Accelerating the evolution of SARS-CoV-2 - a risk of combining dexamethasone and tocilizumab for severe COVID-19.

Emerging data from open-label randomized trials without placebo controls suggest potential mortality benefits for combining corticosteroids with the IL-6 receptor antagonist tocilizumab in severe COVID-19. Conversely, dual immunomodulation may weaken anti-viral responses and delay viral clearance, allowing SARS-CoV-2 to expand its population and accrue genetic diversity within individual hosts. Generating a pool of hosts with genetically diverse viral populations while introducing new selective pressures in the form of vaccination-induced immunity, could accelerate the process of antigenic drift in SARS-CoV-2. However, clinical trials to date have largely disregarded viral outcomes, and data on viral kinetics in response to immunomodulation is scarce. Co-administration of antiviral agents with immunomodulation could serve as a potential strategy to aid viral clearance and reduce the risk of genetic diversification.