Tabriz University of Medical Sciences Pharmaceutical Sciences 1735-403X 27 Covid-19 2021 11 01 Anti-Rheumatic Drugs as Potential Anti-inflammatory, Immunomodulatory Agents against COVID-19: A Systematic Review S13 S28 10.34172/PS.2021.40 EN Reza Sinaei https://orcid.org/0000-0002-2702-5836 Sara Pezeshki https://orcid.org/0000-0001-9795-4713 Ali Asadipour https://orcid.org/0000-0002-1449-2195 Reza Shiari https://orcid.org/0000-0002-7712-279X Roya Sinaei https://orcid.org/0000-0001-9029-9330 Ali Sinaei https://orcid.org/0000-0001-9108-9335 Journal Article 10.34172/PS.2021.40 2020 09 10 2021 07 14 Background: The effective responses of both innate and adaptive immunity are crucial in combating novel coronavirus-2 infection. An excessive response may lead to cytokine storm, which is a challenging problem in therapeutic strategies. Methods: A systematic review was carried out by searching Ovid MEDLINE, PubMed, Google Scholar, and Cochrane library databases from inception, for anti-inflammatory and immunomodulatory drugs against coronavirus disease 2019 (COVID-19). Results: The results of the effectiveness of Hydroxychloroquine are just like a sinusoidal diagram and in a state of ambiguity. Thalidomide was effective in some cases but has not yet been proven. Low-dose Corticosteroids may be effective in the early stages of the illness as a bridge. There is no evidence of benefits or adverse outcomes for the use of non-steroidal anti-inflammatory drugs and Cyclosporine-A. In some critically ill patients, Interleukin-6 (IL-6) and IL-1 blockers and to some extent, Tumor-Necrosis-Factor-α and Janus-Kinase inhibitors are useful. Finally, high-dose intravenous immunoglobulin reversed the deterioration of patients in most trials. Conclusion: One strategy behind the treatments for COVID-19 is based on breaking the cytokine storm. Although avoiding the suppression of anti-viral immunity is crucial by choosing the weaker and more selective anti-inflammatories, some strategies are kept for hyper-inflammatory situations. Scheduling of treatment is also important. Although low-dose steroids may be effective in the early stages of the illness, "Tocilizumab" is more effective in severe situations, when the IL-6 level is high and other drugs are ineffective. Therefore, consideration should be given to each patient separately.