodie Mejean, Arsene Mekinian, Nour Mekki Abdelhadi, Rania Mekni, Thinhinan Sabrina Meliti, Breno Melo Lima, Paris Meng, Soraya Merbah, Fadhila Messani, Yasmine Messaoudi, Baboo-Irwinsingh Mewasing, Lydia Meziane, Carole Michelot-Burger, Françoise Mignot, Fadi Hillary Minka, Makoto Miyara, Pierre Moine, Jean-Michel Molina, Anaïs Montegnies-Boulet, Alexandra Monti, Claire Montlahuc, Anne-Lise Montout, Alexandre Moores, Caroline Morbieu, Helene Mortelette, Stéphane Mouly, Rosita Muzaffar, Cherifa Iness Nacerddine, Marine Nadal, Hajer Nadif, Kladoum Nassarmadji, Pierre Natella, Sandrine Ndingamondze, Stefan Neraal, Caroline Nguyen, Bao N'Guyen, Isabelle Nion Larmurier, Luc Nlomenyengue, Nicolas Noel, Hilario Nunes, Edris Omar, Zineb Ouazene, Elise Ouedraogo, Wassila Ouelaa, Anissa Oukhedouma, Yasmina Ould Amara, Herve Oya, Johanna Oziel, Thomas Padilla, Elena Paillaud, Solenne Paiva, Beatrice Parfait, Perrine Parize, Christophe Parizot, Antoine Parrot, Arthur Pavot, Laetitia Peaudecerf, Frédéric Pene, Marion Pepin, Julie Pernet, Claire Pernin, Mylène Petit, Olivier Peyrony, Marie-Pierre Pietri, Olivia Pietri, Marc Pineton De Chambrun, Michelle Pinson, Claire Pintado, Valentine Piquard, Christine Pires, Benjamin Planquette, Sandrine Poirier, Anne-Laure Pomel, Stéphanie Pons, Diane Ponscarme, Annegaelle Pourcelot, Valérie Pourcher, Anne Pouvaret, Florian Prever, Miresta Previlon, Margot Prevost, Marie-Julie Provoost, Cyril Quemeneur, Cédric Rafat, Agathe Rami, Brigitte Ranque, Maurice Raphael, Jean Herle Raphalen, Anna Rastoin, Mathieu Raux, Amani Rebai, Michael Reby, Alexis Regent, Asma Regrag, Matthieu Resche-Rigon, Quentin Ressaire, Christian Richard, Mariecaroline Richard, Maxence Robert, Benjamin Rohaut, Camille Rolland-Debord, Jacques Ropers, Anne-Marie Roque-Afonso, Charlotte Rosso, Mélanie Rousseaux, Nabila Rousseaux, Swasti Roux, Lorène Roux, Claire Rouzaud, Antoine Rozes, Emma Rubenstein, Jean-Marc Sabate, Sheila Sabet, Sophie-Caroline Sacleux, Nathalie Saidenberg Kermanach, Faouzi Saliba, Dominique Salmon, Laurent Savale, Guillaume Savary, Rebecca Sberro, Anne Scemla, Frederic Schlemmer, Mathieu Schwartz, Saïd Sedfi, Samia Sefir-Kribel, Philippe Seksik, Pierre Sellier, Agathe Selves, Nicole Sembach, Luca Semerano, Marie-Victoire Senat, Damien Sene, Alexandra Serris, Lucile Sese, Naima Sghiouar, Johanna Sigaux, Martin Siguier, Johanne Silvain, Noémie Simon, Tabassome Simon, Lina Innes Skandri, Miassa Slimani, Aurélie Snauwaert, Harry Sokol, Heithem Soliman, Nisrine Soltani, Benjamin Soyer, Gabriel Steg, Lydia Suarez, Tali-Anne Szwebel, Kossi Taffame, Yacine Tandjaoui-Lambiotte, Claire Tantet, Mariagrazia Tateo, Igor Theodose, Pierre clement Thiebaud, Caroline Thomas, Kelly Tiercelet, Julie Tisserand, Carole Tomczak, Krystel Torelino, Fatima Touam-Ext, Lilia Toumi, Gustave Toury, Mireille Toy-Miou, Olivia Tran Dinh Thanh Lien, Alexy Trandinh, Jean-Marc Treluyer, Baptiste Trinque, Jennifer Truchot, Sarah Tubiana, Simone Tunesi, Matthieu Turpin, Agathe Turpin, Tomas Urbina, Rafael Usubillaga Narvaez, Yurdagul Uzunhan, Prabakar Vaittinadaayar, Arnaud Valent, Maelle Valentian, Nadia Valin, Hélène Vallet, Marina Vaz, Miguel-Alejandro Vazquezibarra, Benoit Vedie, Laetitia Velly, Celine Verstuyft, Cedric Viallette, Eric Vicaut, Dorothee Vignes, Damien Vimpere, Myriam Virlouvet, Guillaume Voiriot, Lena Voisot, Emmanuel Weiss, Nicolas Weiss, Anaïs Winchenne, Youri Yordanov, Lara Zafrani, Mohamad Zaidan, Wissem Zaidi, Cathia Zak, Aida Zarhrate-Ghoul, Ouassila Zatout, Suzanne Zeino, Michel Zeitouni, Naïma Zemirli, Lorene Zerah, Ounsa Zia, Marianne Ziol, Oceane Zolario, Julien Zuber, Claire Andrejak, François Angoulvant, Delphine Bachelet, Marie Bartoli, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, Lila Bouadma, Sabelline Bouchez, Maude Bouscambert, Minerva Cervantes-Gonzalez, Anissa Chair, Catherine Chirouze, Alexandra Coelho, Sandrine Couffin-Cadiergues, Eric d’Ortenzio, Marie-Pierre Debray, Laurene Deconinck, Dominique Deplanque, Diane Descamps, Mathilde Desvallée, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Brigitte Elharrar, Vincent Enouf, Hélène Esperou, Marina Esposito-Farese, Manuel Etienne, Eglantine Ferrand Devouge, Nathalie Gault, Alexandre Gaymard, Tristan Gigante, Morgane Gilg, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Ikram Houas, Jean-Sébastien Hulot, Salma Jaafoura, Florentia Kaguelidou, Sabrina Kali, Antoine Khalil, Coralie Khan, Cédric Laouénan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François-Xavier Lescure, Sophie Letrou, Yves Levy, Bruno Lina, Guillaume Lingas, Jean-Christophe Lucet, Denis Malvy, Marina Mambert, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Duc Nguyen, Marion Noret, Saad Nseir, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadja, Thomas Perpoint, Ventzislava Petrov-Sanchez, Gilles Peytavin, Huong Pham, Olivier Picone, Oriane Puéchal, Christian Rabaud, Manuel Rosa-Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Richa Su, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean-François Timsit, Christelle Tual, Sylvie Van Der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanah, Loubna Alavoine, Charlotte Charpentier, Aline Dechanet, Jean-Luc Ecobichon, Wahiba Frezouls, Nadhira Houhou, Jonathan Lehacaut, Pauline Manchon, Mariama Nouroudine, Caroline Quintin, Michael Thy, Sylvie van der Werf, Valérie Vignali, Abir Chahine, Nawal Waucquier, Maria-Claire Migaud, Félix Djossou, Mayka Mergeay-Fabre, Aude Lucarelli, Magalie Demar, Léa Bruneau, Patrick Gérardin, Adrien Maillot, Christine Payet, Bruno Laviolle, Fabrice Laine, Christophe Paris, Mireille Desille-Dugast, Julie Fouchard, Thierry Pistone, Pauline Perreau, Valérie Gissot, Carole L.E. Goas, Samatha Montagne, Lucie Richard, Kévin Bouiller, Maxime Desmarets, Alexandre Meunier, Marilou Bourgeon, Benjamin Lefévre, Hélène Jeulin, Karine Legrand, Sandra Lomazzi, Bernard Tardy, Amandine Gagneux-Brunon, Frédérique Bertholon, Elisabeth Botelho-Nevers, Christelle Kouakam, Leturque Nicolas, Layidé Roufai, Karine Amat, Hélène Espérou, Samia Hendou, Giuseppe Foti, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga, Giacomo Bellani, Jorge Abad, Giulia Accordino, Micol Angelini, Sergio Aguilera-Albesa, Aina Aguiló-Cucurull, Esra Akyüz Özkan, Ilad Alavi Darazam, Jonathan Antonio Roblero Albisures, Juan C. Aldave, Miquel Alfonso Ramos, Taj Ali Khan, Anna Aliberti, Seyed Alireza Nadji, Gulsum Alkan, Suzan A. AlKhater, Jerome Allardet-Servent, Luis M. Allende, Rebeca Alonso-Arias, Mohammed S. Alshahrani, Laia Alsina, Zahir Amoura, Arnau Antolí, Romain Arrestier, Mélodie Aubart, Teresa Auguet, Iryna Avramenko, Gökhan Aytekin, Axelle Azot, Seiamak Bahram, Fanny Bajolle, Fausto Baldanti, Aurélie Baldolli, Maite Ballester, Benoit Barrou, Federica Barzaghi, Sabrina Basso, Gulsum Iclal Bayhan, Liliana Bezrodnik, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blázquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, Elisabeth Botdhlo-Nevers, Aurore Bousquet, David Boutolleau, Claire Bouvattier, Oksana Boyarchuk, Juliette Bravais, M. Luisa Briones, Marie-Eve Brunner, Raffaele Bruno, Maria Rita P. Bueno, Huda Bukhari, Jacinta Bustamante, Juan José Cáceres Agra, Ruggero Capra, Raphael Carapito, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Irene Cassaniti, Martin Castelle, Francesco Castelli, Martín Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Jale Bengi Celik, Alessandro Ceschi, Martin Chalumeau, Bruno Charbit, Cécile Boulanger, Père Clavé, Bonaventura Clotet, Anna Codina, Cloé Comarmond, Patrizia Comoli, Angelo G. Corsico, Taner Coşkuner, Aleksandar Cvetkovski, Cyril Cyrus, David Dalmau, François Danion, David Ross Darley, Vincent Das, Nicolas Dauby, Stéphane Dauger, Paul De Munte, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Isabelle Desguerre, Antonio Di Sabatino, Jean-Luc Diehl, Stephanie Dobbelaere, Elena Domínguez-Garrido, Clément Dubost, Olov Ekwall, Şefika Elmas Bozdemir, Marwa H. Elnagdy, Melike Emiroglu, Akifumi Endo, Emine Hafize Erdeniz, Selma Erol Aytekin, Maria Pilar Etxart Lasa, Romain Euvrard, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Ricard Ferrer, Jose Ferreres, Bruno Francois, Victoria Fumadó, Kitty S.C. Fung, Francesca Fusco, Alenka Gagro, Blanca Garcia Solis, Pierre Garçon, Pascale Gaussem, Zeynep Gayretli, Juana Gil-Herrera, Laurent Gilardin, Audrey Giraud Gatineau, Mònica Girona-Alarcón, Karen Alejandra Cifuentes Godínez, Jean-Christophe Goffard, Nacho Gonzales, Luis I. Gonzalez-Granado, Rafaela González-Montelongo, Antoine Guerder, Belgin Gülhan, Victor Daniel Gumucio, Leif Gunnar Hanitsch, Jan Gunst, Marta Gut, Jérôme Hadjadj, Selda Hancerli, Tetyana Hariyan, Nevin Hatipoglu, Deniz Heppekcan, Elisa Hernandez-Brito, Po-ki Ho, María Soledad Holanda-Peña, Juan P. Horcajada, Sami Hraiech, Linda Humbert, Ivan F.N. Hung, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María Jesús Arranz, Marie-Thérèse Jimeno, Iolanda Jordan, Saliha Kanık-Yüksek, Yalcin Kara, Aydın Karahan, Adem Karbuz, Kadriye Kart Yasar, Ozgur Kasapcopur, Kenichi Kashimada, Sevgi Keles, Yasemin Kendir Demirkol, Yasutoshi Kido, Can Kizil, Ahmet Osman Kılıç, Adam Klocperk, Antonia Koutsoukou, Zbigniew J. Król, Hatem Ksouri, Paul Kuentz, Arthur M.C. Kwan, Yat Wah M. Kwan, Janette S.Y. Kwok, Jean-Christophe Lagier, David S.Y. Lam, Vicky Lampropoulou, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain Lévy, Zhi Li, Daniele Lilleri, Edson Jose Adrian Bolanos Lima, Agnes Linglart, Eduardo López-Collazo, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Kwok-Cheung Lung, Charles-Edouard Luyt, David C. Lye, Cinthia Magnone, Enrico Marchioni, Carola Marioli, Majid Marjani, Laura Marques, Jesus Marquez Pereira, Andrea Martín-Nalda, David Martínez Pueyo, Javier Martinez-Picado, Iciar Marzana, Carmen Mata-Martínez, Alexis Mathian, Larissa R.B. Matos, Gail V. Matthews, Julien Mayaux, Raquel McLaughlin-Garcia, Philippe Meersseman, Jean-Louis Mège, Armand Mekontso-Dessap, Isabelle Melki, Federica Meloni, Jean-François Meritet, Paolo Merlani, Özge Metin Akcan, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Matthieu Million, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Yoko Mizoguchi, Bhavi P. Modi, Francesco Mojoli, Elsa Moncomble, Abián Montesdeoca Melián, Antonio Morales Martinez, Francisco Morandeira, Pierre-Emmanuel Morange, Clémence Mordacq, Guillaume Morelle, Stéphane J. Mouly, Adrián Muñoz-Barrera, Cyril Nafati, Shintaro Nagashima, Yu Nakagama, Bénédicte Neven, João Farela Neves, Yuk-Yung Ng, Hubert Nielly, Yeray Novoa Medina, Esmeralda Nuñez Cuadros, Semsi Nur Karabela, J. Gonzalo Ocejo-Vinyals, Mehdi Oualha, Amani Ouedrani, Tayfun Özçelik, Aslinur Ozkaya-Parlakay, Michele Pagani, Maria Papadaki, Philippe Parola, Tiffany Pascreau, Stéphane Paul, Estela Paz-Artal, Sigifredo Pedraza, Nancy Carolina González Pellecer, Silvia Pellegrini, Rebeca Pérez de Diego, Xosé Luis Pérez-Fernández, Aurélien Philippe, Quentin Philippot, Adrien Picod, Marc Pineton de Chambrun, Antonio Piralla, Laura Planas-Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Garyphallia Poulakou, Marie S. Pouletty, Persia Pourshahnazari, Jia Li Qiu-Chen, Paul Quentric, Thomas Rambaud, Didier Raoult, Violette Raoult, Anne-Sophie Rebillat, Claire Redin, Léa Resmini, Pilar Ricart, Jean-Christophe Richard, Raúl Rigo-Bonnin, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora-Blanch, Mathieu P. Rodero, Carlos Rodrigo, Luis Antonio Rodriguez, Carlos Rodriguez-Gallego, Agustí Rodriguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Damien Roux, Nikoletta Rovina, Flore Rozenberg, Yvon Ruch, Montse Ruiz, Maria Yolanda Ruiz del Prado, Juan Carlos Ruiz-Rodriguez, Joan Sabater-Riera, Kai Saks, Maria Salagianni, Oliver Sanchez, Adrián Sánchez-Montalvá, Silvia Sánchez-Ramón, Laire Schidlowski, Agatha Schluter, Julien Schmidt, Matthieu Schmidt, Catharina Schuetz, Cyril E. Schweitzer, Francesco Scolari, Luis Seijo, Analia Gisela Seminario, Piseth Seng, Sevtap Senoglu, Mikko Seppänen, Alex Serra Llovich, Virginie Siguret, Eleni Siouti, David M. Smadja, Nikaia Smith, Ali Sobh, Xavier Solanich, Jordi Solé-Violán, Catherine Soler, Betül Sözeri, Giulia Maria Stella, Yuriy Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Jean-Luc Taupin, Simon J. Tavernier, Loreto Vidaur Tello, Benjamin Terrier, Guillaume Thiery, Karolina Thorn, Caroline Thumerelle, Imran Tipu, Martin Tolstrup, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Vasiliki Triantafyllia, Jesús Troya, Owen T.Y. Tsang, Liina Tserel, Eugene Y.K. Tso, Alessandra Tucci, Şadiye Kübra Tüter Öz, Matilde Valeria Ursini, Takanori Utsumi, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Valentina Velez-Santamaria, Silvia Patricia Zuniga Veliz, Mateus C. Vidigal, Sébastien Viel, Cédric Villain, Marie E. Vilaire-Meunier, Judit Villar-García, Audrey Vincent, Dimitri Van der Linden, Alla Volokha, Fanny Vuotto, Els Wauters, Alan K.L. Wu, Tak-Chiu Wu, Aysun Yahşi, Osman Yesilbas, Mehmet Yildiz, Barnaby E. Young, Ufuk Yükselmiş, Marco Zecca, Valentina Zuccaro, Jens Van Praet, Bart N. Lambrecht, Eva Van Braeckel, Cédric Bosteels, Levi Hoste, Eric Hoste, Fré Bauters, Jozefien De Clercq, Catherine Heijmans, Hans Slabbynck, Leslie Naesens, Benoit Florkin, Mary-Anne Young, Amanda Willis, Paloma Lapuente-Suanzes, Ana de Andrés-Martín, Matilda Berkell, Valerio Carelli, Alessia Fiorentino, Surbhi Malhotra, Alessandro Mattiaccio, Tommaso Pippucci, Marco Seri, Evelina Tacconelli, Michiel van Agtmael, Anne Geke Algera, Brent Appelman, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Peter Bonta, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve de Bree, Sanne de Bruin, David T.P. Buis, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Mirjam Dijkstra, Dave A. Dongelmans, Romein W.G. Dujardin, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Endry H.T. Lim, Niels van Mourik, Jeaninne Nellen, Esther J. Nossent, Frederique Paulus, Edgar Peters, Dan A.I. Pina-Fuentes, Tom van der Poll, Bennedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Maurits C.F. J. de Rotte, Michiel Schinkel, Marcus J. Schultz, Femke A.P. Schrauwen, Alex Schuurmans, Jaap Schuurmans, Kim Sigaloff, Marleen A. Slim, Patrick Smeele, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa M. Tsonas, Pieter R. Tuinman, Marc van der Valk, Denise P. Veelo, Carolien Volleman, Heder de Vries, Lonneke A. Vught, Michèle van Vugt, Dorien Wouters, A.H. Zwinderman, Matthijs C. Brouwer, W. Joost Wiersinga, Alexander P.J. Vlaar, Miranda F. Tompkins, Camille Alba, Daniel N. Hupalo, John Rosenberger, Gauthaman Sukumar, Matthew D. Wilkerson, Xijun Zhang, Justin Lack, Andrew J. Oler, Kerry Dobbs, Ottavia M. Delmonte, Jeffrey J. Danielson, Andrea Biondi, Laura Rachele Bettini, Mariella D’Angiò, Ilaria Beretta, Luisa Imberti, Alessandra Sottini, Virginia Quaresima, Eugenia Quiros-Roldan, Camillo Rossi, Riccardo Castagnoli, Daniela Montagna, Amelia Licari, and Gian Luigi Marseglia
Subjects: HLA, association, asymptomatic infection, COVID-19, population stratification, Genetics, QH426-470
Abstract: Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.
Published: 2024
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4. Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

Author: Barbara Wanjiru Citarella, Christiana Kartsonaki, Elsa D. Ibáñez-Prada, Bronner P. Gonçalves, Joaquin Baruch, Martina Escher, Mark G. Pritchard, Jia Wei, Fred Philippy, Andrew Dagens, Matthew Hall, James Lee, Demetrios James Kutsogiannis, Evert-Jan Wils, Marília Andreia Fernandes, Bharath Kumar Tirupakuzhi Vijayaraghavan, Prasan Kumar Panda, Ignacio Martin-Loeches, Shinichiro Ohshimo, Arie Zainul Fatoni, Peter Horby, Jake Dunning, Jordi Rello, Laura Merson, Amanda Rojek, Michel Vaillant, Piero Olliaro, Luis Felipe Reyes, S.A. Moharam, Sabriya Abdalasalam, Alaa Abdalfattah Abdalhadi, Naana Reyam Abdalla, Walaa Abdalla, Almthani Hamza Abdalrheem, Ashraf Abdalsalam, Saedah Abdeewi, Esraa Hassan Abdelgaum, Mohamed Abdelhalim, Mohammed Abdelkabir, Israa Abdelrahman, Sheryl Ann Abdukahil, Lamees Adil Abdulbaqi, Salaheddin Abdulhamid, Widyan Abdulhamid, Nurul Najmee Abdulkadir, Eman Abdulwahed, Rawad Abdunabi, Ryuzo Abe, Laurent Abel, Ahmed Mohammed Abodina, Amal Abrous, Lara Absil, Kamal Abu Jabal, Nashat Abu Salah, Abdurraouf Abusalama, Tareg Abdallah Abuzaid, Subhash Acharya, Andrew Acker, Elisabeth Adam, Safia Adem, Manuella Ademnou, Francisca Adewhajah, Diana Adrião, Anthony Afum-Adjei Awuah, Melvin Agbogbatey, Saleh Al Ageel, Aya Mustafa Ahmed, Musaab Mohammed Ahmed, Shakeel Ahmed, Zainab Ahmed Alaraji, Abdulrahman Ahmed Elhefnawy Enan, Reham Abdelhamid Ahmed Khalil, Ali Mostafa Ahmed Mohamed Abdelaziz, Kate Ainscough, Eka Airlangga, Tharwat Aisa, Ali Aisha, Bugila Aisha, Ali Ait Hssain, Younes Ait Tamlihat, Takako Akimoto, Ernita Akmal, Chika Akwani, Eman Al Qasim, Ahmed Alajeeli, Ahmed Alali, Razi Alalqam, Aliya Mohammed Alameen, Mohammed Al-Aquily, Zinah A. Alaraji, Khalid Albakry, Safa Albatni, Angela Alberti, Osama Aldabbourosama, Tala Al-dabbous, Amer Aldhalia, Abdulkarim Aldoukali, Senthilkumar Alegesan, Marta Alessi, Beatrice Alex, Kévin Alexandre, Abdulrahman Al-Fares, Asil Alflite, Huda Alfoudri, Qamrah Alhadad, Hoda Salem Alhaddad, Maali Khalid Mohamed Abdalla Alhasan, Ahmad Nabil Alhouri, Hasan Alhouri, Adam Ali, Imran Ali, Maha TagElser Mohammed Ali, Syed Ali Abbas, Yomna Ali Abdelghafar, Naseem Ali Sheikh, Kazali Enagnon Alidjnou, Mahmoud Aljadi, Sarah Aljamal, Mohammed Alkahlout, Akram Alkaseek, Qabas Alkhafajee, Clotilde Allavena, Nathalie Allou, Lana Almasri, Abdulrahman Almjersah, Raja Ahmed Alqandouz, Walaa Alrfaea, Moayad Alrifaee, Rawan Alsaadi, Yousef Al-Saba'a, Entisar Alshareea, Eslam Alshenawy, Aneela Altaf, João Melo Alves, João Alves, Rita Alves, Joana Alves Cabrita, Maria Amaral, Amro Essam Amer, Nur Amira, Amos Amoako Adusei, John Amuasi, Roberto Andini, Claire Andrejak, Andrea Angheben, François Angoulvant, Sophia Ankrah, Séverine Ansart, Sivanesen Anthonidass, Massimo Antonelli, Carlos Alexandre Antunes de Brito, Ardiyan Apriyana, Yaseen Arabi, Irene Aragao, Francisco Arancibia, Carolline Araujo, Antonio Arcadipane, Patrick Archambault, Lukas Arenz, Jean-Benoît Arlet, Christel Arnold-Day, Lovkesh Arora, Rakesh Arora, Elise Artaud-Macari, Diptesh Aryal, Angel Asensio, Elizabeth A. Ashley, Muhammad Ashraf, Muhammad Sheharyar Ashraf, Abir Ben Ashur, Franklin Asiedu-Bekoe, Namra Asif, Mohammad Asim, Grace Assi, Jean Baptiste Assie, Amirul Asyraf, Fouda Atangana, Ahmed Atia, Minahel Atif, Asia Atif Abdelrhman Abdallahrs, Anika Atique, Moad Atlowly, AM Udara Lakshan Attanyake, Johann Auchabie, Hugues Aumaitre, Adrien Auvet, Abdelmalek Awad Ali Mohammed, Eyvind W. Axelsen, Ared Ayad, Ahmed Ayman Hassan Helmi, Laurène Azemar, Mohammed Azizeldin, Cecile Azoulay, Hakeem Babatunde, Benjamin Bach, Delphine Bachelet, Claudine Badr, Roar Bævre-Jensen, Nadia Baig, John Kenneth Baillie, J Kevin Baird, Erica Bak, Agamemnon Bakakos, Nazreen Abu Bakar, Hibah Bileid Bakeer, Ashraf Bakri, Andriy Bal, Mohanaprasanth Balakrishnan, Irene Bandoh, Firouzé Bani-Sadr, Renata Barbalho, Nicholas Yuri Barbosa, Wendy S. Barclay, Saef Umar Barnett, Michaela Barnikel, Helena Barrasa, Cleide Barrigoto, Marie Bartoli, Joaquín Baruch, Romain Basmaci, Muhammad Fadhli Hassin Basri, AbdAlkarim Batool, Denise Battaglini, Jules Bauer, Diego Fernando Bautista Rincon, Denisse Bazan Dow, Abigail Beane, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Aleksandr Beljantsev, David Bellemare, Anna Beltrame, Beatriz Amorim Beltrão, Marine Beluze, Nicolas Benech, Lionel Eric Benjiman, Suzanne Bennett, Luís Bento, Jan-Erik Berdal, Lamis Berdeweel, Delphine Bergeaud, Hazel Bergin, Giulia Bertoli, Lorenzo Bertolino, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Amar Bhatt, Krishna Bhavsar, Isabella Bianchi, Claudia Bianco, Sandra Bichoka, Farah Nadiah Bidin, Felwa Bin Humaid, Mohd Nazlin Bin Kamarudin, Muhannud Binnawara, Zeno Bisoffi, Patrick Biston, Laurent Bitker, Mustapha Bittaye, Jonathan Bitton, Pablo Blanco-Schweizer, Catherine Blier, Frank Bloos, Mathieu Blot, Filomena Boccia, Laetitia Bodenes, Debby Bogaert, Anne-Hélène Boivin, Ariel Bolanga, Isabela Bolaños, Pierre-Adrien Bolze, François Bompart, Aurelius Bonifasius, Joe Bonney, Diogo Borges, Raphaël Borie, Hans Martin Bosse, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, Sabelline Bouchez, Damien Bouhour, Kévin Bouiller, Laurence Bouillet, Camile Bouisse, Latsaniphone Bountthasavong, Anne-Sophie Boureau, John Bourke, Maude Bouscambert, Aurore Bousquet, Marielle Boyer-Besseyre, Maria Boylan, Fernando Augusto Bozza, Axelle Braconnier, Cynthia Braga, Timo Brandenburger, Filipa Brás Monteiro, Luca Brazzi, Dorothy Breen, Patrick Breen, David Brewster, Kathy Brickell, Tessa Broadley, Helen Brotherton, Alex Browne, Nicolas Brozzi, Sonja Hjellegjerde Brunvoll, Marjolein Brusse-Keizer, Petra Bryda, Nina Buchtele, Polina Bugaeva, Marielle Buisson, Danilo Buonsenso, Erlina Burhan, Donald Buri, Aidan Burrell, Ingrid G. Bustos, Denis Butnaru, André Cabie, Susana Cabral, Joana Cabrita, Eder Caceres, Cyril Cadoz, Rui Caetano Garcês, Kate Calligy, Jose Andres Calvache, João Camões, Valentine Campana, Paul Campbell, Josie Campisi, Cecilia Canepa, Mireia Cantero, Janice Caoili, Pauline Caraux-Paz, Sheila Cárcel, Filipa Cardoso, Filipe Cardoso, Nelson Cardoso, Sofia Cardoso, Simone Carelli, Nicolas Carlier, Thierry Carmoi, Gayle Carney, Inês Carqueja, Marie-Christine Carret, François Martin Carrier, Ida Carroll, Gail Carson, Maire-Laure Casanova, Mariana Cascão, Siobhan Casey, José Casimiro, Bailey Cassandra, Silvia Castañeda, Nidyanara Castanheira, Guylaine Castor-Alexandre, Ivo Castro, Ana Catarino, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Giulio Giovanni Cavalli, Alexandros Cavayas, Adrian Ceccato, Masaneh Ceesay, Shelby Cerkovnik, Minerva Cervantes-Gonzalez, Muge Cevik, Anissa Chair, Catherine Chakveatze, Adrienne Chan, Meera Chand, Jean-Marc Chapplain, Charlotte Charpentier, Julie Chas, Muhammad Mobin Chaudry, Jonathan Samuel Chávez Iñiguez, Anjellica Chen, Yih-Sharng Chen, Léo Chenard, Matthew Pellan Cheng, Antoine Cheret, Thibault Chiarabini, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Catherine Chirouze, Davide Chiumello, Sung-Min Cho, Bernard Cholley, Danoy Chommanam, Marie-Charlotte Chopin, Yock Ping Chow, Ting Soo Chow, Nathaniel Christy, Hiu Jian Chua, Jonathan Chua, Jose Pedro Cidade, José Miguel Cisneros Herreros, Anna Ciullo, Jennifer Clarke, Rolando Claure-Del Granado, Sara Clohisey, Cassidy Codan, Caitriona Cody, Jennifer Coles, Megan Coles, Gwenhaël Colin, Michael Collins, Pamela Combs, Jennifer Connolly, Marie Connor, Anne Conrad, Elaine Conway, Graham S. Cooke, Hugues Cordel, Amanda Corley, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Andrea Cortegiani, Grégory Corvaisier, Camille Couffignal, Sandrine Couffin-Cadiergues, Roxane Courtois, Stéphanie Cousse, Juthaporn Cowan, Rachel Cregan, Gloria Crowl, Jonathan Crump, Claudina Cruz, Marc Csete, Ailbhe Cullen, Matthew Cummings, Gerard Curley, Elodie Curlier, Colleen Curran, Paula Custodio, Ana da Silva Filipe, Charlene Da Silveira, Al-Awwab Dabaliz, John Arne Dahl, Darren Dahly, Umberto D'Alessandro, Peter Daley, Zaina Dalloul, Heidi Dalton, Jo Dalton, Seamus Daly, Juliana Damas, Joycelyn Dame, Cammandji Damien, Nick Daneman, Jorge Dantas, Frédérick D'Aragon, Gillian de Loughry, Diego de Mendoza, Etienne De Montmollin, Rafael Freitas de Oliveira França, Ana Isabel de Pinho Oliveira, Rosanna De Rosa, Cristina De Rose, Thushan de Silva, Peter de Vries, Jillian Deacon, David Dean, Alexa Debard, Bianca DeBenedictis, Marie-Pierre Debray, Nathalie DeCastro, William Dechert, Romain Decours, Eve Defous, Isabelle Delacroix, Alexandre Delamou, Eric Delaveuve, Karen Delavigne, Nathalie M. Delfos, Ionna Deligiannis, Andrea Dell'Amore, Christelle Delmas, Pierre Delobel, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Dominique Deplanque, Pieter Depuydt, Diane Descamps, Mathilde Desvallées, Santi Dewayanti, Pathik Dhangar, Alpha Diallo, Souleymane Taran Diallo, Sylvain Diamantis, André Dias, Fernanda Dias Da Silva, Rodrigo Diaz, Juan Jose Diaz, Priscila Diaz, Bakary K. Dibba, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Jérôme Dimet, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Cedric Djadda, Félix Djossou, Annemarie B. Docherty, Helen Doherty, Arjen M. Dondorp, Christl A. Donnelly, Yoann Donohue, Sean Donohue, Peter Doran, Céline Dorival, Eric D'Ortenzio, Yash Doshi, Phouvieng Douangdala, James Joshua Douglas, Renee Douma, Nathalie Dournon, Joanne Downey, Mark Downing, Thomas Drake, Aoife Driscoll, Ibrahim Kwaku Duah, Claudio Duarte Fonseca, Vincent Dubee, François Dubos, Audrey Dubot-Pérès, Alexandre Ducancelle, Toni Duculan, Susanne Dudman, Abhijit Duggal, Paul Dunand, Mathilde Duplaix, Emanuele Durante-Mangoni, Lucian Durham, III, Bertrand Dussol, Juliette Duthoit, Xavier Duval, Anne Margarita Dyrhol-Riise, Sim Choon Ean, Ada Ebo, Marco Echeverria-Villalobos, Michael Edelstein, Siobhan Egan, Linn Margrete Eggesbø, Khadeja Ehzaz, Carla Eira, Mohammed El Sanharawi, Marwan El Sayed, Mohammed Elabid, Mohamed Bashir Elagili, Subbarao Elapavaluru, Mohammad Elbahnasawy, Sohail Elboshra, Brigitte Elharrar, Jacobien Ellerbroek, Merete Ellingjord-Dale, Hamida ELMagrahi, Mohammad Muatasm Elmubark, Loubna Elotmani, Lauren Eloundou, Philippine Eloy, Basma Elshaikhy, Tarek Elshazly, Wafa Elsokni, Aml Ahmed Eltayeb, Iqbal Elyazar, Zarief Kamel Emad, Hussein Embarek, Isabelle Enderle, Tomoyuki Endo, Gervais Eneli, Chan Chee Eng, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Haneen Esaadi, Mariano Esperatti, Hélène Esperou, Catarina Espírito Santo, Marina Esposito-Farese, Rachel Essaka, Lorinda Essuman, João Estevão, Manuel Etienne, Anna Greti Everding, Mirjam Evers, Isabelle Fabre, Marc Fabre, Ismaila Fadera, Asgad Osman Abdalla Fadlalla, Amna Faheem, Arabella Fahy, Cameron J. Fairfield, Zul Fakar, Komal Fareed, Pedro Faria, Ahmed Farooq, Hanan Fateena, Mohamed Fathi, Salem Fatima, Karine Faure, Raphaël Favory, Mohamed Fayed, Niamh Feely, Jorge Fernandes, Susana Fernandes, François-Xavier Ferrand, Eglantine Ferrand Devouge, Joana Ferrão, Mário Ferraz, Benigno Ferreira, Isabel Ferreira, Bernardo Ferreira, Sílvia Ferreira, Nicolas Ferriere, Céline Ficko, Claudia Figueiredo-Mello, William Finlayson, Thomas Flament, Tom Fletcher, Aline-Marie Florence, Letizia Lucia Florio, Brigid Flynn, Deirdre Flynn, Jean Foley, Victor Fomin, Tatiana Fonseca, Patricia Fontela, Karen Forrest, Simon Forsyth, Denise Foster, Giuseppe Foti, Berline Fotso, Erwan Fourn, Robert A. Fowler, Marianne Fraher, Diego Franch-Llasat, Christophe Fraser, John F. Fraser, Marcela Vieira Freire, Ana Freitas Ribeiro, Craig French, Caren Friedrich, Ricardo Fritz, Stéphanie Fry, Nora Fuentes, Masahiro Fukuda, G. Argin, Valérie Gaborieau, Rostane Gaci, Massimo Gagliardi, Jean-Charles Gagnard, Amandine Gagneux-Brunon, Abdou Gai, Sérgio Gaião, Linda Gail Skeie, Adham Mohamed Galal Mohamed Ramadan, Phil Gallagher, Carrol Gamble, Yasmin Gani, Arthur Garan, Rebekha Garcia, Julia Garcia-Diaz, Esteban Garcia-Gallo, Navya Garimella, Denis Garot, Valérie Garrait, Basanta Gauli, Anatoliy Gavrylov, Alexandre Gaymard, Johannes Gebauer, Eva Geraud, Louis Gerbaud Morlaes, Nuno Germano, Malak Ghemmeid, Praveen Kumar Ghisulal, Jade Ghosn, Marco Giani, Tristan Gigante, Elaine Gilroy, Guillermo Giordano, Michelle Girvan, Valérie Gissot, Gezy Giwangkancana, Daniel Glikman, Petr Glybochko, Eric Gnall, Geraldine Goco, François Goehringer, Siri Goepel, Jean-Christophe Goffard, Jin Yi Goh, Brigitta Golács, Jonathan Golob, Kyle Gomez, Joan Gómez-Junyent, Marie Gominet, Alicia Gonzalez, Patricia Gordon, Isabelle Gorenne, Laure Goubert, Cécile Goujard, Tiphaine Goulenok, Margarite Grable, Jeronimo Graf, Edward Wilson Grandin, Pascal Granier, Giacomo Grasselli, Lorenzo Grazioli, Christopher A. Green, Courtney Greene, William Greenhalf, Segolène Greffe, Domenico Luca Grieco, Matthew Griffee, Fiona Griffiths, Ioana Grigoras, Albert Groenendijk, Fassou Mathias Grovogui, Heidi Gruner, Yusing Gu, Jérémie Guedj, Martin Guego, Anne-Marie Guerguerian, Daniela Guerreiro, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Maisa Guimarães de Castro, Thomas Guimard, Marieke Haalboom, Daniel Haber, Ali Hachemi, Abdurrahman Haddud, Nadir Hadri, Wael Hafez, Fakhir Raza Haidri, Fatima Mhd Rida Hajij, Sheeba Hakak, Adam Hall, Sophie Halpin, Shaher Hamdan, Abdelhafeez Hamdi, Jawad Hameed, Ansley Hamer, Raph L. Hamers, Rebecca Hamidfar, Bato Hammarström, Naomi Hammond, Terese Hammond, Lim Yuen Han, Matly Hanan, Rashan Haniffa, Kok Wei Hao, Hayley Hardwick, Ewen M. Harrison, Janet Harrison, Samuel Bernard Ekow Harrison, Alan Hartman, Sulieman Hasan, Mohammad Ali Nabil Hasan, Mohd Shahnaz Hasan, Junaid Hashmi, Madiha Hashmi, Amoni Hassan, Ebtisam Hassanin, Muhammad Hayat, Ailbhe Hayes, Leanne Hays, Jan Heerman, Lars Heggelund, Ahmed Helmi, Ross Hendry, Martina Hennessy, Aquiles Rodrigo Henriquez-Trujillo, Maxime Hentzien, Diana Hernandez, Andrew Hershey, Liv Hesstvedt, Astarini Hidayah, Eibhlin Higgins, Rupert Higgins, Samuel Hinton, Hiroaki Hiraiwa, Haider Hirkani, Hikombo Hitoto, Antonia Ho, Yi Bin Ho, Alexandre Hoctin, Isabelle Hoffmann, Wei Han Hoh, Oscar Hoiting, Rebecca Holt, Jan Cato Holter, Juan Pablo Horcajada, Ikram Houas, Mabrouka Houderi, Catherine L. Hough, Stuart Houltham, Jimmy Ming-Yang Hsu, Jean-Sébastien Hulot, Abby Hurd, Iqbal Hussain, Aliae Mohamed Hussein, Mahmood Hussein, Fatima Ibrahim, Bashir Ibran, Samreen Ijaz, M. Arfan Ikram, Carlos Cañada Illana, Patrick Imbert, Muhammad Imran Ansari, Rana Imran Sikander, Hugo Inácio, Carmen Infante Dominguez, Yun Sii Ing, Mariachiara Ippolito, Vera Irawany, Sarah Isgett, Tiago Isidoro, Nadiah Ismail, Margaux Isnard, Mette Stausland Istre, Junji Itai, Daniel Ivulich, Danielle Jaafar, Salma Jaafoura, Hamza Jaber, Julien Jabot, Clare Jackson, Abubacarr Jagne, Stéphane Jaureguiberry, Denise Jaworsky, Florence Jego, Anilawati Mat Jelani, Synne Jenum, Ruth Jimbo-Sotomayor, Ong Yiaw Joe, Ruth Noemí Jorge García, Silje Bakken Jørgensen, Cédric Joseph, Mark Joseph, Swosti Joshi, Mercé Jourdain, Philippe Jouvet, Anna Jung, Hanna Jung, Dafsah Juzar, Ouifiya Kafif, Florentia Kaguelidou, Neerusha Kaisbain, Thavamany Kaleesvran, Sabina Kali, Karl Trygve Kalleberg, Smaragdi Kalomoiri, Muhammad Aisar Ayadi Kamaluddin, Armand Saloun Kamano, Zul Amali Che Kamaruddin, Nadiah Kamarudin, Kavita Kamineni, Darshana Hewa Kandamby, Kong Yeow Kang, Darakhshan Kanwal, Dyah Kanyawati, Mohamed Karghul, Pratap Karpayah, Todd Karsies, Daisuke Kasugai, Kevin Katz, Christy Kay, Lamees Kayyali, Seán Keating, Pulak Kedia, Andrea Kelly, Aoife Kelly, Claire Kelly, Niamh Kelly, Sadie Kelly, Yvelynne Kelly, Maeve Kelsey, Kalynn Kennon, Sommay Keomany, Maeve Kernan, Younes Kerroumi, Sharma Keshav, Shams Khail, Sarah Khaled, Imrana Khalid, Antoine Khalil, Irfan Khan, Quratul Ain Khan, Sushil Khanal, Abid Khatak, Krish Kherajani, Michelle E. Kho, Denisa Khoo, Ryan Khoo, Saye Khoo, Muhammad Nasir Khoso, Amin Khuwaja, Khor How Kiat, Yuri Kida, Peter Kiiza, Beathe Kiland Granerud, Anders Benjamin Kildal, Jae Burm Kim, Antoine Kimmoun, Detlef Kindgen-Milles, Nobuya Kitamura, Eyrun Floerecke Kjetland Kjetland, Paul Klenerman, Rob Klont, Gry Kloumann Bekken, Stephen R. Knight, Robin Kobbe, Paa Kobina Forson, Chamira Kodippily, Malte Kohns Vasconcelos, Sabin Koirala, Mamoru Komatsu, Franklina Korkor Abebrese, Volkan Korten, Stephanie Kouba, Mohamed Lamine Kourouma, Karifa Kourouma, Arsène Kpangon, Karolina Krawczyk, Ali Kredan, Vinothini Krishnan, Sudhir Krishnan, Oksana Kruglova, Anneli Krund, Pei Xuan Kuan, Ashok Kumar, Deepali Kumar, Ganesh Kumar, Mukesh Kumar, Dinesh Kuriakose, Ethan Kurtzman, Demetrios Kutsogiannis, Galyna Kutsyna, Ama Kwakyewaa Bedu-Addo, Sylvie Kwedi, Konstantinos Kyriakoulis, Marie Lachatre, Marie Lacoste, John G. Laffey, Nadhem Lafhej, Marie Lagrange, Fabrice Laine, Olivier Lairez, Sanjay Lakhey, Marc Lambert, François Lamontagne, Marie Langelot-Richard, Vincent Langlois, Eka Yudha Lantang, Marina Lanza, Cédric Laouénan, Samira Laribi, Delphine Lariviere, Stéphane Lasry, Sakshi Lath, Naveed Latif, Youssef Latifeh, Odile Launay, Didier Laureillard, Yoan Lavie-Badie, Andy Law, Cassie Lawrence, Teresa Lawrence, Minh Le, Clément Le Bihan, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Soizic Le Mestre, Gwenaël Le Moal, Vincent Le Moing, Hervé Le Nagard, Ema Leal, Marta Leal Santos, Biing Horng Lee, Heng Gee Lee, Su Hwan Lee, Jennifer Lee, Todd C. Lee, Yi Lin Lee, Gary Leeming, Bénédicte Lefebvre, Laurent Lefebvre, Benjamin Lefèvre, Sylvie LeGac, Merili-Helen Lehiste, Jean-Daniel Lelievre, François Lellouche, Adrien Lemaignen, Véronique Lemee, Anthony Lemeur, Gretchen Lemmink, Ha Sha Lene, Jenny Lennon, Rafael León, Marc Leone, Tanel Lepik, Quentin Lepiller, François-Xavier Lescure, Olivier Lesens, Mathieu Lesouhaitier, Amy Lester-Grant, Andrew Letizia, Sophie Letrou, Bruno Levy, Yves Levy, Claire Levy-Marchal, Katarzyna Lewandowska, Erwan L'Her, Gianluigi Li Bassi, Janet Liang, Ali Liaquat, Geoffrey Liegeon, Kah Chuan Lim, Wei Shen Lim, Chantre Lima, Bruno Lina, Lim Lina, Andreas Lind, Maja Katherine Lingad, Guillaume Lingas, Sylvie Lion-Daolio, Keibun Liu, Marine Livrozet, Patricia Lizotte, Antonio Loforte, Navy Lolong, Leong Chee Loon, Diogo Lopes, Dalia Lopez-Colon, Anthony L. Loschner, Paul Loubet, Bouchra Loufti, Guillame Louis, Silvia Lourenco, Lara Lovelace-Macon, Lee Lee Low, Marije Lowik, Jia Shyi Loy, Jean Christophe Lucet, Carlos M. Luna, Olguta Lungu, Miles Lunn, Liem Luong, Nestor Luque, Dominique Luton, Olavi Maasikas, Moïse Machado, Sara Machado, Gabriel Macheda, Mustafa Magzoub, Rafael Mahieu, Sophie Mahy, Ana Raquel Maia, Lars S. Maier, Oumou Maiga Ascofare, Mylène Maillet, Thomas Maitre, Nimisha Abdul Majeed, Maximilian Malfertheiner, Nadia Malik, Paddy Mallon, Fernando Maltez, Denis Malvy, Victoria Manda, Laurent Mandelbrot, Frank Manetta, Julie Mankikian, Edmund Manning, Aldric Manuel, Veronika Maráczi, Ceila Maria Sant′Ana Malaque, Flávio Marino, Samuel Markowicz, Ana Marques, Catherine Marquis, Laura Marsh, Brian Marsh, Megan Marshal, John Marshall, Celina Turchi Martelli, Dori-Ann Martin, Emily Martin, Guillaume Martin-Blondel, Alessandra Martinelli, F. Eduardo Martinez, Martin Martinot, Alejandro Martín-Quiros, Ana Martins, João Martins, Nuno Martins, Caroline Martins Rego, Gennaro Martucci, Olga Martynenko, Eva Miranda Marwali, Marsilla Marzukie, David Maslove, Sabina Mason, Sobia Masood, Fatma Masoud, Moise Massoma, Palmer Masumbe, Mohd Basri Mat Nor, Moshe Matan, Henrique Mateus Fernandes, Meghena Mathew, Christina Mathew, Mathieu Mattei, Laurence Maulin, Juergen May, Javier Maynar, Mayfong Mayxay, Thierry Mazzoni, Lisa Mc Sweeney, Colin McArthur, Naina McCann, Peter McCanny, Aine McCarthy, Anne McCarthy, Colin McCloskey, Rachael McConnochie, Sherry McDermott, Sarah E. McDonald, Aine McElroy, Samuel McElwee, Natalie McEvoy, Allison McGeer, Kenneth A. McLean, Paul McNally, Bairbre McNicholas, Edel Meaney, Cécile Mear-Passard, Maggie Mechlin, Nastia Medombou, Omar Mehkri, Ferruccio Mele, Luis Melo, Kashif Ali Memon, João João Mendes, Ogechukwu Menkiti, Kusum Menon, France Mentré, Alexander J. Mentzer, Emmanuelle Mercier, Noémie Mercier, Antoine Merckx, Mayka Mergeay-Fabre, Blake Mergler, António Mesquita, Roberta Meta, Osama Metwally, Agnès Meybeck, Dan Meyer, Alison M. Meynert, Vanina Meysonnier, Mehdi Mezidi, Céline Michelanglei, Isabelle Michelet, Efstathia Mihelis, Vladislav Mihnovit, Duha Milad Abdullah, Jennene Miller, Hugo Miranda-Maldonado, Nor Arisah Misnan, Nik Nur Eliza Mohamed, Nouralsabah Mohamed, Tahira Jamal Mohamed, Alaa Mohamed Ads, Ahmed Reda Mohamed Elsayed Abdelhalim, Libya Mohammed, Shrouk Fawze Mohammed Mostafa, Manahil Omer Abdelrahman Mohammedahmed, Omer Abdullah Mohammedelhassan, Asma Moin, Walaa Mokhtar, Elena Molinos, Brenda Molloy, Mary Mone, Agostinho Monteiro, Claudia Montes, Giorgia Montrucchio, Sarah Moore, Shona C. Moore, Lina Morales Cely, Marwa Morgom, Lucia Moro, Catherine Motherway, Ana Motos, Hugo Mouquet, Clara Mouton Perrot, Julien Moyet, Suleiman Haitham Mualla, Mohamed Muftah, Aisha Kalsoom Mufti, Ng Yong Muh, Mo'nes Muhaisen, Dzawani Muhamad, Jimmy Mullaert, Fredrik Müller, Karl Erik Müller, Daniel Munblit, Syed Muneeb Ali, Nadeem Munir, Laveena Munshi, Aisling Murphy, Patrick Murray, Marlène Murris, Srinivas Murthy, Himed Musaab, Alamin Mustafa, Mus'ab Mustafa, Dana Mustafa, Himasha Muvindi, Dimitra Melia Myrodia, Farah Nadia Mohd-Hanafiah, Behzad Nadjm, Dave Nagpal, Alex Nagrebetsky, Blanka Nagybányai-Nagy, Herwin Nanda Boudoin, Mangala Narasimhan, Nageswaran Narayanan, Prashant Nasa, Rashid Nasim Khan, Ahmad Nasrallah, Adel Gerges Nassif Metri, Alasdair Nazerali-Maitland, Nadège Neant, Holger Neb, Nikita Nekliudov, Matthew Nelder, Erni Nelwan, Raul Neto, Emily Neumann, Wing Yiu Ng, Pauline Yeung Ng, Anthony Nghi, Duc Nguyen, Orna Ni Choileain, Niamh Ni Leathlobhair, Nerissa Niba, Alistair D. Nichol, Prompak Nitayavardhana, Stephanie Nonas, Nurul Amani Mohd Noordin, Nurul Faten Izzati Norharizam, Anita North, Alessandra Notari, Mahdad Noursadeghi, Adam Nowinski, Saad Nseir, Leonard Numfor, Nurnaningsih Nurnaningsih, Dwi Utomo Nusantara, Elsa Nyamankolly, Anders Benteson Nygaard, Fionnuala O. Brien, Annmarie O. Callaghan, Annmarie O'Callaghan, Giovanna Occhipinti, Derbrenn OConnor, Max O'Donnell, Lawrence Ofori-Boadu, Tawnya Ogston, Takayuki Ogura, Tak-Hyuk Oh, Sophie O'Halloran, Katie O'Hearn, Sally-Ann Ohene, João Oliveira, Larissa Oliveira, Piero L. Olliaro, Cinderella Omar Rageh Elnaggar, Alsarrah Ali Mohammed Omer, Pierre Ondobo, David S.Y. Ong, Jee Yan Ong, Wilna Oosthuyzen, Anne Opavsky, Peter Openshaw, Saijad Orakzai, Claudia Milena Orozco-Chamorro, Jamel Ortoleva, Mohamed Osama Elsayed Soliman, Javier Osatnik, Linda O'Shea, Miriam O'Sullivan, Eman Othman, Siti Zubaidah Othman, Nadia Ouamara, Rachida Ouissa, Micheal Owusu, Ama Akyampomaa Owusu-Asare, Eric Oziol, Maïder Pagadoy, Justine Pages, Amanda Palacios, Massimo Palmarini, Giovanna Panarello, Hem Paneru, Lai Hui Pang, Mauro Panigada, Nathalie Pansu, Aurélie Papadopoulos, Rachael Parke, Melissa Parker, Jérémie Pasquier, Bruno Pastene, Fabian Patauner, Drashti Patel, Mohan Dass Pathmanathan, Luís Patrão, Patricia Patricio, Lisa Patterson, Rajyabardhan Pattnaik, Christelle Paul, Mical Paul, Jorge Paulos, William A. Paxton, Jean-François Payen, Sandra L. Peake, Kalaiarasu Peariasamy, Giles J. Peek, Florent Peelman, Nathan Peiffer-Smadja, Vincent Peigne, Mare Pejkovska, Paolo Pelosi, Ithan D. Peltan, Rui Pereira, Daniel Perez, Thomas Perpoint, Antonio Pesenti, Vincent Pestre, Lenka Petrou, Michele Petrovic, Ventzislava Petrov-Sanchez, Frank Olav Pettersen, Gilles Peytavin, Richard Odame Philips, Ooyanong Phonemixay, Soulichanya Phoutthavong, Michael Piagnerelli, Walter Picard, Olivier Picone, Maria de Piero, Djura Piersma, Carlos Pimentel, Raquel Pinto, Catarina Pires, Lionel Piroth, Ayodhia Pitaloka, Chiara Piubelli, Riinu Pius, Simone Piva, Laurent Plantier, Hon Shen Png, Julien Poissy, Ryadh Pokeerbux, Sergio Poli, Georgios Pollakis, Diane Ponscarme, Diego Bastos Porto, Andra-Maris Post, Douwe F. Postma, Pedro Povoa, Diana Póvoas, Jeff Powis, Sofia Prapa, Viladeth Praphasiri, Sébastien Preau, Christian Prebensen, Jean-Charles Preiser, Anton Prinssen, Gamage Dona Dilanthi Priyadarshani, Lucia Proença, Sravya Pudota, Bambang Pujo Semedi, Mathew Pulicken, Peter Puplampu, Gregory Purcell, Luisa Quesada, Vilmaris Quinones-Cardona, Else Quist-Paulsen, Mohammed Quraishi, Fadi Qutishat, Maia Rabaa, Christian Rabaud, Ebenezer Rabindrarajan, Aldo Rafael, Marie Rafiq, Abdelrahman Ragab, Mutia Rahardjani, Arslan Rahat Ullah, Ahmad Kashfi Haji Ab Rahman, Rozanah Abd Rahman, Fernando Rainieri, Giri Shan Rajahram, Pratheema Ramachandran, Nagarajan Ramakrishnan, José Ramalho, Ahmad Afiq Ramli, Blandine Rammaert, Grazielle Viana Ramos, Asim Rana, Rajavardhan Rangappa, Ritika Ranjan, Christophe Rapp, Aasiyah Rashan, Thalha Rashan, Ghulam Rasheed, Menaldi Rasmin, Indrek Rätsep, Cornelius Rau, Tharmini Ravi, Ali Raza, Andre Real, Stanislas Rebaudet, Sarah Redl, Brenda Reeve, Attaur Rehman, Muhammad Osama Rehman Khalid, Dag Henrik Reikvam, Renato Reis, Jonathan Remppis, Martine Remy, Hongru Ren, Hanna Renk, Anne-Sophie Resseguier, Matthieu Revest, Oleksa Rewa, Maria Ines Ribeiro, Antonia Ricchiuto, David Richardson, Denise Richardson, Laurent Richier, Siti Nurul Atikah Ahmad Ridzuan, Ana L. Rios, Asgar Rishu, Patrick Rispal, Karine Risso, Maria Angelica Rivera Nuñez, Chiara Robba, André Roberto, Stephanie Roberts, Charles Roberts, David L. Robertson, Olivier Robineau, Anna Roca, Ferran Roche-Campo, Paola Rodari, Simão Rodeia, Bernhard Roessler, Claire Roger, Pierre-Marie Roger, Roberto Roncon-Albuquerque, Jr., Mélanie Roriz, Manuel Rosa-Calatrava, Michael Rose, Dorothea Rosenberger, Andrea Rossanese, Matteo Rossetti, Patrick Rossignol, Carine Roy, Benoît Roze, Desy Rusmawatiningtyas, Clark D. Russell, Maeve Ryan, Steffi Ryckaert, Aleksander Rygh Holten, Isabela Saba, Sairah Sadaf, Musharaf Sadat, Valla Sahraei, Abdurraouf Said, Nadia Saidani, Pranya Sakiyalak, Fodé Bangaly Sako, Moamen Salah, Ali Alaa Salah Eldin Mohamed Abbas, Nawal Salahuddin, Leonardo Salazar, Jodat Saleem, Mohammed Saleh Alyasiri, Talat Ahmed Abu Salem, Gabriele Sales, Charlotte Salmon Gandonniere, Hélène Salvator, Dana Samardali, Shaden Samardali, Yehia Samir Shaaban Aly Orabi, Emely Sanchez, Olivier Sanchez, Kizy Sanchez de Oliveira, Angel Sanchez-Miralles, Vanessa Sancho-Shimizu, Gyan Sandhu, Zulfiqar Sandhu, Pierre-François Sandrine, Oana Săndulescu, Marlene Santos, Shirley Sarfo-Mensah, Bruno Sarmento Banheiro, Iam Claire E. Sarmiento, Benjamine Sarton, Ankana Satya, Sree Satyapriya, Rumaisah Satyawati, Egle Saviciute, Yen Tsen Saw, Justin Schaffer, Tjard Schermer, Arnaud Scherpereel, Marion Schneider, János Schnur, Stephan Schroll, Michael Schwameis, Gary Schwartz, Janet T. Scott, James Scott-Brown, Nicholas Sedillot, Tamara Seitz, Jaganathan Selvanayagam, Mageswari Selvarajoo, Malcolm G. Semple, Rasidah Bt Senian, Eric Senneville, Claudia Sepulveda, Filipa Sequeira, Tânia Sequeira, Ary Serpa Neto, Ellen Shadowitz, Syamin Asyraf Shahidan, Hamza Shahla, Laila Shalabi, Haitam Shames, Anuraj Shankar, Shaikh Sharjeel, Pratima Sharma, Catherine A. Shaw, Victoria Shaw, John Robert Sheenan, Dr. Rajesh Mohan Shetty, Rohan Shetty, Mohiuddin Shiekh, Nobuaki Shime, Keiki Shimizu, Sally Shrapnel, Shubha Kalyan Shrestha, Pramesh Sundar Shrestha, Hoi Ping Shum, Nassima Si Mohammed, Ng Yong Siang, Moses Siaw-Frimpong, Jeanne Sibiude, Bountoy Sibounheuang, Nidhal Siddig, Atif Siddiqui, Maqsood Ahmed Siddiqui, Louise Sigfrid, Fatoumata Sillah, Piret Sillaots, Catarina Silva, Maria Joao Silva, Rogério Silva, Benedict Sim Lim Heng, Wai Ching Sin, Dario Sinatti, Mahendra Singh, Punam Singh, Pompini Agustina Sitompul, Karisha Sivam, Vegard Skogen, Sue Smith, Benjamin Smood, Coilin Smyth, Morgane Snacken, Dominic So, Tze Vee Soh, Lene Bergendal Solberg, Joshua Solomon, Tom Solomon, Emily Somers, Agnès Sommet, Myung Jin Song, Rima Song, Tae Song, Jack Song Chia, Arne Søraas, Albert Sotto, Edouard Soum, Ana Chora Sousa, Marta Sousa, Maria Sousa Uva, Vicente Souza-Dantas, Mamadou Saliou Sow, Alexandra Sperry, Elisabetta Spinuzza, B. P. Sanka Ruwan Sri Darshana, Shiranee Sriskandan, Sarah Stabler, Thomas Staudinger, Stephanie-Susanne Stecher, Trude Steinsvik, Ymkje Stienstra, Birgitte Stiksrud, Eva Stolz, Amy Stone, Anca Streinu-Cercel, Adrian Streinu-Cercel, Geoff Strong, Ami Stuart, David Stuart, Richa Su, Decy Subekti, Gabriel Suen, Jacky Y. Suen, Prasanth Sukumar, Asfia Sultana, Charlotte Summers, Dubravka Supic, Deepashankari Suppiah, Magdalena Surovcová, Atie Suwarti, Andrey Svistunov, Sarah Syahrin, Augustina Sylverken, Konstantinos Syrigos, Jaques Sztajnbok, Konstanty Szuldrzynski, Shirin Tabrizi, Fabio S. Taccone, Lysa Tagherset, Shahdattul Mawarni Taib, Sara Taleb, Cheikh Talla, Jelmer Talsma, Renaud Tamisier, Maria Lawrensia Tampubolon, Kim Keat Tan, Yan Chyi Tan, Hiroyuki Tanaka, Taku Tanaka, Hayato Taniguchi, Huda Taqdees, Arshad Taqi, Coralie Tardivon, Yousef Tarek Kamal Mostafa, Ali Tarhabat, Pierre Tattevin, M Azhari Taufik, Hassan Tawfik, Tze Yuan Tee, João Teixeira, Sofia Tejada, Marie-Capucine Tellier, Sze Kye Teoh, Vanessa Teotonio, François Téoulé, Olivier Terrier, Nicolas Terzi, Hubert Tessier-Grenier, Adrian Tey, Alif Adlan Mohd Thabit, Anand Thakur, Zhang Duan Tham, Suvintheran Thangavelu, Elmi Theron, Vincent Thibault, Simon-Djamel Thiberville, Benoît Thill, Jananee Thirumanickam, Niamh Thompson, Shaun Thompson, Emma C. Thomson, David Thomson, Mathew Thorpe, Surain Raaj Thanga Thurai, Ryan S. Thwaites, Paul Tierney, Vadim Tieroshyn, Peter S. Timashev, Jean-François Timsit, Noémie Tissot, Fiona Toal, Jordan Zhien Yang Toh, Maria Toki, Kristian Tonby, Sia Loong Tonnii, Marta Torre, Antoni Torres, Margarida Torres, Rosario Maria Torres Santos-Olmo, Hernando Torres-Zevallos, Aboubacar Tounkara, Michael Towers, Fodé Amara Traoré, Tony Trapani, Cécile Tromeur, Ioannis Trontzas, Tiffany Trouillon, Jeanne Truong, Christelle Tual, Sarah Tubiana, Helen Tuite, Alexis F. Turgeon, Jean-Marie Turmel, Lance C.W. Turtle, Anders Tveita, Pawel Twardowski, Makoto Uchiyama, PG Ishara Udayanga, Andrew Udy, Roman Ullrich, Alberto Uribe, Asad Usman, Effua Usuf, Timothy M. Uyeki, Cristinava Vajdovics, Piero Valentini, Luís Val-Flores, Stijn Van de Velde, Marcel van den Berge, Machteld van der Feltz, Job van der Palen, Paul van der Valk, Nicky Van Der Vekens, Peter Van der Voort, Sylvie Van Der Werf, Laura van Gulik, Jarne Van Hattem, Carolien van Netten, Ilonka van Veen, Noémie Vanel, Henk Vanoverschelde, Michael Varrone, Shoban Raj Vasudayan, Charline Vauchy, Pavan Kumar Vecham, Shaminee Veeran, Aurélie Veislinger, Sebastian Vencken, Sara Ventura, Annelies Verbon, José Ernesto Vidal, César Vieira, Deepak Vijayan, Judit Villar, Pierre-Marc Villeneuve, Andrea Villoldo, Gayatri Vishwanathan, Benoit Visseaux, Hannah Visser, Chiara Vitiello, Manivanh Vongsouvath, Harald Vonkeman, Fanny Vuotto, Suhaila Abdul Wahab, Noor Hidayu Wahab, Nadirah Abdul Wahid, Marina Wainstein, Laura Walsh, Wan Fadzlina Wan Muhd Shukeri, Chih-Hsien Wang, Steve Webb, Katharina Weil, Tan Pei Wen, Hassi Wesam, Sanne Wesselius, T. Eoin West, Murray Wham, Bryan Whelan, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Surya Otto Wijaya, Keith Wille, Sue Willems, Bailey Williams, Patricia J. Williams, Virginie Williams, Jessica Wittman, Calvin Wong, Xin Ci Wong, Yew Sing Wong, Teck Fung Wong, Natalie Wright, Lim Saio Xian, Ioannis Xynogalas, Siti Rohani Binti Mohd Yakop, Masaki Yamazaki, Elizabeth Yarad, Yazdan Yazdanpanah, Nicholas Yee Liang Hing, Abdelrahman Yehia Mahmoud Abdelaal, Cécile Yelnik, Chian Hui Yeoh, Stephanie Yerkovich, Touxiong Yiaye, Toshiki Yokoyama, Hodane Yonis, Obada Yousif, Saptadi Yuliarto, Akram Zaaqoq, Marion Zabbe, Gustavo E. Zabert, Kai Zacharowski, Masliza Zahid, Maram Zahran, Nor Zaila Binti Zaidan, Maria Zambon, Miguel Zambrano, Alberto Zanella, Nurul Zaynah, Hiba Zayyad, Alexander Zoufaly, and David Zucman
Subjects: COVID-19, Non-respiratory symptoms, Respiratory symptoms, Risk factors, Mortality, Science (General), Q1-390, Social sciences (General), H1-99
Abstract: Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.
Published: 2024
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5. Accuracy of the Infectious Diseases Society of America and British Thoracic Society Criteria for Acute Pneumonia in Differentiating Chemical and Bacterial Complications of Aspiration in Comatose Ventilated Patients Following Drug Poisoning

Author: Quentin Delforge, Alexandre Gaudet, Pauline Boddaert, Frédéric Wallet, Benoit Voisin, and Saad Nseir
Subjects: drug poisoning, aspiration pneumonia, pneumonitis, antibiotics, mechanical ventilation, Therapeutics. Pharmacology, RM1-950
Abstract: Drug poisoning frequently leads to admission to intensive care units, often resulting in aspiration, a potentially life-threatening condition if not properly managed. Aspiration can manifest as either bacterial aspiration pneumonia (BAP) or aspiration pneumonitis (AP), which are challenging to distinguish potentially leading to overprescription of antibiotics and the emergence of multidrug-resistant bacteria. This study aims to assess the accuracy of the Infectious Diseases Society of America (IDSA) and British Thoracic Society (BTS) criteria in differentiating BAP from AP in comatose ventilated patients following drug poisoning. This cross-sectional study included 95 patients admitted for drug poisoning at the Lille University Hospital intensive care department, between 2013 and 2017, requiring mechanical ventilation and receiving antibiotics for aspiration. Patients were categorized as having bacterial complications if tracheal sampling yielded positive culture results, and if they were otherwise considered to have chemical complications. The sensitivity, specificity, positive predictive value, and negative predictive value of IDSA and BTS criteria in identifying patients with bacterial complications were evaluated. Among the patients, 34 (36%) experienced BAP. The IDSA criteria demonstrated a sensitivity of 62% and specificity of 33%, while the BTS criteria showed a sensitivity of 50% and specificity of 38%. Both the IDSA and BTS criteria exhibited poor sensitivity and specificity in identifying microbiologically confirmed pneumonia in comatose ventilated patients following drug poisoning.
Published: 2024
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6. Inhaled nitric oxide in patients with acute respiratory distress syndrome caused by COVID-19: treatment modalities, clinical response, and outcomes

Author: Armand Mekontso Dessap, Laurent Papazian, Manuella Schaller, Saad Nseir, Bruno Megarbane, Luc Haudebourg, Jean-François Timsit, Jean-Louis Teboul, Khaldoun Kuteifan, Marc Gainnier, Michel Slama, Patrick Houeto, Laurent Lecourt, Alain Mercat, and Antoine Vieillard-Baron
Subjects: COVID-19, Acute respiratory distress syndrome, Inhaled nitric oxide, Refractory hypoxaemia, ECMO, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Inhaled nitric oxide (iNO) has been widely used in patients with COVID-19-related acute respiratory distress syndrome (C-ARDS), though its physiological effects and outcome are debated in this setting. The objective of this cohort study was to describe the modalities of iNO use, clinical response, and outcomes in a large cohort of C-ARDS patients. Methods Multicentre, retrospective cohort study conducted in France. Results From end February to December 2020, 300 patients (22.3% female) were included, 84.5% were overweight and 69.0% had at least one comorbidity. At ICU admission, their median (IQR) age, SAPS II, and SOFA score were 66 (57–72) years, 37 (29–48), and 5 (3–8), respectively. Patients were all ventilated according to a protective ventilation strategy, and 68% were prone positioned before iNO initiation. At iNO initiation, 2%, 37%, and 61% of patients had mild, moderate, and severe ARDS, respectively. The median duration of iNO treatment was 2.8 (1.1–5.5) days with a median dosage of 10 (7–13) ppm at initiation. Responders (PaO2/FiO2 ratio improving by 20% or more) represented 45.7% of patients at 6 h from iNO initiation. The severity of ARDS was the only predictive factor associated with iNO response. Among all evaluable patients, the crude mortality was not significantly different between responders at 6 h and their counterparts. Of the 62 patients with refractory ARDS (who fulfilled extracorporeal membrane oxygenation criteria before iNO initiation), 32 (51.6%) no longer fulfilled these criteria after 6 h of iNO. The latter showed significantly lower mortality than the other half (who remained ECMO eligible), including after confounder adjustment (adjusted OR: 0.23, 95% CI 0.06, 0.89, p = 0.03). Conclusions Our study reports the benefits of iNO in improving arterial oxygenation in C-ARDS patients. This improvement seems more relevant in the most severe cases. In patients with ECMO criteria, an iNO-driven improvement in gas exchange was associated with better survival. These results must be confirmed in well-designed prospective studies.
Published: 2023
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7. Efficacy of carbapenem vs non carbapenem β-lactam therapy as empiric antimicrobial therapy in patients with extended-spectrum β-lactamase-producing Enterobacterales urinary septic shock: a propensity-weighted multicenter cohort study

Author: Erwann Cariou, Romain Griffier, Arthur Orieux, Stein Silva, Stanislas Faguer, Thierry Seguin, Saad Nseir, Emmanuel Canet, Arnaud Desclaux, Bertrand Souweine, Kada Klouche, Olivier Guisset, Jerome Pillot, Walter Picard, Tahar Saghi, Pierre Delobel, Didier Gruson, Renaud Prevel, and Alexandre Boyer
Subjects: Extended-spectrum β-lactamase-producing Enterobacterales, Non carbapenem β-lactam therapy, Antimicrobial resistance, Septic shock, Urinary tract infection, Aminoglycosides, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background The rise in antimicrobial resistance is a global threat responsible for about 33,000 deaths in 2015 with a particular concern for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) and has led to a major increase in the use of carbapenems, last-resort antibiotics. Methods In this retrospective propensity-weighted multicenter observational study conducted in 11 ICUs, the purpose was to assess the efficacy of non carbapenem regimen (piperacillin–tazobactam (PTZ) + aminoglycosides or 3rd-generation cephalosporin (3GC) + aminoglycosides) as empiric therapy in comparison with carbapenem in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) urinary septic shock. The primary outcome was Day-30 mortality. Results Among 156 patients included in this study, 69 received a carbapenem and 87 received non carbapenem antibiotics as empiric treatment. Baseline clinical characteristics were similar between the two groups. Patients who received carbapenem had similar Day-30 mortality (10/69 (15%) vs 6/87 (7%), OR = 1.99 [0.55; 5.34] p = 0.16), illness severity, resolution of septic shock, and ESBL-E infection recurrence rates than patients who received an empiric non carbapenem therapy. The rates of secondary infection with C. difficile were comparable. Conclusions In ESBL-E urinary septic shock, empiric treatment with a non carbapenem regimen, including systematically aminoglycosides, was not associated with higher mortality, compared to a carbapenem regimen.
Published: 2023
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8. Long-term outcomes after severe acute kidney injury in critically ill patients: the SALTO study

Author: Khalil Chaïbi, Franck Ehooman, Bertrand Pons, Laurent Martin-Lefevre, Eric Boulet, Alexandre Boyer, Guillaume Chevrel, Nicolas Lerolle, Dorothée Carpentier, Nicolas de Prost, Alexandre Lautrette, Anne Bretagnol, Julien Mayaux, Saad Nseir, Bruno Megarbane, Marina Thirion, Jean-Marie Forel, Julien Maizel, Hodane Yonis, Philippe Markowicz, Guillaume Thiery, Frédérique Schortgen, Cécile Couchoud, Didier Dreyfuss, and Stephane Gaudry
Subjects: Acute kidney injury, Renal replacement therapy, Long-term outcomes, Worsening renal failure, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background The extent of the consequences of an episode of severe acute kidney injury (AKI) on long-term outcome of critically ill patients remain debated. We conducted a prospective follow-up of patients included in a large multicenter clinical trial of renal replacement therapy (RRT) initiation strategy during severe AKI (the Artificial Kidney Initiation in Kidney Injury, AKIKI) to investigate long-term survival, renal outcome and health related quality of life (HRQOL). We also assessed the influence of RRT initiation strategy on these outcomes. Results Follow-up of patients extended from 60 days to a median of 3.35 years [interquartile range (IQR), 1.89 to 4.09] after the end of initial study. Of the 619 patients included in the AKIKI trial, 316 survived after 60 days. The overall survival rate at 3 years from inclusion was 39.4% (95% CI 35.4 to 43.4). A total of 46 patients (on the 175 with available data on long-term kidney function) experienced worsening of renal function (WRF) at the time of follow-up [overall incidence of 26%, cumulative incidence at 4 years: 20.6% (CI 95% 13.0 to 28.3)]. Fifteen patients required chronic dialysis (5% of patients who survived after day 90). Among the 226 long-term survivors, 80 (35%) answered the EQ-5D questionnaire. The median index value reported was 0.67 (IQR 0.40 to 1.00) indicating a noticeable alteration of quality of life. Initiation strategy for RRT had no effect on any long-term outcome. Conclusion Severe AKI in critically ill patients was associated with a high proportion of death within the first 2 months but less so during long-term follow-up. A quarter of long-term survivors experienced a WRF and suffered from a noticeable impairment of quality of life. Renal replacement therapy initiation strategy was not associated with mortality outcome. Graphical Abstract
Published: 2023
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9. Critically ill severe hypothyroidism: a retrospective multicenter cohort study

Author: Simon Bourcier, Maxime Coutrot, Alexis Ferré, Nicolas Van Grunderbeeck, Julien Charpentier, Sami Hraiech, Elie Azoulay, Saad Nseir, Nadia Aissaoui, Jonathan Messika, Pierre Fillatre, Romain Persichini, Serge Carreira, Alexandre Lautrette, Clément Delmas, Nicolas Terzi, Bruno Mégarbane, Jean-Baptiste Lascarrou, Keyvan Razazi, Xavier Repessé, Claire Pichereau, Damien Contou, Aurélien Frérou, François Barbier, Stephan Ehrmann, Etienne de Montmollin, Benjamin Sztrymf, Elise Morawiec, Naïke Bigé, Danielle Reuter, David Schnell, Olivier Ellrodt, Jean Dellamonica, Alain Combes, and Matthieu Schmidt
Subjects: Hypothyroidism, Myxedema, Coma, Cardiogenic shock, Critical care, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Severe hypothyroidism (SH) is a rare but life-threatening endocrine emergency. Only a few data are available on its management and outcomes of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management, and in-ICU and 6-month survival rates of these patients. Methods We conducted a retrospective, multicenter study over 18 years in 32 French ICUs. The local medical records of patients from each participating ICU were screened using the International Classification of Disease 10th revision. Inclusion criteria were the presence of biological hypothyroidism associated with at least one cardinal sign among alteration of consciousness, hypothermia and circulatory failure, and at least one SH-related organ failure. Results Eighty-two patients were included in the study. Thyroiditis and thyroidectomy represented the main SH etiologies (29% and 19%, respectively), while hypothyroidism was unknown in 44 patients (54%) before ICU admission. The most frequent SH triggers were levothyroxine discontinuation (28%), sepsis (15%), and amiodarone-related hypothyroidism (11%). Clinical presentations included hypothermia (66%), hemodynamic failure (57%), and coma (52%). In-ICU and 6-month mortality rates were 26% and 39%, respectively. Multivariable analyses retained age > 70 years [odds ratio OR 6.01 (1.75–24.1)] Sequential Organ-Failure Assessment score cardiovascular component ≥ 2 [OR 11.1 (2.47–84.2)] and ventilation component ≥ 2 [OR 4.52 (1.27–18.6)] as being independently associated with in-ICU mortality. Conclusions SH is a rare life-threatening emergency with various clinical presentations. Hemodynamic and respiratory failures are strongly associated with worse outcomes. The very high mortality prompts early diagnosis and rapid levothyroxine administration with close cardiac and hemodynamic monitoring.
Published: 2023
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10. Impact of renal replacement therapy strategy on beta-lactam plasma concentrations: the BETAKIKI study—an ancillary study of a randomized controlled trial

Author: Damien Roux, Nicolas Benichou, David Hajage, Laurent Martin-Lefèvre, Nicolas de Prost, Nicolas Lerolle, Dimitri Titeca-Beauport, Eric Boulet, Julien Mayaux, Bruno Mégarbane, Khaoula Mahjoub, Dorothée Carpentier, Saad Nseir, Florence Tubach, Jean-Damien Ricard, Didier Dreyfuss, Stéphane Gaudry, and for the AKIKI Study group
Subjects: Acute kidney injury, Beta-lactam, Concentration, Septic shock, Renal replacement therapy, Antibiotic, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Sepsis prognosis correlates with antibiotic adequacy at the early phase. This adequacy is dependent on antibacterial spectrum, bacterial resistance profile and antibiotic dosage. Optimal efficacy of beta-lactams mandates concentrations above the minimal inhibitory concentration (MIC) of the targeted bacteria for the longest time possible over the day. Septic acute kidney injury (AKI) is the most common AKI syndrome in ICU and often mandates renal replacement therapy (RRT) initiation. Both severe AKI and RRT may increase outside target antibiotic concentrations and ultimately alter patient’s prognosis. Patients and methods This is a secondary analysis of a randomized controlled trial that compared an early RRT initiation strategy with a delayed one in 620 critically ill patients undergoing severe AKI (defined by KDIGO 3). We compared beta-lactam trough concentrations between the two RRT initiation strategies. The primary outcome was the proportion of patients with sufficient trough plasma concentration of beta-lactams defined by trough concentration above 4 times the MIC. We hypothesized that early initiation of RRT could be associated with an insufficient antibiotic plasma trough concentration compared to patients allocated to the delayed strategy. Results One hundred and twelve patients were included: 53 in the early group and 59 in the delayed group. Eighty-three patients (74%) had septic shock on inclusion. Trough beta-lactam plasma concentration was above 4 times the MIC breakpoint in 80.4% (n = 90) of patients of the whole population, without differences between the early and the delayed groups (79.2% vs. 81.4%, respectively, p = 0.78). On multivariate analysis, the presence of septic shock and a higher mean arterial pressure were significantly associated with a greater probability of adequate antibiotic trough concentration [OR 3.95 (1.14;13.64), p = 0.029 and OR 1.05 (1.01;1.10), p = 0.013, respectively). Evolution of procalcitonin level and catecholamine-free days as well as mortality did not differ whether beta-lactam trough concentration was above 4 times the MIC or not. Conclusions In this secondary analysis of a randomized controlled trial, renal replacement therapy initiation strategy did not significantly influence plasma trough concentrations of beta-lactams in ICU patients with severe AKI. Presence of septic shock on inclusion was the main variable associated with a sufficient beta-lactam concentration. Trial registration: The AKIKI trial was registered on ClinicalTrials.gov (Identifier: NCT01932190) before the inclusion of the first patient.
Published: 2023
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11. Relationship between corticosteroid use and incidence of ventilator-associated pneumonia in COVID-19 patients: a retrospective multicenter study

Author: Ouriel Saura, Anahita Rouzé, Ignacio Martin-Loeches, Pedro Povoa, Louis Kreitmann, Antoni Torres, Matthieu Metzelard, Damien Du Cheyron, Fabien Lambiotte, Fabienne Tamion, Marie Labruyere, Claire Boulle Geronimi, Charles-Edouard Luyt, Martine Nyunga, Olivier Pouly, Arnaud W. Thille, Bruno Megarbane, Anastasia Saade, Eleni Magira, Jean-François Llitjos, Iliana Ioannidou, Alexandre Pierre, Jean Reignier, Denis Garot, Jean-Luc Baudel, Guillaume Voiriot, Gaëtan Plantefeve, Elise Morawiec, Pierre Asfar, Alexandre Boyer, Armand Mekontso-Dessap, Fotini Bardaka, Emili Diaz, Christophe Vinsonneau, Pierre-Edouard Floch, Nicolas Weiss, Adrian Ceccato, Antonio Artigas, David Nora, Alain Duhamel, Julien Labreuche, Saad Nseir, and coVAPid Study Group
Subjects: SARS-CoV-2, COVID-19, Ventilator-associated lower respiratory tract infections, Corticosteroids, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Ventilator-associated pneumonia (VAP) is common in patients with severe SARS-CoV-2 pneumonia. The aim of this ancillary analysis of the coVAPid multicenter observational retrospective study is to assess the relationship between adjuvant corticosteroid use and the incidence of VAP. Methods Planned ancillary analysis of a multicenter retrospective European cohort in 36 ICUs. Adult patients receiving invasive mechanical ventilation for more than 48 h for SARS-CoV-2 pneumonia were consecutively included between February and May 2020. VAP diagnosis required strict definition with clinical, radiological and quantitative microbiological confirmation. We assessed the association of VAP with corticosteroid treatment using univariate and multivariate cause-specific Cox’s proportional hazard models with adjustment on pre-specified confounders. Results Among the 545 included patients, 191 (35%) received corticosteroids. The proportional hazard assumption for the effect of corticosteroids on the incidence of VAP could not be accepted, indicating that this effect varied during ICU stay. We found a non-significant lower risk of VAP for corticosteroid-treated patients during the first days in the ICU and an increased risk for longer ICU stay. By modeling the effect of corticosteroids with time-dependent coefficients, the association between corticosteroids and the incidence of VAP was not significant (overall effect p = 0.082), with time-dependent hazard ratios (95% confidence interval) of 0.47 (0.17–1.31) at day 2, 0.95 (0.63–1.42) at day 7, 1.48 (1.01–2.16) at day 14 and 1.94 (1.09–3.46) at day 21. Conclusions No significant association was found between adjuvant corticosteroid treatment and the incidence of VAP, although a time-varying effect of corticosteroids was identified along the 28-day follow-up.
Published: 2022
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12. Antibiotic Prescriptions in Critically Ill Patients with Bloodstream Infection Due to ESBL-Producing Enterobacteriaceae: Compliance with the French Guidelines for the Treatment of Infections with Third-Generation Cephalosporin-Resistant Enterobacteriaceae—A Multicentric Retrospective Cohort Study

Author: Camille Le Berre, Marion Houard, Anne Vachée, Hugues Georges, Frederic Wallet, Pierre Patoz, Patrick Herbecq, Saad Nseir, Pierre-Yves Delannoy, and Agnès Meybeck
Subjects: extended-spectrum beta-lactamase-producing Enterobacteriaceae, carbapenem sparing, guidelines, antibiotics, critical care, bacteremia, Biology (General), QH301-705.5
Abstract: National and international guidelines were recently published regarding the treatment of Enterobacteriaceae resistant to third-generation cephalosporins infections. We aimed to assess the implementation of the French guidelines in critically ill patients suffering from extended-spectrum β-lactamase-producing Enterobacteriaceae bloodstream infection (ESBL-E BSI). We conducted a retrospective observational cohort study in the ICU of three French hospitals. Patients treated between 2018 and 2022 for ESBL-E BSI were included. The primary assessment criterion was the proportion of adequate empirical carbapenem prescriptions, defined as prescriptions consistent with the French guidelines. Among the 185 included patients, 175 received an empirical anti-biotherapy within 24 h of ESBL-E BSI onset, with a carbapenem for 100 of them. The proportion of carbapenem prescriptions consistent with the guidelines was 81%. Inconsistent prescriptions were due to a lack of prescriptions of a carbapenem, while it was recommended in 25% of cases. The only factor independently associated with adequate empirical carbapenem prescription was ESBL-E colonization (OR: 107.921 [9.303–1251.910], p = 0.0002). The initial empirical anti-biotherapy was found to be appropriate in 83/98 patients (85%) receiving anti-biotherapy in line with the guidelines and in 56/77 (73%) patients receiving inadequate anti-biotherapy (p = 0.06). Our results illustrate the willingness of intensivists to spare carbapenems. Promoting implementation of the guidelines could improve the proportion of initial appropriate anti-biotherapy in critically ill patients with ESBL-E BSI.
Published: 2023
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13. ICU-Acquired Colonization and Infection Related to Multidrug-Resistant Bacteria in COVID-19 Patients: A Narrative Review

Author: Alexandre Gaudet, Louis Kreitmann, and Saad Nseir
Subjects: antimicrobial resistance, multidrug resistance, cross-infection, ventilator-associated pneumonia, COVID-19, bloodstream infection, Therapeutics. Pharmacology, RM1-950
Abstract: A large proportion of ICU-acquired infections are related to multidrug-resistant bacteria (MDR). Infections caused by these bacteria are associated with increased mortality, and prolonged duration of mechanical ventilation and ICU stay. The aim of this narrative review is to report on the association between COVID-19 and ICU-acquired colonization or infection related to MDR bacteria. Although a huge amount of literature is available on COVID-19 and MDR bacteria, only a few clinical trials have properly evaluated the association between them using a non-COVID-19 control group and accurate design and statistical methods. The results of these studies suggest that COVID-19 patients are at a similar risk of ICU-acquired MDR colonization compared to non-COVID-19 controls. However, a higher risk of ICU-acquired infection related to MDR bacteria has been reported in several studies, mainly ventilator-associated pneumonia and bloodstream infection. Several potential explanations could be provided for the high incidence of ICU-acquired infections related to MDR. Immunomodulatory treatments, such as corticosteroids, JAK2 inhibitors, and IL-6 receptor antagonist, might play a role in the pathogenesis of these infections. Additionally, a longer stay in the ICU was reported in COVID-19 patients, resulting in higher exposure to well-known risk factors for ICU-acquired MDR infections, such as invasive procedures and antimicrobial treatment. Another possible explanation is the surge during successive COVID-19 waves, with excessive workload and low compliance with preventive measures. Further studies should evaluate the evolution of the incidence of ICU-acquired infections related to MDR bacteria, given the change in COVID-19 patient profiles. A better understanding of the immune status of critically ill COVID-19 patients is required to move to personalized treatment and reduce the risk of ICU-acquired infections. The role of specific preventive measures, such as targeted immunomodulation, should be investigated.
Published: 2023
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14. Invasive pulmonary aspergillosis among intubated patients with SARS-CoV-2 or influenza pneumonia: a European multicenter comparative cohort study

Author: Anahita Rouzé, Elise Lemaitre, Ignacio Martin-Loeches, Pedro Povoa, Emili Diaz, Rémy Nyga, Antoni Torres, Matthieu Metzelard, Damien Du Cheyron, Fabien Lambiotte, Fabienne Tamion, Marie Labruyere, Claire Boulle Geronimi, Charles-Edouard Luyt, Martine Nyunga, Olivier Pouly, Arnaud W. Thille, Bruno Megarbane, Anastasia Saade, Eleni Magira, Jean-François Llitjos, Iliana Ioannidou, Alexandre Pierre, Jean Reignier, Denis Garot, Louis Kreitmann, Jean-Luc Baudel, Guillaume Voiriot, Gaëtan Plantefeve, Elise Morawiec, Pierre Asfar, Alexandre Boyer, Armand Mekontso-Dessap, Demosthenes Makris, Christophe Vinsonneau, Pierre-Edouard Floch, Clémence Marois, Adrian Ceccato, Antonio Artigas, Alexandre Gaudet, David Nora, Marjorie Cornu, Alain Duhamel, Julien Labreuche, Saad Nseir, and the coVAPid study group
Subjects: Invasive pulmonary aspergillosis, Severe influenza, COVID-19, Mechanical ventilation, Intensive care unit, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Recent multicenter studies identified COVID-19 as a risk factor for invasive pulmonary aspergillosis (IPA). However, no large multicenter study has compared the incidence of IPA between COVID-19 and influenza patients. Objectives To determine the incidence of putative IPA in critically ill SARS-CoV-2 patients, compared with influenza patients. Methods This study was a planned ancillary analysis of the coVAPid multicenter retrospective European cohort. Consecutive adult patients requiring invasive mechanical ventilation for > 48 h for SARS-CoV-2 pneumonia or influenza pneumonia were included. The 28-day cumulative incidence of putative IPA, based on Blot definition, was the primary outcome. IPA incidence was estimated using the Kalbfleisch and Prentice method, considering extubation (dead or alive) within 28 days as competing event. Results A total of 1047 patients were included (566 in the SARS-CoV-2 group and 481 in the influenza group). The incidence of putative IPA was lower in SARS-CoV-2 pneumonia group (14, 2.5%) than in influenza pneumonia group (29, 6%), adjusted cause-specific hazard ratio (cHR) 3.29 (95% CI 1.53–7.02, p = 0.0006). When putative IPA and Aspergillus respiratory tract colonization were combined, the incidence was also significantly lower in the SARS-CoV-2 group, as compared to influenza group (4.1% vs. 10.2%), adjusted cHR 3.21 (95% CI 1.88–5.46, p
Published: 2022
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15. Characteristics and prognosis of bloodstream infection in patients with COVID-19 admitted in the ICU: an ancillary study of the COVID-ICU study

Author: Nicolas Massart, Virginie Maxime, Pierre Fillatre, Keyvan Razazi, Alexis Ferré, Pierre Moine, Francois Legay, Guillaume Voiriot, Marlene Amara, Francesca Santi, Saad Nseir, Stephanie Marque-Juillet, Rania Bounab, Nicolas Barbarot, Fabrice Bruneel, Charles-Edouard Luyt, and the COVID ICU Bacteremia Study Group on behalf of the COVID-ICU Investigators
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring intensive care unit (ICU) have a high incidence of hospital-acquired infections; however, data regarding hospital acquired bloodstream infections (BSI) are scarce. We aimed to investigate risk factors and outcome of BSI in critically ill coronavirus infectious disease-19 (COVID-19) patients. Patients and methods We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU study) that included 4010 COVID-19 ICU patients. For the present analysis, only those with data regarding primary outcome (death within 90 days from admission) or BSI status were included. Risk factors for BSI were analyzed using Fine and Gray competing risk model. Then, for outcome comparison, 537 BSI-patients were matched with 537 controls using propensity score matching. Results Among 4010 included patients, 780 (19.5%) acquired a total of 1066 BSI (10.3 BSI per 1000 patients days at risk) of whom 92% were acquired in the ICU. Higher SAPS II, male gender, longer time from hospital to ICU admission and antiviral drug before admission were independently associated with an increased risk of BSI, and interestingly, this risk decreased over time. BSI was independently associated with a shorter time to death in the overall population (adjusted hazard ratio (aHR) 1.28, 95% CI 1.05–1.56) and, in the propensity score matched data set, patients with BSI had a higher mortality rate (39% vs 33% p = 0.036). BSI accounted for 3.6% of the death of the overall population. Conclusion COVID-19 ICU patients have a high risk of BSI, especially early after ICU admission, risk that increases with severity but not with corticosteroids use. BSI is associated with an increased mortality rate.
Published: 2021
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16. Multinational Observational Cohort Study of COVID-19–Associated Pulmonary Aspergillosis

Author: Nico A.F. Janssen, Rémy Nyga, Lore Vanderbeke, Cato Jacobs, Mehmet Ergün, Jochem B. Buil, Karin van Dijk, Josje Altenburg, Catherine S.C. Bouman, Hans I. van der Spoel, Bart J.A. Rijnders, Albert Dunbar, Jeroen A. Schouten, Katrien Lagrou, Marc Bourgeois, Marijke Reynders, Niels van Regenmortel, Lynn Rutsaert, Piet Lormans, Simon Feys, Yves Debavaye, Fabienne Tamion, Damien Costa, Julien Maizel, Hervé Dupont, Taieb Chouaki, Saad Nseir, Boualem Sendid, Roger J.M. Brüggemann, Frank L. van de Veerdonk, Joost Wauters, and Paul E. Verweij
Subjects: respiratory infections, severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, SARS, COVID-19, coronavirus disease, Medicine, Infectious and parasitic diseases, RC109-216
Abstract: We performed an observational study to investigate intensive care unit incidence, risk factors, and outcomes of coronavirus disease–associated pulmonary aspergillosis (CAPA). We found 10%–15% CAPA incidence among 823 patients in 2 cohorts. Several factors were independently associated with CAPA in 1 cohort and mortality rates were 43%–52%.
Published: 2021
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17. Incidence, clinical characteristics, and outcome after unexpected cardiac arrest among critically ill adults with COVID-19: insight from the multicenter prospective ACICOVID-19 registry

Author: Jonathan Chelly, Gaetan Plantefève, Toufik Kamel, Cédric Bruel, Saad Nseir, Christopher Lai, Giulia Cirillo, Elena Skripkina, Sébastien Ehrminger, Fernando-Daniel Berdaguer-Ferrari, Julien Le Marec, Marine Paul, Aurélie Autret, Nicolas Deye, and the ACICOVID-19 study group
Subjects: In-hospital cardiac arrest, Intensive care unit, SARS-CoV-2, COVID-19, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Initial reports have described the poor outcome of unexpected cardiac arrest (CA) in intensive care unit (ICU) among COVID-19 patients in China and the USA. However, there are scarce data on characteristics and outcomes of such CA patients in Europe. Methods Prospective registry in 35 French ICUs, including all in-ICU CA in COVID-19 adult patients with cardiopulmonary resuscitation (CPR) attempt. Favorable outcome was defined as modified Rankin scale ranging from 0 to 3 at day 90 after CA. Results Among the 2425 COVID-19 patients admitted to ICU from March to June 2020, 186 (8%) experienced in-ICU CA, of whom 146/186 (78%) received CPR. Among these 146 patients, 117 (80%) had sustained return of spontaneous circulation, 102 (70%) died in the ICU, including 48 dying within the first day after CA occurrence and 21 after withdrawal of life-sustaining therapy. Most of CA were non-shockable rhythm (90%). At CA occurrence, 132 patients (90%) were mechanically ventilated, 83 (57%) received vasopressors and 75 (51%) had almost three organ failures. Thirty patients (21%) had a favorable outcome. Sepsis-related organ failure assessment score > 9 before CA occurrence was the single parameter constantly associated with unfavorable outcome in multivariate analysis. Conclusions In-ICU CA incidence remains high among a large multicenter cohort of French critically ill adults with COVID-19. However, 21% of patients with CPR attempt remained alive at 3 months with good functional status. This contrasts with other recent reports showing poor outcome in such patients. Trial registration: This study was retrospectively registered in ClinicalTrials.gov (NTC04373759) in April 2020 ( https://www.clinicaltrials.gov/ct2/show/NCT04373759?term=acicovid&draw=2&rank=1 ).
Published: 2021
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18. Nationwide retrospective study of critically ill adults with sickle cell disease in France

Author: Maïté Agbakou, Armand Mekontso-Dessap, Morgane Pere, Guillaume Voiriot, Muriel Picard, Jérémy Bourenne, Stephan Ehrmann, Emmanuel Canet, Alexandre Boyer, Saad Nseir, Fabienne Tamion, Arnaud W. Thille, Laurent Argaud, Emmanuel Pontis, Jean-Pierre Quenot, Francis Schneider, Arnaud Hot, Gilles Capellier, Cécile Aubron, Keyvan Razazi, Agathe Masseau, Noëlle Brule, Jean Reignier, and Jean-Baptiste Lascarrou
Subjects: Medicine, Science
Abstract: Abstract Little is known about patients with sickle cell disease (SCD) who require intensive care unit (ICU) admission. The goals of this study were to assess outcomes in patients admitted to the ICU for acute complications of SCD and to identify factors associated with adverse outcomes. This multicenter retrospective study included consecutive adults with SCD admitted to one of 17 participating ICUs. An adverse outcome was defined as death or a need for life-sustaining therapies (non-invasive or invasive ventilation, vasoactive drugs, renal replacement therapy, and/or extracorporeal membrane oxygenation). Factors associated with adverse outcomes were identified by mixed multivariable logistic regression. We included 488 patients admitted in 2015–2017. The main reasons for ICU admission were acute chest syndrome (47.5%) and severely painful vaso-occlusive event (21.3%). Sixteen (3.3%) patients died in the ICU, mainly of multi-organ failure following a painful vaso-occlusive event or sepsis. An adverse outcome occurred in 81 (16.6%; 95% confidence interval [95% CI], 13.3%–19.9%) patients. Independent factors associated with adverse outcomes were low mean arterial blood pressure (adjusted odds ratio [aOR], 0.98; 95% CI 0.95–0.99; p = 0.027), faster respiratory rate (aOR, 1.09; 95% CI 1.05–1.14; p
Published: 2021
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19. Paediatric COVID-19 mortality: a database analysis of the impact of health resource disparity

Author: Nick Daneman, John Marshall, Vinod Kumar, Aasiyah Rashan, Jérôme Dimet, Sylvain Diamantis, John F Fraser, Dominique Deplanque, Anne Conrad, François Lellouche, Heidi Gruner, Detlef Kindgen-Milles, Agnes Meybeck, Maxime Hentzien, Clotilde Allavena, André Cabié, Firouzé Bani-Sadr, Patrick Rossignol, Arjen M Dondorp, Rashan Haniffa, Harald Vonkeman, Lionel Piroth, Mathieu Blot, Yaseen Arabi, Marie-Pierre Debray, François Angoulvant, Marc Leone, Maria Zambon, Florentia Kaguelidou, Marc Lambert, Olivier Lairez, Tom Solomon, Carrol Gamble, Laura Marsh, David Richardson, Christiana Kartsonaki, Philippe Jouvet, Asgar Rishu, Eman Al Qasim, Rachael Parke, Srinivas Murthy, Alistair Nichol, Calum Semple, Colin McArthur, Gail Carson, Jake Dunning, Laura Merson, Peter Horby, David Maslove, Nadia Malik, Stephen R Knight, Annelies Verbon, Oana Sândulescu, Patrick Archambault, Paul McNally, Marlene Murris, Aurore Bousquet, Kenneth A McLean, Hugues Cordel, Marc Fabre, Laurence Bouillet, Melissa Parker, Xavier Duval, Amanda Corley, James Lee, Kusum Menon, Christian Rabaud, Paul Klenerman, Jean-François Timsit, Jennifer Lee, Nicolas Terzi, Saad Nseir, Gwenhaël Colin, Steve Webb, Kalynn Kennon, Caroline Mudara, Diana Hernández, Yazdan Yazdanpanah, Elias Iosifidis, Emmanuel Roilides, Yi Lin Lee, Pieter Depuydt, Jean-François Payen, Ana Martins, Samreen Ijaz, Meera Chand, Wei Shen Lim, Bruno Levy, Eric D'ortenzio, Jean-Charles Preiser, Pierre Delobel, Claudia Figueiredo-Mello, Jaques Sztajnbok, Ana Freitas Ribeiro, Tiphaine Goulenok, Bronner P Gonçalves, Arnaud Scherpereel, Chloe Donohue, Carlo Giaquinto, Karolina Nowicka, Adrien Auvet, Debby Bogaert, Elisabeth Botelho-Nevers, Amandine Gagneux-Brunon, Merce Jourdain, Anne McCarthy, Todd C Lee, António Mesquita, Sue Smith, Jia Wei, Jenny Lennon, Antoine Khalil, Nathalie Pansu, Victor Fomin, Audrey Barrelet, Christophe Fraser, Daniel Munblit, Robert A Fowler, William Greenhalf, François-Xavier Lescure, Nicolas Carlier, Saye Khoo, Riinu Pius, Lisa Norman, Louise Sigfrid, Sophie Halpin, Clare Jackson, Antonia Ho, Andrew Dagens, Thomas Flament, Julie Mankikian, Romain Basmaci, Peter Openshaw, Mary Copland, Brenda Reeve, William Dechert, Patricia Lizotte, Felwa Bin Humaid, Tom Fletcher, Adrien Lemaignen, Pierre Tattevin, Christelle Delmas, Hélène Espérou, Claire Lévy-Marchal, Olivier Picone, Jeanne Sibiude, Cecile Yelnik, Olivia V Swann, Michelle Girvan, Piero L Olliaro, Beatrice Alex, Benjamin Bach, Alexander J Mentzer, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, Georgios Pollakis, Vanessa Sancho-Shimizu, Shiranee Sriskandan, David Stuart, Charlotte Summers, Ryan S Thwaites, Hayley Hardwick, Wilna Oosthuyzen, Fiona Griffiths, Jo Dalton, Egle Saviciute, Stephanie Roberts, Janet Harrison, Marie Connor, Gary Leeming, Ross Hendry, Victoria Shaw, Jade Ghosn, Lucille Blumberg, Nicolas Benech, James Scott-Brown, Odile Launay, Todd Karsies, Yoan Lavie-Badie, Minh Le, Elise Artaud-Macari, Mylène Maillet, Huda Alfoudri, Djura Piersma, Didier Laureillard, Graham S. Cooke, Nicholas Sedillot, Anne-Sophie Boureau, Tony Trapani, Laurent Abel, Samuel Hinton, Sally Shrapnel, Heidi Dalton, Guillaume Martin-Blondel, Valérie Garrait, Isabelle Delacroix, Samantha Lissauer, Malte Kohns Vasconcelos, Oleksa Rewa, Erlina Burhan, Sara Machado, Jean-Benoît Arlet, Raphaël Borie, Kévin Bouiller, Vincent Langlois, Mélanie Roriz, Mical Paul, Vincent Dubée, Erwan L'her, Michael Rose, Luis Felipe Reyes, Anna Beltrame, Stéphanie Fry, Andrew Udy, Laurent Plantier, Jean-Christophe Goffard, Denis Malvy, Nina Jamieson, Irfan Khan, François Dubos, Jean-Sébastien Hulot, Paola Rodari, Paul Campbell, Abigail Beane, Cécile Tromeur, Paul Loubet, Marina Esposito-Farèse, France Mentré, Valérie Gaborieau, Anne-Marie Guerguerian, Cécile Goujard, Vincent Thibault, Rodrigo Díaz, Patricia Gordon, Sadie Kelly, Bertrand Dussol, Simon Forsyth, Marion Schneider, Nathalie Gault, Marielle Buisson, Yves Levy, Prasan Kumar Panda, Marjolein Brusse-Keizer, Carine Roy, Walter Picard, Tom Drake, Paul Tierney, Olivier Sanchez, Antoine Kimmoun, David Thomson, Nathan Peiffer-Smadja, Julien Poissy, Lila Bouadma, Bruno Lina, Maude Bouscambert, Alexandre Gaymard, Gilles Peytavin, Jeremie Guedj, Claire Andrejak, Cedric Laouenan, Anissa Chair, Samira Laribi, Marie-Capucine Tellier, Sandrine Couffin-Cadiergues, Soizic Le Mestre, Ventzislava Petrov-Sanchez, Alpha Diallo, NoéMie Mercier, Sarah Tubiana, Marion Noret, Oriane Puechal, Caroline Semaille, Patrick Imbert, Jonathan Remppis, Emmanuelle Mercier, Rui Pereira, Sylvie Van Der Werf, Waasila Jassat, Arsene Kpangon, Dominique Luton, Sophie Mahy, Pierre-Adrien Bolze, Sarah Moore, Adrienne Chan, Raphael Favory, Daniel Mathieu, Andrea Angheben, Andrea Rossanese, Matthew Hall, Johann Auchabie, Mohammed Quraishi, Katharina Weil, Hanna Renk, Hans Martin Bosse, Christophe Rapp, Vincent Peigne, Tae Song, Dewi Guellec, Mark G. Pritchard, Adrian Streinu-Cercel, Christl A Donnelly, François Goehringer, Elodie Curlier, Catherine Chirouze, Stéphane Jaureguiberry, Ary Serpa Neto, Jose Andres Calvache, Laurent Bitker, Hodane Yonis, Neerusha Kaisbain, Coline Jaud-Fischer, Laurent Mandelbrot, Jérémie Pasquier, Juliette Patrier, Gianluigi Li Bassi, Sheryl Ann Abdukahil, Jia Shyi Loy, Filipe Cardoso, Diptesh Aryal, Polina Bugaeva, Evert-Jan Wils, Stephanie Yerkovich, Julie Chas, Thushan de Silva, Ruth Lyons, Murray Wham, Sara Clohisey, Seán Keating, Thibault Chiarabini, Agnes Sommet, Hugues Aumaître, Sylvie LeGac, Sarah E McDonald, Jeanne Truong, Camille Couffignal, Anne-Hélène Boivin, Timo Brandenburger, Diane Descamps, Tala Al-Dabbous, Mark Joseph, Hwa Jin Cho, Desy Rusmawatiningtyas, Muhammad Rayhan, Christel Arnold-Day, Navy Lolong, Ernita Akmal, Menaldi Rasmin, Daniel Marino, Neurinda Permata Kusumastuti, Stéphane Lasry, Amanda Rojek, Sebastien Preau, Jean-Marie Turmel, Nowneet Kumar Bhat, Cynthia Braga, Pavan Kumar Vecham, Benoit Thill, Karine Faure, Denis Garot, Grégory Corvaisier, Elsa Nyamankolly, Joshua Solomon, Emma Clarke, Patricia Fontela, Eva Geraud, Eva Miranda Marwali, Aria Kekalih, Saptadi Yuliarto, Dyah Kanya Wati, Ivy Cerelia Valerie, Maureen Masha, Jolanta Popielska, Anca Streinu-Cercel, Mohan Dass Pathmanathan, Barbara Wanjiru Citarella, Heidi Jean Dalton, Nurul Najmee Abdulkadir, Lara Absil, Subhash Acharya, Diana Adrião, Younes Ait Tamlihat, Kévin Alexandre, Kazali Enagnon Alidjnou, Nathalie Allou, Rita Alves, Joana Alves Cabrita, Maria Amaral, Nur Amira, Phoebe Ampaw, Séverine Ansart, Sivanesen Anthonidass, Carlos Alexandre Brito, Ardiyan Apriyana, Carolline Araujo, Muhammad Ashraf, Jean Baptiste Assie, Amirul Asyraf, Anika Atique, AM Udara Attanyake, Laurène Azemar, Cecile Azoulay, Delphine Bachelet, Claudine Badr, J. Kenneth Baillie, Nazreen Abu Bakar, Mohanaprasanth Balakrishnan, Valeria Balan, Renata Barbalho, Wendy S. Barclay, Saef Umar Barnett, Marie Bartoli, Joaquín Baruch, Muhammad Fadhli Basri, Jules Bauer, Diego Fernando Rincon, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Marine Beluze, Lionel Eric Benjiman, Dehbia Benkerrou, Delphine Bergeaud, José Luis Sobrino, Giulia Bertoli, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Krishna Bhavsar, Farah Nadiah Bidin, Mohd Nazlin Kamarudin, François Bissuel, Jonathan Bitton, Laetitia Bodenes, Isabela Bolaños, François Bompart, Diogo Borges, Olivier Bouchaud, Sabelline Bouchez, Dounia Bouhmani, Damien Bouhour, Camile Bouisse, Jason Bouziotis, Bianca Boxma, Marielle Boyer-Besseyre, Fernando Augusto Bozza, Axelle Braconnier, Kathy Brickell, Aidan Burrell, Ingrid G Bustos, Denis Butnaru, Eder Caceres, Cyril Cadoz, Rui Caetano Garcês, Valentine Campana, Pauline Caraux-Paz, Chiara Simona Cardellino, Sofia Cardoso, Filipa Cardoso, Thierry Carmoi, Marie-Christine Carret, François Martin Carrier, Maire-Laure Casanova, Mariana Cascão, José Casimiro, Nidyanara Castanheira, Guylaine Castor-Alexandre, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Minerva Cervantes-Gonzalez, Catherine Chakveatze, Christelle Chantalat Auger, Jean-Marc Chapplain, Anjellica Chen, Matthew Pellan Cheng, Antoine Cheret, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Bernard Cholley, Marie-Charlotte Chopin, Ting Soo Chow, Hiu Jian Chua, Jonathan Chua, Alexandra Coelho, Megan Coles, Pamela Combs, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Emma Costigan, Roxane Courtois, Stéphanie Cousse, Rachel Cregan, Sabine Croonen, Claudina Cruz, Juan Luis Bermúdez, Jaime Cruz Rojo, Paula Custodio, Ana Silva Filipe, Charlene Da Silveira, Juliana Damas, Corinne Daniel, Emmanuelle A Dankwa, Jorge Dantas, Etienne De Montmollin, Rafael Freitas França, Peter de Vries, Jillian Deacon, Alexa Debard, Nathalie DeCastro, Lauren Deconninck, Romain Decours, Eve Defous, Eric Delaveuve, Karen Delavigne, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Mathilde Desvallées, Santi Dewayanti, Pathik Dhanger, André Dias, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Félix Djossou, Annemarie B. Docherty, Maria Donnelly, Céline Dorival, James Joshua Douglas, Nathalie Dournon, Murray Dryden, Claudio Duarte Fonseca, Alexandre Ducancelle, Paul Dunand, Sim Choon Ean, Mohammed El Sanharawi, Brigitte Elharrar, Philippine Eloy, Isabelle Enderle, Chan Chee Eng, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Martina Escher, Catarina Espírito Santo, João Estevão, Manuel Etienne, Nadia Ettalhaoui, Mirjam Evers, Isabelle Fabre, Amna Faheem, Arabella Fahy, Cameron J. Fairfield, Pedro Faria, Ahmed Farooq, Hanan Fateena, Jorge Fernandes, Marília Andreia Fernandes, François-Xavier Ferrand, Eglantine Ferrand Devouge, Joana Ferrão, Mário Ferraz, Bernardo Ferreira, Nicolas Ferriere, Céline Ficko, Clara Flateau, Tatiana Fonseca, Erwan Fourn, Robert A. Fowler, Marcela Vieira Freire, Rostane Gaci, Jean-Charles Gagnard, Yasmin Gani, Noelia García Barrio, Esteban Garcia-Gallo, Louis Gerbaud Morlaes, Nuno Germano, Jess Gibson, Tristan Gigante, Morgane Gilg, Guillermo Giordano, Valérie Gissot, Daniel Glikman, Petr Glybochko, Geraldine Goco, Siri Goepel, Jin Yi Goh, Marie Gominet, Bronner P. Gonçalves, Isabelle Gorenne, Laure Goubert, Pascal Granier, Christopher A. Green, Courtney Greene, Segolène Greffe, Albert Groenendijk, Anja Grosse Lordemann, Yusing Gu, Martin Guego, Daniela Guerreiro, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Thomas Guimard, Marieke Haalboom, Daniel Haber, Hannah Habraken, Ali Hachemi, Nadir Hadri, Fakhir Haidri, Ansley Hamer, Rebecca Hamidfar, Lim Yuen Han, Kok Wei Hao, Ewen M. Harrison, Lars Heggelund, Astarini Hidayah, Rupert Higgins, Hikombo Hitoto, Yi Bin Ho, Alexandre Hoctin, Isabelle Hoffmann, Wei Han Hoh, Ikram Houas, Catherine L. Hough, Jimmy Ming-Yang Hsu, Arfan Ikram, Hajnal-Gabriela Illes, Hugo Inácio, Yun Sii Ing, Sarah Isgett, Tiago Isidoro, Nadiah Ismail, Margaux Isnard, Danielle Jaafar, Salma Jaafoura, Julien Jabot, Pierre Jaquet, Florence Jego, Anilawati Mat Jelani, Ong Yiaw Joe, Cédric Joseph, Swosti Joshi, Dafsah Juzar, Ouifiya Kafif, Thavamany Kaleesvran, Sabina Kali, Muhammad Aisar Kamaluddin, Zul Amali Kamaruddin, Nadiah Kamarudin, Kong Yeow Kang, Pratap Karpayah, Anant Kataria, Kevin Katz, Yvelynne Kelly, Younes Kerroumi, Sharma Keshav, Coralie Khan, Quratul Ain Khan, Sushil Khanal, Abid Khatak, Ryan Khoo, Denisa Khoo, Khor How Kiat, Peter Kiiza, Rob Klont, Gry Kloumann Bekken, Robin Kobbe, Chamira Kodippily, Vinothini Krishnan, Ganesh Kumar, Bharath Kumar Vijayaraghavan, Demetrios Kutsogiannis, Marie Lachatre, Marie Lacoste, Marie Lagrange, Fabrice Laine, Antonio Lalueza, Marie Langelot-Richard, Marina Lanza, Delphine Lariviere, Andy Law, Teresa Lawrence, Clément Le Bihan, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Gwenaël Le Moal, Vincent Le Moing, Hervé Le Nagard, Paul Le Turnier, Ema Leal, Marta Leal Santos, Heng Gee Lee, Biing Horng Lee, Laurent Lefebvre, Bénédicte Lefebvre, Benjamin Lefèvre, Jean-Daniel Lelievre, Véronique Lemee, Anthony Lemeur, Ha Sha Lene, Quentin Lepiller, Olivier Lesens, Mathieu Lesouhaitier, Geoffrey Liegeon, Kah Chuan Lim, Lim Lina, Guillaume Lingas, Sylvie Lion-Daolio, Marine Livrozet, Leong Chee Loon, Diogo Lopes, Anthony L. Loschner, Bouchra Loufti, Guillame Louis, Lee Lee Low, Marije Lowik, Jean Christophe Lucet, Carlos Lumbreras Bermejo, Liem Luong, Oryane Mabiala, Moïse Machado, Gabriel Macheda, Hashmi Madiha, Guillermo Maestro de la Calle, Rafael Mahieu, Thomas Maitre, Fernando Maltez, Victoria Manda, Jose M. Mandei, Edmund Manning, Aldric Manuel, Ceila Sant'Ana Malaque, Samuel Markowicz, Celina Turchi Martelli, Martin Martinot, Caroline Martins Rego, Marsilla Marzukie, Sabina Mason, Sobia Masood, Basri Mat Nor, Moshe Matan, Mathieu Mattei, Romans Matulevics, Laurence Maulin, Thierry Mazzoni, Cécile Mear-Passard, Ogechukwu Menkiti, Antoine Merckx, Mayka Mergeay-Fabre, Alison M. Meynert, Vanina Meysonnier, Amina Meziane, Mehdi Mezidi, Céline Michelanglei, Isabelle Michelet, Nor Arisah Misnan, Tahira Jamal Mohamed, Nik Nur Mohamed, Asma Moin, Agostinho Monteiro, Claudia Montes, Lina Morales Cely, Lucia Moro, Hugo Mouquet Ben Morton, Clara Mouton Perrot, Julien Moyet, Ng Yong Muh, Dzawani Muhamad, Jimmy Mullaert, Karl Erik Müller, Himed Musaab, Himasha Muvindi, Gugapriyaa Muyandy, Nadège Neant, Nikita Nekliudov, Raul Neto, Anthony Nghi, Duc Nguyen, Nurul Amani Noordin, Nurul Faten Norharizam, Nurnaningsih Nurnaningsih, Annmarie O'Callaghan, Katie O'Hearn, Agnieszka Oldakowska, Piero L. Olliaro, David S.Y. Ong, Jee Yan Ong, Saijad Orakzai, Claudia Milena Orozco-Chamorro, Linda O'Shea, Siti Zubaidah Othman, Nadia Ouamara, Rachida Ouissa, Eric Oziol, Justine Pages Maïder Pagadoy, Lai Hui Pang, Aurélie Papadopoulos, Bruno Pastene, Christelle Paul, Jorge Paulos, William A. Paxton, Kalaiarasu Peariasamy, Miguel Pedrera Jiménez, Florent Peelman, Ithan D. Peltan, Daniel Perez, Thomas Perpoint, Vincent Pestre, Michele Petrovic, Scott Pharand, Carola Pierobon, Carlos Pimentel, Raquel Pinto, Catarina Pires, Isabelle Pironneau, Hon Shen Png, Ryadh Pokeerbux, Maria Pokorska-Spiewak, Diane Ponscarme, Douwe F. Postma, Diana Póvoas, Gamage Dona Priyadarshani, Vilmaris Quinones-Cardona, Víctor Quirós González, Marie Rafiq, Rozanah Abd Rahman, Ahmad Kashfi Rahman, Giri Shan Rajahram, Nagarajan Ramakrishnan, José Ramalho, Ahmad Afiq Ramli, Blandine Rammaert, Grazielle Viana Ramos, Thalha Rashan, Cornelius Rau, Tharmini Ravi, Stanislas Rebaudet, Sarah Redl, Attaur Rehman, Martine Remy, Hongru Ren, Anne-Sophie Resseguier, Matthieu Revest, Laurent Richier, Siti Nurul Ridzuan, Ana L Rios, Patrick Rispal, Karine Risso, David L. Robertson, Olivier Robineau, Pierre-Marie Roger, Juliette Romaru, Manuel Rosa-Calatrava, Bénédicte Rossignol, Stella Rousset, Benoît Roze, Clark D. Russell, Musharaf Sadat, Valla Sahraei, Maximilien Saint-Gilles, Stéphane Sallaberry, Charlotte Salmon Gandonniere, Hélène Salvator, Zulfiqar Sandhu, Pierre-François Sandrine, Shirley Sarfo-Mensah, Benjamine Sarton, Parthena Savvidou, Yen Tsen Saw, Janet T. Scott, Jaganathan Selvanayagam, Mageswari Selvarajoo, Malcolm G. Semple, Rasidah Bt Senian, Eric Senneville, Tânia Sequeira, Pablo Serrano Balazote, Ellen Shadowitz, Syamin Asyraf Shahidan, Mohammad Shamsah, Shaikh Sharjeel, Catherine A. Shaw, Ashraf Sheharyar, Mohiuddin Shiekh, Nassima Si Mohammed, Ng Yong Siang, Benedict Sim Heng, Karisha Sivam, Morgane Snacken, Tze Vee Soh, Rima Song, Azlan Mat Soom, Albert Sotto, B. P Edouard Soum, Sanka Sri Darshana, Sarah Stabler, Ymkje Stienstra, Jacky Y. Suen, Deepashankari Suppiah, Andrey Svistunov, Sarah Syahrin, Shirin Tabrizi, Fabio S. Taccone, Lysa Tagherset, Shahdattul Mawarni Taib, Ewa Talarek, Kim Keat Tan, Yan Chyi Tan, Coralie Tardivon, M Azhari Taufik, Richard S. Tedder, Tze Yuan Tee, João Teixeira, Sze Kye Teoh, François Téoulé, Olivier Terrier, Hubert Tessier-Grenier, Alif Adlan Thabit, Zhang Duan Tham, Suvintheran Thangavelu, Simon-Djamel Thiberville, Jananee Thirumanickam, Emma C. Thomson, Surain Raaj Thurai, Peter S Timashev, Noémie Tissot, Jordan Zhien Toh, Sia Loong Tonnii, Marta Torre, Margarida Torres, Théo Treoux, Tiffany Trouillon, Christelle Tual, Lance C.W. Turtle, PG Ishara Udayanga, Timothy M. Uyeki, Luís Val-Flores, Amélie Valran, Marcel van den Berge, Job van der Palen, Paul van der Valk, Peter Van der Voort, Jarne Van Hattem, Carolien van Netten, Ilonka van Veen, Noémie Vanel, Shoban Raj Vasudayan, Charline Vauchy, Shaminee Veeran, Aurélie Veislinger, James Vickers, José Ernesto Vidal, César Vieira, Benoit Visseaux, Fanny Vuotto, Noor Hidayu Wahab, Suhaila Abdul Wahab, Nadirah Abdul Wahid, Tan Pei Wen, Sanne Wesselius, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Calvin Wong, Xin Ci Wong, Yew Sing Wong, Teck Fung Wong, Gan Ee Xian, Lim Saio Xian, Kuan Pei Xuan, Siti Rohani Yakop, Nicholas Yee Hing, Chian Hui Yeoh, Obada Yousif, Marion Zabbe, Masliza Zahid, Maram Zahran, Nor Zaila Zaidan, Konrad Zawadka, Nurul Zaynah, Hiba Zayyad, and David Zucman
Subjects: Pediatrics, RJ1-570
Abstract: Background The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.Methods The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.Results A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).Conclusion Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities.
Published: 2022
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20. Relationship between COVID-19 and ICU-Acquired Bloodstream Infections Related to Multidrug-Resistant Bacteria

Author: Antoine Piantoni, Marion Houard, Gaetan Piga, Ghadi Zebian, Sarah Ruffier des Aimes, Bérénice Holik, Frédéric Wallet, Anahita Rouzé, Louis Kreitmann, Caroline Loiez, Julien Labreuche, and Saad Nseir
Subjects: SARS-CoV-2, COVID-19, bloodstream infection, ICU, multidrug-resistant bacteria, critical illness, Therapeutics. Pharmacology, RM1-950
Abstract: A bloodstream infection (BSI) is a severe ICU-acquired infection. A growing proportion is caused by multidrug-resistant bacteria (MDRB). COVID-19 was reported to be associated with a high rate of secondary infections. However, there is a lack of data on the relationship between COVID-19 and the incidence of MDRB ICU-acquired BSI. The aim of this study was to evaluate the relationship between COVID-19 and ICU-acquired BSI related to MDRB. This retrospective study was conducted in a single-center ICU during a one-year period. All adult patients admitted for more than 48 h were included. The cumulative incidence of ICU-acquired BSI related to MDRB was estimated using the Kalbfleisch and Prentice method. The association of COVID-19 status with the risk of ICU-acquired BSI related to MDRB was assessed using cause-specific Cox’s proportional hazard model. Among the 1320 patients included in the analysis, 497 (37.65%) had COVID-19. ICU-acquired BSI related to MDRB occurred in 50 patients (36 COVID patients (7%) and 14 non-COVID patients (1.6%)). Extended-spectrum beta-lactamase Enterobacteriacae (46%) and carbapenem-resistant Acinetobacter baumannii (30%) were the most commonly isolated MDRB. COVID-19 was significantly associated with a higher risk of MDRB ICU-acquired BSI (adjusted cHR 2.65 (1.25 to 5.59) for the whole study period). However, this relationship was only significant for the period starting at day 15 after ICU admission. ICU-acquired BSI related to MDRB was significantly associated with ICU mortality (HR (95%CI) 1.73 (1–3)), although COVID-19 had no significant impact on this association (p het 0.94). COVID-19 is significantly associated with an increased risk of ICU-acquired BSI related to MDRB, mainly during the period starting at day 15 after ICU admission.
Published: 2023
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21. Noninvasive ventilation vs. high-flow nasal cannula oxygen for preoxygenation before intubation in patients with obesity: a post hoc analysis of a randomized controlled trial

Author: Maeva Rodriguez, Stéphanie Ragot, Rémi Coudroy, Jean-Pierre Quenot, Philippe Vignon, Jean-Marie Forel, Alexandre Demoule, Jean-Paul Mira, Jean-Damien Ricard, Saad Nseir, Gwenhael Colin, Bertrand Pons, Pierre-Eric Danin, Jérome Devaquet, Gwenael Prat, Hamid Merdji, Franck Petitpas, Emmanuel Vivier, Armand Mekontso-Dessap, Mai-Anh Nay, Pierre Asfar, Jean Dellamonica, Laurent Argaud, Stephan Ehrmann, Muriel Fartoukh, Christophe Girault, René Robert, Arnaud W. Thille, Jean-Pierre Frat, and REVA Network
Subjects: Preoxygenation, Intubation, Non-invasive ventilation, High-flow oxygen, Respiratory failure, Obesity, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Critically ill patients with obesity may have an increased risk of difficult intubation and subsequent severe hypoxemia. We hypothesized that pre-oxygenation with noninvasive ventilation before intubation as compared with high-flow nasal cannula oxygen may decrease the risk of severe hypoxemia in patients with obesity. Methods Post hoc subgroup analysis of critically ill patients with obesity (body mass index ≥ 30 kg·m−2) from a multicenter randomized controlled trial comparing preoxygenation with noninvasive ventilation and high-flow nasal oxygen before intubation of patients with acute hypoxemic respiratory failure (PaO2/FiO2 5 points and respiratory primary failure as reason for admission. Conclusions Patients with obesity and acute hypoxemic respiratory failure had an increased risk of severe hypoxemia during intubation procedure as compared to patients without obesity. However, preoxygenation with noninvasive ventilation may not reduce this risk compared with high-flow nasal oxygen. Trial registration Clinical trial number: NCT02668458 ( http://www.clinicaltrials.gov )
Published: 2021
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22. Mental health and stress among ICU healthcare professionals in France according to intensity of the COVID-19 epidemic

Author: Alexandra Laurent, Alicia Fournier, Florent Lheureux, Guillaume Louis, Saad Nseir, Gwenaelle Jacq, Cyril Goulenok, Grégoire Muller, Julio Badie, Bélaïd Bouhemad, Marjolaine Georges, Paul-Michel Mertes, Hamid Merdji, Vincent Castelain, Caroline Abdulmalak, Olivier Lesieur, Gaëtan Plantefeve, Jean-Claude Lacherade, Jean-Philippe Rigaud, Nicholas Sedillot, Damien Roux, Nicolas Terzi, Pascal Beuret, Antoine Monsel, Anne-Laure Poujol, Khaldoun Kuteifan, Thierry Vanderlinden, Anne Renault, Bérengère Vivet, Christophe Vinsonneau, Saber Davide Barbar, Gilles Capellier, Jean Dellamonica, Stephan Ehrmann, Thomas Rimmelé, Julien Bohé, Pierre Bouju, Sébastien Gibot, Bruno Lévy, Johanna Temime, Cyrille Pichot, David Schnell, Diane Friedman, Pierre Asfar, Eddy Lebas, Philippe Mateu, Kada Klouche, Juliette Audibert, Fiona Ecarnot, Nicolas Meunier-Beillard, Mélanie Loiseau, Irène François-Pursell, Christine Binquet, Jean-Pierre Quenot, and PsyCOVID-ICU Trial Investigators and the CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis)
Subjects: Mental health, Stress factors, ICU, Healthcare professionals, COVID-19, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background We investigated the impact of the COVID-19 crisis on mental health of professionals working in the intensive care unit (ICU) according to the intensity of the epidemic in France. Methods This cross-sectional survey was conducted in 77 French hospitals from April 22 to May 13 2020. All ICU frontline healthcare workers were eligible. The primary endpoint was the mental health, assessed using the 12-item General Health Questionnaire. Sources of stress during the crisis were assessed using the Perceived Stressors in Intensive Care Units (PS-ICU) scale. Epidemic intensity was defined as high or low for each region based on publicly available data from Santé Publique France. Effects were assessed using linear mixed models, moderation and mediation analyses. Results In total, 2643 health professionals participated; 64.36% in high-intensity zones. Professionals in areas with greater epidemic intensity were at higher risk of mental health issues (p
Published: 2021
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23. Relationship between ventilator-associated pneumonia and mortality in COVID-19 patients: a planned ancillary analysis of the coVAPid cohort

Author: Saad Nseir, Ignacio Martin-Loeches, Pedro Povoa, Matthieu Metzelard, Damien Du Cheyron, Fabien Lambiotte, Fabienne Tamion, Marie Labruyere, Demosthenes Makris, Claire Boulle Geronimi, Marc Pinetonde Chambrun, Martine Nyunga, Olivier Pouly, Bruno Mégarbane, Anastasia Saade, Gemma Gomà, Eleni Magira, Jean-François Llitjos, Antoni Torres, Iliana Ioannidou, Alexandre Pierre, Luis Coelho, Jean Reignier, Denis Garot, Louis Kreitmann, Jean-Luc Baudel, Guillaume Voiriot, Damien Contou, Alexandra Beurton, Pierre Asfar, Alexandre Boyer, Arnaud W. Thille, Armand Mekontso-Dessap, Vassiliki Tsolaki, Christophe Vinsonneau, Pierre-Edouard Floch, Loïc Le Guennec, Adrian Ceccato, Antonio Artigas, Mathilde Bouchereau, Julien Labreuche, Alain Duhamel, Anahita Rouzé, and the coVAPid study group
Subjects: Ventilator-associated pneumonia, Mortality, COVID-19, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. Methods Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox’s regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. Findings Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 (adjusted HR 1.70 (95% CI 1.16–2.47), p = 0.006), and influenza groups (1.75 (1.03–3.02), p = 0.045), but not in the no viral infection group (1.07 (0.64–1.78), p = 0.79). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. Interpretation VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693.
Published: 2021
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24. Ventilator-associated pneumonia in critically ill patients with COVID-19 infection: a narrative review

Author: Sean Boyd, Saad Nseir, Alejandro Rodriguez, and Ignacio Martin-Loeches
Subjects: Medicine
Abstract: COVID pneumonitis can cause patients to become critically ill. They may require intensive care and mechanical ventilation. Ventilator-associated pneumonia (VAP) is a concern. This review discusses VAP in this group. Several reasons have been proposed to explain the elevated rates of VAP in critically ill COVID patients compared to non-COVID patients. Extrinsic factors include understaffing, lack of personal protective equipment and use of immunomodulating agents. Intrinsic factors include severe parenchymal damage and immune dysregulation, along with pulmonary vascular endothelial inflammation and thrombosis. The rate of VAP has been reported at 45.4%, with an intensive care unit mortality rate of 42.7%. Multiple challenges to diagnosis exist. Other conditions such as acute respiratory distress syndrome, pulmonary oedema and atelectasis can present with similar features. Frequent growth of gram-negative bacteria has been shown in multiple studies, with particularly high rates of Pseudomonas aeruginosa. The rate of invasive pulmonary aspergillosis has been reported at 4–30%. We would recommend the use of invasive techniques when possible. This will enable de-escalation of antibiotics as soon as possible, decreasing overuse. It is also important to keep other possible causes of VAP in mind, e.g. COVID-19-associated pulmonary aspergillosis or cytomegalovirus. Diagnostic tests such as galactomannan and β-D-glucan should be considered. These patients may face a long treatment course, with risk of re-infection, along with prolonged weaning, which carries its own long-term consequences.
Published: 2022
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25. Vascular access for renal replacement therapy among 459 critically ill patients: a pragmatic analysis of the randomized AKIKI trial

Author: Nicolas Benichou, Saïd Lebbah, David Hajage, Laurent Martin-Lefèvre, Bertrand Pons, Eric Boulet, Alexandre Boyer, Guillaume Chevrel, Nicolas Lerolle, Dorothée Carpentier, Nicolas de Prost, Alexandre Lautrette, Anne Bretagnol, Julien Mayaux, Saad Nseir, Bruno Megarbane, Marina Thirion, Jean-Marie Forel, Julien Maizel, Hodane Yonis, Philippe Markowicz, Guillaume Thiery, Frederique Schortgen, Florence Tubach, Jean-Damien Ricard, Didier Dreyfuss, and Stéphane Gaudry
Subjects: Renal replacement therapy, Acute kidney injury, Vascular access, Catheter, Critical care, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Vascular access for renal replacement therapy (RRT) is routine question in the intensive care unit. Randomized trials comparing jugular and femoral sites have shown similar rate of nosocomial events and catheter dysfunction. However, recent prospective observational data on RRT catheters use are scarce. We aimed to assess the site of RRT catheter, the reasons for catheter replacement, and the complications according to site in a large population of critically ill patients with acute kidney injury. Patients and methods We performed an ancillary study of the AKIKI study, a pragmatic randomized controlled trial, in which patients with severe acute kidney injury (KDIGO 3 classification) with invasive mechanical ventilation, catecholamine infusion or both were randomly assigned to either an early or a delayed RRT initiation strategy. The present study involved all patients who underwent at least one RRT session. Number of RRT catheters, insertion sites, factors potentially associated with the choice of insertion site, duration of catheter use, reason for catheter replacement, and complications were prospectively collected. Results Among the 619 patients included in AKIKI, 462 received RRT and 459 were finally included, with 598 RRT catheters. Femoral site was chosen preferentially (n = 319, 53%), followed by jugular (n = 256, 43%) and subclavian (n = 23, 4%). In multivariate analysis, continuous RRT modality was significantly associated with femoral site (OR = 2.33 (95% CI (1.34–4.07), p = 0.003) and higher weight with jugular site [88.9 vs 83.2 kg, OR = 0.99 (95% CI 0.98–1.00), p = 0.03]. Investigator site was also significantly associated with the choice of insertion site (p = 0.03). Cumulative incidence of catheter replacement did not differ between jugular and femoral site [sHR 0.90 (95% CI 0.64—1.25), p = 0.67]. Catheter dysfunction was the main reason for replacement (n = 47), followed by suspected infection (n = 29) which was actually seldom proven (n = 4). No mechanical complication (pneumothorax or hemothorax) occurred. Conclusion Femoral site was preferentially used in this prospective study of RRT catheters in 31 French intensive care units. The choice of insertion site depended on investigating center habits, weight, RRT modality. A high incidence of catheter infection suspicion led to undue replacement.
Published: 2021
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26. Ventilator-Associated Pneumonia in Immunosuppressed Patients

Author: Louis Kreitmann, Alexandre Gaudet, and Saad Nseir
Subjects: ventilator-associated pneumonia, immunosuppression, multidrug resistance, critical illness, Therapeutics. Pharmacology, RM1-950
Abstract: Immunocompromised patients—including patients with cancer, hematological malignancies, solid organ transplants and individuals receiving immunosuppressive therapies for autoimmune diseases—account for an increasing proportion of critically-ill patients. While their prognosis has improved markedly in the last decades, they remain at increased risk of healthcare- and intensive care unit (ICU)-acquired infections. The most frequent of these are ventilator-associated lower respiratory tract infections (VA-LTRI), which include ventilator-associated pneumonia (VAP) and tracheobronchitis (VAT). Recent studies have shed light on some of the specific features of VAP and VAT in immunocompromised patients, which is the subject of this narrative review. Contrary to previous belief, the incidence of VAP and VAT might actually be lower in immunocompromised than non-immunocompromised patients. Further, the relationship between immunosuppression and the incidence of VAP and VAT related to multidrug-resistant (MDR) bacteria has also been challenged recently. Etiological diagnosis is essential to select the most appropriate treatment, and the role of invasive sampling, specifically bronchoscopy with bronchoalveolar lavage, as well as new molecular syndromic diagnostic tools will be discussed. While bacteria—especially gram negative bacteria—are the most commonly isolated pathogens in VAP and VAT, several opportunistic pathogens are a special concern among immunocompromised patients, and must be included in the diagnostic workup. Finally, the impact of immunosuppression on VAP and VAT outcomes will be examined in view of recent papers using improved statistical methodologies and treatment options—more specifically empirical antibiotic regimens—will be discussed in light of recent findings on the epidemiology of MDR bacteria in this population.
Published: 2023
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27. Is COPD associated with increased risk for microaspiration in intubated critically ill patients?

Author: Thècle Degroote, Emmanuelle Jaillette, Jean Reignier, Farid Zerimech, Christophe Girault, Guillaume Brunin, Arnaud Chiche, Jean-Claude Lacherade, Jean-Paul MIRA, Patrice Maboudou, Malika Balduyck, Saad Nseir, and for the MicroCOPD study group
Subjects: COPD, Intubation, Mechanical ventilation, Microaspiration, Pneumonia, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Although COPD patients are at higher risk for aspiration when breathing spontaneously, no information is available on the risk for microaspiration in invasively ventilated COPD patients. The aim of our study was to determine the relationship between COPD and abundant microaspiration in intubated critically ill patients. Methods This was a retrospective analysis of prospectively collected data, provided by 3 randomized controlled trials on microaspiration in critically ill patients receiving invasive mechanical ventilation for more than 48 h. Abundant microaspiration was defined as the presence of pepsin and or alpha-amylase at significant levels in tracheal aspirates. In all study patients, pepsin and alpha-amylase were quantitatively measured in all tracheal aspirates collected during a 48-h period. COPD was defined using spirometry criteria. Results Among the 515 included patients, 70 (14%) had proven COPD. Pepsin and alpha-amylase were quantitatively measured in 3873 and 3764 tracheal aspirates, respectively. No significant difference was found in abundant microaspiration rate between COPD and non-COPD patients (62 of 70 patients (89%) vs 366 of 445 (82%) patients, p = 0.25). Similarly, no significant difference was found in abundant microaspiration of gastric contents (53% vs 45%, p = 0.28), oropharyngeal secretions (71% vs 71%, p = 0.99), or VAP (19% vs 22%, p = 0.65) rates between the two groups. No significant difference was found between COPD and non-COPD patients in duration of mechanical ventilation, ICU length of stay, or ICU mortality. Conclusions Our results suggest that COPD is not associated with increased risk for abundant microaspiration in intubated critically ill patients.
Published: 2021
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28. Performance of the ROX index to predict intubation in immunocompromised patients receiving high-flow nasal cannula for acute respiratory failure

Author: Virginie Lemiale, Guillaume Dumas, Alexandre Demoule, Frederic Pène, Achille Kouatchet, Magali Bisbal, Saad Nseir, Laurent Argaud, Loay Kontar, Kada Klouche, Francois Barbier, Amelie Seguin, Guillaume Louis, Jean-Michel Constantin, Julien Mayaux, Florent Wallet, Vincent Peigne, Christophe Girault, Johanna Oziel, Martine Nyunga, Nicolas Terzi, Lila Bouadma, Alexandre Lautrette, Naike Bige, Jean-Herle Raphalen, Laurent Papazian, Fabrice Bruneel, Christine Lebert, Dominique Benoit, Anne-Pascale Meert, Samir Jaber, Djamel Mokart, Michael Darmon, Elie Azoulay, and The Groupe de Recherche en Reanimation Respiratoire du patient d’Onco-Hématologie (GRRR-OH)
Subjects: High-flow nasal oxygen, Immunocompromised, Acute respiratory failure, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Delayed intubation is associated with high mortality. There is a lack of objective criteria to decide the time of intubation. We assessed a recently described combined oxygenation index (ROX index) to predict intubation in immunocompromised patients. The study is a secondary analysis of randomized trials in immunocompromised patients, including all patients who received high-flow nasal cannula (HFNC). The first objective was to evaluate the accuracy of the ROX index to predict intubation for patients with acute respiratory failure. Results In the study, 302 patients received HFNC. Acute respiratory failure was mostly related to pneumonia (n = 150, 49.7%). Within 2 (1–3) days, 115 (38.1%) patients were intubated. The ICU mortality rate was 27.4% (n = 83). At 6 h, the ROX index was lower for patients who needed intubation compared with those who did not [4.79 (3.69–7.01) vs. 6.10 (4.48–8.68), p
Published: 2021
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29. Transesophageal echocardiography-associated tracheal microaspiration and ventilator-associated pneumonia in intubated critically ill patients: a multicenter prospective observational study

Author: François Bagate, Anahita Rouzé, Farid Zerimech, Florence Boissier, Vincent Labbe, Keyvan Razazi, Guillaume Carteaux, Nicolas de Prost, Malika Balduyck, Patrice Maboudou, Saad Nseir, and Armand Mekontso Dessap
Subjects: Microaspiration, Transesophageal echocardiography, Pepsin, Salivary amylase, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Microaspiration of gastric and oropharyngeal secretions is the main causative mechanism of ventilator-associated pneumonia (VAP). Transesophageal echocardiography (TEE) is a routine investigation tool in intensive care unit and could enhance microaspiration. This study aimed at evaluating the impact of TEE on microaspiration and VAP in intubated critically ill adult patients. Methods It is a four-center prospective observational study. Microaspiration biomarkers (pepsin and salivary amylase) concentrations were quantitatively measured on tracheal aspirates drawn before and after TEE. The primary endpoint was the percentage of patients with TEE-associated microaspiration, defined as: (1) ≥ 50% increase in biomarker concentration between pre-TEE and post-TEE samples, and (2) a significant post-TEE biomarker concentration (> 200 μg/L for pepsin and/or > 1685 IU/L for salivary amylase). Secondary endpoints included the development of VAP within three days after TEE and the evolution of tracheal cuff pressure throughout TEE. Results We enrolled 100 patients (35 females), with a median age of 64 (53–72) years. Of the 74 patients analyzed for biomarkers, 17 (23%) got TEE-associated microaspiration. However, overall, pepsin and salivary amylase levels were not significantly different between before and after TEE, with wide interindividual variability. VAP occurred in 19 patients (19%) within 3 days following TEE. VAP patients had a larger tracheal tube size and endured more attempts of TEE probe introduction than their counterparts but showed similar aspiration biomarker concentrations. TEE induced an increase in tracheal cuff pressure, especially during insertion and removal of the probe. Conclusions We could not find any association between TEE-associated microaspiration and the development of VAP during the three days following TEE in intubated critically ill patients. However, our study cannot formally rule out a role for TEE because of the high rate of VAP observed after TEE and the limitations of our methods.
Published: 2020
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30. Measurement site of inferior vena cava diameter affects the accuracy with which fluid responsiveness can be predicted in spontaneously breathing patients: a post hoc analysis of two prospective cohorts

Author: Morgan Caplan, Arthur Durand, Perrine Bortolotti, Delphine Colling, Julien Goutay, Thibault Duburcq, Elodie Drumez, Anahita Rouze, Saad Nseir, Michael Howsam, Thierry Onimus, Raphael Favory, and Sebastien Preau
Subjects: Inferior vena cava, Fluids, Fluid responsiveness, Hemodynamic, Sepsis, Severe infection, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background The collapsibility index of the inferior vena cava (cIVC) has potential for predicting fluid responsiveness in spontaneously breathing patients, but a standardized approach for measuring the inferior vena cava diameter has yet to be established. The aim was to test the accuracy of different measurement sites of inferior vena cava diameter to predict fluid responsiveness in spontaneously breathing patients with sepsis-related circulatory failure and examine the influence of a standardized breathing manoeuvre. Results Among the 81 patients included in the study, the median Simplified Acute Physiologic Score II was 34 (24; 42). Sepsis was of pulmonary origin in 49 patients (60%). Median volume expansion during the 24 h prior to study inclusion was 1000 mL (0; 2000). Patients were not severely ill: none were intubated, only 20% were on vasopressors, and all were apparently able to perform a standardized breathing exercise. Forty-one (51%) patients were responders to volume expansion (i.e. a ≥ 10% stroke volume index increase). The cIVC was calculated during non-standardized (cIVC-ns) and standardized breathing (cIVC-st) conditions. The accuracy with which both cIVC-ns and cIVC-st predicted fluid responsiveness differed significantly by measurement site (interaction p
Published: 2020
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31. Influence of socioeconomic status on functional recovery after ARDS caused by SARS-CoV-2: a multicentre, observational study

Author: Cyrille Delpierre, Pierre-louis Declercq, Vanessa Bironneau, Nicolas Terzi, Jean Dellamonica, Jean-Pierre Quenot, Saad Nseir, Christine Binquet, Laura Federici, Elise Artaud-Macari, Gaetan Beduneau, Agathe Delbove, Nicholas Sedillot, Jean-Philippe Rigaud, Isabelle Fournel, Nicolas Meunier-Beillard, Julio Badie, Julien Maizel, Gaetan Plantefeve, Thierry Vanderlinden, Marjolaine Georges, Paul Abraham, David Schnell, Bertrand Sauneuf, Matthieu Demeyere, Eléa Ksiazek, Antoine Rivière, Caroline Clarot, Alexandre Ampere, Cédric Daubin, Pierre Kalfon, Élise Redureau, Mehdi Bousta, Laurie Lagache, Béatrice La Combe, Gaël Bourdin, Mehran Monchi, Martine Nyunga, Michel Ramakers, Walid Oulehri, Hugues Georges, Charlotte Salmon Gandonniere, Xavier Monnet, Nicolas Delberghe, Gurvan Le Bouar, Arnaud-Felix Miailhe, Sami Hraiech, Marie-Anne Hoppe, Saber Davide Barbar, George-Daniel Calcaianu, Stéphanie Gélinotte, and Marie Labruyère
Subjects: Medicine
Published: 2022
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32. Accuracy of the clinical pulmonary infection score to differentiate ventilator-associated tracheobronchitis from ventilator-associated pneumonia

Author: Alexandre Gaudet, Ignacio Martin-Loeches, Pedro Povoa, Alejandro Rodriguez, Jorge Salluh, Alain Duhamel, Saad Nseir, and TAVeM study group
Subjects: Mechanical ventilation, Lower respiratory tract infection, Tracheobronchitis, Pneumonia, CPIS, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Differentiating Ventilator-Associated Tracheobronchitis (VAT) from Ventilator-Associated Pneumonia (VAP) may be challenging for clinicians, yet their management currently differs. In this study, we evaluated the accuracy of the Clinical Pulmonary Infection Score (CPIS) to differentiate VAT and VAP. Methods We performed a retrospective analysis based on the data from 2 independent prospective cohorts. Patients of the TAVeM database with a diagnosis of VAT (n = 320) or VAP (n = 369) were included in the derivation cohort. Patients admitted to the Intensive Care Centre of Lille University Hospital between January 1, 2016 and December 31, 2017 who had a diagnosis of VAT (n = 70) or VAP (n = 139) were included in the validation cohort. The accuracy of the CPIS to differentiate VAT from VAP was assessed within the 2 cohorts by calculating sensitivity and specificity values, establishing the ROC curves and choosing the best threshold according to the Youden index. Results The areas under ROC curves of CPIS to differentiate VAT from VAP were calculated at 0.76 (95% CI [0.72–0.79]) in the derivation cohort and 0.67 (95% CI [0.6–0.75]) in the validation cohort. A CPIS value ≥ 7 was associated with the highest Youden index in both cohorts. With this cut-off, sensitivity and specificity were respectively found at 0.51 and 0.88 in the derivation cohort, and at 0.45 and 0.89 in the validation cohort. Conclusions A CPIS value ≥ 7 reproducibly allowed to differentiate VAT from VAP with high specificity and PPV and moderate sensitivity and NPV in our derivation and validation cohorts.
Published: 2020
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33. Mucormycosis in intensive care unit: surgery is a major prognostic factor in patients with hematological malignancy

Author: Johanna Claustre, Romaric Larcher, Thomas Jouve, Anne-Sophie Truche, Saad Nseir, Julien Cadiet, Yoann Zerbib, Alexandre Lautrette, Jean-Michel Constantin, Pierre-Emmanuel Charles, Cedric Daubin, Remi Coudroy, Jean Dellamonica, Laurent Argaud, Pierre Phelouzat, Damien Contou, Juliette Pocquet, Guillaume Voiriot, Jean-Christophe Navellou, Pierre Lavagne, Michel Durand, Muriel Cornet, Carole Schwebel, and Nicolas Terzi
Subjects: Mucormycosis, Hematological malignancy, Intensive care unit, Surgery, Prognostic factors, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Mucormycosis is an invasive fungal infection, with an increasing incidence especially in patients with hematological malignancies. Its prognosis is poor because of its high invasive power and its intrinsic low susceptibility to antifungal agents. We aimed to describe the epidemiology of mucormycosis in intensive care units (ICU) and evaluate the outcomes. We performed a retrospective multi-center study in 16 French ICUs between 2008 and 2017. We compared the patients who survived in ICU and the patients who did not to identify factors associated with ICU survival. Then, we focused on the subgroup of patients with hematological malignancies. Results Mucormycosis was diagnosed in 74 patients during the study period. Among them, 60 patients (81%) were immunocompromised: 41 had hematological malignancies, 9 were solid organ transplant recipients, 31 received long-term steroids, 11 had diabetes, 24 had malnutrition. Only 21 patients survived to ICU stay (28.4%) with a median survival of 22 days (Q1–Q3 = 9–106) and a survival rate at day 28 and day 90, respectively, of 35.1% and 26.4%. Survivors were significantly younger (p = 0.001), with less frequently hematological malignancies (p = 0.02), and less malnutrition (p = 0.05). Median survival in patients with hematological malignancies (n = 41) was 15 days (Q1–Q3 = 5–23.5 days). In this subgroup, curative surgery was a major factor associated with survival in multivariate analysis (odds ratio = 0.71, [0.45–0.97], p
Published: 2020
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34. Accuracy of ventilator-associated events for the diagnosis of ventilator-associated lower respiratory tract infections

Author: Olivier Pouly, Sylvain Lecailtel, Sophie Six, Sébastien Préau, Frédéric Wallet, Saad Nseir, and Anahita Rouzé
Subjects: Ventilator-associated events, Ventilator-associated tracheobronchitis, Ventilator-associated pneumonia, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background The aim of this study was to investigate the concordance between ventilator-associated events (VAE) and ventilator-associated lower respiratory tract infections (VA-LRTI), and their impact on outcome. Methods This retrospective study was performed in five 10-bed ICUs of a teaching hospital, during a 2-year period. Ventilator-associated lower respiratory tract infections (VA-LRTI), including ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP) were prospectively diagnosed. The agreement between VAE, VAT and VAP was assessed by k statistics. Results A total of 1059 patients (15,029 ventilator-days) were included. 268 VAP (17.8 per 1000 ventilator-days), 127 VAT (8.5 per 1000 ventilator-days) and 262 VAE (17.4 per 1000 ventilator-days) were diagnosed. There was no agreement between VAT and VAE, and the agreement was poor between VAP and VAE (k = 0.12, 95% CI 0.03–0.20). VAE and VA-LRTI were associated with significantly longer duration of mechanical ventilation, ICU and hospital length of stay. VAP, VAT and VAE were not significantly associated with mortality in multivariate analysis. Conclusions The agreement was poor between VAE and VAP. No agreement was found between VAE and VAT. VAE episodes were significantly associated with longer duration of mechanical ventilation and length of stay, but not with ICU mortality.
Published: 2020
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35. Traqueobronquite associada à ventilação mecânica: uma atualização

Author: Jorge Ibrain Figueira Salluh, Vicente Cés de Souza-Dantas, Ignacio Martin-Loeches, Thiago Costa Lisboa, Ligia Sarmet Cunha Farah Rabello, Saad Nseir, and Pedro Póvoa
Subjects: Terapia intensiva, Mortalidade, Infecção nosocomial, Pneumonia, Pneumonia associada a assistência à saúde, Pneumonia associada à ventilação mecânica, Traqueobronquite associada a ventilação mecânica, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: RESUMO As infecções do trato respiratório inferior associadas à ventilação mecânica são uma das complicações mais frequentes em pacientes em ventilação mecânica. Há muitos anos, a traqueobronquite associada à ventilação mecânica tem sido considerada uma doença que não demanda antibioticoterapia. Na última década, diversos estudos demonstraram que a traqueobronquite associada à ventilação mecânica deve ser considerada um processo intermediário que leva à pneumonia associada à ventilação mecânica, uma vez que apesar de ter impacto limitado sobre a mortalidade dos pacientes gravemente enfermos internados nas unidades de terapia intensiva, em contrapartida, demonstra associação significativa com o aumento dos custos hospitalares desses pacientes, assim como do tempo de internação na unidade de terapia intensiva e hospitalar, do uso de antibióticos, e da duração da ventilação mecânica. Embora ainda necessitemos de evidências científicas mais robustas, especialmente no que tange às modalidades terapêuticas, os dados atuais a respeito da traqueobronquite associada à ventilação mecânica salientam que há desfechos suficientemente importantes que exigem vigilância epidemiológica e controle clínico adequados.
Published: 2020
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36. The Artificial Kidney Initiation in Kidney Injury 2 (AKIKI2): study protocol for a randomized controlled trial

Author: Stéphane Gaudry, David Hajage, Laurent Martin-Lefevre, Guillaume Louis, Sébastien Moschietto, Dimitri Titeca-Beauport, Béatrice La Combe, Bertrand Pons, Nicolas de Prost, Sébastien Besset, Alain Combes, Adrien Robine, Marion Beuzelin, Julio Badie, Guillaume Chevrel, Jean Reignier, Julien Bohé, Elisabeth Coupez, Nicolas Chudeau, Saber Barbar, Christophe Vinsonneau, Jean-Marie Forel, Didier Thevenin, Eric Boulet, Karim Lakhal, Nadia Aissaoui, Steven Grange, Marc Leone, Guillaume Lacave, Saad Nseir, Florent Poirson, Julien Mayaux, Karim Asehnoune, Guillaume Geri, Kada Klouche, Guillaume Thiery, Laurent Argaud, Jean-Damien Ricard, Jean-Pierre Quenot, and Didier Dreyfuss
Subjects: Acute kidney injury, Critical care, Renal replacement therapy, Treatment outcome, Medicine (General), R5-920
Abstract: Abstract Background The Artificial Kidney Initiation in Kidney Injury (AKIKI) trial showed that a delayed renal replacement therapy (RRT) strategy for severe acute kidney injury (AKI) in critically ill patients was safe and associated with major reduction in RRT initiation compared with an early strategy. The five criteria which mandated RRT initiation in the delayed arm were: severe hyperkalemia, severe acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia, serum urea concentration > 40 mmol/l and oliguria/anuria > 72 h. However, duration of anuria/oliguria and level of blood urea are still criteria open to debate. The objective of the study is to compare the delayed strategy used in AKIKI (now termed “standard”) with another in which RRT is further delayed for a longer period (termed “delayed strategy”). Methods/design This is a prospective, multicenter, open-label, two-arm randomized trial. The study is composed of two stages (observational and randomization stages). At any time, the occurrence of a potentially severe condition (severe hyperkalemia, severe metabolic or mixed acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia) suggests immediate RRT initiation. Patients receiving (or who have received) intravenously administered catecholamines and/or invasive mechanical ventilation and presenting with AKI stage 3 of the KDIGO classification and with no potentially severe condition are included in the observational stage. Patients presenting a serum urea concentration > 40 mmol/l and/or an oliguria/anuria for more than 72 h are randomly allocated to a standard (RRT is initiated within 12 h) or a delayed RRT strategy (RRT is initiated only if an above-mentioned potentially severe condition occurs or if the serum urea concentration reaches 50 mmol/l). The primary outcome will be the number of RRT-free days at day 28. One interim analysis is planned. It is expected to include 810 patients in the observational stage and to randomize 270 subjects. Discussion The AKIKI2 study should improve the knowledge of RRT initiation criteria in critically ill patients. The potential reduction in RRT use allowed by a delayed RRT strategy might be associated with less invasive care and decreased costs. Enrollment is ongoing. Inclusions are expected to be completed by November 2019. Trial registration ClinicalTrials.gov, ID: NCT03396757. Registered on 11 January 2018.
Published: 2019
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37. Bacterial Aspiration Pneumonia in Generalized Convulsive Status Epilepticus: Incidence, Associated Factors and Outcome

Author: Romain Tortuyaux, Frédéric Wallet, Philippe Derambure, and Saad Nseir
Subjects: status epilepticus, intensive care unit, bacterial aspiration pneumonia, 3-month outcome, Medicine
Abstract: Suspicion of bacterial aspiration pneumonia (BAP) is frequent during generalized convulsive status epilepticus (GCSE). Early identification of BAP is required in order to avoid useless antibiotic therapy. In this retrospective monocentric study, we aimed to determine the incidence of aspiration syndrome and BAP in GCSE requiring mechanical ventilation (MV) and factors associated with the occurrence of BAP. Patients were older than 18 years and had GCSE requiring MV. To distinguish BAP from pneumonitis, tracheal aspirate and quantitative microbiological criterion were used. Out of 226 consecutive patients, 103 patients (46%) had an aspiration syndrome, including 54 (52%) with a BAP. Staphylococcus aureus represented 33% of bacterial strains. No relevant baseline characteristics differed, including serum levels of CRP, PCT, and albumin. The median duration of treatment for BAP was 7 days (5–7). Patients with BAP did not have a longer duration of MV (p = 0.18) and ICU stay (p = 0.18) than those with pneumonitis. At 3 months, 24 patients (44%) with BAP and 10 (27%) with pneumonitis had a poor functional outcome (p = 0.06). In conclusion, among patients with GCSE, half of the patients had an aspiration syndrome and one-quarter suffered from BAP. Clinical characteristics and biomarkers were not useful for differentiating BAP from pneumonitis. These results highlight the need for a method to rapidly differentiate BAP from pneumonitis, such as polymerase-chain-reaction-based techniques.
Published: 2022
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38. Combined use of a broad-panel respiratory multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe community-acquired pneumonia (MULTI-CAP): a multicentre, parallel-group, open-label, individual randomised trial conducted in French intensive care units

Author: Isabelle Durand-Zaleski, Eric Maury, Bruno Megarbane, Tabassome Simon, Jean-François Timsit, Jean Dellamonica, Saad Nseir, Alexandra Rousseau, Laurence Bérard, Kada Klouche, Yacine Tandjaoui-Lambiotte, Jean Reignier, Laurent Argaud, Muriel Fartoukh, Keyvan Razazi, Laurence Armand-Lefevre, Bertrand Souweine, Guillaume Voiriot, Charlotte Verdet, Juliette Patrier, Jean-Christophe Richard, Carole Schwebel, Jean-Christophe Navellou, Pierre-Francois Dequin, Pierre-Edouard Bollaert, Marc Gainnier, and Julien Bohe
Subjects: Medicine
Abstract: Introduction At the time of the worrying emergence and spread of bacterial resistance, reducing the selection pressure by reducing the exposure to antibiotics in patients with community-acquired pneumonia (CAP) is a public health issue. In this context, the combined use of molecular tests and biomarkers for guiding antibiotics discontinuation is attractive. Therefore, we have designed a trial comparing an integrated approach of diagnosis and treatment of severe CAP to usual care.Methods and analysis The multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe-CAP (MULTI-CAP) trial is a multicentre (n=20), parallel-group, superiority, open-label, randomised trial. Patients are included if adult admitted to intensive care unit for a CAP. Diagnosis of pneumonia is based on clinical criteria and a newly appeared parenchymal infiltrate. Immunocompromised patients are excluded. Subjects are randomised (1:1 ratio) to either the intervention arm (experimental strategy) or the control arm (usual strategy). In the intervention arm, the microbiological diagnosis combines a respiratory multiplex PCR (mPCR) and conventional microbiological investigations. An algorithm of early antibiotic de-escalation or discontinuation is recommended, based on mPCR results and the procalcitonin value. In the control arm, only conventional microbiological investigations are performed and antibiotics de-escalation remains at the clinician’s discretion. The primary endpoint is the number of days alive without any antibiotic from the randomisation to day 28. Based on our hypothesis of 2 days gain in the intervention arm, we aim to enrol a total of 450 patients over a 30-month period.Ethics and dissemination The MULTI-CAP trial is conducted according to the principles of the Declaration of Helsinki, is registered in Clinical Trials and has been approved by the Committee for Protection of Persons and the National French Drug Safety Agency. Written informed consents are obtained from all the patients (or representatives). The results will be disseminated through educational institutions, submitted to peer-reviewed journals for publication and presented at medical congresses.Trial registration number NCT03452826; Pre-results.
Published: 2021
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39. Are Cirrhotic Patients Receiving Invasive Mechanical Ventilation at Risk of Abundant Microaspiration

Author: Clementine Levy, Alexandre Gaudet, Emmanuelle Jaillette, Jean Reignier, Guillaume Lassailly, Malika Balduyck, Emeline Cailliau, Anahita Rouze, Saad Nseir, and on behalf of the Micro Cirrhosis Study Group
Subjects: cirrhosis, ventilator-associated pneumonia, microaspiration, Medicine
Abstract: Previous studies have identified cirrhosis as a risk factor for ventilator-associated pneumonia (VAP). The aim of our study was to determine the relationship between cirrhosis and abundant gastric-content microaspiration in intubated critically ill patients. We performed a matched cohort study using data from three randomized controlled trials on abundant microaspiration in patients under mechanical ventilation. Each cirrhotic patient was matched with three to four controls for gender, age ± 5 years and simplified acute physiology score II (SAPS II) ± 5 points. Abundant microaspiration was defined by significant levels of pepsin and alpha-amylase in >30% of tracheal aspirates. All tracheal aspirates were collected for the first 48 h of the study period. The percentage of patients with abundant gastric-content microaspiration was the primary outcome. The abundant microaspiration of oropharyngeal secretions, VAP incidence, the duration of mechanical ventilation, length of intensive care unit (ICU) stay and mortality were the secondary outcomes. A. total of 39 cirrhotic patients were matched to 138 controls. The percentage of patients with abundant gastric-content microaspiration did not differ between the two groups (relative risk: 0.91 (95% CI: 0.75 to 1.10)). There was no significant difference between the two groups in terms of the abundant microaspiration of oropharyngeal secretions, VAP, the duration of mechanical ventilation, the length of ICU stay and mortality. Our results suggest that cirrhosis is not associated with abundant gastric-content microaspiration.
Published: 2022
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40. The Changing Landscape of Invasive Fungal Infections in ICUs: A Need for Risk Stratification to Better Target Antifungal Drugs and the Threat of Resistance

Author: Julien Poissy, Anahita Rouzé, Marjorie Cornu, Saad Nseir, and Boualem Sendid
Subjects: invasive candidiasis, candidemia, invasive aspergillosis, risk factors, antifungal, diagnosis algorithm, Biology (General), QH301-705.5
Abstract: The landscape of invasive candidiasis and invasive aspergillosis has changed dramatically in intensive care units over the past two decades. Today, we are faced with new risk factors such as the emergence of resistance, but are also equipped with new therapeutic strategies and diagnostic tools which are changing epidemiological data and diagnostic algorithms. Some common points need to be addressed: (i) the best way to use microbiological tools and to integrate their results in decisional algorithms; (ii) the need to find the optimum balance between under-diagnosis and overtreatment; (iii) and the need to decipher pathophysiology. In this short review, we will try to illustrate these points.
Published: 2022
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41. Correction to: Characteristics and prognosis of bloodstream infection in patients with COVID‑19 admitted in the ICU: an ancillary study of the COVID‑ICU study

Author: Nicolas Massart, Virginie Maxime, Pierre Fillatre, Keyvan Razazi, Alexis Ferré, Pierre Moine, Francois Legay, Guillaume Voiriot, Marlene Amara, Francesca Santi, Saad Nseir, Stephanie Marque-Juillet, Rania Bounab, Nicolas Barbarot, Fabrice Bruneel, Charles-Edouard Luyt, and the COVID ICU Bacteremia Study Group on behalf of the COVID-ICU Investigators
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2022
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42. Center effect in intubation risk in critically ill immunocompromised patients with acute hypoxemic respiratory failure

Author: Guillaume Dumas, Alexandre Demoule, Djamel Mokart, Virginie Lemiale, Saad Nseir, Laurent Argaud, Frédéric Pène, Loay Kontar, Fabrice Bruneel, Kada Klouche, François Barbier, Jean Reignier, Annabelle Stoclin, Guillaume Louis, Jean-Michel Constantin, Florent Wallet, Achille Kouatchet, Vincent Peigne, Pierre Perez, Christophe Girault, Samir Jaber, Yves Cohen, Martine Nyunga, Nicolas Terzi, Lila Bouadma, Christine Lebert, Alexandre Lautrette, Naike Bigé, Jean-Herlé Raphalen, Laurent Papazian, Dominique Benoit, Michael Darmon, Sylvie Chevret, and Elie Azoulay
Subjects: Center effect, Intubation, Neutropenia, Leukemia, Hypoxemia, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Acute respiratory failure is the leading reason for intensive care unit (ICU) admission in immunocompromised patients, and the need for invasive mechanical ventilation has become a major clinical endpoint in randomized controlled trials (RCTs). However, data are lacking on whether intubation is an objective criteria that is used unbiasedly across centers. This study explores how this outcome varies across ICUs. Methods Hierarchical models and permutation procedures for testing multiple random effects were applied on both data from an observational cohort (the TRIAL-OH study: 703 patients, 17 ICUs) and a randomized controlled trial (the HIGH trial: 776 patients, 31 ICUs) to characterize ICU variation in intubation risk across centers. Results The crude intubation rate varied across ICUs from 29 to 80% in the observational cohort and from 0 to 86% in the RCT. This center effect on the mean ICU intubation rate was statistically significant, even after adjustment on individual patient characteristics (observational cohort: p value = 0.013, median OR 1.48 [1.30–1.72]; RCT: p value 0.004, median OR 1.51 [1.36–1.68]). Two ICU-level characteristics were associated with intubation risk (the annual rate of intubation procedure per center and the time from respiratory symptoms to ICU admission) and could partly explain this center effect. In the RCT that controlled for the use of high-flow oxygen therapy, we did not find significant variation in the effect of oxygenation strategy on intubation risk across centers, despite a significant variation in the need for invasive mechanical ventilation. Conclusion Intubation rates varied considerably among ICUs, even after adjustment on individual characteristics.
Published: 2019
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43. High-flow nasal cannula therapy: clinical practice in intensive care units

Author: Emmanuel Besnier, Sinad Hobeika, Saad NSeir, Fabien Lambiotte, Damien Du Cheyron, Bertrand Sauneuf, Benoit Misset, Fabienne Tamion, Guillaume Schnell, Jack Richecoeur, Julien Maizel, Christophe Girault, and for the BoReal study group
Subjects: Oxygen therapy, High-flow nasal cannula, Acute respiratory failure, Intensive care unit, Clinical practices, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Despite the extensive use of high-flow nasal cannula (HFNC) therapy in intensive care units (ICU) for acute respiratory failure (ARF), its daily clinical practice has not been assessed. We designed a regional survey in ICUs in North-west France to evaluate ICU physicians’ clinical practice with HFNC. Materials and methods We sent an observational survey to ICU physicians from 34 French ICUs over a 6-month period in 2016–2017. The survey included questions regarding the indications and expected efficiency of HFNC, practical aspects of use (initiation, weaning) and satisfaction. Comparisons between junior and senior ICU physicians were performed using a Fischer exact test. Results Among the 235 ICU physicians contacted, 137 responded (58.3%) all of whom regularly used HFNC. Hypoxemic ARF was considered a good indication for HFNC by all 137, but only 30% expected HFNC success (i.e., avoiding intubation in at least 60% of cases). Among hypoxemic indications, 30% of juniors considered acute pulmonary edema a good indication versus 74% of seniors (p
Published: 2019
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44. Impact of nutrition route on microaspiration in critically ill patients with shock: a planned ancillary study of the NUTRIREA-2 trial

Author: Saad Nseir, Amélie Le Gouge, Jean-Baptiste Lascarrou, Jean-Claude Lacherade, Emmanuelle Jaillette, Jean-Paul Mira, Emmanuelle Mercier, Pierre-Louis Declercq, Michel Sirodot, Gaël Piton, François Tinturier, Elisabeth Coupez, Stéphane Gaudry, Michel Djibré, Didier Thevenin, Jeremy Pasco, Malika Balduyck, Farid Zerimech, and Jean Reignier
Subjects: Microaspiration, Gastric contents, Oropharyngeal secretions, Pneumonia, Pathophysiology, Critical care, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Microaspiration of gastric and oropharyngeal secretions is the main mechanism of entry of bacteria into the lower respiratory tract in intubated critically ill patients. The aim of this study is to determine the impact of enteral nutrition, as compared with parenteral nutrition, on abundant microaspiration of gastric contents and oropharyngeal secretions. Methods Planned ancillary study of the randomized controlled multicenter NUTRIREA2 trial. Patients with shock receiving invasive mechanical ventilation were randomized to receive early enteral or parenteral nutrition. All tracheal aspirates were collected during the 48 h following randomization. Abundant microaspiration of gastric contents and oropharyngeal secretions was defined as the presence of significant levels of pepsin (> 200 ng/ml) and salivary amylase (> 1685 UI/ml) in > 30% of tracheal aspirates. Results A total of 151 patients were included (78 and 73 patients in enteral and parenteral nutrition groups, respectively), and 1074 tracheal aspirates were quantitatively analyzed for pepsin and amylase. Although vomiting rate was significantly higher (31% vs 15%, p = 0.016), constipation rate was significantly lower (6% vs 21%, p = 0.010) in patients with enteral than in patients with parenteral nutrition. No significant difference was found regarding other patient characteristics. The percentage of patients with abundant microaspiration of gastric contents was significantly lower in enteral than in parenteral nutrition groups (14% vs 36%, p = 0.004; unadjusted OR 0.80 (95% CI 0.69, 0.93), adjusted OR 0.79 (0.76, 0.94)). The percentage of patients with abundant microaspiration of oropharyngeal secretions was significantly higher in enteral than in parenteral nutrition groups (74% vs 54%, p = 0.026; unadjusted OR 1.21 (95% CI 1.03, 1.44), adjusted OR 1.23 (1.01, 1.48)). No significant difference was found in percentage of patients with ventilator-associated pneumonia between enteral (8%) and parenteral (10%) nutrition groups (HR 0.78 (0.26, 2.28)). Conclusions Our results suggest that enteral and parenteral nutrition are associated with high rates of microaspiration, although oropharyngeal microaspiration was more common with enteral nutrition and gastric microaspiration was more common with parenteral nutrition. Trial registration ClinicalTrials.gov, NCT03411447. Registered 18 July 2017. Retrospectively registered.
Published: 2019
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45. Brief summary of French guidelines for the prevention, diagnosis and treatment of hospital-acquired pneumonia in ICU

Author: Marc Leone, Lila Bouadma, Bélaïd Bouhemad, Olivier Brissaud, Stéphane Dauger, Sébastien Gibot, Sami Hraiech, Boris Jung, Eric Kipnis, Yoann Launey, Charles-Edouard Luyt, Dimitri Margetis, Fabrice Michel, Djamel Mokart, Philippe Montravers, Antoine Monsel, Saad Nseir, Jérôme Pugin, Antoine Roquilly, Lionel Velly, Jean-Ralph Zahar, Rémi Bruyère, Gérald Chanques, ADARPEF, and GFRUP
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background The French Society of Anaesthesia and Intensive Care Medicine and the French Society of Intensive Care edited guidelines focused on hospital-acquired pneumonia (HAP) in intensive care unit. The goal of 16 French-speaking experts was to produce a framework enabling an easier decision-making process for intensivists. Results The guidelines were related to 3 specific areas related to HAP (prevention, diagnosis and treatment) in 4 identified patient populations (COPD, neutropenia, post-operative and paediatric). The literature analysis and the formulation of the guidelines were conducted according to the Grade of Recommendation Assessment, Development and Evaluation methodology. An extensive literature research over the last 10 years was conducted based on publications indexed in PubMed™ and Cochrane™ databases. Conclusions HAP should be prevented by a standardised multimodal approach and the use of selective digestive decontamination in units where multidrug-resistant bacteria prevalence was below 20%. Diagnosis relies on clinical assessment and microbiological findings. Monotherapy, in the absence of risk factors for multidrug-resistant bacteria, non-fermenting Gram-negative bacilli and/or increased mortality (septic shock, organ failure), is strongly recommended. After microbiological documentation, it is recommended to reduce the spectrum and to prefer monotherapy for the antibiotic therapy of HAP, including for non-fermenting Gram-negative bacilli.
Published: 2018
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46. Comparison of high-flow nasal oxygen therapy and non-invasive ventilation in ICU patients with acute respiratory failure and a do-not-intubate orders: a multicentre prospective study OXYPAL

Author: Denis Frasca, Christophe Guitton, Jean-Pierre Frat, Stephan Ehrmann, Nicolas Terzi, Damien Contou, Jean-Pierre Quenot, Saad Nseir, Didier Thévenin, Arnaud W Thille, Bertrand Guidet, Laura Federici, Jean Reignier, René Robert, Christophe Vinsonneau, Michel Djibré, C Girault, Suela Demiri, Juliette Masse, Olivier Lesieur, Pascal Beuret, Julie Badin, Dalila Benzekri-Llefevre, Hassène Rahmani, Laurent Argaud Argaud, Erwan I'her, Khaldoune Kuteifan, Francois Thouy, Martial Thyrault, Juliette Audibert, Alexandre Boyer, Riad Chelha, G Piton, and Nadia Aissaoui
Subjects: Medicine
Abstract: Introduction A palliative approach to intensive care unit (ICU) patients with acute respiratory failure and a do-not-intubate order corresponds to a poorly evaluated target for non-invasive oxygenation treatments. Survival alone should not be the only target; it also matters to avoid discomfort and to restore the patient’s quality of life. We aim to conduct a prospective multicentre observational study to analyse clinical practices and their impact on outcomes of palliative high-flow nasal oxygen therapy (HFOT) and non-invasive ventilation (NIV) in ICU patients with do-not-intubate orders.Methods and analysis This is an investigator-initiated, multicentre prospective observational cohort study comparing the three following strategies of oxygenation: HFOT alone, NIV alternating with HFOT and NIV alternating with standard oxygen in patients admitted in the ICU for acute respiratory failure with a do-not-intubate order. The primary outcome is the hospital survival within 14 days after ICU admission in patients weaned from NIV and HFOT. The sample size was estimated at a minimum of 330 patients divided into three groups according to the oxygenation strategy applied. The analysis takes into account confounding factors by modelling a propensity score.Ethics and dissemination The study has been approved by the ethics committee and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.Trial registration number NCT03673631
Published: 2021
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47. Correction to: Relationship between ventilator-associated pneumonia and mortality in COVID-19 patients: a planned ancillary analysis of the coVAPid cohort

Author: Saad Nseir, Ignacio Martin-Loeches, Pedro Povoa, Matthieu Metzelard, Damien Du Cheyron, Fabien Lambiotte, Fabienne Tamion, Marie Labruyere, Demosthenes Makris, Claire Boulle Geronimi, Marc Pinetonde Chambrun, Martine Nyunga, Olivier Pouly, Bruno Mégarbane, Anastasia Saade, Gemma Gomà, Eleni Magira, Jean-François Llitjos, Antoni Torres, Iliana Ioannidou, Alexandre Pierre, Luis Coelho, Jean Reignier, Denis Garot, Louis Kreitmann, Jean-Luc Baudel, Guillaume Voiriot, Damien Contou, Alexandra Beurton, Pierre Asfar, Alexandre Boyer, Arnaud W. Thille, Armand Mekontso-Dessap, Vassiliki Tsolaki, Christophe Vinsonneau, Pierre-Edouard Floch, Loïc Le Guennec, Adrian Ceccato, Antonio Artigas, Mathilde Bouchereau, Julien Labreuche, Alain Duhamel, Anahita Rouzé, and the coVAPid study group
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2021
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48. Usefulness of Sepsis-3 in diagnosing and predicting mortality of ventilator-associated lower respiratory tract infections.

Author: Alexandre Gaudet, Matthieu Devos, Sylvain Keignart, Olivier Pouly, Sylvain Lecailtel, Frédéric Wallet, and Saad Nseir
Subjects: Medicine, Science
Abstract: BackgroundEarly distinguishing ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP) remains difficult in the daily practice. However, this question appears clinically relevant, as treatments of VAT and VAP currently differ. In this study, we assessed the accuracy of sepsis criteria according to the Sepsis-3 definition in the early distinction between VAT and VAP.MethodsRetrospective single-center cohort, including all consecutive patients with a diagnosis of VAT (n = 70) or VAP (n = 136), during a 2-year period. Accuracy of sepsis criteria according to Sepsis-3, total SOFA and respiratory SOFA, calculated at time of microbiological sampling were assessed in differentiating VAT from VAP, and in predicting mortality on ICU discharge.ResultsSensitivity and specificity of sepsis criteria were found respectively at 0.4 and 0.91 to distinguish VAT from VAP, and at 0.38 and 0.75 for the prediction of mortality in VA-LRTI. A total SOFA ≥ 6 and a respiratory SOFA ≥ 3 were identified as the best cut-offs for these criteria in differentiating VAT from VAP, with sensitivity and specificity respectively found at 0.63 and 0.69 for total SOFA, and at 0.49 and 0.7 for respiratory SOFA. Additionally, for prediction of mortality, a total SOFA ≥ 7 and a respiratory SOFA = 4 were identified as the best-cut-offs, respectively yielding sensitivity and specificity at 0.56 and 0.61 for total SOFA, and at 0.22 and 0.95 for respiratory SOFA.ConclusionsSepsis criteria according to the Sepsis-3 definition show a high specificity but a low sensitivity for the diagnosis of VAP. Our results do not support the use of these criteria for the early diagnosis of VAP in patients with VA-LRTI.
Published: 2021
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49. Hyperbaric hyperoxemia as a risk factor for ventilator-acquired pneumonia?

Author: Morgan Caplan, Thibault Duburcq, Anne-Sophie Moreau, Julien Poissy, Saad Nseir, and Erika Parmentier-Decrucq
Subjects: Medicine, Science
Abstract: ObjectivesVentilator-acquired pneumonia (VAP) is the leading cause of serious associated infections in Intensive Care Units (ICU) and is associated with significant morbidity. The use of hyperbaric oxygen therapy (HBOT) in patients on mechanical ventilation may increase exposure to certain risk factors such as hyperoxemia and the need for multiple transfers. The aim of our study was to assess the relationship between HBOT and VAP.MethodThis retrospective observational study was performed from March 2017 to March 2018 in a 10-bed ICU using HBOT. All patients receiving mechanical ventilation (MV) for more than 48 hours were eligible. VAP was defined using clinical and radiological criteria. Data collection was carried out via digital medical records. Risk factors for VAP were determined by univariate and multivariate analysis.ResultsForty-two (23%) of the 182 patients enrolled developed at least one episode of VAP. One hundred and twenty-four (68%) patients received HBOT. The incidence rate of VAP was 34 per 1000 ventilator days. The occurrence of VAP was significantly associated with immunosuppression (pConclusionKnown risk factors for VAP are to be found within our ICU population. HBOT, however, is not an extra risk factor for VAP within this group. Further experimental and clinical investigations are needed to understand the impact of HBOT on the occurrence of VAP and on physiological microbiome.
Published: 2021
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50. Assessment of Metabolic Dysfunction in Sepsis in a Retrospective Single-Centre Cohort

Author: Julien Goutay, Juliette Perche, Aurelia Toussaint, Elodie Drumez, Michael Howsam, Claire Bourel, Benoit Brassart, Alexandre Pierre, Morgan Caplan, Arthur Durand, Marion Houard, Saad Nseir, Raphael Favory, and Sébastien Preau
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Objective. Our primary aim was to assess selected metabolic dysfunction parameters, both independently and as a complement to the SOFA score, as predictors of short-term mortality in patients with infection admitted to the intensive care unit (ICU). Methods. We retrospectively enrolled all consecutive adult patients admitted to the eight ICUs of Lille University Hospital, between January 2015 and September 2016, with suspected or confirmed infection. We selected seven routinely measured biological and clinical parameters of metabolic dysfunction (maximal arterial lactatemia, minimal and maximal temperature, minimal and maximal glycaemia, cholesterolemia, and triglyceridemia), in addition to age and the Charlson’s comorbidity score. All parameters and SOFA scores were recorded within 24 h of admission. Results. We included 956 patients with infection, among which 295 (30.9%) died within 90 days. Among the seven metabolic parameters investigated, only maximal lactatemia was associated with higher risk of 90-day hospital mortality in SOFA-adjusted analyses (SOFA-adjusted OR, 1.17; 95%CI, 1.10 to 1.25; p
Published: 2021
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