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

Sreekala Nampoothiri, Florent Sauve, Gaëtan Ternier, Daniela Fernandois, Caio Coelho, Monica Imbernon, Eleonora Deligia, Romain Perbet, Vincent Florent, Marc Baroncini, Florence Pasquier, François Trottein, Claude-Alain Maurage, Virginie Mattot, Paolo Giacobini, S. Rasika, View ORCID ProfileVincent Prevot
doi: https://doi.org/10.1101/2020.06.08.139329
Sreekala Nampoothiri
1Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, FHU 1000 days for health, EGID, School of Medicine, Lille, France
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Florent Sauve
1Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, FHU 1000 days for health, EGID, School of Medicine, Lille, France
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Gaëtan Ternier
1Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, FHU 1000 days for health, EGID, School of Medicine, Lille, France
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Daniela Fernandois
1Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, FHU 1000 days for health, EGID, School of Medicine, Lille, France
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Caio Coelho
1Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, FHU 1000 days for health, EGID, School of Medicine, Lille, France
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Monica Imbernon
1Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, FHU 1000 days for health, EGID, School of Medicine, Lille, France
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Eleonora Deligia
1Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, FHU 1000 days for health, EGID, School of Medicine, Lille, France
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Romain Perbet
1Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France
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Vincent Florent
1Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, FHU 1000 days for health, EGID, School of Medicine, Lille, France
3Nutrition, Arras General Hospital, Arras, France
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Marc Baroncini
1Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, FHU 1000 days for health, EGID, School of Medicine, Lille, France
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Florence Pasquier
1Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France
4Centre mémoire ressources et recherche, CHU Lille, LiCEND, Lille, France
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François Trottein
5Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille (CIIL), Lille, France
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Claude-Alain Maurage
1Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, FHU 1000 days for health, EGID, School of Medicine, Lille, France
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Virginie Mattot
1Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, FHU 1000 days for health, EGID, School of Medicine, Lille, France
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Paolo Giacobini
1Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, FHU 1000 days for health, EGID, School of Medicine, Lille, France
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S. Rasika
1Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, FHU 1000 days for health, EGID, School of Medicine, Lille, France
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  • For correspondence: vincent.prevot@inserm.fr sowmyalakshmi.rasika@inserm.fr
Vincent Prevot
1Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, FHU 1000 days for health, EGID, School of Medicine, Lille, France
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  • ORCID record for Vincent Prevot
  • For correspondence: vincent.prevot@inserm.fr sowmyalakshmi.rasika@inserm.fr
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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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵‡ These authors directed this work

  • We now provide the first proof of SARS-CoV-2 in the brain parenchyma and neural cells, as opposed to the CSF or vascular tissues, as well as two plausible infection routes and putative pathophysiological mechanisms.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 19, 2020.
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The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis
Sreekala Nampoothiri, Florent Sauve, Gaëtan Ternier, Daniela Fernandois, Caio Coelho, Monica Imbernon, Eleonora Deligia, Romain Perbet, Vincent Florent, Marc Baroncini, Florence Pasquier, François Trottein, Claude-Alain Maurage, Virginie Mattot, Paolo Giacobini, S. Rasika, Vincent Prevot
bioRxiv 2020.06.08.139329; doi: https://doi.org/10.1101/2020.06.08.139329
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The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis
Sreekala Nampoothiri, Florent Sauve, Gaëtan Ternier, Daniela Fernandois, Caio Coelho, Monica Imbernon, Eleonora Deligia, Romain Perbet, Vincent Florent, Marc Baroncini, Florence Pasquier, François Trottein, Claude-Alain Maurage, Virginie Mattot, Paolo Giacobini, S. Rasika, Vincent Prevot
bioRxiv 2020.06.08.139329; doi: https://doi.org/10.1101/2020.06.08.139329

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