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

Abstract

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.

Clinical efficacy and safety of Janus kinase inhibitors for COVID-19: A systematic review and meta-analysis of randomized controlled trials

“…Janus kinase (JAK) inhibitors can downregulate the JAK/signal transducer and activator of transcription protein signaling pathways and decrease cytokine concentrations, and therefore they have been proposed as a potential therapies to mitigate the immune response and prevent a hyperinflammatory state, which may further improve clinical outcomes of hospitalized COVID-19 patients [7] , [8] , [9] , [10] . The clinical uses of JAK inhibitors, including ruxolitinib, baricitinib, and tofacitinib for COVID-19 patients have been reported in many observational studies [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , in which adding JAK inhibitors could help resolve a hyperinflammatory state, improve respiratory function, reduce mortality, and increase survival discharge for patients with SARS-CoV-2 infections.…”

Analysis of related factors for RA flares after SARS-CoV-2 infection: a retrospective study from patient survey

“…It has also been reported that using Baricitinib can increase the risk of critical illness of COVID-19 in RA patients. As a potent immunosuppressant, Baricitinib cannot distinguish between infected host cells and healthy cells and has an inhibitory effect on the immune response of patients during the treatment 26 . In particular, RA patients have autoimmune dysfunction, and the use of JAK inhibitors (compared with TNF-α inhibitors) will increase the risk of infection, major adverse cardiovascular events (MACE), and thrombosis in RA patients 27 .…”

The potential impact of Covid-19 on CNS and psychiatric sequels

“…The detection of COVID-19 RNA and protein particles in CNS specimens, including fluid or parenchyma and brain tissue edema, as well as partial neuronal degeneration in deceased individuals due to respiratory failure, can indicate the possibility of SARS-CoV-2 directly infecting the neurological system ( Soltani Zangbar et al, 2021 ). SARS-CoV-2 can infect tissues via connecting to the angiotensin-converting enzyme 2 (ACE2) receptor on particular host cells, according to new research ( Bahari et al, 2021 , Meftahi et al, 2020 ). This binding, like that of SARS-CoV, is mediated by the spike protein found on the surface of SARS-CoV-2.…”