Immunomodulatory cytokines as a novel therapeutic avenue in COVID-19 infection :Towards cytokine-based therapy

Abstract

Introduction: The recently emerging COVID-19 is continuing to be a great challenge to health systems throughout the world and its scenario is still getting worse. The rapidly flaring global threat, COVID-19, is caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). (SARS-CoV-2) may lead to severe disease in some cases, leading to acute respiratory distress syndrome, multi-organ failure, and death. This severe phenotype seems to be associated with a cytokine storm (CS) and immune dysregulation. Immune-pathological damage, in COVID-19 patients, with its inflammatory axis that is caused by complex crosstalk between host epithelial cells and excessively activated immune cells results in tremendous release of inflammatory cytokines known as (CS) or CS syndrome. CS is composed of a wide array of cytokines release as tumour necrosis alpha (TNF-α), interleukin (IL)-1, (IL-2, 6, 8, 10), IFN-γ; granulocyte colony-stimulating factor (G-CSF); monocyte chemo attractant protein-1, and granulocyte/macrophage colony-stimulating factor. Aim: So the main objective of our project is to explore the potential role of the immune-modulatory therapies in treatment of COVID-19 patients and their impact on clinical outcome. Methods: 29 studies were selected following a PRISMA search strategy focusing on terms of COVID-19 and its related inflammatory markers (cytokines storm) or potential intervention with a immune modulatory agents like antimalarials, corticosteroids, immunosuppressives, anakinra, chloroquine, hydroxychloroquine, tocilizumab, “low-molecular-weight heparin”, heparin, immunoglobulins, “JAK inhibitors” and cyclosporine. Papers were first selected based on screening of study title and abstract to ensure search terms were included. PRISMA based selected papers were then subjected to both inclusion and exclusion criteria. Results: Recently multiple potential therapies that target the dysregulated immune response and curtail the (COVID-19) associated CS have become a critical focus of several clinical trials. The included studies in the current review displayed a contradicting results across the twenty nine selected studies. While some clinical studies supported use of immune modulatory agents as adjuvant to the traditional anti-(COVD-19) protocols or as an alternative therapeutic option that provide better clinical outcome. Other trials didn’t support the use immune modulatory agents as therapeutic tool in (COVD-19) patients. Conclusion: SARS-CoV-2 outcome is influenced not only by viral virulence but also with the dysregulated inflammatory reaction, so a probable combination therapeutic approach using antiviral agents plus immune modulatory agents may be considered as an effective therapeutic modality. The appropriate timing of diagnosis together with effective control of the CS appears to be crucial to improve clinical out come and enhance the survival rate in COVID-19 patients, but there is a further need to validate their safety and efficacy through larger randomized clinical trials.