Neurological Affection and Perspectives on the Orexigenic System during COVID-19 Pandemic

Abstract

The history of coronaviruses revealed that these viruses were responsible for previous outbreaks, including the 2003 outbreak of the severe acute respiratory syndrome (SARS). A severe pandemic, SARS-CoV-2, began in 2019 and has continued to peak in successive waves as a result of the virus' ability to mutate versus the body's short-term immunity to it. Obesity and diabetes mellitus (DM), which are both associated with low-grade inflammatory states and defective lung reparative mechanisms, as well as low tissue-to-lung ACE2 expression in DM, were among the risk factors connected to COVID-19 morbidity and neurological affection. These risk factors included ACE2 overexpression in obesity and DM. Such neurological affection is predisposed by the ACE2 that SARS-CoV-2 sheds upon entering the brain and by the inflammatory cytokines that also invade the brain. However, ACE2 was not sufficient to justify the occurrence of neurological disorders with COVID-19, owing to its lower brain expression, relative to other tissues. Other mediators should have contributed to such neurological disorders, of which, orexins (OXs) are discussed, owing to multiple functional similarities to ACE2. Eventually, this review highlights such similarities selected according to their possible relevance to COVID-19 symptomatology and pathology. As OXs agonists and antagonists are readily available, it is advantageous to be able to confirm or refute the potential benefits of targeting the orexigenic system for COVID-19 neurological affliction. It is advised to conduct detailed research using both in vivo and in vitro models to confirm or deny such perspective involvement.