Estrogens as a Possible Therapeutic Strategy for the Management of Neuroinflammation and Neuroprotection in COVID-19

The Coronavirus disease 2019 (COVID-19) affects several tissues, including the central and peripheral nervous system. It has also been related to signs and symptoms that suggest neuroinflammation with possible effects in the short, medium, and long term. Estrogens could have a positive impact on the management of the disease, not only due to its already known immunomodulator effect, but also activating other pathways that may be important in the pathophysiology of COVID-19, such as the regulation of the virus receptor and its metabolites. In addition, they can have a positive effect on neuroinflammation secondary to pathologies other than COVID-19. The aim of this study is to analyze the molecular mechanisms that link estrogens with their possible therapeutic effect for neuroinflammation related to COVID-19. Advanced searches were performed in scientific databases as PubMed, ProQuest, EBSCO, the Science Citation index, and clinical trials. Estrogens have been shown to participate in the immune modulation of the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to this mechanism, we propose that estrogens can regulate the expression and activity of the Angiotensin-converting enzyme 2 (ACE2), reestablishing its cytoprotective function, which may be limited by its interaction with SARS-CoV-2. In this proposal, estrogens and estrogenic compounds could increase the synthesis of Angiotensin-(1-7) (Ang-(1-7)) that acts through the Mas receptor (MasR) in cells that are being attacked by the virus. Estrogens can be a promising, accessible, and low-cost treatment for neuroprotection and neuroinflammation in patients with COVID-19, due to its direct immunomodulatory capacity in decreasing cytokine storm and increasing cytoprotective capacity of the axis ACE2/Ang (1-7)/MasR.