A framework for treating the host with repurposed drugs.

Treating the host in COVID-19 brings together two key pharmacological principals. The first involves the understanding of how a proposed therapeutic agent integrates within the pathogenic response. This approach thus involves understanding initially the integration of the host into the consequences of viral pathogenesis. This relationship has been well described for microbial pathogenesis in the Damage–Response Framework (DRF) in infectious diseases (9). The damaging host factors described in this microbial model, namely cytokine release (storm), chemical mediators signalling, oxygen radical production and immune complexes leading to aberrant inflammation are not specific and in fact apply equally to viruses such as influenza and the current COVID-19 disease.
The second principal involves the appropriate use of therapeutics approved for one indication but used effectively in a different setting within the DRF. Approaches used for drug repurposing, the challenges and ways in which these challenges may be tackled have been described recently in detail (10). The application to COVID-19 involves identification of drugs that in a new indication, in the correct dosage for the new disease have a substantial impact on the consequences of infection in the host.
A logical framework based on the above considerations for identifying repurposed drugs for treatment of the host would potentially include:
Using similar deduction, in 2020 Fedson et al. proposed clinical trials should be undertaken with combinations of the RAS agents angiotensin receptor blockers (ARB) and statins in patients with severe COVID-19 infection (5). His proposal provides an excellent opportunity to use our framework in evaluating repurposed RAS drugs for use in COVID-19. In the following example we focused upon drugs targeted to the RAS, but the procedure would equally apply to statins either alone or in combination with ARBs.