Cytokine regulation disbalance: the basis for COVID-19 immunopathogenesis

Abstract

Coronavirus infection activates two main signaling pathways for type I and III IFN and the gene expression and synthesis of proinflammatory cytokines. These cytokines are required for antiviral defense and inflammatory reaction formation. SARS-CoV-2 coronavirus could inhibit the IFN system by depressing signaling pathways for IFN gene expression, synthesis, and secretion. IFN inhibition should be considered the primary reason for coronavirus escape from the immune system and a key factor for COVID-19 immunopathogenesis. Cytokine regulation disbalance in patients with severe COVID-19 is closely associated with low and delayed IFN synthesis, while proinflammatory cytokine production by macrophages and T-lymphocytes continues simultaneously with intensive virus replication. Thus, the reason for COVID-19 immunopathogenesis is the cytokine regulation disbalance where IFN inhibition and intensive proinflammatory cytokine synthesis lead to cytokine storm, inadequate inflammation, respiratory distress syndrome development, respiratory failure, systemic inflammatory complications, and polyorganic failure.