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

Florent Sauvé; Sreekala S. Nampoothiri; Sophie A. Clarke; Daniela Fernandois; Caio Fernando Ferreira Coêlho; Julie Dewisme; Edouard Mills; Gaëtan Ternier; Ludovica Cotellessa; Cristina Iglesias; Helge Müller‐Fielitz; Thibaud Lebouvier; Romain Perbet; V. Florent; Marc Baroncini; Ariane Sharif; June Ereño‐Orbea; María Mercado-Gómez; Asís Palazón; Virginie Mattot; Florence Pasquier; Sophie Catteau-Jonard; Maria Luz Martínez‐Chantar; Erik Hrabovszky; Mercé Jourdain; Dominique Deplanque; Annamaria Morelli; Giulia Guarnieri; Laurent Storme; Cyril Robil

doi:10.1016/j.ebiom.2023.104784

NeuroscienceEBioMedicineSep 13, 2023

Peer-reviewed journal article

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

Florent Sauvé iD, Sreekala S. Nampoothiri iD, Sophie A. Clarke iD, Daniela Fernandois iD, Caio Fernando Ferreira Coêlho iD, Julie Dewisme iD, Edouard Mills iD, Gaëtan Ternier iD, Ludovica Cotellessa iD, Cristina Iglesias iD, Helge Müller‐Fielitz iD, Thibaud Lebouvier iD, Romain Perbet iD, V. Florent iD, Marc Baroncini iD, Ariane Sharif iD, June Ereño‐Orbea iD, María Mercado-Gómez iD, Asís Palazón iD, Virginie Mattot iD, Florence Pasquier iD, Sophie Catteau-Jonard iD, Maria Luz Martínez‐Chantar iD, Erik Hrabovszky iD, Mercé Jourdain iD, , Vincent Prévot iD

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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.