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

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Nampoothiri, Sreekala | Sauve, Florent | Ternier, Gaëtan | Fernandois, Daniela | Coelho, Caio | Imbernon, Monica | Deligia, Eleonora | Perbet, Romain | Florent, Vincent | Baroncini, Marc | Pasquier, Florence | Trottein, François | Maurage, Claude-Alain | Mattot, Virginie | Giacobini, Paolo | Rasika, S. | Prevot, Vincent

Edité par CCSD -

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.

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