Int J Infect Dis. Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study

[Giuseppe]

[Source: ScienceDirect, full page: (LINK). Abstract, edited.]


Journal of Infectious Diseases, Available online 6 January 2014 / In Press, Accepted Manuscript

Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study

Jaffar A. Al-Tawfiq<SUP>a</SUP><SUP>, </SUP><SUP>b</SUP> Hisham Momattin<SUP>c </SUP>Jean Dib<SUP>c </SUP>Ziad A. Memish<SUP>d</SUP><SUP>, </SUP><SUP>e</SUP>
<SUP></SUP>
<SUP>a</SUP> Internal Medicine, Saudi Aramco Medical Services Organization, PO Box 76, Room A-428-2, Building 61, Dhahran Health Center, Dhahran 31311, Saudi Arabia; <SUP>b</SUP> Indiana University School of Medicine, Indiana, USA; <SUP>c</SUP> Pharmacy Services Division, Saudi Aramco Medical Services Organization, Dhahran, Saudi Arabia; <SUP>d</SUP> WHO Collaborating Center for Mass Gathering Medicine, Ministry of Health, Riyadh, Saudi Arabia; <SUP>e</SUP> Al-Faisal University, Riyadh, Saudi Arabia

Received 9 December 2013 - Accepted 9 December 2013 - Available online 6 January 2014

Open Access


Summary

Background

The Middle East respiratory syndrome coronavirus (MERS-CoV) has been reported to have a high case-fatality rate. Currently, there is no specific therapy or vaccine with proven effectiveness for MERS-CoV infections.


Methods

A combination of ribavirin and interferon therapy was used for the treatment of five MERS-CoV-positive patients. We reviewed the therapeutic schedule and the outcome of these patients.


Results

All patients were critically ill with acute respiratory distress syndrome treated with adjunctive corticosteroids and were on mechanical ventilation at the time of initiation of therapy. The median time from admission to therapy with ribavirin and interferon was 19 (range 10?22) days. None of the patients responded to the supportive or therapeutic interventions and all died of their illness.


Conclusions

While ribavirin and interferon may be effective in some patients, our practical experience suggests that critically ill patients with multiple comorbidities who are diagnosed late in the course of their illness may not benefit from combination antiviral therapy as preclinical data suggest. There is clearly an urgent need for a novel effective antiviral therapy for this emerging global threat.


Keywords

MERS-CoV, Interferon ;, Ribavirin ;, Pegylated interferon

Corresponding author. Tel.: +966 13 877 3524, fax: +966 13 877 3790
Copyright ? 2014 Published by Elsevier Ltd.


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[sharon sanders]

Re: Int J Infect Dis. Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study

Monday, January 06, 2014

JID: Early Observational Study On Ribavirin & Interferon Treatment of MERS-CoV





# 8133

Last September, in Nature: Animal Testing Of Drug Combo Shows Potential For Treating MERS, we looked at the the potential role of Interferon-α2b & ribavirin in the treatment of MERS-CoV infection, based on a NIAID led study conducted on rhesus macaques. At the time I cautioned that, while encouraging, the following caveats should be kept in mind:

• First, the macaque model is not a perfect substitute for humans, as they tend not to be as severely impacted by the MERS virus.
• Second, treatment was initiated 8 hours post infection, which is an earlier pharmacological intervention than most humans could hope to see.
• And third, most severe human infections have been seen in people with co-morbidities like COPD, cancer, diabetes, asthma . . . variables this study does not attempt to replicate.

Today we get a study, appearing in the Journal of Infectious Diseases (h/t @ironorehopper on FluTrackers), that looks at an early attempt at using this drug combo in treating critically ill MERS-CoV cases in Saudi Arabia last spring. First a link to the study and some excerpts from the abstract, after which I?ll return with more.

Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study
Jaffar A. Al-Tawfiq, Hisham Momattin, Jean Dib, Ziad A. Memish
Summary

Results
All patients were critically ill with acute respiratory distress syndrome treated with adjunctive corticosteroids and were on mechanical ventilation at the time of initiation of therapy. The median time from admission to therapy with ribavirin and interferon was 19 (range 10?22) days. None of the patients responded to the supportive or therapeutic interventions and all died of their illness.
Conclusions
While ribavirin and interferon may be effective in some patients, our practical experience suggests that critically ill patients with multiple comorbidities who are diagnosed late in the course of their illness may not benefit from combination antiviral therapy as preclinical data suggest. There is clearly an urgent need for a novel effective antiviral therapy for this emerging global threat.

Not exactly a rousing success, but then these were critically ill patients (all on ventilators) with profound comorbidities (4 on maintenance dialysis), and treatment was begun (on average) 19 days into their illness.

Essentially, at that stage of their illness, attempts to use this, or any other antiviral therapy, was pretty much a long shot.

During the SARS epidemic a decade ago, the early administration of Ribavirin was associated with a better outcome (see CMAJ Ribavirin in the treatment of SARS: A new trick for an old drug?), but the number of patients treated in this way was fairly small and the results far from conclusive.

Of note, of the 5 patients in this observational study, 3 developed adverse side effects from the Interferon-α2b & ribavirin combo therapy, including pancreatic enzyme elevation (n=2) and significant hemolysis (destruction of red blood cells) (n=1), both known side effects of ribavirin.

None of which knocks this drug combo out of contention as a potential MERS treatment, as it may eventually prove beneficial if administered early enough in the illness. Despite the potential for side effects, the Ribavirin and Interferon combination has previously found success as a treatment for chronic hepatitis C.

While we still lack an effective antiviral to treat the MERS coronavirus, another avenue of investigation is in the use of convalescent plasma from patients who have recovered from the virus (see my 2011 blog Plasma Therapy For Severe H1N1 for a broader discussion of this type of therapy).

This from the World Health OrganizationNovel coronavirus summary and literature update ? as of 8 May 2013.

An international network of clinical experts has been convened to discuss therapeutic options. It concluded that in the absence of clinical evidence for disease-specific interventions, convalescent plasma is the most promising therapy. A memo containing advice for setting up international or regional serum centers, to obtain and share convalescent plasma, has been circulated by WHO to ministries of health in affected countries. WHO and the International Severe Acute Respiratory and Emerging Infection Consortium have developed and shared a set of research protocols and case report forms to help clinical investigators establish studies of pathogenesis and pharmacology. These are available at http://www.prognosis.org/isaric/.

This does highlight the need, however, for rapid diagnosis and early intervention, regardless of what treatment is eventually found to be effective.

Posted by Michael Coston at <a class="timestamp-link" href="http://afludiary.blogspot.com/2014/01/jid-early-observational-study-on.html" rel="bookmark" title="permanent link"><abbr class="published" itemprop="datePublished" title="2014-01-06T13:48:00-05:00">1:48 PM</abbr>

[Emily]

Re: Int J Infect Dis. Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study

Also the human ARDS patients had been given corticosteroids for an average of 19 days prior to additional treatments given.

See:
Corticosteroids and ARDS: A review of treatment and prevention evidence

SARS unanswered questions