Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV–infected rhesus macaques
Darryl Falzarano,Emmie de Wit,Angela L. Rasmussen,Friederike Feldmann,Atsushi Okumura,Dana P. Scott,Doug Brining,Trenton Bushmaker,Cynthia Martellaro,Laura Baseler,Arndt Benecke,Arndt Benecke,Michael G. Katze,Vincent J. Munster,Heinz Feldmann,Heinz Feldmann +15 more
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TLDR
Treatment of MERS-CoV infected rhesus macaques with IFN-α2b and ribavirin reduces virus replication, moderates the host response and improves clinical outcome.Abstract:
The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) is of global concern: the virus has caused severe respiratory illness, with 111 confirmed cases and 52 deaths at the time of this article's publication. Therapeutic interventions have not been evaluated in vivo; thus, patient management relies exclusively on supportive care, which, given the high case-fatality rate, is not highly effective. The rhesus macaque is the only known model organism for MERS-CoV infection, developing an acute localized to widespread pneumonia with transient clinical disease that recapitulates mild to moderate human MERS-CoV cases. The combination of interferon-α2b and ribavirin was effective in reducing MERS-CoV replication in vitro; therefore, we initiated this treatment 8 h after inoculation of rhesus macaques. In contrast to untreated, infected macaques, treated animals did not develop breathing abnormalities and showed no or very mild radiographic evidence of pneumonia. Moreover, treated animals showed lower levels of systemic (serum) and local (lung) proinflammatory markers, in addition to fewer viral genome copies, distinct gene expression and less severe histopathological changes in the lungs. Taken together, these data suggest that treatment of MERS-CoV infected rhesus macaques with IFN-α2b and ribavirin reduces virus replication, moderates the host response and improves clinical outcome. As these two drugs are already used in combination in the clinic for other infections, IFN-α2b and ribavirin should be considered for the management of MERS-CoV cases.read more
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References
More filters
Journal ArticleDOI
Isolation of a Novel Coronavirus from a Man with Pneumonia in Saudi Arabia
Ali Moh Zaki,Sander van Boheemen,Theo M. Bestebroer,Albert D. M. E. Osterhaus,Ron A. M. Fouchier +4 more
TL;DR: The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
Journal ArticleDOI
Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study.
Joseph S. M. Peiris,Chung-Ming Chu,V. C. C. Cheng,Kin Sang Chan,Ivan Hung,Leo L.M. Poon,K I Law,Bone S.F. Tang,T Y W Hon,CS Chan,Kwok-ning Chan,J S C Ng,Bo-Jian Zheng,Wing-Chun Ng,Raymond Lai,Yi Guan,Kwok-Yung Yuen +16 more
TL;DR: The consistent clinical progression, shifting radiological infiltrates, and an inverted V viral-load profile suggest that worsening in week 2 is unrelated to uncontrolled viral replication but may be related to immunopathological damage.
Journal ArticleDOI
Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings.
Chung-Ming Chu,V C C Cheng,Ivan Hung,M M L Wong,K H Chan,K S Chan,Richard Y.T. Kao,Leo L.M. Poon,C L P Wong,Yi Guan,Joseph S. M. Peiris,Kwok-Yung Yuen +11 more
TL;DR: The apparent favourable clinical response with lopinavir/ritonavir and ribavirin supports further randomised placebo controlled trials in patients with SARS and shows that age, hepatitis B carrier status, and lack of treatment with this antiviral combination were independent predictors of an adverse outcome.
Journal ArticleDOI
Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area.
Christopher M. Booth,Larissa M. Matukas,George Tomlinson,Anita Rachlis,David Rose,Hy A. Dwosh,Sharon Walmsley,Tony Mazzulli,Tony Mazzulli,Monica Avendano,Peter Derkach,Issa E. Ephtimios,Ian Kitai,Barbara Mederski,Steven Shadowitz,Wayne L. Gold,Wayne L. Gold,Laura Hawryluck,Elizabeth Rea,Elizabeth Rea,Jordan Chenkin,David W. Cescon,Susan M. Poutanen,Susan M. Poutanen,Susan M. Poutanen,Allan S. Detsky,Allan S. Detsky +26 more
TL;DR: The majority of cases in the SARS outbreak in the greater Toronto area were related to hospital exposure, and several features of the clinical presentation will be useful in raising the suspicion of SARS.
Journal ArticleDOI
SARS: Systematic Review of Treatment Effects
TL;DR: It was not possible to determine whether treatments benefited patients during the SARS outbreak, but clinical trials should be designed to validate a standard protocol for dosage and timing and to accrue data in real time during future outbreaks to monitor specific adverse effects and help inform treatment.