Renalase Challenges the Oxidative Stress and Fibroproliferative Response in COVID-19

The hallmark of the coronavirus disease 2019 (COVID-19) pathophysiology was reported to be an inappropriate and uncontrolled immune response, evidenced by activated macrophages, and a robust surge of proinflammatory cytokines, followed by the release of reactive oxygen species, that synergistically result in acute respiratory distress syndrome, fibroproliferative lung response, and possibly even death. For these reasons, all identified risk factors and pathophysiological processes of COVID-19, which are feasible for the prevention and treatment, should be addressed in a timely manner. Accordingly, the evolving anti-inflammatory and antifibrotic therapy for severe COVID-19 and hindering post-COVID-19 fibrosis development should be comprehensively investigated. Experimental evidence indicates that renalase, a novel amino-oxidase, derived from the kidneys, exhibits remarkable organ protection, robustly addressing the most powerful pathways of cell trauma: inflammation and oxidative stress, necrosis, and apoptosis. As demonstrated, systemic renalase administration also significantly alleviates experimentally induced organ fibrosis and prevents adverse remodeling. The recognition that renalase exerts cytoprotection via sirtuins activation, by raising their NAD⁺ levels, provides a "proof of principle" for renalase being a biologically impressive molecule that favors cell protection and survival and maybe involved in the pathogenesis of COVID-19. This premise supports the rationale that renalase's timely supplementation may prove valuable for pathologic conditions, such as cytokine storm and related acute respiratory distress syndrome. Therefore, the aim for this review is to acknowledge the scientific rationale for renalase employment in the experimental model of COVID-19, targeting the acute phase mechanisms and halting fibrosis progression, based on its proposed molecular pathways. Novel therapies for COVID-19 seek to exploit renalase's multiple and distinctive cytoprotective mechanisms; therefore, this review should be acknowledged as the thorough groundwork for subsequent research of renalase's employment in the experimental models of COVID-19.