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1. Intra-abdominal infections survival guide: a position statement by the Global Alliance For Infections In Surgery

Author

Massimo Sartelli, Philip Barie, Vanni Agnoletti, Majdi N. Al-Hasan, Luca Ansaloni, Walter Biffl, Luis Buonomo, Stijn Blot, William G. Cheadle, Raul Coimbra, Belinda De Simone, Therese M. Duane, Paola Fugazzola, Helen Giamarellou, Timothy C. Hardcastle, Andreas Hecker, Kenji Inaba, Andrew W. Kirkpatrick, Francesco M. Labricciosa, Marc Leone, Ignacio Martin-Loeches, Ronald V. Maier, Sanjay Marwah, Ryan C. Maves, Andrea Mingoli, Philippe Montravers, Carlos A. Ordóñez, Miriam Palmieri, Mauro Podda, Jordi Rello, Robert G. Sawyer, Gabriele Sganga, Pierre Tattevin, Dipendra Thapaliya, Jeffrey Tessier, Matti Tolonen, Jan Ulrych, Carlo Vallicelli, Richard R. Watkins, Fausto Catena, and Federico Coccolini

Subjects
Antimicrobial resistance, Antimicrobial therapy, Intra-abdominal infections, Source control, Surgery, RD1-811, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Intra-abdominal infections (IAIs) are an important cause of morbidity and mortality in hospital settings worldwide. The cornerstones of IAI management include rapid, accurate diagnostics; timely, adequate source control; appropriate, short-duration antimicrobial therapy administered according to the principles of pharmacokinetics/pharmacodynamics and antimicrobial stewardship; and hemodynamic and organ functional support with intravenous fluid and adjunctive vasopressor agents for critical illness (sepsis/organ dysfunction or septic shock after correction of hypovolemia). In patients with IAIs, a personalized approach is crucial to optimize outcomes and should be based on multiple aspects that require careful clinical assessment. The anatomic extent of infection, the presumed pathogens involved and risk factors for antimicrobial resistance, the origin and extent of the infection, the patient’s clinical condition, and the host’s immune status should be assessed continuously to optimize the management of patients with complicated IAIs.

Published
2024
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2. Doxycycline Prophylaxis for Skin and Soft Tissue Infections in Naval Special Warfare Trainees, United States

Author

Jeffrey Spiro, Piotr Wisniewski, Julia Schwartz, Alfred G. Smith, Sara Burger, Drake H. Tilley, and Ryan C. Maves

Subjects
bacteria, doxycycline, prophylaxis, skin and soft tissue infection, SSTI, saltwater exposure, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

In 2015, several severe cases of skin and soft tissue infection (SSTI) among US Naval Special Warfare trainees prompted the introduction of doxycycline prophylaxis during the highest-risk portion of training, Hell Week. We performed a retrospective analysis of the effect of this intervention on SSTI incidence and resulting hospital admissions during 2013–2020. In total, 3,371 trainees underwent Hell Week training during the study period; 284 SSTIs were diagnosed overall, 29 of which led to hospitalization. After doxycycline prophylaxis was introduced, admission rates for SSTI decreased from 1.37 to 0.64 admissions/100 trainees (p = 0.036). Overall SSTI rates remained stable at 7.42 to 8.86 SSTIs/100 trainees (p = 0.185). Hospitalization rates per diagnosed SSTI decreased from 18.4% to 7.2% (p = 0.009). Average length of hospitalization decreased from 9.01 days to 4.33 days (p = 0.034). Doxycycline prophylaxis was associated with decreased frequency and severity of hospitalization for SSTIs among this population.

Published
2024
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3. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trialsResearch in context

Author

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

Subjects
Acute respiratory distress syndrome, Acute hypoxemic respiratory failure, Pneumonia, Critically ill, Cancer, Medicine (General), R5-920
Abstract

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Published
2024
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4. A geopositioned and evidence-graded pan-species compendium of Mayaro virus occurrence

Author

Michael Celone, Alexander M. Potter, Barbara A. Han, Sean P. Beeman, Bernard Okech, Brett Forshey, James Dunford, George Rutherford, Neida K. Mita-Mendoza, Elizabet Lilia Estallo, Ricardo Khouri, Isadora Cristina de Siqueira, Kyle Petersen, Ryan C. Maves, Assaf Anyamba, and Simon Pollett

Subjects
Science
Abstract

Abstract Mayaro Virus (MAYV) is an emerging health threat in the Americas that can cause febrile illness as well as debilitating arthralgia or arthritis. To better understand the geographic distribution of MAYV risk, we developed a georeferenced database of MAYV occurrence based on peer-reviewed literature and unpublished reports. Here we present this compendium, which includes both point and polygon locations linked to occurrence data documented from its discovery in 1954 until 2022. We describe all methods used to develop the database including data collection, georeferencing, management and quality-control. We also describe a customized grading system used to assess the quality of each study included in our review. The result is a comprehensive, evidence-graded database of confirmed MAYV occurrence in humans, non-human animals, and arthropods to-date, containing 262 geo-positioned occurrences in total. This database - which can be updated over time - may be useful for local spill-over risk assessment, epidemiological modelling to understand key transmission dynamics and drivers of MAYV spread, as well as identification of major surveillance gaps.

Published
2023
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5. Fatal septic shock due to disseminated coccidioidomycosis: a case series and review of the literature

Author

Piotr Wisniewski, Isaac McCool, John C. Walsh, Chelsea Ausman, Jenifer Edmondson, Alexandra Perry, Evan C. Ewers, and Ryan C. Maves

Subjects
Coccidioidomycosis, Coccidioides, Sepsis, Septic shock, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Coccidioidomycosis is a fungal infection endemic to the southwestern United States and regions of Latin America. Disseminated disease occurs in

Published
2023
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6. SARS-CoV-2 infection is associated with self-reported post-acute neuropsychological symptoms within six months of follow-up

Author

Liana R. Andronescu, Stephanie A. Richard, Ann I. Scher, David A. Lindholm, Katrin Mende, Anuradha Ganesan, Nikhil Huprikar, Tahaniyat Lalani, Alfred Smith, Rupal M. Mody, Milissa U. Jones, Samantha E. Bazan, Rhonda E. Colombo, Christopher J. Colombo, Evan Ewers, Derek T. Larson, Ryan C. Maves, Catherine M. Berjohn, Carlos J. Maldonado, Caroline English, Margaret Sanchez Edwards, Julia S. Rozman, Jennifer Rusiecki, Celia Byrne, Mark P. Simons, David Tribble, Timothy H. Burgess, Simon D. Pollett, and Brian K. Agan

Subjects
Medicine, Science
Published
2024

7. Risk of COVID-19 after natural infection or vaccinationResearch in context

Author

Anne-Marie Rick, Matthew B. Laurens, Ying Huang, Chenchen Yu, Thomas C.S. Martin, Carina A. Rodriguez, Christina A. Rostad, Rebone M. Maboa, Lindsey R. Baden, Hana M. El Sahly, Beatriz Grinsztejn, Glenda E. Gray, Cynthia L. Gay, Peter B. Gilbert, Holly E. Janes, James G. Kublin, Yunda Huang, Brett Leav, Ian Hirsch, Frank Struyf, Lisa M. Dunkle, Kathleen M. Neuzil, Lawrence Corey, Paul A. Goepfert, Stephen R. Walsh, Dean Follmann, Karen L. Kotloff, Atoya Adams, Eric Miller, Bruce G. Rankin, Steven Shinn, Marshall Nash, Sinikka L. Green, Colleen Jacobsen, Jayasree Krishnankutty, Sikhongi Phungwayo, Richard M. Glover, II, Stacy Slechta, Troy Holdeman, Robyn Hartvickson, Amber Grant, Terry L. Poling, Terry D. Klein, Thomas C. Klein, Tracy R. Klein, William B. Smith, Richard L. Gibson, Jennifer Winbigler, Elizabeth Parker, Priyantha N. Wijewardane, Eric Bravo, Jeffrey Thessing, Michelle Maxwell, Amanda Horn, Catherine Mary Healy, Christine Akamine, Laurence Chu, R. Michelle Chouteau, Michael J. Cotugno, George H. Bauer, Jr., Greg Hachigian, Masaru Oshita, Michael Cancilla, Kristen Kiersey, William Seger, Mohammed Antwi, Allison Green, Anthony Kim, Michael Desjardins, Jennifer A. Johnson, Amy Sherman, Judith Borger, Nafisa Saleem, Joel Solis, Martha Carmen Medina, Westly Keating, Edgar Garcia, Cynthia Bueno, Nathan Segall, Douglas S. Denham, Thomas Weiss, Ayoade Avworo, Parke Hedges, Cynthia Becher Strout, Rica Santiago, Yvonne Davis, Patty Howenstine, Alison Bondell, Kristin Marks, Tina Wang, Timothy Wilkin, Mary Vogler, Carrie Johnston, Michele P. Andrasik, Jessica G. Andriesen, Gail Broder, Niles Eaton, Huub G. Gelderblom, Rachael McClennen, Nelson Michael, Merlin Robb, Carrie Sopher, Vicki E. Miller, Fredric Santiago, Blanca Gomez, Insiya Valika, Amy Starr, Valeria D. Cantos, Sheetal Kandiah, Carlos del Rio, Nadine Rouphael, Srilatha Edupuganti, Evan J. Anderson, Andres Camacho-Gonzalez, Satoshi Kamidani, Meghan Teherani, David J. Diemert, Elissa Malkin, Marc Siegel, Afsoon Roberts, Gary Simon, Bindu Balani, Carolene Stephenson, Steven Sperber, Cristina Cicogna, Marcus J. Zervos, Paul Kilgore, Mayur Ramesh, Erica Herc, Kate Zenlea, Abram Burgher, Ann M. Milliken, Joseph D. Davis, Brendan Levy, Sandra Kelman, Matthew W. Doust, Denise Sample, Sandra Erickson, Shane G. Christensen, Christopher Matich, James Longe, John Witbeck, James T. Peterson, Alexander Clark, Gerald Kelty, Issac Pena-Renteria, Michael J. Koren, Darlene Bartilucci, Alpa Patel, Carolyn Tran, Christina Kennelly, Robert Brownlee, Jacob Coleman, Hala Webster, Carlos A. Fierro, Natalia Leistner, Amy Thompson, Celia Gonzalez, Lisa A. Jackson, Janice Suyehira, Milton Haber, Maria M. Regalado, Veronica Procasky, Alisha Lutat, Carl P. Griffin, Ripley R. Hollister, Jeremy Brown, Melody Ronk, Wayne L. Harper, Lisa Cohen, Lynn Eckert, Matthew Hong, Rambod Rouhbakhsh, Elizabeth Danford, John Johnson, Richard Calderone, Shishir K. Khetan, Oyebisi Olanrewaju, Nan Zhai, Kimberly Nieves, Allison O'Brien, Paul S. Bradley, Amanda Lilienthal, Jim Callis, Adam B. Brosz, Andrea Clement, Whitney West, Luke Friesen, Paul Cramer, Frank S. Eder, Ryan Little, Victoria Engler, Heather Rattenbury-Shaw, David J. Ensz, Allie Oplinger, Brandon J. Essink, Jay Meyer, Frederick Raiser, III, Kimberly Mueller, Keith W. Vrbicky, Charles Harper, Chelsie Nutsch, Wendell Lewis, III, Cathy Laflan, Jordan L. Whatley, Nicole Harrell, Amie Shannon, Crystal Rowell, Christopher Dedon, Mamodikoe Makhene, Gregory M. Gottschlich, Kate Harden, Melissa Gottschlich, Mary Smith, Richard Powell, Murray A. Kimmel, Simmy Pinto, Timothy P. Vachris, Mark Hutchens, Stephen Daniels, Margaret Wells, Mimi Van Der Leden, Peta-Gay Jackson-Booth, Mira Baron, Pamela Kane, Shannen Seversen, Mara Kryvicky, Julia Lord, Jamshid Saleh, Matthew Miles, Rafael Lupercio, John W. McGettigan, Jr., Walter Patton, Riemke Brakema, Karin Choquette, Jonlyn McGettigan, Judith L. Kirstein, Marcia Bernard, Mary Beth Manning, Joan Rothenberg, Toby Briskin, Denise Roadman, Sharita Tedder-Edwards, Howard I. Schwartz, Surisday Mederos, Shobha Swaminathan, Amesika Nyaku, Tilly Varughese, Michelle DallaPiazza, Sharon E. Frey, Irene Graham, Getahun Abate, Daniel Hoft, Leland N. Allen, III, Leslie A. Edwards, William S. Davis, Jr., Jessica M. Mena, Mark E. Kutner, Jorge Caso, Maria Hernandez Moran, Marianela Carvajal, Janet Mendez, Larkin T. Wadsworth, III, Michael R. Adams, Leslie Iverson, Joseph L. Newberg, Laura Pearlman, Paul J. Nugent, Michele D. Reynolds, Jennifer Bashour, Robert Schmidt, Neil P. Sheth, Kenneth Steil, Ramy J. Toma, William Kirby, Pink Folmar, Samantha Williams, Paul Pickrell, Stefanie Mott, Carol Ann Linebarger, Hussain Malbari, David Pampe, Veronica G. Fragoso, Lisa Holloway, Cecilia McKeown-Bragas, Teresa Becker, Barton G. Williams, William H. Jones, Jesse L. Clark, Steven Shoptaw, Michele Vertucci, Will Hernandez, Stephen A. Spector, Amaran Moodley, Jill Blumenthal, Lisa Stangl, Karen Deutsch, Kathleen M. Mullane, David Pitrak, Cheryl Nuss, Judy Pi, Carl Fichtenbaum, Margaret Powers-Fletcher, Michelle Saemann, Sharon Kohrs, Thomas B. Campbell, Andrew Lauria, Jose C. Mancilla, Hillary Dunlevy, Richard M. Novak, Andrea Wendrow, Scott Borgetti, Ben Ladner, Lisa Chrisley, Cheryl Young, Susanne Doblecki-Lewis, Maria L. Alcaide, Jose Gonzales-Zamora, Stephen Morris, David Wohl, Joseph Eron, Jr., Ian Frank, Debora Dunbar, David Metzger, Florence Momplaisir, Judith Martin, Alejandro Hoberman, Timothy Shope, Gysella Muniz, Richard Rupp, Amber Stanford, Megan Berman, Laura Porterfield, Michael Lewis, Elham Ghadishah, Joseph Yusin, Mai Pham, Clarence B. Creech, II, Shannon Walker, Stephanie Rolsma, Robert Samuels, Isaac Thomsen, Spyros A. Kalams, Greg Wilson, Gregg H. Lucksinger, Kevin Parks, Ryan Israelsen, Jaleh Ostovar, Kary Kelly, Jeffrey S. Overcash, Hanh Chu, Kia Lee, Luis I. De La Cruz, Steve Clemons, Elizabeth Everette, Suzanna Studdard, Gowdhami Mohan, Stefanie Tyson, Alyssa-Kay Peay, Danyel Johnson, Gregory J. Feldman, May-Yin Suen, Jacqueline Muenzner, Joseph Boscia, Farhan Siddiqui, John Sanders, James Peacock, Julio Nasim, Michael L. Levin, Julie Hussey, Marcy Kulic, Mark M. McKenzie, Teresa Deese, Erica Osmundsen, Christy Sweet, Valentine M. Ebuh, Elwaleed Elnagar, Georgette Ebuh, Genevieve Iwuala, Laurie J. Han-Conrad, Todd Simmons, Denis Tarakjian, Jeremy Ackermann, Mark S. Adams, José O. Alemán, Mohamed S. Al-Ibrahim, David R. Andes, Jeb Andrews, Roberto C. Arduino, Martín Bäcker, Diana Badillo, Emma Bainbridge, Teresa A. Batteiger, Jose A. Bazan, Roger J. Bedimo, Jorge A. Benitez, Annette R. Bennett, David I. Bernstein, Kristin Bialobok, Rebecca Boas, Judith Brady, Cynthia Brown, Catherine A. Bunce, Robert S. Call, Wesley Campbell, Ellie Carmody, Christopher Carpenter, Steven E. Carsons, Marvin Castellon, Mario Castro, Hannah Catan, Jennifer Chang, Mouna G. Chebib, Corey M. Chen, Margaret Cheng, Brian D.W. Chow, Annie Ciambruschini, Joseph P. Connor, James H. Conway, Maureen Cooney, Marcel Curlin, Claudia De La Matta Rodriguez, Jon F. Dedon, Emily Degan, Michelle Dickey, Craig Dietz, Jennifer L. Dong, Brenda Dorcely, Michael P. Dube, Carmel B. Dyer, Benjamin Eckhardt, Edward Ellerbeck, Evan C. Ewers, Amy Falk, Brittany Feijoo, Uriel R. Felsen, Tom Fiel, David Fitz-Patrick, Charles M. Fogarty, Stacy Ford, Lina M. Forero, Elizabeth Formentini, Doris Franco-Vitteri, Robert W. Frenck, Jr., Elie Gharib, Suzanne Gharib, Rola G. Rucker, James N. Goldenberg, Luis H. González, Brett Gray, Rusty Greene, Robert M. Grossberg, Juan V. Guanira-Carranza, Alfredo Gilberto Guerreros Benavides, Clint C. Guillory, Shauna H. Gunaratne, David Halpert, Holli Hamilton, William R. Hartman, Sheryl L. Henderson, Ramin Herati, Laura Hernandez Guarin, Robin Hilder, Ken Ho, Leila Hojat, Sybil G. Hosek, Jeffrey M. Jacobson, Melanie Jay, Diane H. Johnson, Kathleen S. Jones, Edward C. Jones-López, Jessica E. Justman, Scott Kahney, Lois Katz, Melinda Katz, Daniel Kaul, Michael C. Keefer, Ashley Kennedy, Jennifer Knishinsky, Laura Kogelman, Susan L. Koletar, Angelica Kottkamp, Maryrose Laguio-Vila, Raphael J. Landovitz, Jessica L. Lee, Albert Liu, Eneyda Giuvanela Llerena Zegarra, Anna S. Lok, James Lovell, Ronald Lubelchek, John Lucaj, Gary Luckasen, Annie Luetkemeyer, Njira Lucia Lugogo, Janine Maenza, Carlos Malvestutto, Monica Mauri, Ryan C. Maves, Kenneth H. Mayer, Michael J. McCartney, Margaret E. McCort, M. Juliana McElrath, Meredith McNairy, Fernando L. Merino, Eric A. Meyerowitz, Carol L. Mitchell, Cynthia L. Monaco, Sauda Muhammad, Sigridh Muñoz-Gómez, Sonal Munsiff, Paul Nee, Nicole L. Nollen, Asif Noor, Claudio Nuñez Lagos, Jason F. Okulicz, Patrick A. Oliver, Jessica Ortega, Steven Palmer, Lalitha Parameswaran, Purvi Parikh, Susan Parker, Reza Parungao, Juana R. Pavie, Rebecca P. Madan, Henry Peralta, Jennifer Petts, Kristen K. Pierce, E. Javier Pretell Alva, Lawrence J. Purpura, Vanessa Raabe, Sergio E. Recuenco, Tamara Richards, Sharon A. Riddler, Barbara Rizzardi, Rachel Rokser, Charlotte-Paige Rolle, Adam Rosen, Jeffrey Rosen, Lena R. Freese, María E. Santolaya, Linda M. Schipani, Adam Schwartz, Tiffany Schwasinger-Schmidt, Hyman Scott, Beverly E. Sha, Shivanjali Shankaran, Adrienne E. Shapiro, Stephan C. Sharp, Bo Shopsin, Matthew D. Sims, Stephanie Skipper, Derek M. Smith, Michael J. Smith, M. Mahdee Sobhanie, Brit Sovic, Stephanie Sterling, Robert Striker, Karla Beatriz Tafur Bances, Kawsar R. Talaat, Edward M. Tavel, Jr., Hong V. Tieu, Christian Tomaszewski, Ryan Tomlinson, Juan P. Torres, Julian A. Torres, John J. Treanor, Sade Tukuru, Robert J. Ulrich, Gregory C. Utz, Veronica Viar, Roberto A. Viau Colindres, Edward E. Walsh, Mary C. Walsh, Emmanuel B. Walter, Jessica L. Weidler, Yi H. Wu, Kinara S. Yang, Juan Luis Yrivarren Giorza, Arthur L. Zemanek, Kevin Zhang, Barry S. Zingman, Richard Gorman, Carmen A. Paez, Edith Swann, Simbarashe G. Takuva, Alex Greninger, Pavitra Roychoudhury, Robert W. Coombs, Keith R. Jerome, Flora Castellino, Xiaomi Tong, Corrina Pavetto, Teletha Gipson, Tina Tong, Marina Lee, James Zhou, Michael Fay, Kelly McQuarrie, Chimeremma Nnadi, Obiageli Sogbetun, Nina Ahmad, Ian De Proost, Cyrus Hoseyni, Paul Coplan, Najat Khan, Peter Ronco, Dawn Furey, Jodi Meck, Johan Vingerhoets, Boerries Brandenburg, Jerome Custers, Jenny Hendriks, Jarek Juraszek, Anne Marit de Groot, Griet Van Roey, Dirk Heerwegh, Ilse Van Dromme, Jorge F. Méndez Galván, Monica B. Carrascal, Adriana Sordo Duran, Laura Ruy Sanchez Guerrero, Martha Cecilia Gómora Madrid, Alejandro Quintín Barrat Hernández, Sharzhaad Molina Guizar, Denisse Alejandra González Estrada, Silvano Omar Martínez Pérez, Zindy Yazmín Zárate Hinojosa, Guillermo Miguel Ruiz-Palacios, Aurelio Cruz-Valdez, Janeth Pacheco-Flores, Anyela Lara, Secia Díaz-Miralrio, María José Reyes Fentanes, Jocelyn Zuleica Olmos Vega, Daniela Pineda Méndez, Karina Cano Martínez, Winniberg Stephany Alvarez León, Vida Veronica Ruiz Herrera, Eduardo Gabriel Vázquez Saldaña, Laura Julia Camacho Choza, Karen Sofia Vega Orozco, Sandra Janeth Ortega Domínguez, Jorge A. Chacón, Juan J. Rivera, Erika A. Cutz, Maricruz E. Ortegón, María I. Rivera, David Browder, Cortney Burch, Terri Moye, Paul Bondy, Lesley Browder, Rickey D. Manning, James W. Hurst, Rodney E. Sturgeon, Paul H. Wakefield, John A. Kirby, James Andersen, Szheckera Fearon, Rosa Negron, Amy Medina, John M. Hill, Vivek Rajasekhar, Hayes Williams, LaShondra Cade, Rhodna Fouts, Connie Moya, Corey G. Anderson, Naomi Devine, James Ramsey, Ashley Perez, David Tatelbaum, Michael Jacobs, Kathleen Menasche, Vincent Mirkil, Peter J. Winkle, Amina Z. Haggag, Michelle Haynes, Marysol Villegas, Sabina Raja, Robert Riesenberg, Stanford Plavin, Mark Lerman, Leana Woodside, Maria Johnson, C. Mary Healy, Jennifer A. Whitaker, Wendy A. Keitel, Robert L. Atmar, Gary Horwith, Robin Mason, Lisa Johnson, Tambra Dora, Deborah Murray, Logan Ledbetter, Beverly Ewing, Kathryn E. Stephenson, Chen S. Tan, Rebecca Zash, Jessica L. Ansel, Kate Jaegle, Caitlin J. Guiney, Jeffrey A. Henderson, Marcia O'Leary, Kendra Enright, Jill Kessler, Pete Ducheneaux, Asha Inniss, Donald M. Brandon, William B. Davis, Daniel T. Lawler, Yaa D. Oppong, Ryan P. Starr, Scott N. Syndergaard, Rozeli Shelly, Mashrur Islam Majumder, Danny Sugimoto, Jeffrey Dugas, Sr., Dolores Rijos, Sandra Shelton, Stephan Hong, Howard Schwartz, Nelia Sanchez-Crespo, Jennifer Schwartz, Terry Piedra, Barbara Corral, Carmen Medina, Michael E. Dever, Mitul Shah, Michael Delgado, Tameika Scott, Lisa S. Usdan, Lora J. McGill, Valerie K. Arnold, Carolyn Scatamacchia, Codi M. Anthony, Rajan Merchant, Anelgine C. Yoon, Janet Hill, Lucy Ng-Price, Teri Thompson-Seim, Ronald Ackerman, Jamie Ackerman, Florida Aristy, Nzeera Ketter, Jon Finley, Mildred Stull, Monica Murray, Zainab Rizvi, Sonia Guerrero, Yogesh K. Paliwal, Amit Paliwal, Sarah Gordon, Bryan Gordon, Cynthia Montano-Pereira, Christopher Galloway, Candice Montros, Lily Aleman, Samira Shairi, Wesley Van Ever, George H. Freeman, Esther L. Harmon, Marshall A. Cross, Kacie Sales, Catherine Q. Gular, Matthew Hepburn, Nathan Alderson, Shana Harshell, Siham Mahgoub, Celia Maxwell, Thomas Mellman, Karl M. Thompson, Glenn Wortman, Jeff Kingsley, April Pixler, LaKondria Curry, Sarah Afework, Austin Swanson, Jeffry Jacqmein, Maggie Bowers, Dawn Robison, Victoria Mosteller, Janet Garvey, Mary Easley, Rebecca J. Kurnat, Raymond Cornelison, Shanda Gower, William Schnitz, Destiny S. Heinzig-Cartwright, Derek Lewis, Fred E. Newton, Aeiress Duhart, Breanz Watkins, Brandy Ball, Jill York, Shelby Pickle, David B. Musante, William P. Silver, Linda R. Belhorn, Nicholas A. Viens, David Dellaero, Priti Patel, Kendra Lisec, Beth Safirstein, Luz Zapata, Lazaro Gonzalez, Evelyn Quevedo, Farah Irani, Joseph Grillo, Amy Potts, Julie White, Patrick Flume, Gary Headden, Brandie Taylor, Ashley Warden, Amy Chamberlain, Robert Jeanfreau, Susan Jeanfreau, Paul G. Matherne, Amy Caldwell, Jessica Stahl, Mandy Vowell, Lauren Newhouse, Vladimir Berthaud, Zudi-Mwak Takizala, Genevieve Beninati, Kimberly Snell, Sherrie Baker, James Walker, Tavane Harrison, Meagan Miller, Janet Otto, Roni Gray, Christine Wilson, Tiffany Nemecek, Hannah Harrington, Sally Eppenbach, Wendell Lewis, Tana Bourgeois, Lyndsea Folsom, Gregory Holt, Mehdi Mirsaeidi, Rafael Calderon, Paola Lichtenberger, Jalima Quintero, Becky Martinez, Lilly Immergluck, Erica Johnson, Austin Chan, Norberto Fas, LaTeshia Thomas-Seaton, Saadia Khizer, Jonathan Staben, Tatiana Beresnev, Maryam Jahromi, Mary A. Marovich, Julia Hutter, Martha Nason, Julie Ledgerwood, John Mascola, Mark Leibowitz, Fernanda Morales, Mike Delgado, Rosario Sanchez, Norma Vega, Germán Áñez, Gary Albert, Erin Coston, Chinar Desai, Haoua Dunbar, Mark Eickhoff, Jenina Garcia, Margaret Kautz, Angela Lee, Maggie Lewis, Alice McGarry, Irene McKnight, Joy Nelson, Patrick Newingham, Patty Price-Abbott, Patty Reed, Diana Vegas, Bethanie Wilkinson, Katherine Smith, Wayne Woo, Iksung Cho, Gregory M. Glenn, Filip Dubovsky, David L. Fried, Lynne A. Haughey, Ariana C. Stanton, Lisa Stevens Rameaka, David Rosenberg, Lee Tomatsu, Viviana Gonzalez, Millie Manalo, Bernard Grunstra, Donald Quinn, Phillip Claybrook, Shelby Olds, Amy Dye, Kevin D. Cannon, Mesha M. Chadwick, Bailey Jordan, Morgan Hussey, Hannah Nevarez, Colleen F. Kelley, Michael Chung, Caitlin Moran, Paulina Rebolledo, Christina Bacher, Elizabeth Barranco-Santana, Jessica Rodriguez, Rafael Mendoza, Karen Ruperto, Odette Olivieri, Enrique Ocaña, Paul E. Wylie, Renea Henderson, Natasa Jenson, Fan Yang, Amy Kelley, Kenneth Finkelstein, David Beckmann, Tanya Hutchins, Sebastian Garcia Escallon, Kristen Johnson, Teresa S. Sligh, Parul Desai, Vincent Huynh, Carlos Lopez, Erika Mendoza, Jeffrey Adelglass, Jerome G. Naifeh, Kristine J. Kucera, Waseem Chughtai, Shireen H. Jaffer, Matthew G. Davis, Jennifer Foley, Michelle L. Burgett, Tammi L. Shlotzhauer, Sarah M. Ingalsbe-Geno, Daniel Duncanson, Kelly Kush, Lori Nesbitt, Cora Sonnier, Jennifer McCarter, Michael B. Butcher, James Fry, Donna Percy, Karen Freudemann, Bruce C. Gebhardt, Padma N. Mangu, Debra B. Schroeck, Rajesh K. Davit, Gayle D. Hennekes, Benjamin J. Luft, Melissa Carr, Sharon Nachman, Alison Pellecchia, Candace Smith, Bruno Valenti, Maria I. Bermudez, Noris Peraita, Ernesto Delgado, Alicia Arrazcaeta, Natalie Ramirez, Carmen Amador, Horacio Marafioti, Lyly Dang, Lauren Clement, Jennifer Berry, Mohammed Allaw, Georgettea Geuss, Chelsea Miles, Zachary Bittner, Melody Werne, Cornell Calinescu, Shannon Rodman, Joshua Rindt, Erin Cooksey, Kristina Harrison, Deanna Cooper, Manisha Horton, Amanda Philyaw, William Jennings, Hilario Alvarado, Michele Baka, Malina Regalado, Linda Murray, Sherif Naguib, Justin Singletary, Sha-Wanda Richmond, Sarah Omodele, Emily Oppenheim, Reuben Martinez, Victoria Andriulis, Leonard Singer, Jeanne Blevins, Meagan Thomas, Christine Hull, Isabel Pereira, Gina Rivero, Tracy Okonya, Frances Downing, Paulina Miller, Margaret Rhee, Katherine Stapleton, Jeffrey Klein, Rosamond Hong, Suzanne Swan, Tami Wahlin, Elizabeth Bennett, Amy Salzl, Sharine Phan, Jewel J. White, Amanda Occhino, Ruth Paiano, Morgan McLaughlin, Elisa Swieboda, Veronica Garcia-Fragoso, Maria G. Becerra, Toni White, Christine B. Turley, Andrew McWilliams, Tiffany Esinhart, Natasha Montoya, Shamika Huskey, Leena Paul, Karen Tashima, Jennie Johnson, Marguerite Neill, Martha Sanchez, Natasha Rybak, Maria Mileno, Stuart H. Cohen, Monica Ruiz, Dean M. Boswell, Elizabeth E. Robison, Trina L. Reynolds, Sonja Neumeister, Carmen D. Zorrilla, Juana Rivera, Jessica Ibarra, Iris García, Dianca Sierra, Wanda Ramon, Suzanne Fiorillo, Rebecca Pitotti, Victoria R. Anderson, Jose Castillo Mancilla, Nga Le, Patricia L. Winokur, Dilek Ince, Theresa Hegmann, Jeffrey Meier, Jack Stapleton, Laura Stulken, Monica McArthur, Andrea Berry, Milagritos Tapia, Elizabeth Hammershaimb, Toni Robinson, Rosa MacBryde, Susan Kline, Joanne L. Billings, Winston Cavert, Les B. Forgosh, Timothy W. Schacker, Tyler D. Bold, Dima Dandachi, Taylor Nelson, Andres Bran, Grant Geiger, S. Hasan Naqvi, Diana F. Florescu, Richard Starlin, David Kline, Andrea Zimmer, Anum Abbas, Natasha Wilson, Joseph J. Eron, Michael Sciaudone, A. Lina Rosengren, John S. Kizer, Sarah E. Rutstein, Elizabeth Bruce, Claudia Espinosa, Lisa J. Sanders, Kami Kim, Denise Casey, Barbara S. Taylor, Thomas Patterson, Ruth S. Pinilla, Delia Bullock, Philip Ponce, Jan Patterson, R. Scott McClelland, Dakotah C. Lane, Anna Wald, Frank James, Elizabeth Duke, Kirsten Hauge, Jessica Heimonen, Erin A. Goecker, Youyi Fong, Carol Kauffman, Kathleen Linder, Kimberly Nofz, Andrew McConnell, Robert J. Buynak, Angella Webb, Taryn Petty, Stephanie Andree, Erica Sanchez, Nolan Mackey, Clarisse Baudelaire, Sarah Dzigiel, Adrienna Marquez, Kim Quillin, Michelle King, Vanessa Abad, Jennifer Knowles, Michael Waters, Karla Zepeda, Jordan Coslet, Dalia Tovar, Marian E. Shaw, Mark A. Turner, Cory J. Huffine, Esther S. Huffine, Julie A. Ake, Elizabeth Secord, Eric McGrath, Phillip Levy, Brittany Stewart, Charnell Cromer, Ayanna Walters, Grant Ellsworth, Caroline Greene, Sarah Galloway, Shashi Kapadia, Elliot DeHaan, Clint Wilson, Jason Milligan, Danielle Raley, Joseph Bocchini, Bruce McClenathan, Mary Hussain, Evelyn Lomasney, Evelyn Hall, Sherry Lamberth, Christy Schmeck, Vickie Leathers, Deborah A. Theodore, Angela R. Branche, Daniel S. Graciaa, Timothy J. Hatlen, Jacqueline Miller, Jerald Sadoff, Ann R. Falsey, and Magdalena E. Sobieszczyk

Subjects
COVID-19, Natural infection, Hybrid immunity, Vaccination, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

Published
2023
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8. Distinct blood inflammatory biomarker clusters stratify host phenotypes during the middle phase of COVID-19

Author

Paul W. Blair, Joost Brandsma, Josh Chenoweth, Stephanie A. Richard, Nusrat J. Epsi, Rittal Mehta, Deborah Striegel, Emily G. Clemens, Sultanah Alharthi, David A. Lindholm, Ryan C. Maves, Derek T. Larson, Katrin Mende, Rhonda E. Colombo, Anuradha Ganesan, Tahaniyat Lalani, Christopher J. Colombo, Allison A. Malloy, Andrew L. Snow, Kevin L. Schully, Charlotte Lanteri, Mark P. Simons, John S. Dumler, David Tribble, Timothy Burgess, Simon Pollett, Brian K. Agan, Danielle V. Clark, and the EPICC COVID-19 Cohort Study Group

Subjects
Medicine, Science
Abstract

Abstract The associations between clinical phenotypes of coronavirus disease 2019 (COVID-19) and the host inflammatory response during the transition from peak illness to convalescence are not yet well understood. Blood plasma samples were collected from 129 adult SARS-CoV-2 positive inpatient and outpatient participants between April 2020 and January 2021, in a multi-center prospective cohort study at 8 military hospitals across the United States. Plasma inflammatory protein biomarkers were measured in samples from 15 to 28 days post symptom onset. Topological Data Analysis (TDA) was used to identify patterns of inflammation, and associations with peak severity (outpatient, hospitalized, ICU admission or death), Charlson Comorbidity Index (CCI), and body mass index (BMI) were evaluated using logistic regression. The study population (n = 129, 33.3% female, median 41.3 years of age) included 77 outpatient, 31 inpatient, 16 ICU-level, and 5 fatal cases. Three distinct inflammatory biomarker clusters were identified and were associated with significant differences in peak disease severity (p

Published
2022
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9. Coccidioidomycosis Seroincidence and Risk among Military Personnel, Naval Air Station Lemoore, San Joaquin Valley, California, USA

Author

Graham C. Ellis, Charlotte A. Lanteri, Hsing-Chuan Hsieh, Paul C.F. Graf, Gabriel Pineda, Nancy F. Crum-Cianflone, Catherine M. Berjohn, Terrel Sanders, Ryan C. Maves, and Robert Deiss

Subjects
coccidioidomycosis, Coccidioides, infections, endemic diseases, lung disease, fungi, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

We conducted a retrospective cohort study that tested 2,000 US military personnel for Coccidioides antibodies in a disease-endemic region. The overall incidence of seroconversion was 0.5 cases/100 person-years; 12.5% of persons who seroconverted had illnesses requiring medical care. No significant association was found between demographic characteristics and seroconversion or disease.

Published
2022
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10. Clinical factors and outcomes associated with immune non-response among virally suppressed adults with HIV from Africa and the United States

Author

Adi Noiman, Allahna Esber, Xun Wang, Emmanuel Bahemana, Yakubu Adamu, Michael Iroezindu, Francis Kiweewa, Jonah Maswai, John Owuoth, Lucas Maganga, Anuradha Ganesan, Ryan C. Maves, Tahaniyat Lalani, Rhonda E. Colombo, Jason F. Okulicz, Christina Polyak, Trevor A. Crowell, Julie A. Ake, and Brian K. Agan

Subjects
Medicine, Science
Abstract

Abstract A significant minority of people living with HIV (PLWH) achieve viral suppression (VS) on antiretroviral therapy (ART) but do not regain healthy CD4 counts. Clinical factors affecting this immune non-response (INR) and its effect on incident serious non-AIDS events (SNAEs) have been challenging to understand due to confounders that are difficult to control in many study settings. The U.S. Military HIV Natural History Study (NHS) and African Cohort Study (AFRICOS). PLWH with sustained VS (

Published
2022
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11. A machine learning approach identifies distinct early-symptom cluster phenotypes which correlate with hospitalization, failure to return to activities, and prolonged COVID-19 symptoms

Author

Nusrat J. Epsi, John H. Powers, David A. Lindholm, Katrin Mende, Allison Malloy, Anuradha Ganesan, Nikhil Huprikar, Tahaniyat Lalani, Alfred Smith, Rupal M. Mody, Milissa U. Jones, Samantha E. Bazan, Rhonda E. Colombo, Christopher J. Colombo, Evan C. Ewers, Derek T. Larson, Catherine M. Berjohn, Carlos J. Maldonado, Paul W. Blair, Josh Chenoweth, David L. Saunders, Jeffrey Livezey, Ryan C. Maves, Margaret Sanchez Edwards, Julia S. Rozman, Mark P. Simons, David R. Tribble, Brian K. Agan, Timothy H. Burgess, Simon D. Pollett, and for the EPICC COVID-19 Cohort Study Group

Subjects
Medicine, Science
Abstract

Background Accurate COVID-19 prognosis is a critical aspect of acute and long-term clinical management. We identified discrete clusters of early stage-symptoms which may delineate groups with distinct disease severity phenotypes, including risk of developing long-term symptoms and associated inflammatory profiles. Methods 1,273 SARS-CoV-2 positive U.S. Military Health System beneficiaries with quantitative symptom scores (FLU-PRO Plus) were included in this analysis. We employed machine-learning approaches to identify symptom clusters and compared risk of hospitalization, long-term symptoms, as well as peak CRP and IL-6 concentrations. Results We identified three distinct clusters of participants based on their FLU-PRO Plus symptoms: cluster 1 (“Nasal cluster”) is highly correlated with reporting runny/stuffy nose and sneezing, cluster 2 (“Sensory cluster”) is highly correlated with loss of smell or taste, and cluster 3 (“Respiratory/Systemic cluster”) is highly correlated with the respiratory (cough, trouble breathing, among others) and systemic (body aches, chills, among others) domain symptoms. Participants in the Respiratory/Systemic cluster were twice as likely as those in the Nasal cluster to have been hospitalized, and 1.5 times as likely to report that they had not returned-to-activities, which remained significant after controlling for confounding covariates (P < 0.01). Respiratory/Systemic and Sensory clusters were more likely to have symptoms at six-months post-symptom-onset (P = 0.03). We observed higher peak CRP and IL-6 in the Respiratory/Systemic cluster (P < 0.01). Conclusions We identified early symptom profiles potentially associated with hospitalization, return-to-activities, long-term symptoms, and inflammatory profiles. These findings may assist in patient prognosis, including prediction of long COVID risk.

Published
2023

12. ICU Resource Limitations During Peak Seasonal Influenza: Results of a 2018 National Feasibility Study

Author

Christianne Joy Lane, PhD, Manas Bhatnagar, MS, Karen Lutrick, PhD, Ryan C. Maves, MD, Debra Weiner, MD, PhD, Daisy Rios Olvera, BA, Timothy M. Uyeki, MD, MPH, MPP, J. Perren Cobb, MD, Joan C. Brown, EdD, MBA, CCE, and for the Discovery Program Resilience and Emergency Preparedness (Discovery PREP)

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. Demonstrate the feasibility of weekly data collection and analysis of public health emergency (PHE) data. Assess fluctuations in, and challenges of, resource matching and potential effect on patient care for influenza in ICUs. DESIGN:. Multicenter prospective noninterventional study testing effectiveness of leveraging the Discovery Critical Care Research Network Program for Resilience and Emergency Preparedness (Discovery-PREP) in performing PHE research. A 20-question internet survey was developed to prospectively assess ICU influenza-related resource stress. An informatics tool was designed to track responses; data were analyzed within 24 hours of weekly survey completion by the team biostatistician for timely reporting. PARTICIPANTS:. Critical care and Emergency Medicine Discovery-PREP network investigators self-selected to participate in the voluntary query. SETTING:. ICUs of 13 hospitals throughout the United States, 12 academic, and one community. INTERVENTIONS:. ICU physicians were electronically surveyed weekly over 17 weeks during the influenza season (January 2018–April 2018). Responses were collected for 48 hours after each email query. MEASUREMENTS AND MAIN RESULTS:. The average weekly response among the sites was 79% (range, 65–100%). Significant stress, defined as alterations in ICU staffing and/or resource allocation, occurred in up to 41% of sites during the national peak of influenza activity. These alterations included changes in staffing, not accepting external patient transfers, and canceling elective surgery. During this same period, up to 17% of the sites indicated that these changes might not have been sufficient to prevent potentially avoidable patient harm. CONCLUSIONS:. This novel approach to querying ICU operational stress indicated that almost half of participating sites experienced critical care resource limitations during peak influenza season and required process and/or staffing changes to better balance resources with patient care demands. This weekly national reporting infrastructure could be adapted and expanded to better inform providers, hospital emergency management teams, and government leaders during PHEs.

Published
2022
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13. Performance Analysis of the National Early Warning Score and Modified Early Warning Score in the Adaptive COVID-19 Treatment Trial Cohort

Author

Christopher J. Colombo, MD, MA, FACP, FCCM, Rhonda E. Colombo, MD, MHS, FACP, FIDSA, Ryan C. Maves, MD, FCCM, FCCP, FIDSA, Angela R. Branche, MD, Stuart H. Cohen, MD, Marie-Carmelle Elie, MD, Sarah L. George, MD, Hannah J. Jang, PhD, RN, CNL, PHN, Andre C. Kalil, MD, MPH, David A. Lindholm, MD, FACP, Richard A. Mularski, MD, MSHS, MCR, ATSF, FCCP, FACP, Justin R. Ortiz, MD, MS, FACP, FCCP, Victor Tapson, MD, C. Jason Liang, PhD, On behalf of the ACTT-1 Study Group, Aneesh K. Mehta, Nadine G. Rouphael, Jessica J. Traenkner, Valeria D Cantos, Ghina Alaaeddine, Barry S. Zingman, Robert Grossberg, Paul F. Riska, Elizabeth Hohmann, Mariam Torres-Soto, Nikolaus Jilg, Helen Y. Chu, Anna Wald, Margaret Green, Annie Luetkemeyer, Pierre-Cedric B. Crouch, Hannah Jang, Susan Kline, Joanne Billings, Brooke Noren, Diego Lopez de Castilla, Jason W. Van Winkle, Francis X. Riedo, Robert W. Finberg, Jennifer P. Wang, Mireya Wessolossky, Kerry Dierberg, Benjamin Eckhardt, Henry J Neumann, Victor Tapson, Jonathan Grein, Fayyaz Sutterwala, Lanny Hsieh, Alpesh N. Amin, Thomas F. Patterson, Heta Javeri, Trung Vu, Roger Paredes, Lourdes Mateu, Daniel A. Sweeney, Constance A. Benson, Farhana Ali, William R. Short, Pablo Tebas, Jessie Torgersen, Giota Touloumi, Vicky Gioukari, David Chien Lye, Sean WX Ong, Norio Ohmagari, Ayako Mikami, Gerd Fätkenheuer, Jakob J. Malin, Philipp Koehler, Andre C. Kalil, LuAnn Larson, Angela Hewlett, Mark G. Kortepeter, C. Buddy Creech, Isaac Thomsen, Todd W. Rice, Babafemi Taiwo, Karen Krueger, Stuart H. Cohen, George R. Thompson, 3rd, Cameron Wolfe, Emmanuel B. Walter, Maria Frank, Heather Young, Ann R. Falsey, Angela R. Branche, Paul Goepfert, Nathaniel Erdmann, Otto O. Yang, Jenny Ahn, Anna Goodman, Blair Merrick, Richard M. Novak, Andrea Wendrow, Henry Arguinchona, Christa Arguinchona, Sarah L. George, Janice Tennant, Robert L. Atmar, Hana M. El Sahly, Jennifer Whitaker, D. Ashley Price, Christopher J. A. Duncan, Simeon Metallidis, Theofilos Chrysanthidis, F. McLellan, Myoung-don Oh, Wan Beom Park, Eu Suk Kim, Jongtak Jung, Justin R. Ortiz, Karen L. Kotloff, Brian Angus, Jack David Germain Seymour, Noreen A. Hynes, Lauren M. Sauer, Neera Ahuja, Kari Nadeau, Patrick E. H. Jackson, Taison D. Bell, Anastasia Antoniadou, Konstantinos Protopapas, Richard T Davey, Jocelyn D. Voell, Jose Muñoz, Montserrat Roldan, Ioannis Kalomenidis, Spyros G. Zakynthinos, Catharine I. Paules, Fiona McGill, Jane Minton, Nikolaos Koulouris, Zafeiria Barmparessou, Edwin Swiatlo, Kyle Widmer, Nikhil Huprikar, Anuradha Ganesan, Guillermo M. Ruiz-Palacios, Alfredo Ponce de León, Sandra Rajme, Justino Regalado Pineda, José Arturo Martinez-Orozco, Mark Holodniy, Aarthi Chary, Timo Wolf, Christoph Stephan, Jan-Christian Wasmuth, Christoph Boesecke, Martin Llewelyn, Barbara Philips, Christopher J. Colombo, Rhonda E. Colombo, David A. Lindholm, Katrin Mende, Tida Lee, Tahaniyat Lalani, Ryan C. Maves, Gregory C. Utz, Jens Lundgren, Marie Helleberg, Jan Gerstoft, Thomas Benfield, Tomas Jensen, Birgitte Lindegaard, Lothar Weise, Lene Knudsen, Isik Johansen, Lone W Madsen, Lars Østergaard, Nina Stærke, Henrik Nielsen, Timothy H. Burgess, Michelle Green, Mat Makowski, Jennifer L. Ferreira, Michael R. Wierzbicki, Tyler Bonnett, Nikki Gettinger, Theresa Engel, Jing Wang, John H. Beigel, Kay M. Tomashek, Seema Nayak, Lori E. Dodd, Walla Dempsey, Effie Nomicos, Marina Lee, Peter Wolff, Rhonda PikaartTautges, Mohamed Elsafy, Robert Jurao, Hyung Koo, Michael Proschan, Dean Follmann, and H. Clifford Lane

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. We sought to validate prognostic scores in coronavirus disease 2019 including National Early Warning Score, Modified Early Warning Score, and age-based modifications, and define their performance characteristics. DESIGN:. We analyzed prospectively collected data from the Adaptive COVID-19 Treatment Trial. National Early Warning Score was collected daily during the trial, Modified Early Warning Score was calculated, and age applied to both scores. We assessed prognostic value for the end points of recovery, mechanical ventilation, and death for score at enrollment, average, and slope of score over the first 48 hours. SETTING:. A multisite international inpatient trial. PATIENTS:. A total of 1,062 adult nonpregnant inpatients with severe coronavirus disease 2019 pneumonia. INTERVENTIONS:. Adaptive COVID-19 Treatment Trial 1 randomized participants to receive remdesivir or placebo. The prognostic value of predictive scores was evaluated in both groups separately to assess for differential performance in the setting of remdesivir treatment. MEASUREMENTS AND MAIN RESULTS:. For mortality, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.60–0.68), and improved with addition of age (c-index, 0.66–0.74). For recovery, baseline National Early Warning Score and Modified Early Warning Score demonstrated somewhat better prognostic ability (c-index, 0.65–0.69); however, National Early Warning Score+age and Modified Early Warning Score+age further improved performance (c-index, 0.68–0.71). For deterioration, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.59–0.69) and improved with addition of age (c-index, 0.63–0.70). All prognostic performance improvements due to addition of age were significant (p < 0.05). CONCLUSIONS:. In the Adaptive COVID-19 Treatment Trial 1 cohort, National Early Warning Score and Modified Early Warning Score demonstrated moderate prognostic performance in patients with severe coronavirus disease 2019, with improvement in predictive ability for National Early Warning Score+age and Modified Early Warning Score+age. Area under receiver operating curve for National Early Warning Score and Modified Early Warning Score improved in patients receiving remdesivir versus placebo early in the pandemic for recovery and mortality. Although these scores are simple and readily obtainable in myriad settings, in our data set, they were insufficiently predictive to completely replace clinical judgment in coronavirus disease 2019 and may serve best as an adjunct to triage, disposition, and resourcing decisions.

Published
2021
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14. Volume Resuscitation and Progression to Organ Failure in Shiga Toxin-Producing Escherichia coli Infection in Adults

Author

Charles G. Volk, MD, Paul M. Cusmano, DO, Richard J. Bower, MD, Terrel Sanders, MD, and Ryan C. Maves, MD

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. Shiga toxin-producing Escherichia coli infection is associated with dysentery and the hemolytic uremic syndrome, marked by the triad of microangiopathic hemolytic anemia, acute kidney failure, and thrombocytopenia. Descriptions of Shiga toxin-producing Escherichia coli outbreaks causing hemolytic uremic syndrome in adults are sparse, and management strategies are largely adapted from pediatric literature where aggressive fluid administration is recommended. However, these may not be ideal for adults. DESIGN:. We present a case series of an Shiga toxin-producing Escherichia coli outbreak in U.S. Marine Corps recruits. SETTING:. We review the clinical course, laboratory data, and fluid resuscitation used in hospitalized patients during the 2017 Shiga toxin-producing Escherichia coli outbreak at Marine Corps Recruit Depot, San Diego. PATIENTS:. Patients admitted to the hospital for complications from Shiga toxin-producing Escherichia coli infection. All were previously healthy men between the ages of 17 and 20 years. INTERVENTIONS:. Isotonic crystalloid fluid resuscitation during the first 72 hours. MEASUREMENTS AND MAIN RESULTS:. Of 244 identified cases of Shiga toxin-producing Escherichia coli infection, 30 required hospitalization, 15 progressed to hemolytic uremic syndrome, and five required hemodialysis. Patients were admitted and given aggressive IV fluid hydration. Those who progressed to hemolytic uremic syndrome received on average 8.4 L of isotonic crystalloid over the initial 72 hours, with up to 18% of body weight delivered. The six critically ill patients received a mean 12.2 L in the first 72 hours. Those who did not progress to hemolytic uremic syndrome received a mean 3.0 L of crystalloid. If oligoanuria developed, a net-even fluid balance was maintained. The amount of volume infused was not associated with improved outcomes. The patients with the highest fluid balance totals more often required dialysis than those who received less fluid. One hemolytic uremic syndrome patient developed flash pulmonary edema. CONCLUSIONS:. The aggressive IV hydration protocols (as a percentage of body weight) in the pediatric literature may not be applicable to adults diagnosed with hemolytic uremic syndrome. A more conservative fluid strategy in adults with hemolytic uremic syndrome merits further investigation.

Published
2021
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15. Hemoptysis Associated with Leptospirosis Acquired in Hawaii, USA

Author

Christopher A. DuPlessis, Marvin J. Sklar, Ryan C. Maves, Anne Spichler, Braden Hale, Mark Johnson, Mary Bavaro, and Joseph M. Vinetz

Subjects
leptospirosis, hemoptysis, bacteria, Hawaii, severe pulmonary hemorrhagic syndrome, SPHS, Medicine, Infectious and parasitic diseases, RC109-216
Published
2011
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16. Multibacillary Leprosy in an Active Duty Military Member

Author

Catherine M. Berjohn, Christopher A. DuPlessis, Kathy Tieu, and Ryan C. Maves

Subjects
leprosy, Hansen disease, multibacillary leprosy, Mycobacterium leprae, bacteria, tuberculosis and other mycobacteria, Medicine, Infectious and parasitic diseases, RC109-216
Published
2015
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19. Temporal Improvements in COVID-19 Outcomes for Hospitalized Adults: A Post Hoc Observational Study of Remdesivir Group Participants in the Adaptive COVID-19 Treatment Trial

Author

Gail E. Potter, Tyler Bonnett, Kevin Rubenstein, David A. Lindholm, Rekha R. Rapaka, Sarah B. Doernberg, David C. Lye, Richard A. Mularski, Noreen A. Hynes, Susan Kline, Catharine I. Paules, Cameron R. Wolfe, Maria G. Frank, Nadine G. Rouphael, Gregory A. Deye, Daniel A. Sweeney, Rhonda E. Colombo, Richard T. Davey, Aneesh K. Mehta, Jennifer A. Whitaker, Jose G. Castro, Alpesh N. Amin, Christopher J. Colombo, Corri B. Levine, Mamta K. Jain, Ryan C. Maves, Vincent C. Marconi, Robert Grossberg, Sameh Hozayen, Timothy H. Burgess, Robert L. Atmar, Anuradha Ganesan, Carlos A. Gomez, Constance A. Benson, Diego Lopez de Castilla, Neera Ahuja, Sarah L. George, Seema U. Nayak, Stuart H. Cohen, Tahaniyat Lalani, William R. Short, Nathaniel Erdmann, Kay M. Tomashek, and Pablo Tebas

Subjects
Adult, Prevention, Clinical Trials and Supportive Activities, Rehabilitation, Evaluation of treatments and therapeutic interventions, General Medicine, Antiviral Agents, Medical and Health Sciences, Dexamethasone, COVID-19 Drug Treatment, Phase III as Topic, Treatment Outcome, Good Health and Well Being, Clinical Trials, Phase III as Topic, Double-Blind Method, Clinical Research, 6.1 Pharmaceuticals, General & Internal Medicine, Complementary and Integrative Health, Internal Medicine, Humans, Clinical Trials, Randomized Controlled Trials as Topic
Abstract

BackgroundThe COVID-19 standard of care (SOC) evolved rapidly during 2020 and 2021, but its cumulative effect over time is unclear.ObjectiveTo evaluate whether recovery and mortality improved as SOC evolved, using data from ACTT (Adaptive COVID-19 Treatment Trial).DesignACTT is a series of phase 3, randomized, double-blind, placebo-controlled trials that evaluated COVID-19 therapeutics from February 2020 through May 2021. ACTT-1 compared remdesivir plus SOC to placebo plus SOC, and in ACTT-2 and ACTT-3, remdesivir plus SOC was the control group. This post hoc analysis compared recovery and mortality between these comparable sequential cohorts of patients who received remdesivir plus SOC, adjusting for baseline characteristics with propensity score weighting. The analysis was repeated for participants in ACTT-3 and ACTT-4 who received remdesivir plus dexamethasone plus SOC. Trends in SOC that could explain outcome improvements were analyzed. (ClinicalTrials.gov: NCT04280705 [ACTT-1], NCT04401579 [ACTT-2], NCT04492475 [ACTT-3], and NCT04640168 [ACTT-4]).Setting94 hospitals in 10 countries (86% U.S. participants).ParticipantsAdults hospitalized with COVID-19.InterventionSOC.Measurements28-day mortality and recovery.ResultsAlthough outcomes were better in ACTT-2 than in ACTT-1, adjusted hazard ratios (HRs) were close to 1 (HR for recovery, 1.04 [95% CI, 0.92 to 1.17]; HR for mortality, 0.90 [CI, 0.56 to 1.40]). Comparable patients were less likely to be intubated in ACTT-2 than in ACTT-1 (odds ratio, 0.75 [CI, 0.53 to 0.97]), and hydroxychloroquine use decreased. Outcomes improved from ACTT-2 to ACTT-3 (HR for recovery, 1.43 [CI, 1.24 to 1.64]; HR for mortality, 0.45 [CI, 0.21 to 0.97]). Potential explanatory factors (SOC trends, case surges, and variant trends) were similar between ACTT-2 and ACTT-3, except for increased dexamethasone use (11% to 77%). Outcomes were similar in ACTT-3 and ACTT-4. Antibiotic use decreased gradually across all stages.LimitationUnmeasured confounding.ConclusionChanges in patient composition explained improved outcomes from ACTT-1 to ACTT-2 but not from ACTT-2 to ACTT-3, suggesting improved SOC. These results support excluding nonconcurrent controls from analysis of platform trials in rapidly changing therapeutic areas.Primary funding sourceNational Institute of Allergy and Infectious Diseases.

Published
2022

20. Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial

Author

Cameron R Wolfe, Kay M Tomashek, Thomas F Patterson, Carlos A Gomez, Vincent C Marconi, Mamta K Jain, Otto O Yang, Catharine I Paules, Guillermo M Ruiz Palacios, Robert Grossberg, Michelle S Harkins, Richard A Mularski, Nathaniel Erdmann, Uriel Sandkovsky, Eyad Almasri, Justino Regalado Pineda, Alexandra W Dretler, Diego Lopez de Castilla, Angela R Branche, Pauline K Park, Aneesh K Mehta, William R Short, Susan L F McLellan, Susan Kline, Nicole M Iovine, Hana M El Sahly, Sarah B Doernberg, Myoung-don Oh, Nikhil Huprikar, Elizabeth Hohmann, Colleen F Kelley, Mark Holodniy, Eu Suk Kim, Daniel A Sweeney, Robert W Finberg, Kevin A Grimes, Ryan C Maves, Emily R Ko, John J Engemann, Barbara S Taylor, Philip O Ponce, LuAnn Larson, Dante Paolo Melendez, Allan M Seibert, Nadine G Rouphael, Joslyn Strebe, Jesse L Clark, Kathleen G Julian, Alfredo Ponce de Leon, Anabela Cardoso, Stephanie de Bono, Robert L Atmar, Anuradha Ganesan, Jennifer L Ferreira, Michelle Green, Mat Makowski, Tyler Bonnett, Tatiana Beresnev, Varduhi Ghazaryan, Walla Dempsey, Seema U Nayak, Lori E Dodd, John H Beigel, Andre C Kalil, Lana Wahid, Emmanuel B. Walter, Akhila G. Belur, Grace Dreyer, Jan E. Patterson, Jason E. Bowling, Danielle O. Dixon, Angela Hewlett, Robert Odrobina, Jakrapun Pupaibool, Satish Mocherla, Suzana Lazarte, Meilani Cayabyab, Rezhan H. Hussein, Reshma R. Golamari, Kaleigh L. Krill, Sandra Rajme, Paul F. Riska, Barry S. Zingman, Gregory Mertz, Nestor Sosa, Paul A. Goepfert, Mezgebe Berhe, Emma Dishner, Mohamed Fayed, Kinsley Hubel, José Arturo Martinez-Orozco, Nora Bautista Felix, Sammy T. Elmor, Amer Ryan Bechnak, Youssef Saklawi, Jason W. Van Winkle, Diego F. Zea, Maryrose Laguio-Vila, Edward E. Walsh, Ann R. Falsey, Karen Carvajal, Robert C. Hyzy, Sinan Hanna, Norman Olbrich, Jessica J. Traenkner, Colleen S. Kraft, Pablo Tebas, Jillian T Baron, Corri Levine, Joy Nock, Joanne Billings, Hyun Kim, Marie-Carmelle Elie-Turenne, Jennifer A. Whitaker, Anne F. Luetkemeyer, Jay Dwyer, Emma Bainbridge, Pyoeng Gyun Choe, Chang Kyung Kang, Nikolaus Jilg, Valeria D Cantos, Divya R. Bhamidipati, Srinivasa Nithin Gopalsamy, Aarthi Chary, Jongtak Jung, Kyoung-Ho Song, Hong Bin Kim, Constance A. Benson, Kimberly McConnell, Jennifer P. Wang, Mireya Wessolossky, Katherine Perez, Taryn A Eubank, Catherine Berjohn, Gregory C. Utz, Patrick E.H. Jackson, Taison D. Bell, Heather M. Haughey, Abeer Moanna, Sushma Cribbs, Telisha Harrison, Christopher J. Colombo, Christina Schofield, Rhonda E. Colombo, Victor F. Tapson, Jonathan Grein, Fayyaz Sutterwala, Dilek Ince, Patricia L. Winokur, Monica Fung, Hannah Jang, David Wyles, Maria G. Frank, Ellen Sarcone, Henry Neumann, Anand Viswanathan, Sarah Hochman, Mark Mulligan, Benjamin Eckhardt, Ellie Carmody, Neera Ahuja, Kari Nadeau, David Svec, Jeffrey C. Macaraeg, Lee Morrow, Dave Quimby, Mary Bessesen, Lindsay Nicholson, Jill Adams, Princy Kumar, Allison A. Lambert, Henry Arguinchona, Radica Z. Alicic, Sho Saito, Norio Ohmagari, Ayako Mikami, David Chien Lye, Tau Hong Lee, Po Ying Chia, Lanny Hsieh, Alpesh N. Amin, Miki Watanabe, Keith A. Candiotti, Jose G. Castro, Maria A. Antor, Tida Lee, Tahaniyat Lalani, Richard M. Novak, Andrea Wendrow, Scott A. Borgetti, Sarah L. George, Daniel F. Hoft, James D. Brien, Stuart H. Cohen, George R. Thompson, Melony Chakrabarty, Faheem Guirgis, Richard T. Davey, Jocelyn Voell, Jeffrey R. Strich, David A. Lindholm, Katrin Mende, Trevor R. Wellington, Rekha R. Rapaka, Jennifer S. Husson, Andrea R. Levine, Seow Yen Tan, Humaira Shafi, Jaime M F Chien, David C. Hostler, Jordanna M. Hostler, Brian T. Shahan, David H. Adams, Anu Osinusi, Huyen Cao, Timothy H. Burgess, Julia Rozman, Kevin K. Chung, Christina Nieuwoudt, Jill A. El-Khorazaty, Heather Hill, Stephanie Pettibone, Nikki Gettinger, Theresa Engel, Teri Lewis, Jing Wang, Gregory A. Deye, Effie Nomicos, Rhonda Pikaart-Tautges, Mohamed Elsafy, Robert Jurao, Hyung Koo, Michael Proschan, Tammy Yokum, Janice Arega, and Ruth Florese

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, ACTT-4 Study Group, Adolescent, Clinical Trials and Supportive Activities, Clinical Sciences, Dexamethasone, Double-Blind Method, Clinical Research, Humans, Lung, Sulfonamides, Other Medical and Health Sciences, SARS-CoV-2, Prevention, Evaluation of treatments and therapeutic interventions, Middle Aged, COVID-19 Drug Treatment, Oxygen, Good Health and Well Being, Treatment Outcome, Purines, 6.1 Pharmaceuticals, Public Health and Health Services, Azetidines, Pyrazoles, Female
Abstract

BackgroundBaricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19.MethodsIn this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168.FindingsBetween Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012).InterpretationIn hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered.FundingNational Institute of Allergy and Infectious Diseases.

Published
2022

21. Management Principles for the Cardiac Catheterization Laboratory During the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Pandemic

Author

Keshav R, Nayak, Ryan C, Maves, and Timothy D, Henry

Subjects
Cardiac Catheterization, SARS-CoV-2, Myocardial Infarction, COVID-19, Humans, Cardiology and Cardiovascular Medicine, Pandemics
Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious pathogen resulting in the 2019 coronavirus disease (COVID-19) pandemic with direct impact on cardiac catheterization laboratory (CCL) operations. Initially, major challenges in limiting the spread of aerosolized pathogens existed until protocols were implemented to limit infectivity to staff and patients. COVID-19 increases the risk of myocardial infarctions and cardiogenic shock requiring acute management in the CCL. In this review, we specify best practices in the CCL for the management of infected patients in the preprocedure, intraprocedure, and postprocedure environments harmonizing available evidence, recommendations from international heart associations, and consensus opinion.

Published
2022

22. Critical COVID-19 disease explained by type I interferon autoantibodies found in patients within the Military Health System.

Author

Preventive Medicine and Biostatistics (PMB), SOM, Maria Leondaridis, Debra Yee, Marana Tso, Elana Shaw, Lindsey B. Rosen, Emily Samuels, Paul Bastard, Jean-Laurent Casanova, Steven M. Holland, Helen C. Su, Stephanie Richard, Katrin Mende, Tahaniyat Lalani, David Lindholm, Catherine M. Berjohn, Ryan C. Maves, Rhonda E. Colombo, Christopher J. Colombo, Derek T. Larson, Evan C. Ewers, Anuradha Ganesan, Nikhil Huprikar, Rupal M. Mody, Milissa U. Jones, Mark P Simons, David Tribble, Eric D. Laing, Brian Agan, Simon Pollett, Timothy H. Burgess, Andrew L. Snow, The EPICC Study Group, Preventive Medicine and Biostatistics (PMB), SOM, Maria Leondaridis, and Debra Yee, Marana Tso, Elana Shaw, Lindsey B. Rosen, Emily Samuels, Paul Bastard, Jean-Laurent Casanova, Steven M. Holland, Helen C. Su, Stephanie Richard, Katrin Mende, Tahaniyat Lalani, David Lindholm, Catherine M. Berjohn, Ryan C. Maves, Rhonda E. Colombo, Christopher J. Colombo, Derek T. Larson, Evan C. Ewers, Anuradha Ganesan, Nikhil Huprikar, Rupal M. Mody, Milissa U. Jones, Mark P Simons, David Tribble, Eric D. Laing, Brian Agan, Simon Pollett, Timothy H. Burgess, Andrew L. Snow, The EPICC Study Group

Abstract

Background Methods Acknowledgments Correspondence Critical COVID-19 disease explained by type I interferon autoantibodies found in patients within the Military Health System. Maria Leondaridis1, Debra Yee1, Marana Tso2, Elana Shaw3, Lindsey B. Rosen3, Emily Samuels2, Paul Bastard4,5,6, Jean-Laurent Casanova4,5,6, Steven M. Holland3, Helen C. Su3, Stephanie Richard7,8, Katrin Mende7,8,9, Tahaniyat Lalani7,8,10, David Lindholm9, Catherine M. Berjohn11, Ryan C. Maves11, Rhonda E. Colombo7,8,12, Christopher J Colombo12, Derek T. Larson13, Evan C. Ewers13, Anuradha Ganesan7,8,14, Nikhil Huprikar14, Rupal M. Mody15, Milissa U. Jones16, Mark P Simons7, David Tribble7, Eric D. Laing2, Brian Agan7,8, Simon Pollett7,8, Timothy H Burgess7, Andrew L. Snow1 & the EPICC Study Group. This work was supported by awards from the Defense Health Program (HU00012020067) and the National Institute of Allergy and Infectious Disease (HU00011920111). The protocol was executed by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed by the Uniformed Services University of the Health Sciences (USUHS) through a cooperative agreement by the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF). This project has been funded in part by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, under an interagency agreement (Y1-AI-5072). The authors declare no conflicts of interest. Results Results Neutralizing auto-antibodies (auto-Abs) that target type I interferons (IFN), a group of cytokines that induce innate immune responses upon viral infection, are found within approximately 10-20% of patients with critical COVID-19. We sought to determine if neutralizing type I IFN auto- Abs contribute to severe COVID-19 in patients within the Military Health System (MHS). The Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potent, RITM0037391, Neutralizing auto-antibodies (auto-Abs) that target type I interferons (IFN), a group of cytokines that induce innate immune responses upon viral infection, are found within approximately 10-20% of patients with critical COVID-19. We sought to determine if neutralizing type I IFN auto- Abs contribute to severe COVID-19 in patients within the Military Health System (MHS). The Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) cohort collected demographic data, clinical data and sera from SARS-CoV-2 infected patients enrolled across 10 U.S. military treatment facilities. We screened sera collected <21 days post-symptom onset from 249 COVID-19 inpatients and 312 COVID-19 outpatients for IFN auto-Ab positivity and neutralizing activity using Luminex and intracellular flow cytometry, respectively. Similar to previous reports, we detected neutralizing auto-Abs against IFN-? and/or IFN-? in a significantly higher frequency of inpatients (10 total, 4%) versus outpatients (1, 0.32%) (p=0.009). Remarkably, IFN auto- Abs persisted 6-12 months post-infection in most inpatients, including several with a history of autoimmune disease. Among inpatients, multivariate logistic regression analyses demonstrated that type I IFN auto-Abs were associated with a greater risk of severe and critical COVID-19 (adjusted odds ratio (aOR) = 3.99 and 4.69, respectively) after adjusting for age, sex and comorbidity burden. Our results confirm a robust association between critical COVID-19 and the presence of type I IFN auto-Abs, which may predispose to other severe respiratory viral infections that cause substantial morbidity and mortality in the MHS.

Published
2023

23. Baricitinib Treatment of Coronavirus Disease 2019 Is Associated With a Reduction in Secondary Infections

Author

Daniel A Sweeney, Bonifride Tuyishimire, Neera Ahuja, John H Beigel, Tatiana Beresnev, Valeria D Cantos, Jose G Castro, Stuart H Cohen, Kaitlyn Cross, Lori E Dodd, Nathan Erdmann, Monica Fung, Varduhi Ghazaryan, Sarah L George, Kevin A Grimes, Noreen A Hynes, Kathleen G Julian, Sheetal Kandiah, Hannah Jang Kim, Corri B Levine, David A Lindholm, David C Lye, Ryan C Maves, Myoung-don Oh, Catharine Paules, Rekha R Rapaka, Willam R Short, Kay M Tomashek, Cameron R Wolfe, and Andre C Kalil

Subjects
secondary infections, Good Health and Well Being, Infectious Diseases, Oncology, Clinical Research, 6.1 Pharmaceuticals, Clinical Trials and Supportive Activities, COVID-19, baricitinib, Evaluation of treatments and therapeutic interventions
Abstract

We performed a secondary analysis of the National Institutes of Health-sponsored Adaptive COVID-19 Treatment Trial (ACTT-2) randomized controlled trial and found that baricitinib was associated with a 50% reduction in secondary infections after controlling for baseline and postrandomization patient characteristics. This finding provides a novel mechanism of benefit for baricitinib and supports the safety profile of this immunomodulator for the treatment of coronavirus disease 2019.

Published
2023

24. A geopositioned, evidence-graded, pan-species compendium of Mayaro Virus occurrence

Author

Michael Celone, Alex Potter, Barbara A. Han, Sean P. Beeman, Bernard Okech, Brett Forshey, James Dunford, George Rutherford, Neida Karen Mita-Mendoza, Elizabet Lilia Estallo, Ricardo Khouri, Isadora Cristina de Siqueira, Kyle Petersen, Ryan C. Maves, Assaf Anyamba, and Simon Pollett

Abstract

Mayaro Virus (MAYV) is an emerging health threat in the Americas that can cause febrile illness as well as debilitating arthralgia or arthritis. To better understand the geographic distribution of MAYV risk, we developed a georeferenced database of MAYV occurrence based on peer-reviewed literature and unpublished reports. Here we present this compendium, which includes both point and polygon locations linked to occurrence data documented from its discovery in 1954 until 2022. We describe all methods used to develop the database including data collection, georeferencing, management and quality-control. We also describe a customized grading system used to assess the quality of each study included in our review. The result is a comprehensive, evidence-graded database of confirmed MAYV occurrence in humans, non-human animals, and arthropods to-date, containing 266 geo-positioned occurrences in total. This database - which can be updated over time - may be useful for local spill-over risk assessment, epidemiological modelling to understand key transmission dynamics and drivers of MAYV spread, as well as identification of major surveillance gaps.

Published
2023

25. Critical Care Staffing in Pandemics and Disasters

Author

Charles L. Sprung, Asha V. Devereaux, Marya Ghazipura, Lisa D. Burry, Tanzib Hossain, Mitchell T. Hamele, Ramon E. Gist, Timothy M. Dempsey, Jeffrey R. Dichter, Kiersten N. Henry, Alexander S. Niven, Timur Alptunaer, Meredith Huffines, Kasey R. Bowden, Anne Marie O. Martland, Jamie R. Felzer, Steven H. Mitchell, Pritish K. Tosh, Jason Persoff, Vikramjit Mukherjee, James Downar, Amado A. Báez, and Ryan C. Maves

Subjects
Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published
2023

26. Mass Critical Care Surge Response During COVID-19

Author

Jeffrey R. Dichter, Asha V. Devereaux, Charles L. Sprung, Vikramjit Mukherjee, Jason Persoff, Karyn D. Baum, Douglas Ornoff, Amit Uppal, Tanzib Hossain, Kiersten N. Henry, Marya Ghazipura, Kasey R. Bowden, Henry J. Feldman, Mitchell T. Hamele, Lisa D. Burry, Anne Marie O. Martland, Meredith Huffines, Pritish K. Tosh, James Downar, John L. Hick, Michael D. Christian, Ryan C. Maves, Anwar Al-Awadhi, Timur Alptunaer, Marie Baldisseri, Wanda Barfield, Joshua Benditt, Kasey Bowden, Richard Branson, Michael Christian, Guillermo Dominguez-Cherit, David Dries, Sharon Einav, Mill Etienne, Laura Evans, James Geiling, Ramon Gist, Kelly Griffin, Neil Halpern, Kiersten Henry, Attila Hertelendy, John Hick, Nathaniel Hupert, David Ingbar, Sameer S. Kadri, Sarah Kesler, Mary A. King, Niranjan Kissoon, Kristi Koenig, Joseph Lamana, Lindsay Leif, Deborah Levy, Alicia Livinsky, Christie Martin, Anne Marie Martland, Steven Mitchell, Mangala Narasimhan, Alexander Niven, Juan Ochoa, Doug Ornoff, J. Scott Parrish, Tia Powell, M.J. Reed, Dario Rodriguez, Gilbert Seda, Jaspal Singh, Julie Solar, Eric Toner, and Marian Von-Maszewski

Subjects
Pulmonary and Respiratory Medicine, Telemedicine, Surge Capacity, business.industry, Staffing, Guideline, Critical Care and Intensive Care Medicine, Triage, Nursing, Incident Command System, Interim, Intensive care, Medicine, Cardiology and Cardiovascular Medicine, business
Abstract

Background Following the publication of 2014 consensus statement regarding mass critical care during public health emergencies, much has been learned about surge responses and the care of overwhelming numbers of patients during the COVID-19 pandemic.1 Gaps in prior pandemic planning were identified and require modification in the midst of ongoing surge throughout the world. Methods The Task Force for Mass Critical Care (TFMCC) adopted a modified version of established rapid guideline methodologies from the World Health Organization2 and the Guidelines International Network-McMaster Guideline Development Checklist.3 With a consensus development process incorporating expert opinion to define important questions and extract evidence, TFMCC developed relevant pandemic surge suggestions in a structured manner, incorporating peer-reviewed literature, “gray” evidence from lay media sources, and anecdotal experiential evidence. Results Ten suggestions were identified regarding staffing, load-balancing, communication, and technology. Staffing models are suggested with resilience strategies to support critical care staff. Intensive care unit (ICU) surge strategies and strain indicators are suggested to enhance ICU prioritization tactics to maintain contingency level care and avoid crisis triage, with early transfer strategies to further load-balance care. We suggest intensivists and hospitalists be engaged with the incident command structure to ensure two-way communication, situational awareness, and the use of technology to support critical care delivery and families of patients in intensive care units (ICUs). Conclusions A subcommittee from the Task Force for Mass Critical Care offers interim evidence-informed operational strategies to assist hospitals and communities to plan for and respond to surge capacity demands from COVID-19.

Published
2022

28. 80. SARS-CoV-2 infection is associated with decreased reported physical fitness in a US military longitudinal cohort

Author

Stephanie A Richard, Ann Scher, Jennifer Rusiecki, Celia Byrne, Catherine M Berjohn, Anthony C Fries, Tahaniyat Lalani, Alfred G Smith, Rupal Mody, Anuradha Ganesan, Nikhil Huprikar, Rhonda E Colombo, Christopher Colombo, David A Lindholm, Katrin Mende, Milissa Jones, Derek Larson, Evan C Ewers, Samantha Bazan, Charlotte Lanteri, David Saunders, Ryan C Maves, Jeffrey Livezey, Margaret Sanchez Edwards, Julia S Rozman, David R Tribble, Brian Agan, Simon Pollett, Mark P Simons, and Timothy Burgess

Subjects
Infectious Diseases, Oncology
Abstract

Background COVID-19 may have deleterious effects on the fitness of active duty US military service members. We seek to understand the long-term functional consequences of SARS-CoV-2 infection in this critical population, and in other military healthcare beneficiaries. Methods The Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) study is a longitudinal cohort study to describe the outcomes of SARS-CoV-2 infection in US Military Health System beneficiaries. Subjects provided information about difficulties experienced with daily activities, exercise, and physical fitness performance via electronic surveys. Subjects completed surveys at enrollment and at 1, 3, 6, 9, and 12 months. Results 5,910 subjects completed survey fitness questions, 3,244 (55%) of whom tested SARS-CoV-2 positive at least once during the period of observation. Over 75% of subjects were young adults and over half were male (Table 1). 1,093 (34.3%) of SARS-CoV-2-positive subjects reported new or increased difficulty exercising compared to 393 (14.8%) SARS-CoV-2 negative subjects (p < 0.01) (Table 2). The most commonly reported symptoms related to problems with exercise and activities were dyspnea and fatigue. Among the active-duty members who answered the question about their service-mandated physical fitness test scores, 43.2% of SARS-CoV-2-positive participants reported that their scores had worsened in the study period, compared with 24.3% of SARS-CoV-2 negative participants. Among SARS-CoV-2-positive subjects, reports of difficulty exercising and performing daily activities were highest within one month of the first positive test, decreasing in prevalence among the cohort only slightly to 24% and 18%, respectively, at 12 months (Figure 1). Conclusion A substantial proportion of military service-members in this cohort have reported impairment of their service-mandated physical fitness scores after COVID-19; this proportion is significantly higher than those who are SARS-CoV-2 negative and persists to 12 months in many; similar complaints were reported among non-active duty. Further objective evaluation of post-COVID fitness impairment in this population is warranted. Disclosures Ryan C. Maves, MD, AiCuris: Grant/Research Support|Sound Pharmaceuticals: Grant/Research Support|Trauma Insights, LLC: Advisor/Consultant Julia S. Rozman, n/a, Astra Zeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response David R. Tribble, DrPH, AstraZeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response Simon Pollett, MBBS, Astra Zeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response Mark P. Simons, PhD, AstraZeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response Timothy Burgess, MD, MPH, AstraZeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response.

Published
2022

29. 1102. The Host Response to SARS-CoV-2 Infection Differs by Age

Author

Emily Parsons, Stephanie A Richard, Eric D Laing, Anthony C Fries, Jeffrey Livezey, Milissa Jones, David A Lindholm, Katrin Mende, Julia S Rozman, Anuradha Ganesan, Nikhil Huprikar, Tahaniyat Lalani, Alfred G Smith, Rupal Mody, Samantha Bazan, David Saunders, Rhonda E Colombo, Christopher Colombo, Evan C Ewers, Derek Larson, Ryan C Maves, Catherine M Berjohn, Carlos Maldonado, Mark P Simons, David Tribble, Brian Agan, Timothy Burgess, Simon Pollett, and Allison M Malloy

Subjects
Infectious Diseases, Oncology
Abstract

Background Infection with SARS-CoV-2 and the resulting host immune response has been primarily characterized in middle and older aged populations due to a higher incidence of symptoms in these age groups. Due to reduced severity of disease, children were poorly studied and assumed to be less frequently infected compared to older age groups. We measured the viral load and adaptive immune response across the age-spectrum to define the age-dependent viral and host responses. Methods From March 2020-March 2022, we enrolled individuals across the age spectrum who presented to U.S. military medical treatment facilities with COVID-19-like symptoms. In this longitudinal cohort study, demographic and clinical data were collected in addition to nasopharyngeal swabs and peripheral blood. Magnitude of viral RNA was measured by quantitative PCR (qPCR) from nasopharyngeal samples and SARS-CoV-2-specific IgG antibodies were measured from blood with multiplex microsphere immunoassays. Results 4,768 SARS-CoV-2 positive participants were enrolled, among whom 42, 64, 89, 380, 948 and 245 individuals were in age brackets 0-4y, 5-11y, 12-17y, 18-44, 45-64y, and >65y, respectively. Viral load as measured by qPCR was determined to be similar across age groups within the first week post symptom onset. The magnitude of the IgG antibody response against the spike protein was also compared across age groups at early and convalescent time points and was higher in those over the age of 65 years. Conclusion Early viral load during acute infection did not correlate with age in individuals who experienced COVID-19. These findings diverge from other respiratory viruses, such as respiratory syncytial virus and influenza where children tend to have higher viral loads. In contrast, the magnitude of the antibody response against the spike protein correlated with older age at acute and convalescent time points. Together our data suggest that the host response against SAR-CoV-2 differs with age and is not associated with the acute viral load. Defining age-dependent immunity against SARS-CoV-2 has the potential to identify key immunologic responses that can be used to optimize treatment and vaccine strategies. Disclosures Julia S. Rozman, n/a, Astra Zeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response Ryan C. Maves, MD, AiCuris: Grant/Research Support|Sound Pharmaceuticals: Grant/Research Support|Trauma Insights, LLC: Advisor/Consultant Mark P. Simons, PhD, AstraZeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response David Tribble, MD, DrPH, Astra Zeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response Timothy Burgess, MD, MPH, AstraZeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response Simon Pollett, MBBS, Astra Zeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response.

Published
2022

30. 295. SARS-CoV-2 Associated Multisystem Inflammatory Syndrome in Adults (MIS-A): a Multicenter Case Series

Author

Ricardo Trigueros, Travis Denmeade, Danielle Pannebaker, and Ryan C Maves

Subjects
Infectious Diseases, Oncology
Abstract

Background MIS-A frequently presents with symptoms including fevers, cardiovascular, gastrointestinal mucocutaneous, and neurologic involvement in both children and adults. Predominantly occurs in previously healthy children and young adults, disproportionately affecting individuals of African,Latino and Asian descent. Represents one of the most significant and yet under-recognized clinical consequences of SARS-CoV-2 infection. Methods A retrospective review was performed of the identified MIS-A cases admitted to two institutions between January 2020-December 2021. Included cases required evidence of present or previous SARS-CoV-2 infection by either PCR or antigen testing; and meeting the CDC definition for MIS-A. After case identification, we collected clinical and laboratory data to analyze demographics, clinical symptoms, laboratory result, imaging, length of hospitalization and therapeutic interventions. Results Ten cases were identified in the established period of time. The average interval to hospital admission was 31days. Clinical symptoms included fever, malaise, gastrointestinal complaints, dyspnea, diffuse rash. Males outnumbered females in a ratio of 7:3,with African American and Latino patients comprising 80% of the cases. All patients had elevated inflammatory markers and the most commonly manifesting organ dysfunction was cardiovascular system. Conclusion This case series helps reinforce the characterization of an as yet incompletely understood and challenging clinical syndrome, providing insight to guide diagnosis and treatment of MIS-A. A greater understanding of MIS-A may facilitate earlier syndromic recognition in order to improve outcomes, reduce unnecessary antimicrobial use, and reduce costs. Disclosures Ryan C. Maves, MD, AiCuris: Grant/Research Support|Sound Pharmaceuticals: Grant/Research Support|Trauma Insights, LLC: Advisor/Consultant.

Published
2022

31. 1066. Precision phenotyping of 'long COVID' through machine learning

Author

Nusrat J Epsi, David A Lindholm, Anuradha Ganesan, Tahaniyat Lalani, Alfred G Smith, Rupal Mody, Milissa Jones, Samantha Bazan, Rhonda E Colombo, Christopher Colombo, Evan C Ewers, Derek Larson, Catherine M Berjohn, Ryan C Maves, Anthony C Fries, Ann Scher, Celia Byrne, Jennifer Rusiecki, Margaret Sanchez Edwards, Julia S Rozman, Katrin Mende, Mark P Simons, David R Tribble, Brian Agan, Timothy Burgess, Simon Pollett, and Stephanie A Richard

Subjects
Infectious Diseases, Oncology
Abstract

Background Characterizing, diagnosing, and caring for “long COVID” patients has proven to be challenging due to heterogenous symptoms and broad definitions of these post-acute sequelae. Here, we take a machine learning approach to identify discrete clusters of long COVID symptoms which may define specific long COVID phenotypes. Figure 1: (A) Principal component analysis followed by K-means clustering identified three groups of participants. (B) Heatmap depicting three distinct clusters (high values are in red and low value are in blue); Cluster 1 exhibits sensory symptoms (e.g., loss of smell and/or taste), Cluster 2 exhibits fatigue and difficulty thinking (e.g., changes in ability to think) symptoms, and Cluster 3 exhibits difficulty breathing and exercise intolerance symptoms. (C) Clinical and demographic characteristics of 97 military health system beneficiaries by identified clusters Methods The Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) study is a longitudinal COVID-19 cohort study with data and biospecimens collected from 10 military treatment facilities and online recruitment. Demographic and clinical characteristics were collected using case report forms and surveys completed at enrollment and at 1, 3, 6, 9, and 12 months. For this analysis, we identified those who reported any moderate to severe persistent symptoms on surveys collected 6-months post-COVID-19 symptom onset. Using the survey responses, we applied principal component analysis (PCA) followed by unsupervised machine learning clustering algorithm K-means to identify groups with distinct clusters of symptoms. Results Of 1299 subjects with 6-month survey responses, 97 (7.47%) reported moderate to severe persistent symptoms. Among these subjects, three clusters were identified using PCA (Figure 1A). Cluster 1 is characterized by sensory symptoms (loss of taste and/or smell), Cluster 2 by fatigue and difficulty thinking, and Cluster 3 by difficulty breathing and exercise intolerance (Figure 1B). More than half of these subjects (57%) were female, 64% were 18-44 years old, and 64% had no comorbidities at enrollment (Figure 1C). Those in the sensory symptom cluster were all outpatients at the time of initial COVID-19 presentation (p < 0.01). The difficulty breathing and exercise intolerance symptom-clusters had a higher proportion of older participants (Age group ≥ 45-64) with more comorbidities (CCI ≥ 1-2). Conclusion We identified three distinct ‘long COVID’ phenotypes among those with moderate to severe COVID-19 symptoms at 6-months post-symptom onset. With further validation and characterization, this framework may allow more precise classification of long COVID cases, and potentially improve the diagnosis, prognosis, and treatment of post- infectious sequelae. Disclosures Ryan C. Maves, MD, AiCuris: Grant/Research Support|Sound Pharmaceuticals: Grant/Research Support|Trauma Insights, LLC: Advisor/Consultant Julia S. Rozman, n/a, Astra Zeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response Mark P. Simons, PhD, AstraZeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response David R. Tribble, DrPH, AstraZeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response Timothy Burgess, MD, MPH, AstraZeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response Simon Pollett, MBBS, Astra Zeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response.

Published
2022

32. 1380. Impact of Doxycycline Prophylaxis on Skin and Soft Tissue Infections in Naval Special Warfare Trainees

Author

Jeffrey Spiro, Piotr Wisniewski, Julia Schwartz, Alfred G Smith, Sara Burger, Drake Tilley, and Ryan C Maves

Subjects
Infectious Diseases, Oncology
Abstract

Background Several severe cases of SSTIs caused by salt-water associated Gram-negative pathogens (mainly Shewanella algae) among U.S. Naval Special Warfare (NSW) trainees prompted introduction of doxycycline prophylaxis during the highest risk portion of training, “Hell Week”. We present analysis of this intervention’s impact on disease incidence and hospital admission for serious SSTI. Necrotizing fasciitis caused by Vibrio harveyi in an NSW trainee during “Hell Week” prior to introduction of doxycycline prophylaxis. Methods We performed a retrospective cohort study examining data from hospital admissions for SSTI in trainees between 2013-2020. We assessed hospital admission rates for SSTIs, hospitalization rates per SSTI diagnosed at the clinic level, overall rates of SSTI, length of hospital stays and blood and wound culture data. We then compared data from pre- and post-intervention cohorts. Results 3371 NSW trainees participated in “Hell Week” training during the study period with 284 SSTIs diagnosed overall, 29 of which led to hospital admission. After introduction of doxycycline prophylaxis, admission rates for SSTI decreased from 1.37 to 0.64 admissions per 100 trainees (p=0.036). Overall SSTI rates diagnosed at the clinic level remained stable from 7.42 to 8.86 SSTI per 100 trainees (p=0.185). Hospitalization rates per diagnosed SSTI decreased from 18.4% to 7.2% (p=0.009). Average length of hospitalization decreased from 9.01 days to 4.33 days (p=0.034). Blood and wound culture data showed a notable decrease in SSTI from salt-water associated Gram-negative rods (Shewanella algae and Vibrio spp.). Total number of SSTI diagnosed at Naval Special Warfare Center (NSWCEN) medical clinic each “Hell Week” training period with corresponding percentage of NSW trainees diagnosed with SSTI in each class. Date of doxycycline prophylaxis initiation labeled for reference. Wound and blood culture (Cx) data from the pre-intervention and post-intervention cohorts Conclusion Doxycycline prophylaxis during “Hell Week” training for NSW trainees was associated with decreased frequency and severity of hospitalization for SSTI, as well as near elimination of infection with invasive salt-water associated pathogens. Disclosures All Authors: No reported disclosures.

Published
2022

33. Statin usage and cardiovascular risk among people living with HIV in the U.S. Military HIV Natural History Study

Author

Ryan C. Maves, Robert Deiss, Seung Hyun Won, Thomas O'Bryan, Derek T Larson, Jason F. Okulicz, Xiuping Chu, Anuradha Ganesan, Christina Schofield, Karl Kronmann, and Brian K. Agan

Subjects
medicine.medical_specialty, Statin, medicine.drug_class, Human immunodeficiency virus (HIV), HIV Infections, Primary care, medicine.disease_cause, Article, Risk Factors, medicine, Humans, Pharmacology (medical), Medical prescription, Retrospective Studies, U s military, business.industry, Health Policy, Odds ratio, United States, Confidence interval, Cross-Sectional Studies, Infectious Diseases, Cardiovascular Diseases, Heart Disease Risk Factors, Family medicine, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Natural history study
Abstract

Objectives Using the American College of Cardiology/American Heart Association 2013 atherosclerotic cardiovascular disease (ASCVD) management guidelines, we conducted a retrospective cross-sectional analysis of people living with HIV in the US Military HIV Natural History Study to determine whether individuals were receiving statins when indicated. Methods Prescription data was taken from Military Health System data. Statin eligibility was defined by ASCVD guidelines. We used the 10-year ASCVD pooled cohorts' equation to evaluate risk for each participant. Results Across all categories, 31.9% (n = 390) of individuals met criteria for statin use, and when adding these subjects to the number of those already receiving statins (n = 96), 62.1% of all eligible subjects (n = 302/486) were actually receiving statin therapy. In multivariable analysis, individuals of African American race [odds ratio (OR) = 0.48, 95% confidence interval (CI): 0.31-0.73] or Hispanic ethnicity (OR = 0.42, 95% CI: 0.19-0.94) were less likely to receive statin prescriptions than white individuals. Individuals with a higher CD4 count (OR = 1.12, 95% CI: 1.05-1.20 per 100 cells/μL]) were significantly more likely to receive a statin prescription. Conclusions These data highlight discrepancies between ASCVD guidelines and primary care management of people living with HIV (PLWH) in the military health system, along with important racial differences. Targeted interventions are critical to identify and treat appropriate candidates for statin therapy among PLWH in the military and other settings.

Published
2021

35. Uses of Procalcitonin as a Biomarker in Critical Care Medicine

Author

Ryan C. Maves and Chukwunyelu H. Enwezor

Subjects
Microbiology (medical), Infectious Diseases, Critical Care, Virus Diseases, Critical Illness, Sepsis, Humans, COVID-19, Bacterial Infections, Procalcitonin, Biomarkers, Anti-Bacterial Agents
Abstract

Procalcitonin is a commonly used biomarker for infection and severity in the intensive care unit. Although relatively specific for bacterial, as opposed to viral, infections, serum procalcitonin levels also correlate with disease severity and thus cannot reliably distinguish between bacterial and nonbacterial infections in the setting of critical illness, particularly in cases of severe influenza and coronavirus disease-2019. Baseline procalcitonin levels are insufficiently discriminative to permit the withholding of antibiotics in patients with critical illness and suspected sepsis. Trends in procalcitonin levels over time, however, give us the opportunity to individualize the duration of antibiotics without negative impacts on mortality.

Published
2022

36. Welder's Anthrax: A Tale of 2 Cases

Author

Katherine Hendricks, Roosecelis Brasil Martines, Hannah Bielamowicz, Anne E Boyer, Stephen Long, Paul Byers, Robyn A Stoddard, Kathryn Taylor, Cari Beesley Kolton, Maribel Gallegos-Candela, Christine Roberts, Marlene DeLeon-Carnes, Johanna Salzer, Patrick Dawson, Dannette Brown, Lindsey Templeton-LeBouf, Ryan C Maves, Chris Gulvik, David Lonsway, John R Barr, William A Bower, and Alex Hoffmaster

Subjects
Microbiology (medical), Anthrax, Infectious Diseases, Bacillus cereus, Metal Workers, Bacillus anthracis, Humans, Supplement Article, Antitoxins, Plasmids
Abstract

Bacillus anthracis has traditionally been considered the etiologic agent of anthrax. However, anthrax-like illness has been documented in welders and other metal workers infected with Bacillus cereus group spp. harboring pXO1 virulence genes that produce anthrax toxins. We present 2 recent cases of severe pneumonia in welders with B. cereus group infections and discuss potential risk factors for infection and treatment options, including antitoxin.

Published
2022

38. Prospective Evaluation of an Abbreviated Test Battery to Screen for Neurocognitive Impairment in HIV-Positive Military Members

Author

Brian K. Agan, Edmund C. Tramont, Seung Hyun Won, Camille Estupigan, Bryan Smith, Avindra Nath, Anuradha Ganesan, Ryan C. Maves, Hsing-Chuan Hsieh, Gregory Utz, and Joseph Snow

Subjects
Adult, Test battery, Pediatrics, medicine.medical_specialty, Social Psychology, Neurocognitive Disorders, Human immunodeficiency virus (HIV), HIV Infections, Neuropsychological Tests, medicine.disease_cause, HIV-associated neurocognitive disorder, Article, Prospective evaluation, HIV Seropositivity, medicine, Humans, business.industry, Public Health, Environmental and Occupational Health, Neuropsychological battery, medicine.disease, Clinic visit, Military Personnel, Infectious Diseases, business, Neurocognitive, Natural history study
Abstract

BACKGROUND: Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) affects around 20–50% of people living with HIV (PLWH). Although batteries of tests are used to identify neurocognitive impairment (NCI), they are long and difficult to perform during a routine clinic visit, thus impairing the ability to diagnose HAND. Therefore, a brief yet sensitive screening tool to identify NCI is necessary. This study prospectively evaluated an abbreviated screening battery with reported 86.5%/87.1% sensitivity/specificity, identified from a planned post-hoc analysis in a prior neurocognitive study among military PLWH. METHODS: Adult HIV-positive military beneficiaries in the U.S. Military HIV Natural History Study, who agreed to undergo a comprehensive seven-domain neuropsychological battery (16 tests), and who completed an additional 20-minute abbreviated battery (AB), comprised of four tests, prior to the full battery (FB) were included in this analysis. RESULTS: A group of 169 individuals completed both tests, of which 25.4% had a positive AB and 17.8% had NCI on FB (global deficit score ≥0.5). With the FB as the reference standard, the specificity for the AB was 79.9% (73.2–86.5), however the sensitivity was 50.0% (32.1–67.9). In those with NCI by FB but not AB, the most common impaired domains were executive function (73.3%) and memory (73.3%), both being domains not fully tested by the AB. CONCLUSION: An abbreviated HAND screening battery of four tests requiring approximately 20 minutes provided a relatively high level of specificity but lacked sensitivity for detection of NCI. Inclusion of additional domains or alternative scoring approaches may improve sensitivity but require further study. Continued efforts are needed to develop an effective brief screening test for HAND.

Published
2021

39. Effects of Human Immunodeficiency Virus Status on Symptom Severity in Influenza-Like Illness in An Otherwise Healthy Adult Outpatient Cohort

Author

John C. Arnold, Eugene V. Millar, Rhonda E Colombo, Michelande Ridore, Anuradha Ganesan, Ryan C. Maves, Tahaniyat Lalani, Stephanie A Richard, Patrick Danaher, Timothy Burgess, Christian L. Coles, Brian K. Agan, Wei-Ju Chen, Christina Schofield, and Mary P. Fairchok

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, HIV Positivity, 030106 microbiology, HIV Infections, medicine.disease_cause, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Influenza, Human, Outpatients, Pandemic, medicine, Humans, 030212 general & internal medicine, acute disease, Original Research, Influenza-like illness, Picornaviridae Infections, business.industry, Confounding, virus diseases, General Medicine, respiratory tract diseases, Diarrhea, Cohort, medicine.symptom, Rhinovirus, business, Cohort study
Abstract

The impact of HIV on influenza-like illness (ILI) has been incompletely described in the era of combination antiretroviral therapy, particularly in the post-H1N1 pandemic period. This analysis informs on ILI in an otherwise healthy, predominantly outpatient cohort of adults with HIV in the USA. From September 2010 to March 2015, this multisite observational cohort study enrolled otherwise healthy adults presenting to a participating US military medical center with ILI, a subset of whom were HIV positive. Demographics, clinical data, and self-reported symptom severity were ascertained, and enrollees completed a daily symptom diary for up to 10 days. 510 men were included in the analysis; 50 (9.8%) were HIV positive. Subjects with HIV were older and less likely to be on active duty. Rhinovirus and influenza A were the most commonly identified pathogens. Moderate-severe diarrhea (p

Published
2021

40. Clinical, Immunological, and Virological SARS-CoV-2 Phenotypes in Obese and Nonobese Military Health System Beneficiaries

Author

Stephanie A Richard, David A Lindholm, Nusrat J. Epsi, Caroline English, Nikhil Huprikar, Mark P Simons, Timothy Burgess, Anthony C. Fries, Cristian Madar, Christopher J Colombo, Ryan C. Maves, Anuradha Ganesan, Simon Pollett, Rhonda E Colombo, Eric D Laing, David R. Tribble, Eugene V. Millar, Katrin Mende, Sharon Chi, Tahaniyat Lalani, Christopher C. Broder, Brian K. Agan, and Derek T Larson

Subjects
medicine.medical_specialty, business.industry, medicine.medical_treatment, Odds ratio, Anthropometry, Logistic regression, medicine.disease, Obesity, Confidence interval, Infectious Diseases, Oxygen therapy, Internal medicine, medicine, Immunology and Allergy, business, Body mass index, Viral load
Abstract

Background The mechanisms underlying the association between obesity and coronavirus disease 2019 (COVID-19) severity remain unclear. After verifying that obesity was a correlate of severe COVID-19 in US Military Health System (MHS) beneficiaries, we compared immunological and virological phenotypes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in both obese and nonobese participants. Methods COVID-19–infected MHS beneficiaries were enrolled, and anthropometric, clinical, and demographic data were collected. We compared the SARS-CoV-2 peak IgG humoral response and reverse-transcription polymerase chain reaction viral load in obese and nonobese patients, stratified by hospitalization, utilizing logistic regression models. Results Data from 511 COVID-19 patients were analyzed, among whom 24% were obese and 14% severely obese. Obesity was independently associated with hospitalization (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.15–3.18) and need for oxygen therapy (aOR, 3.39; 95% CI, 1.61–7.11). In outpatients, severely obese had a log10 (1.89) higher nucleocapsid (N1) genome equivalents (GE)/reaction and log10 (2.62) higher N2 GE/reaction than nonobese (P = 0.03 and P < .001, respectively). We noted a correlation between body mass index and peak anti-spike protein IgG in inpatients and outpatients (coefficient = 5.48, P < .001). Conclusions Obesity is a strong correlate of COVID-19 severity in MHS beneficiaries. These findings offer new pathophysiological insights into the relationship between obesity and COVID-19 severity.

Published
2021

41. Response

Author

Ryan C. Maves and Mary A. King

Subjects
Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published
2022

42. Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history

Author

Wei Wang, Sabrina Lusvarghi, Rahul Subramanian, Nusrat J. Epsi, Richard Wang, Emilie Goguet, Anthony C. Fries, Fernando Echegaray, Russell Vassell, Si’Ana A. Coggins, Stephanie A. Richard, David A. Lindholm, Katrin Mende, Evan C. Ewers, Derek T. Larson, Rhonda E. Colombo, Christopher J. Colombo, Janet O. Joseph, Julia S. Rozman, Alfred Smith, Tahaniyat Lalani, Catherine M. Berjohn, Ryan C. Maves, Milissa U. Jones, Rupal Mody, Nikhil Huprikar, Jeffrey Livezey, David Saunders, Monique Hollis-Perry, Gregory Wang, Anuradha Ganesan, Mark P. Simons, Christopher C. Broder, David R. Tribble, Eric D. Laing, Brian K. Agan, Timothy H. Burgess, Edward Mitre, Simon D. Pollett, Leah C. Katzelnick, and Carol D. Weiss

Subjects
Virology, Parasitology, Microbiology
Abstract

The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, or both. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diversity. Antigenic maps of primary infection sera showed that Omicron sublineages BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased neutralization of BA.1 more than BA.4/BA.5 or BA.2.12.1. BA.1 post-vaccination infection elicited higher neutralization titers to all variants than three vaccinations alone, although with less neutralization to BA.2.12.1 and BA.4/BA.5. Those with BA.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic recognition. Accounting for antigenic differences among variants when interpreting neutralization titers can aid the understanding of complex patterns in humoral immunity that informs the selection of future COVID-19 vaccine strains.

Published
2022

44. The US Strategic National Stockpile Ventilators in Coronavirus Disease 2019

Author

Joshua O. Benditt, Lewis Rubinson, Marie R. Baldisseri, Tanzib Hossain, Guillermo Domingiuez-Cherit, Henry A. Feldman, Kiersten N Henry, Dario Rodriquez, Marya Ghazipura, Jeffrey R. Dichter, Doug Ornoff, David J. Dries, Asha V. Devereaux, Niranjan Kissoon, Rich Branson, Meredith Huffines, Michael D. Christian, Ryan C. Maves, Jason Persoff, Mary King, and Anne Marie O. Martland

Subjects
Pulmonary and Respiratory Medicine, Emergency Use Authorization, Government, Coronavirus disease 2019 (COVID-19), business.industry, MEDLINE, Critical Care and Intensive Care Medicine, medicine.disease, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Strategic National Stockpile, Pandemic, Medicine, 030212 general & internal medicine, Medical emergency, Cardiology and Cardiovascular Medicine, business, Research question
Abstract

Background Early in the COVID-19 pandemic, there was serious concern that the United States (US) would encounter a short fall of mechanical ventilators. In response, the US government, utilizing the Defense Production Act ordered the development of 200,000 ventilators from 11 different manufacturers. These ventilators have different capabilities and it is not evident whether all are able to support COVID-19 patients. Research question Evaluate ventilator requirements for affected COVID-19 patients, assess the clinical performance of current SNS ventilators employed during the pandemic, and finally compare ordered ventilators functionality based on COVID-19 patient needs. Study design and methods Current published literature, publicly available documents, and lay press articles were reviewed by a diverse team of disaster experts. Data was assembled into tabular format which formed the basis for analysis and future recommendations. Results COVID-19 patients often develop severe hypoxemic acute respiratory failure and ARDS requiring high levels of ventilator support. Current SNS ventilators were unable to fully support all COVID-19 patients, and only about half of newly ordered ventilators have the capacity to support the most severely affected patients; ventilators with less capacity for providing high level support are still of significant value in caring for many patients. Interpretation Current SNS ventilators and those on order are capable of supporting most but not all COVID-19 patients. Technologic, logistic, and educational challenges encountered from current SNS ventilators are summarized, with potential next generation SNS ventilator updates offered. Clinical trial registration N/A.

Published
2021

45. It Takes a Village…

Author

David Williamson, Michael D. Christian, Brian L. Erstad, Lisa Burry, Ryan C. Maves, James A. Geiling, Salmaan Kanji, Jeffrey F. Barletta, and Jeffrey R. Dichter

Subjects
Pulmonary and Respiratory Medicine, Drug, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, media_common.quotation_subject, Supply chain, Economic shortage, Context (language use), Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Pandemic, Medicine, Hoarding (economics), 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business, Intensive care medicine, Neuromuscular Blockers, media_common
Abstract

Critical drug shortages have been widely documented during the coronavirus disease 2019 (COVID-19) pandemic, particularly for IV sedatives used to facilitate mechanical ventilation. Surges in volume of patients requiring mechanical ventilation coupled with prolonged ventilator days and the high sedative dosing requirements observed quickly led to the depletion of "just-in-time" inventories typically maintained by institutions. This manuscript describes drug shortages in the context of global, manufacturing, regional and institutional perspectives in times of a worldwide crisis such as a pandemic. We describe etiologic factors that lead to drug shortages including issues related to supply (eg, manufacturing difficulties, supply chain breakdowns) and variables that influence demand (eg, volatile prescribing practices, anecdotal or low-level data, hoarding). In addition, we describe methods to mitigate drug shortages as well as conservation strategies for sedatives, analgesics and neuromuscular blockers that could readily be applied at the bedside. The COVID-19 pandemic has accentuated the need for a coordinated, multi-pronged approach to optimize medication availability as individual or unilateral efforts are unlikely to be successful.

Published
2020

46. An Analysis of SARS-CoV-2 Vaccine Reactogenicity: Variation by Type, Dose, and History, Severity, and Recency of Prior SARS-CoV-2 Infection

Author

Ann I, Scher, Catherine M, Berjohn, Celia, Byrne, Rhonda E, Colombo, Christopher J, Colombo, Margaret Sanchez, Edwards, Evan C, Ewers, Anuradha, Ganesan, Milissa, Jones, Derek T, Larson, Daniel, Libraty, David A, Lindholm, Cristian S, Madar, Carlos J, Maldonado, Ryan C, Maves, Katrin, Mende, Stephanie A, Richard, Julia S, Rozman, Jennifer, Rusiecki, Alfred, Smith, Mark, Simons, David, Tribble, Brian, Agan, Timothy H, Burgess, Simon D, Pollett, and Maj N, Huprikar

Subjects
Infectious Diseases, Oncology
Abstract

Background There is limited information on the functional consequences of coronavirus disease 2019 (COVID-19) vaccine side effects. To support patient counseling and public health messaging, we describe the risk and correlates of COVID-19 vaccine side effects sufficient to prevent work or usual activities and/or lead to medical care (“severe” side effects). Methods The EPICC study is a longitudinal cohort study of Military Healthcare System beneficiaries including active duty service members, dependents, and retirees. We studied 2789 adults who were vaccinated between December 2020 and December 2021. Results Severe side effects were most common with the Ad26.COV2.S (Janssen/Johnson and Johnson) vaccine, followed by mRNA-1273 (Moderna) then BNT162b2 (Pfizer/BioNTech). Severe side effects were more common after the second than first dose (11% vs 4%; P Conclusions Vaccine side effects sufficient to prevent usual activities were more common after the second than first dose and varied by vaccine type. First dose side effects were more likely in those with a history of COVID-19—particularly if that prior illness was severe or associated with inpatient care. These findings may assist clinicians and patients by providing a real-world evaluation of the likelihood of experiencing impactful postvaccine symptoms.

Published
2022

47. SARS-CoV-2 infection is associated with post-acute self-reported neurocognitive symptoms

Author

PMB, Infectious Disease Clinical Research Program (IDCRP), Liana R. Andronescu, Stephanie A. Richard, Ann I. Scher, David A. Lindholm, Katrin Mende, Anuradha Ganesan, Nikhil Huprikar, Tahaniyat Lalani, Alfred Smith, Rupal M. Mody, Milissa U. Jones, Samantha E. Bazan, Rhonda E. Colombo, Christopher J. Colombo, Evan Ewers, Derek T. Larson, Ryan C. Maves, Catherine M. Berjohn, Carlos J Maldonado, Caroline English, Margaret Sanchez Edwards, Julia S. Rozman, Jennifer Rusiecki, Celia Byrne, Mark P. Simons, David Tribble, Timothy H Burgess, Simon D. Pollett, Brian K. Agan, PMB, Infectious Disease Clinical Research Program (IDCRP), Liana R. Andronescu, and Stephanie A. Richard, Ann I. Scher, David A. Lindholm, Katrin Mende, Anuradha Ganesan, Nikhil Huprikar, Tahaniyat Lalani, Alfred Smith, Rupal M. Mody, Milissa U. Jones, Samantha E. Bazan, Rhonda E. Colombo, Christopher J. Colombo, Evan Ewers, Derek T. Larson, Ryan C. Maves, Catherine M. Berjohn, Carlos J Maldonado, Caroline English, Margaret Sanchez Edwards, Julia S. Rozman, Jennifer Rusiecki, Celia Byrne, Mark P. Simons, David Tribble, Timothy H Burgess, Simon D. Pollett, Brian K. Agan

Abstract

Background Correspondence SARS-CoV-2 infection is associated with post-acute self-reported neurocognitive symptoms Liana R. Andronescu, PhD, MPH1,2, Stephanie A. Richard, PhD, MHS 1,2, Ann I. Scher, PhD3, David A. Lindholm, MD4,5, Katrin Mende, PhD1,2,5, Anuradha Ganesan, MBBS, MPH1,2,6, Nikhil Huprikar MD6, Tahaniyat Lalani, MBBS, MHS1,2,7, Alfred Smith MD7, Rupal M. Mody, MD8, Milissa U. Jones, MD9, Samantha E. Bazan, DNP, MS10, Rhonda E. Colombo, MD, MHS1,2,4,11, Christopher J. Colombo, MD4,11, Evan Ewers12, Derek T. Larson, DO12,13, Ryan C. Maves, MD1,13, Catherine M. Berjohn, MD, MPH1,4,13, Carlos J Maldonado, PhD14, Caroline English1,2, Margaret Sanchez Edwards, MS1,2, Julia S. Rozman, BS1,2, Jennifer Rusiecki, PhD3, Celia Byrne, PhD3, Mark P. Simons, PhD1, David Tribble, MD, DrPH1, Timothy H Burgess, MD, MPH1, Simon D. Pollett, MBBS1,2, Brian K. Agan, MD1,2 Objectives Chronic neuropsychological sequelae following SARS-CoV-2 infection, including depression, anxiety, fatigue, and general cognitive difficulties, are a major public health concern. Given the potential impact of long-term neurocognitive impairment on active-duty service members and other Military Health System (MHS) beneficiaries, it is important to characterize this post-infection phenotype and assess potential risk factors for poor neurocognitive outcomes. Email: landronescu@idcrp.org; liana.andronescu.ctr@usuhs.edu USU Infectious Disease Clinical Research Program (IDCRP), Department of Preventive Medicine and Biostatistics Henry M. Jackson Foundation for the Advancement of Military Medicine • Describe the prevalence of self-reported neurocognitive symptoms among SARS-CoV-2 positive vs negative subjects • Identify risk factors for self-reported neurocognitive symptoms among SARS-CoV-2 positive subjects Results 1Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; 2Henry M. Jackso, RITM0027659, Chronic neuropsychological sequelae following SARS-CoV-2 infection, including depression, anxiety, fatigue, and general cognitive difficulties, are a major public health concern. Given the potential impact of long-term neurocognitive impairment on active-duty service members and other Military Health System (MHS) beneficiaries, it is important to characterize this post-infection phenotype and assess potential risk factors for poor neurocognitive outcomes.

Published
2022

48. Comparison of A(H3N2) Neutralizing Antibody Responses Elicited by 2018–2019 Season Quadrivalent Influenza Vaccines Derived from Eggs, Cells, and Recombinant Hemagglutinin

Author

Wei Wang, Ryan C. Maves, Christian L. Coles, Min Z. Levine, Srihari Seshadri, Esmeralda Alvarado-Facundo, Carol D. Weiss, Bruce M. McClenathan, David Hrncir, Stephanie A Richard, Limone Collins, Christina Spooner, Tahaniyat Lalani, Timothy Burgess, Gregory Utz, Anuradha Ganesan, Rhonda E Colombo, Casey Geaney, Ana E Markelz, Tyler E. Warkentien, Christina Schofield, Katrin Mende, Russell Vassell, and Maryna C. Eichelberger

Subjects
Adult, 0301 basic medicine, Microbiology (medical), Influenza vaccine, Hemagglutinin (influenza), Hemagglutinin Glycoproteins, Influenza Virus, Antibodies, Viral, Neutralization, Antigenic drift, 03 medical and health sciences, 0302 clinical medicine, Influenza, Human, Humans, Medicine, 030212 general & internal medicine, Seroconversion, Neutralizing antibody, biology, business.industry, Influenza A Virus, H3N2 Subtype, Immunogenicity, Antibodies, Neutralizing, Virology, Vaccination, Hemagglutinins, 030104 developmental biology, Infectious Diseases, Influenza Vaccines, biology.protein, Seasons, business
Abstract

Background Low vaccine effectiveness against A(H3N2) influenza in seasons with little antigenic drift has been attributed to substitutions in hemagglutinin (HA) acquired during vaccine virus propagation in eggs. Clinical trials comparing recombinant HA vaccine (rHA) and cell-derived inactivated influenza vaccine (IIV) to egg-derived IIVs provide opportunities to assess how egg-adaptive substitutions influence HA immunogenicity. Methods Neutralization titers in pre- and postimmunization sera from 133 adults immunized with 1 of 3 types of influenza vaccines in a randomized, open-label trial during the 2018–2019 influenza season were measured against egg- and cell-derived A/Singapore/INFIMH-16-0019/2016-like and circulating A(H3N2) influenza viruses using HA pseudoviruses. Results All vaccines elicited neutralizing antibodies to all H3 vaccine antigens, but the rHA vaccine elicited the highest titers and seroconversion rates against all strains tested. Egg- and cell-derived IIVs elicited responses similar to each other. Preimmunization titers against H3 HA pseudoviruses containing egg-adaptive substitutions T160K and L194P were high, but lower against H3 HA pseudoviruses without those substitutions. All vaccines boosted neutralization titers against HA pseudoviruses with egg-adaptive substitutions, but poorly neutralized wild-type 2019–2020 A/Kansas/14/2017 (H3N2) HA pseudoviruses. Conclusion Egg- and cell-derived 2018–2019 season influenza vaccines elicited similar neutralization titers and response rates, indicating that the cell-derived vaccine did not improve immunogenicity against the A(H3N2) viruses. The higher responses after rHA vaccination may be due to its higher HA content. All vaccines boosted titers to HA with egg-adaptive substitutions, suggesting boosting from past antigens or better exposure of HA epitopes. Studies comparing immunogenicity and effectiveness of different influenza vaccines across many seasons are needed.

Published
2020

49. Optimizing Scarce Resource Allocation During COVID-19: Rapid Creation of a Regional Health-Care Coalition and Triage Teams in San Diego County, California

Author

Ryan C. Maves, Chiara Leroy, Gilbert Seda, John S. Parrish, Navaz Karanjia, Frederick M. Burkle, Kristi L. Koenig, Paula Goodman-Crews, Jennifer M Tuteur, Holly Yang, Christy Rosenberg, Asha V. Devereaux, Viji Sankar, and Lynette Cederquist

Subjects
medicine.medical_specialty, Population, 8.1 Organisation and delivery of services, Crisis management, 030204 cardiovascular system & hematology, Public administration, health-care rationing, Resource Allocation, Health care rationing, Concepts in Disaster Medicine, disaster medicine, 03 medical and health sciences, 0302 clinical medicine, Incident Command System, Clinical Research, Acute care, Health care, medicine, Humans, education, Strategic, Pandemics, education.field_of_study, business.industry, capacity building, Public Health, Environmental and Occupational Health, COVID-19, Health Services, Triage, Defence & Security Studies, Emerging Infectious Diseases, Infectious Diseases, 030228 respiratory system, Public Health and Health Services, Generic health relevance, Public Health, business, Disaster medicine, mass casualty incidents
Abstract

Successful management of an event where health-care needs exceed regional health-care capacity requires coordinated strategies for scarce resource allocation. Publications for rapid development, training, and coordination of regional hospital triage teams to manage the allocation of scarce resources during coronavirus disease 2019 (COVID-19) are lacking. Over a period of 3 weeks, over 100 clinicians, ethicists, leaders, and public health authorities convened virtually to achieve consensus on how best to save the most lives possible and share resources. This is referred to as population-based crisis management. The rapid regionalization of 22 acute care hospitals across 4500 square miles in the midst of a pandemic with a shifting regulatory landscape was challenging, but overcome by mutual trust, transparency, and confidence in the public health authority. Because many cities are facing COVID-19 surges, we share a process for successful rapid formation of health-care care coalitions, Crisis Standard of Care, and training of Triage Teams. Incorporation of continuous process improvement and methods for communication is essential for successful implementation. Use of our regional health-care coalition communications, incident command system, and the crisis care committee helped mitigate crisis care in the San Diego and Imperial County region as COVID-19 cases surged and scarce resource collaborative decisions were required.

Published
2020

50. Coronavirus Disease 2019 Pandemic Measures: Reports From a National Survey of 9,120 ICU Clinicians

Author

Ryan C. Maves, Steven Greenberg, Sandra L. Kane Gill, Lewis J. Kaplan, Richard D. Branson, Rameela Raman, David Ferraro, Ruth M. Kleinpell, and Jennifer K. Doersam

Subjects
Male, medicine.medical_specialty, Critical Illness, critical care clinician, Pneumonia, Viral, Staffing, MEDLINE, Online Clinical Investigation, Severe Acute Respiratory Syndrome, Critical Care and Intensive Care Medicine, intensive care unit, coronavirus disease 2019, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Intervention (counseling), Outcome Assessment, Health Care, Pandemic, Health care, Medical Staff, Hospital, medicine, Humans, Hospital Mortality, Pandemics, Personal protective equipment, business.industry, pandemic, COVID-19, 030208 emergency & critical care medicine, medicine.disease, United States, critical care, intensive care unit clinician, Intensive Care Units, Pneumonia, 030228 respiratory system, Emergency medicine, Female, Interdisciplinary Communication, Professional association, Coronavirus Infections, business
Abstract

Importance Recent reports identify that among hospitalized coronavirus disease 2019 patients, 30% require ICU care. Understanding ICU resource needs remains an essential component of meeting current and projected needs of critically ill coronavirus disease 2019 patients. Objectives This study queried U.S. ICU clinician perspectives on challenging aspects of care in managing coronavirus disease 2019 patients, current and anticipated resource demands, and personal stress. Design, setting, and participants Using a descriptive survey methodology, an anonymous web-based survey was administered from April 7, 2020, to April 22, 2020 (email and newsletter) to query members of U.S. national critical care organizations. Measurements and main results Through a 16-item descriptive questionnaire, ICU clinician perceptions were assessed regarding current and emerging critical ICU needs in managing the severe acute respiratory syndrome coronavirus 2 infected patients, resource levels, concerns about being exposed to severe acute respiratory syndrome coronavirus 2, and perceived level of personal stress. A total of 9,120 ICU clinicians responded to the survey, representing all 50 U.S. states, with 4,106 (56.9%) working in states with 20,000 or more coronavirus disease 2019 cases. The 7,317 respondents who indicated their profession included ICU nurses (n = 6,731, 91.3%), advanced practice providers (nurse practitioners and physician assistants; n = 334, 4.5%), physicians (n = 212, 2.9%), respiratory therapists (n = 31, 0.4%), and pharmacists (n = 30, 0.4%). A majority (n = 6,510, 88%) reported having cared for a patient with presumed or confirmed coronavirus disease 2019. The most critical ICU needs identified were personal protective equipment, specifically N95 respirator availability, and ICU staffing. Minimizing healthcare worker virus exposure during care was believed to be the most challenging aspect of coronavirus disease 2019 patient care (n = 2,323, 30.9%). Nurses report a high level of concern about exposing family members to severe acute respiratory syndrome coronavirus 2 (median score of 10 on 0-10 scale). Similarly, the level of concern reached the maximum score of 10 in ICU clinicians who had provided care to coronavirus disease 2019 patients. Conclusions This national ICU clinician survey identifies continued concerns regarding personal protective equipment supplies with the chief issue being N95 respirator availability. As the pandemic continues, ICU clinicians anticipate a number of limited resources that may impact ICU care including personnel, capacity, and surge potential, as well as staff and subsequent family members exposure to severe acute respiratory syndrome coronavirus 2. These persistent concerns greatly magnify personal stress, offering a therapeutic target for professional organization and facility intervention efforts.

Published
2020

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