**1. Introduction**

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has set a major healthcare issues and economic burden worldwide. Like other RNA viruses, SARS-CoV-2, while adapting to their new human hosts, is prone to genetic evolution with the development of mutations over time, resulting in mutant variants that may have different characteristics than its ancestral strains. Currently, treatments of COVID-19 are mainly repurposing drugs or symptomatic with no definitive treatment directed against the virus [1].

Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, an unusually large RNA genome, and a unique replication strategy. In the absence of specific treatment or antiviral drugs been proven against SARS-CoV-2, researchers have proposed many therapeutics agents used as adjunctive treatments for COVID-19 patients apart from supplemental oxygen therapy or mechanical ventilation [1, 2].

In Coronavirus infection, viral surface glycoproteins, double-stranded RNA, and intracellular viral proteins all have the capacity to activate signal transduction pathways leading to the expression of cytokines and chemokines. Cytokine storm is one of the main mechanisms of the disease and is believed to trigger an exaggerated immune

response in the host and has been observed more frequently in severe COVID-19 patients associated with complications, such as acute respiratory distress syndrome (ARDS) and other multiple organ injuries [2].

An important consequence of RNA virus infection and COVID-19 disease is cellfree DNA (cfDNA) found in body fluids such as serum or plasma. cfDNA originates from nuclear or mitochondrial DNA released from dead/dying cells, DNA released from live cells, and foreign DNA from invading viruses [3]. The other interesting points are the fact that monoclonal antibody against IL-6 receptors or IL-6 inhibitor has shown to be an effective agent in COVID-19 patients with severe illness. Initially, it is frequently used for the treatment of rheumatoid arthritis patients. These drugs targeting IL-6 as inflammatory mediators will decrease inflammatory response in cytokine storm, hence minimizing the incidence of jeopardize complications, such as ARDS. Tocilizumab and other anti-IL-6 receptors antagonist has been recommended as an immunotherapy in severely ill patients and improved the clinical outcomes as well as decrease in mortality rate [3, 4]. The aim of this review is describe the role of IL-6 in RNA virus infection.
