A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics.
Sabue Mulangu,Lori E. Dodd,Richard T. Davey,Tshiani Mbaya O,Proschan M,Mukadi D,Lusakibanza Manzo M,Didier Nzolo,Tshomba Oloma A,Ibanda A,Ali R,Sheick Oumar Coulibaly,Adam C. Levine,Rebecca F. Grais,Diaz J,H C Lane,Muyembe-Tamfum Jj,Sivahera B,Camara M,Kojan R,Walker R,Bonnie Dighero-Kemp,Huyen Cao,Mukumbayi P,Mbala-Kingebeni P,Ahuka S,Albert S,Tyler Bonnett,Ian Crozier,Duvenhage M,Proffitt C,Teitelbaum M,Moench T,Aboulhab J,Kevin Barrett,Cahill K,Cone K,Eckes R,Lisa E. Hensley,Herpin B,Elizabeth S. Higgs,Ledgerwood J,Pierson J,Smolskis M,Sow Y,Tierney J,Sivapalasingam S,Holman W,Gettinger N,Vallée D,Nordwall J +50 more
TLDR
A shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival, and both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD.Abstract:
Background Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the ...read more
Citations
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Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro.
Manli Wang,Ruiyuan Cao,Leike Zhang,Xing-Lou Yang,Jia Liu,Mingyue Xu,Zhengli Shi,Zhihong Hu,Wu Zhong,Gengfu Xiao +9 more
TL;DR: This study evaluated the antiviral efficiency of five FAD-approved drugs including ribavirin, penciclovir, nitazoxanide, nafamostat, chloroquine and two well-known broad-spectrum antiviral drugs remdesivir and favipiravir against a clinical isolate of 2019-nCoV in vitro.
Journal ArticleDOI
First Case of 2019 Novel Coronavirus in the United States.
Michelle Holshue,Chas DeBolt,Scott Lindquist,Kathy H Lofy,John Wiesman,Hollianne Bruce,Christopher Spitters,Keith M. Marzilli Ericson,Sara Wilkerson,Ahmet Tural,George Diaz,Amanda C. Cohn,LeAnne Fox,Anita Patel,Susan I. Gerber,Lindsay Kim,Suxiang Tong,Xiaoyan Lu,Steve Lindstrom,Mark A. Pallansch,William C. Weldon,Holly M. Biggs,Timothy M. Uyeki,Satish K. Pillai +23 more
TL;DR: This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.
Journal ArticleDOI
Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial.
Yeming Wang,Yeming Wang,Dingyu Zhang,Guanhua Du,Ronghui Du,Jianping Zhao,Yang Jin,Shouzhi Fu,Ling Gao,Zhenshun Cheng,Qiaofa Lu,Yi Hu,Guangwei Luo,Ke Wang,Yang Lu,Huadong Li,Shuzhen Wang,Shunan Ruan,Chengqing Yang,Chunlin Mei,Yi Wang,Dan Ding,Feng Wu,Xin Tang,Xianzhi Ye,Yingchun Ye,Bing Liu,Jie Yang,Wen Yin,Aili Wang,Guohui Fan,Fei Zhou,Zhibo Liu,Xiaoying Gu,Jiuyang Xu,Lianhan Shang,Lianhan Shang,Yi Zhang,Lianjun Cao,Guo Tingting,Yan Wan,Hong Qin,Yushen Jiang,Thomas Jaki,Thomas Jaki,Frederick G. Hayden,Peter Horby,Bin Cao,Chen Wang +48 more
TL;DR: In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits, however, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies.
Journal ArticleDOI
Compassionate Use of Remdesivir for Patients with Severe Covid-19.
Jonathan Grein,Norio Ohmagari,Daniel Shin,George Diaz,Erika Asperges,Antonella Castagna,Torsten Feldt,Gary M. Green,Margaret L. Green,François-Xavier Lescure,Emanuele Nicastri,Rentaro Oda,Kikuo Yo,Eugenia Quiros-Roldan,Alex Studemeister,John Redinski,Seema Ahmed,Jorge Bernett,Daniel Chelliah,Danny Chen,Shingo Chihara,Stuart H. Cohen,Jennifer Cunningham,Antonella D’Arminio Monforte,Saad Ismail,Hideaki Kato,Giuseppe Lapadula,Erwan L’Her,Toshitaka Maeno,Sumit Majumder,Marco Massari,Marta Mora-Rillo,Yoshikazu Mutoh,Duc Nguyen,Ewa Verweij,Alexander Zoufaly,Anu Osinusi,Adam DeZure,Yang Zhao,Lijie Zhong,Anand Chokkalingam,Emon Elboudwarej,Laura Telep,Leighann Timbs,Ilana Henne,Scott Sellers,Huyen Cao,Susanna K. Tan,Lucinda Winterbourne,Polly Desai,Robertino Mera,Anuj Gaggar,Robert P. Myers,Diana M. Brainard,Richard Childs,Timothy Flanigan +55 more
TL;DR: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients, and Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesavir therapy.
Journal ArticleDOI
Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19)
Waleed Alhazzani,Morten Hylander Møller,Yaseen M. Arabi,Mark Loeb,Michelle Ng Gong,Eddy Fan,Simon Oczkowski,Mitchell M. Levy,Mitchell M. Levy,Lennie P. G. Derde,Lennie P. G. Derde,Amy L. Dzierba,Bin Du,Michael S. Aboodi,Hannah Wunsch,Hannah Wunsch,Maurizio Cecconi,Younsuck Koh,Daniel S. Chertow,Kathryn Maitland,Fayez Alshamsi,Emilie P. Belley-Côté,Emilie P. Belley-Côté,Massimiliano Greco,Matthew Laundy,Jill S. Morgan,Jozef Kesecioglu,Allison McGeer,Leonard A. Mermel,Manoj J. Mammen,Paul E. Alexander,Amy S. Arrington,John Centofanti,Giuseppe Citerio,Bandar Baw,Bandar Baw,Ziad A. Memish,Naomi E Hammond,Naomi E Hammond,Frederick G Hayden,Laura Evans,Andrew Rhodes +41 more
TL;DR: The Surviving Sepsis Campaign CO VID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19, and will provide new recommendations in further releases of these guidelines.
References
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Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys
Travis K. Warren,Robert Jordan,Michael K. Lo,Adrian S. Ray,Richard L. Mackman,Veronica Soloveva,Dustin Siegel,Michel Perron,Roy Bannister,Hui Hon Chung,Nate Larson,Robert G. Strickley,Jay Wells,Kelly S. Stuthman,Sean A. Van Tongeren,Nicole L. Garza,Ginger Donnelly,Amy C. Shurtleff,Cary Retterer,Dima N. Gharaibeh,Rouzbeh Zamani,Tara Kenny,Brett P. Eaton,Elizabeth C. Grimes,Lisa S. Welch,Laura Gomba,Catherine L. Wilhelmsen,Donald K. Nichols,Jonathan E. Nuss,Elyse R. Nagle,Jeffrey R. Kugelman,Gustavo Palacios,Edward Doerffler,Sean Neville,Ernest Carra,Michael O. Clarke,Lijun Zhang,Willard Lew,Bruce Ross,Queenie Wang,Kwon Soo Chun,Lydia Wolfe,Darius Babusis,Yeojin Park,Kirsten M. Stray,Iva Trancheva,Joy Y. Feng,Ona Barauskas,Yili Xu,Pamela Wong,Molly R. Braun,Mike Flint,Laura K. McMullan,Shan Shan Chen,Rachel Fearns,S. Swaminathan,Douglas L. Mayers,Christina F. Spiropoulou,William A. Lee,Stuart T. Nichol,Tomas Cihlar,Sina Bavari +61 more
TL;DR: These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates, and the broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenavirus, and coronavirus suggests the potential for wider medical use.
Journal ArticleDOI
Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp
Xiangguo Qiu,Gary Wong,Jonathan Audet,Alexander Bello,Lisa Fernando,Judie B. Alimonti,Hugues Fausther-Bovendo,Haiyan Wei,Jenna Aviles,Ernie Hiatt,Ashley K. Johnson,Josh Morton,Kelsi Swope,Ognian Bohorov,Natasha Bohorova,Charles Goodman,Do Jin Kim,Michael H. Pauly,Jesus Velasco,James Pettitt,Gene G. Olinger,Kevin J. Whaley,Bianli Xu,James E. Strong,Larry Zeitlin,Gary P. Kobinger +25 more
TL;DR: It is shown that a combination of monoclonal antibodies (ZMapp), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge, and ZMapp exceeds the efficacy of any other therapeutics described so far.
Journal ArticleDOI
Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody
Davide Corti,John Misasi,Sabue Mulangu,Daphne A. Stanley,Masaru Kanekiyo,Suzanne E. Wollen,Aurélie Ploquin,Nicole A. Doria-Rose,Ryan P. Staupe,Michael Bailey,Wei Shi,Misook Choe,Hadar Marcus,Emily A. Thompson,Alberto Cagigi,Chiara Silacci,Blanca Fernandez-Rodriguez,Laurent Perez,Federica Sallusto,Fabrizia Vanzetta,Gloria Agatic,Elisabetta Cameroni,Neville K. Kisalu,Ingelise J. Gordon,Julie E. Ledgerwood,John R. Mascola,Barney S. Graham,Jean-jacques Muyembe-Tamfun,John C. Trefry,Antonio Lanzavecchia,Antonio Lanzavecchia,Nancy J. Sullivan +31 more
TL;DR: It is ascertained that a human survivor of the 1995 Kikwit Ebola virus disease outbreak maintained circulating antibodies against the Ebola virus surface glycoprotein for more than a decade after infection, suggesting that a simplified therapeutic strategy for human Ebola infection may be possible.
Journal ArticleDOI
Development of Clinical-Stage Human Monoclonal Antibodies That Treat Advanced Ebola Virus Disease in Nonhuman Primates.
Kristen E. Pascal,Drew Dudgeon,John C. Trefry,Manu Anantpadma,Yasuteru Sakurai,Charles D. Murin,Hannah L. Turner,Jeanette L. Fairhurst,Marcela Torres,Ashique Rafique,Ying Yan,Ashok Badithe,Kevin Yu,Terra Potocky,Sandra L. Bixler,Taylor B. Chance,William D. Pratt,Franco Rossi,Joshua D. Shamblin,Suzanne E. Wollen,Justine M. Zelko,Ricardo Carrion,Gabriella Worwa,Hilary M. Staples,Darya Burakov,Robert Babb,Gang Chen,Joel H. Martin,Tammy T. Huang,Karl J. Erlandson,Melissa S Willis,Kimberly Armstrong,Thomas M Dreier,Andrew B. Ward,Robert A. Davey,Margaret L. Pitt,Leah Lipsich,Peter W. Mason,William C. Olson,Neil Stahl,Christos A. Kyratsous +40 more
TL;DR: A single dose of a cocktail of the 3 antibodies protected nonhuman primates (NHPs) from EBOV disease even after disease symptoms were apparent, and demonstrates high-level postexposure protection from lethal E BOV disease in NHPs.
Journal ArticleDOI
Blood Chemistry Measurements and d-Dimer Levels Associated with Fatal and Nonfatal Outcomes in Humans Infected with Sudan Ebola Virus
TL;DR: Blood samples from patients infected with the Sudan species of Ebola virus were tested for a panel of analytes to evaluate their clinical condition and to compare values obtained, indicating that disseminated intravascular coagulation is an early and important component of EBOV disease.
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