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The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis

2020; Cold Spring Harbor Laboratory; Linguagem: Inglês

10.1101/2020.06.08.139329

Sreekala S. Nampoothiri, Florent Sauvé, Gaëtan Ternier, Daniela Fernandois, Caio Fernando Ferreira Coêlho, Mónica Imbernón, Eleonora Deligia, Romain Perbet, V. Florent, Marc Baroncini, Florence Pasquier, François Trottein, Claude‐Alain Maurage, Virginie Mattot, Paolo Giacobini, Sowmyalakshmí Rasika, Vincent Prévot,

COVID-19 Clinical Research Studies

Abstract Most patients with COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), display neurological symptoms, and respiratory failure in certain cases could be of extra-pulmonary origin. Hypothalamic neural circuits play key roles in sex differences, diabetes, hypertension, obesity and aging, all risk factors for severe COVID-19, besides being connected to olfactory/gustative and brainstem cardiorespiratory centers. Here, human brain gene-expression analyses and immunohistochemistry reveal that the hypothalamus and associated regions express angiotensin-converting enzyme 2 and transmembrane proteinase, serine 2, which mediate SARS-CoV-2 cellular entry, in correlation with genes or pathways involved in physiological functions or viral pathogenesis. A post-mortem patient brain shows viral invasion and replication in both the olfactory bulb and the hypothalamus, while animal studies indicate that sex hormones and metabolic diseases influence this susceptibility.