Anti-inflammatory, immunomodulatory agents as potential strategies against COVID-19: A systematic review

Abstract

Aim: SARS-COV-2 infections are causing substantial morbidity and mortality, especially due to "exuberant cytokine storm". In this study we review effectiveness of anti-inflammatory and immunomodulatory drugs in this situation. Methods: Ovid MEDLINE, PUBMED, Google Scholar and Cochrane library searched for anti-inflammatory and immunomodulatory drugs against COVID-19 including: Anti malaria agents, non-steroidal anti-inflammatory drugs, steroids, cyclosporine, thalidomide, IVIG, interlukin-6 blockade, IL-1 blockade, tumor necrosis factor-α blockade, and Janus kinase inhibitors. Results: We included 95 studies. Unlike preliminary positive results, the effect of Chloroquine is questionable. Thalidomide has been shown to be effective in some studies but not be proved yet. Low dose Corticosteroids may be effective in the early phases of SARS-CoV-2 as a bridge. There is neither evidence of benefits or adverse outcomes for the use of NSAIDs, nor is there evidence indicating that target therapies (IL-1, TNFα and JAK inhibitors) and also cyclosporine are effective. In some cases and clinical trials, interlukin-6 blockade is useful in critically ill patients. Finally, the high dose IVIG reversed the deterioration of patients in most clinical trials. Conclusion: Unlike preliminary positive results, Hydroxychloroquine seems ineffective. Thalidomide is effective in some cases. Although, low dose CS may be effective in the early phases of illness, administration of NSAIDs and steroids is controversial. The effectiveness of more target therapies including IL-1, TNF-α, and JAK inhibitors, also cyclosporine is less clear. Tocilizumab can be used in severe situations, where other drugs are ineffective. IVIG can be used at least as a bridge therapy in deteriorating patients.