Pharmacological mechanism of immunomodulatory agents for the treatment of severe cases of COVID-19 infection

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a world-wide pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, treatment of severe COVID-19 is far from clear. Therefore, it is urgent to develop an effective option for the treatment of patients with COVID-19. Most patients with severe COVID-19 exhibit markedly increased serum levels of pro-inflammatory cytokines, including interferon (IFN)-α, IFN-γ, and interleukin (IL)-1β. Immunotherapeutic strategies have an important role in the suppression of cytokine storm and respiratory failure in patients with COVID-19. METHODS: A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar preprint database using all available MeSH terms for Coronavirus, SARS-CoV-2, anti-rheumatoid agents, COVID-19, cytokine storm, immunotherapeutic drugs, IFN, interleukin, JAK/STAT inhibitors, MCP, MIP, TNF. RESULTS: Here, we first review common complications of COVID-19 patients, particularly neurological symptoms. We next explain host immune responses against COVID-19 particles. Finally, we summarize the existing experimental and clinical immunotherapeutic strategies, particularly anti-rheumatoid agents and also plasma (with a high level of gamma globulin) therapy for severe COVID-19 patients. We discuss both their therapeutic effects and side effects that should be taken into consideration for their clinical application. CONCLUSION: It is suggested that immunosuppressants, such as anti-rheumatoid drugs, could be considered as a potential approach for the treatment of cytokine storm in severe cases of COVID-19. One possible limitation of immunosuppressant therapy is their inhibitory effects on host anti-viral immune response. So, the appropriate timing of administration should be carefully considered.