Reply to “Statins may decrease the Fatality Rate of MERS Infection”

Totura, Allison L.; Baric, Ralph S.

Yuan suggests in a comment on our recent paper (7, 8) that immunomodulatory therapeutic administration of an early, high dose of statins to treat acute MERS or SARS patients should be an experimental course of treatment. The author anticipates that treatment with statins would inhibit MyD88 signaling and downstream NF-B responses, predicting an inhibition of inflammatory responses that would lead to improved disease outcomes in MERS patients. Although there is a linkage in MERS and SARS patient samples between aberrant signaling of interferonstimulated genes or cytokines and severe coronavirus-induced disease, innate immune signaling is still required for an effective immune response that results in less severe disease following coronavirus infection (9, 10) . While testing drugs like statins that are already know to be safe for human use is an attractive concept, there is no evidence that the combination of attenuated MyD88 and NF-B signaling would improve disease outcome compared to the outcome using NF-B-inhibiting drugs, which do increase survival in mouse models of SARS-CoV infection (11) . Importantly, the efficacy of NF-B inhibitors, statins, or other therapeutics should be rigorously evaluated in more vulnerable agedmouse models which replicate the increased severity of coronavirus disease seen in elderly humans (12) .