Monday, 9 September 2013

Combined interferon and ribavirin therapy an option for early MERS-CoV intervention?

Falzarano and colleagues write in Nature Medicine that the combination of ribavirin (an antiviral) and interferon-α2b (a cytokine key to our antiviral defenses) improved the health of MERS-CoV (EMC/2012) inoculated rhesus macaque monkeys. 

This builds on the March Study by Falzarano et al, which reported  the usefulness of this drug cocktail in reducing virus production in a cell culture system.

Treated infected animals did not suffer from increased respiratory rate, breathing difficulties or increased white blood cell counts (mostly due to neutrophils). Treated infected animals also showed no X-Ray changes in their lungs 1-day after infection and little change beyond that. Untreated animals showed mild to marked evidence of pneumonia and also lower levels of markers of inflammation and copies of viral RNA genome.

The macaques were inoculated with 106 tissue culture infective doses (TCID50) by combined intratracheal (lower respiratory tract), intranasal (upper respiratory tract), oral (ingestion) and ocular routes. That seems to represent a fairly "shock-and-awe" cocktail of inoculation routes compared to how humans may get exposed. Viral RNA was detected in spleen, kidney, lymph nodes, upper and lower respiratory tract and airways in the untreated animals - and many of those sites in the treated ones. The relevance of this study to MERS-CoV transmission is probably limited, but then it's not a transmission study, it's a treatment study. There is another article cited as in press from part of this group. It may further address tissue replication; Novel human betacoronavirus causes a transient lower respiratory tract infection in a rhesus macaque model. Proc. Natl. Acad. Sci. USA.

Interestingly, disease in the macaques is at best mild to moderate in severity, so how the drug cocktail would work when faced with severe human disease...which may take longer to develop...remains unclear. Also unclear, is what disease would look like in macaques with a similar degree of comorbidities to those seen in the most severe human MERS cases.

The main proviso is, the cocktail must be administered early; it was administered 8-hours after infecting the monkeys here. 

With a 5-working day to 2-week turnaround in testing for MERS-CoV, treatment would have to be started at first suspicion and even then might not meet this window. Given the Qatar GP story yesterday, that window would be long shut, painted over and boarded up.

Nonetheless, this is a very encouraging finding and a very nice piece of work that adds an important step in the path to providing a therapeutic option to MERS-CoV infections.