Prospects for cytokine therapy in acute respiratory viral infections, including COVID-19

Severe respiratory viral infections are accompanied by an unbalanced immune response due to suppression of endogenous interferon (IFN) synthesis, which leads to hyperproduction of proinflammatory cytokines. This results in inadequate inflammation in the lungs, accompanied by acute respiratory distress syndrome, respiratory failure, and dysfunction of other organs. Cytokine imbalance that underlies the immunopathogenesis of severe acute respiratory viral infections including COVID-19 offers the potential for two principal approaches to cytokine therapy, which are determined by the stage of the infectious process and the severity of clinical symptoms. Cytokine therapy with intranasal recombinant type I and III IFN represent a viable therapeutic strategy in prevention of virus infection or at early stages of the disease, particularly in endogenous IFN deficit at the onset. For example, during the COVID-19 pandemic, intranasal products based on recombinant IFNα2b demonstrated high antiviral activity and good tolerability, and are included in the national guidelines for control of coronavirus infection in Russia and other countries. This therapeutic approach aims at normalizing endogenous IFN expression, which may be inhibited by certain respiratory viruses, such as SARS-CoV-2. In cases of cytokine storm and severe respiratory infections, an anticytokine therapy may effectively inhibit the overproduction of proinflammatory cytokines. Both cytokine immunotherapies are based on using either synthetic analogs of endogenous cytokines or monoclonal antibodies that inhibit the cytokine up-regulation above physiological levels.