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Infection of Certain Neurons With SARS-CoV-2 Could Cause Persistent Symptoms


Illustration of SARS-CoV-2 infection (immunoreactivity for the S-protein in white) in the olfactory neurons expressing the olfactory marker protein (OMP, in red) in the human nasal epithelium. © Vincent Prévot/Inserm

The brain impacts of infection with SARS-CoV-2, responsible for COVID-19, are increasingly well documented in the scientific literature. Researchers from Inserm, Lille University Hospital and Université de Lille, at the Lille Neuroscience & Cognition unit, in collaboration with their colleagues at Imperial College London, focused more specifically on the impacts of this infection on a population of neurons known for regulating sexual reproduction via the hypothalamus (the neurons that express the GnRH hormone). Their findings suggest that SARS-CoV-2 infection can lead to the death of these neurons and cause certain symptoms that persist over time. The findings of this study have been published in eBioMedicine.

Numerous scientific studies have documented the brain impacts of SARS-CoV-2 infection. One such effect is that a significant proportion of men have low testosterone levels that persist over time. Persistence beyond a period of four weeks is referred to as “long COVID”.

For many years, a research team from Inserm, Lille University Hospital and Université de Lille has been studying the role of certain neurons that express gonadotropin-releasing hormone (GnRH). From the hypothalamus, these neurons control all the processes associated with reproductive function: puberty, acquisition of secondary sexual characteristics, and fertility in adulthood.

These are the same scientists who had, for example, previously revealed that GnRH neuron dysfunction in an animal model of Down syndrome could affect the cognitive function impairment associated with this condition.

In this latest study, the scientists wanted to test the hypothesis that SARS-CoV-2 infection may have harmful consequences on this population of neurons that regulate reproduction.


The Virus Penetrates GnRH Neurons and Alters Their Functions

Following hormone measurements (testosterone and luteinizing hormone) performed three months and then one year after infection in a small group of 47 men[1], the scientists observed that contact with the virus could alter the functions of GnRH neurons, leading to a fall in testosterone levels in certain patients some time after the infectious episode.

The scientists then wanted to verify whether the infection of the GnRH neurons and the subsequently observed hormone abnormalities could be associated with cognitive deficits. To do this, they listed the cognitive symptoms reported by the cohort patients, who underwent extensive testing three months and then one year after the infection.

The outcome was that the proportion of patients reporting memory or attention disorders, regardless of frequency or severity, and also concentration difficulties, tended to be slightly higher in the patients with abnormal hormone measurements, characterized by a decrease in testosterone levels.

“Although these were measurements made on a small sample of only male patients, these findings are very interesting and warrant further exploration in other larger-scale studies,” explains Waljit Dhillo, professor at Imperial College London and co-last author of this study.

To supplement their analyses, the researchers went on to study the cortexes of patients who died as a result of COVID-19. They identified the presence of the virus in the hypothalamus and the death of part of the GnRH neuron population.

“These findings may be worrying on several levels in terms of the role of these neurons in reproduction and their involvement in certain cognitive functions. They point to the necessity to optimize and generalize the medical follow-up of people with persistent symptoms following COVID-19 infection,” concludes Vincent Prévot, Inserm research director and co-last author of this study.

The study also encourages further research into the neurological impacts of long COVID.


[1]These data were collected as part of a larger study evaluating adrenal and thyroid function following Sars-CoV-2 infection:

Researcher Contact

Vincent Prévot

Inserm Research Director

Development and Plasticity of the Neuroendocrine Brain team leader

Unit 1172 Inserm/Université de Lille/Lille Regional University Hospital, Lille Neuroscience & Cognition – Lille

Email: rf.mresni@toverp.tnecniv

Telephone number provided upon request


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Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death


Florent Sauve1#, Sreekala Nampoothiri1#, Sophie A. Clarke2#, Daniela Fernandois1#, Caio Fernando Ferreira Coêlho1#, Julie Dewisme1,3, Edouard G. Mills2, Gaetan Ternier1, Ludovica Cotellessa1, Cristina Iglesias-Garcia5, Helge Mueller-Fielitz6, Thibaud Lebouvier1,7, Romain Perbet1,3, Vincent Florent1, Marc Baroncini1, Ariane Sharif1, June Ereño-Orbea8, Maria Mercado-Gómez8, Asis Palazon8, Virginie Mattot1, Florence Pasquier1,7, Sophie Catteau-Jonard1,9, Maria Martinez-Chantar8, Erik Hrabovszky10, Mercé Jourdain11, Dominique Deplanque1,12,13, Annamaria Morelli14, Giulia Guarnieri14, Laurent Storme15, Cyril Robil16, François Trottein16, Ruben Nogueiras5, Markus Schwaninger6, Pascal Pigny17‡, Julien Poissy13,18‡, Konstantina Chachlaki1‡, Claude-Alain Maurage1,3,13‡, Paolo Giacobini1‡, Waljit Dhillo2,19‡, S. Rasika1‡, Vincent Prevot1‡

1 Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, UMR-S 1172, FHU 1000 days for health, EGID, Lille, France

2 Section of Endocrinology and Investigative Medicine, Imperial College London, London, United Kingdom.

3 CHU Lille, Department of Pathology, Centre Biologie Pathologie, France

5 CIMUS, Universidade de Santiago de Compostela, Santiago de Compostela, 15782, Spain

6 Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany

7 CHU Lille, Department of Neurology, Memory Centre, Reference Centre for Early-Onset Alzheimer Disease and Related Disorders, Lille, France

8 CIC bioGUNE, Basque Research and Technology Alliance (BRTACentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. 48160 Derio, Bizkaia

Technology Park, Building 801A, Bizkaia, Spain

9 CHU Lille, Department of Gynecology and Obstetrics, Jeanne de Flandres Hospital, F-59000 Lille, France

10 Laboratory of Reproductive Neurobiology, Institute of Experimental Medicine, Budapest, Hungary

11 Univ. Lille, Inserm, CHU Lille, Service de Médecine Intensive Réanimation, U1190, EGID, F-59000 Lille, France.

12 Univ. Lille, Inserm, CHU Lille, centre d’investigation clinique (CIC) 1403, F-59000 Lille, France.

13 LICORNE study group, CHU Lille, Lille, France

14 Department of Experimental and Clinical Medicine, University of Florence, Italy

15 CHU Lille, Department of Neonatology, Hôpital Jeanne de Flandre, FHU 1000 days for health, F-59000, France

16 Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 – CIIL – Center for Infection and Immunity of Lille, F-59000 Lille, France

17 CHU Lille, Service de Biochimie et Hormonologie, Centre de Biologie Pathologie, Lille, France

18 Univ. Lille, Inserm U1285, CHU Lille, Pôle de réanimation, CNRS, UMR 8576 – UGSF – Unité de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France

19 Department of Endocrinology, Imperial College Healthcare NHS Trust, London, United Kingdom

# These authors contributed equally to this work.

‡ These authors contributed equally to this work


eBioMedicine, 13 septembre 2023