Conclusion
The importance of the host response in infectious disease has been
highlighted very recently including the suggestion that ARBs and
statins, both very cheap, off patent and in our pharmacies currently
could be evaluated to improve outcomes including survival in COVID-19
patients (5). This approach builds upon the pioneering earlier (4,
treating of the host concept, based upon an understanding that a
beneficial clinical phenotype has been observed with a treatment and
this can be employed for the purpose of treating the host.
The approach brings together three concepts; namely the value of
therapeutics in stabilizing patients prior to subsequent interventions,
repurposing therapeutics for new indications and potential of treating
the host. During this review the following became evident;
- There is a need to comprehensively determine if there exists an
alignment of the proposed repurposed drug with the known
pathophysiology of the viral infection. In the case of RASI what is
remarkable is the interplay between an existing predisposition to RAS
induced inflammation with an overlay of severe RAS dysregulation with
COVID-19 disease.
- The fundamental importance of observational (administrative)data as a
pathfinder source of information from which to select candidate drugs
for evaluation in a repurposed context.
- The importance to adhere to the principals of repurposing as they
relate to dose and safety.
We have described a framework for treating the host with repurposed
drugs and illustrated its use for RAS inhibitors. We would caution that
even though there exists observational data highlighting a potential
protective effect of RAS inhibition consistent with a pathophysiological
alignment this outcome may still be due to chance Therefore based on our
analysis we believe a clinical trial for RAS inhibitors would be
justified and note that eight trials of this type have already been
registered.
Finally, with the advent of COVID-19 disease discussion has moved to
delineating the treatment of the host from treatment and elimination of
the infective agent to treating the host as out lined and pioneered by
David Fedson.
Competing Interests’ Statement - None