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bioRxiv · 10.1101/2020.06.08.139329

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

Nampoothiri, S.·Sauve, F.·Ternier, G.·Fernandois, D.·Coelho, C.·Imbernon, M.·Deligia, E.·Perbet, R.·Florent, V.·Baroncini, M.·Pasquier, F.·Trottein, F.·Maurage, C.-A.·Mattot, V.·Giacobini, P.·Rasika, S.·Prevot, V.
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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.

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Nampoothiri, S., Sauve, F., Ternier, G., Fernandois, D., Coelho, C., Imbernon, M., Deligia, E., Perbet, R., Florent, V., Baroncini, M., Pasquier, F., Trottein, F., Maurage, C.-A., Mattot, V., Giacobini, P., Rasika, S., Prevot, V.. 2020-06-09. The hypothalamus as a hub for putative SARS-CoV-2 brain infection. https://doi.org/10.1101/2020.06.08.139329

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