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.
Jaffar A. Al-Tawfiq, Hisham Momattin, Jean Dib, Ziad A. Memish
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.
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).
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.