Accelerating the Evolution of Severe Acute Respiratory Syndrome Coronavirus 2: A Risk of Combining Dexamethasone and Tocilizumab for Severe Coronavirus Disease 2019

Abstract

Emerging data from open-label randomized trials without placebo controls suggest potential mortality benefits for combining corticosteroids with the interleukin 6 receptor antagonist tocilizumab in severe coronavirus disease 2019. Conversely, dual immunomodulation may weaken antiviral responses and delay viral clearance, allowing severe acute respiratory syndrome coronavirus 2 (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 are scarce. Coadministration of antiviral agents with immunomodulation could serve as a potential strategy to aid viral clearance and reduce the risk of genetic diversification.

Keywords: COVID-19; IL-6 receptor inhibitors; SARS-CoV-2; corticosteroids; evolution; tocilizumab.