Hydroelectrolytic Disorder in COVID-19 patients: Evidence Supporting the Involvement of Subfornical Organ and Paraventricular Nucleus of the Hypothalamus

• Published in: Neuroscience and biobehavioral reviews Vol. 124; pp. 216 - 223
• Main Authors: de Melo, Igor Santana, Sabino-Silva, Robinson, Cunha, Thúlio Marquez, Goulart, Luiz Ricardo, Reis, Wagner Luis, Jardim, Ana Carolina Gomes, Shetty, Ashok K., de Castro, Olagide Wagner
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.05.2021
• Subjects: Animals; Brain; COVID-19; COVID-19 - complications; COVID-19 - pathology; Humans; Hydroelectrolyte balance; Hypokalemia; Neuroinvasion; Paraventricular Hypothalamic Nucleus - pathology; Paraventricular Hypothalamic Nucleus - virology; Power Plants; Review; SARS-CoV-2; Subfornical Organ - pathology; Subfornical Organ - virology; Water-Electrolyte Imbalance - etiology; Water-Electrolyte Imbalance - virology; COVID-19; Hypokalemia; Brain; Neuroinvasion; SARS-CoV-2; Hydroelectrolyte balance
• ISSN: 0149-7634; 1873-7528
• DOI: 10.1016/j.neubiorev.2021.02.008

•SARS-CoV-2 invades the central nervous system through the olfactory bulb.•Subfornical organ may be compromised by SARS-CoV-2.•COVID-19 patients present hypokalemia.•Hydroelectrolyte balance is modulated by hypothalamic nuclei and subfornical organ.•The potential neuroinvasion of SARS-CoV-2 promotes hydroelectrolytic disorders. Multiple neurological problems have been reported in coronavirus disease-2019 (COVID-19) patients because severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) likely spreads to the central nervous system (CNS) via olfactory nerves or through the subarachnoid space along olfactory nerves into the brain’s cerebrospinal fluid and then into the brain’s interstitial space. We hypothesize that SARS-CoV-2 enters the subfornical organ (SFO) through the above routes and the circulating blood since circumventricular organs (CVOs) such as the SFO lack the blood-brain barrier, and infection of the SFO causes dysfunction of the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON), leading to hydroelectrolytic disorder. SARS-CoV-2 can readily enter SFO-PVN-SON neurons because these neurons express angiotensin-converting enzyme-2 receptors and proteolytic viral activators, which likely leads to neurodegeneration or neuroinflammation in these regions. Considering the pivotal role of SFO-PVN-SON circuitry in modulating hydroelectrolyte balance, SARS-CoV-2 infection in these regions could disrupt the neuroendocrine control of hydromineral homeostasis. This review proposes mechanisms by which SARS-CoV-2 infection of the SFO-PVN-SON pathway leads to hydroelectrolytic disorder in COVID-19 patients.