1. SARS-CoV-2 infects human GnRH neurons and tanycytes, disrupting hypothalamic-pituitary hormonal axes
- Author
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Erik Hrabovszky, Marc Baroncini, F. Pasquier, Caio Coelho, Claude-Alain Maurage, Ariane Sharif, Sreekala Nampoothiri, Asis Palazon, Pascal Pigny, Julien Poissy, Julie Dam, Florent Sauve, Ralf Jockers, Laurent Storme, François Trottein, Konstantina Chachlaki, Thibaud Lebouvier, Romain Perbet, Paolo Giacobini, Julie Dewisme, Sophie Catteau-Jonard, Vincent Florent, Daniela Fernandois, Sowmyalakshmi Rasika, Maria Mercado-Gómez, Gaetan Ternier, María L. Martínez-Chantar, Erika Cecon, Markus Schwaninger, Rubén Nogueiras, Virginie Mattot, June Ereño-Orbea, Vincent Prevot, Cristina Iglesias, Helge Müller-Fielitz, and Ludovica Cotellessa
- Subjects
medicine.medical_specialty ,Fetus ,Vomeronasal organ ,Biology ,medicine.disease ,Formyl peptide receptor 2 ,Pathogenesis ,Vomeronasal receptor ,Endocrinology ,Hypogonadotropic hypogonadism ,Internal medicine ,medicine ,Receptor ,Hormone - Abstract
Neuroinvasion by SARS-CoV-2 is now accepted. To investigate whether low testosterone levels observed in men with severe COVID-19 could be of central origin, we retrospectively analyzed blood samples from 60 male intensive-care patients and explored SARS-CoV-2 brain entry using animal and cellular models as well as adult COVID-19 patient and fetal human brains. Most hypotestosteronemic patients displayed hypogonadotropic hypogonadism or abnormal hypothalamic-pituitary-gonadal axis regulation. Neurons producing gonadotropin-releasing hormone (GnRH), the master molecule controlling fertility, expressed angiotensin-converting enzyme 2 and neuropilin-1, two host-cell factors mediating infection, and were infected and dying in all COVID-19 patient brains. Tanycytes - hypothalamic glia that regulate GnRH secretion - were also infected. Additionally, human fetal olfactory and vomeronasal epithelia, from which GnRH neurons arise, richly expressed both the above host-cell susceptibility factors and formyl peptide receptor 2, a putative vomeronasal receptor that also appeared involved in SARS-CoV-2 pathogenesis in humans and mice. Finally, a fetal human GnRH cell line expressing all these receptors could be infected by a SARS-CoV-2-like pseudovirus. Together, our findings suggest that GnRH neurons, which may be implicated in brain development and aging in addition to reproduction, are particularly vulnerable to SARS-CoV-2 in both adults and fetuses/newborns, with potentially devastating long-term consequences.
- Published
- 2021