Old drug, new Trick? The rationale for the treatment of COVID-19 with activated protein C.

As the COVID-19 pandemic continues, researchers seek to identify efficacious treatments. Current approaches to COVID-19 therapeutics focus on antiviral agents, convalescent plasma, monoclonal antibodies, immunomodulators and more traditional therapies such as steroids [1-6]. Reversing disturbances in coagulation has also been identified as a priority area for candidate therapies, such as through the Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 adaptive clinical trial (ACTIV-4) which is currently evaluating aspirin, heparins and apixaban [7]. Since there is a clear relationship between mechanisms of coagulation and the immune response, it is possible that reversing disturbances in coagulation may diminish the dysregulated immune response observed in COVID-19. The basis for this hypothesis is described below and is followed by discussion of a proposed candidate therapy - activated protein C. By treating COVID-19 patients using a novel approach, which does not focus on immune-based or antiviral treatments, but instead which addresses both the anti-thrombotic and inflammatory consequences of infection, the hope is that new therapeutic targets can be considered and new candidate therapies, such as activated protein C, may be evaluated.