As we continue to face the challenges of the COVID-19 pandemic, a crucial question arises: how does the virus impact health after the initial infection? Interestingly, many individuals recovering from COVID-19 experience ongoing cognitive difficulties, a condition that forms part of ‘long-COVID’. This situation is reminiscent of the cognitive decline seen in conditions like dementia, which affects millions of people globally. Interestingly, this condition also affects reproductive hormones. A new, insightful study investigates the potential connection between the COVID-19 virus and changes in important hormonal pathways in the brain, including those that are involved in cognition. This research goes beyond just understanding COVID-19’s effects; it also explores how viral infections might broadly impact brain health and hormonal balance, posing critical questions about neurodegenerative diseases.

In a groundbreaking study led by Dr. Vincent Prevot and Dr. Sowmyalakshmi Rasika from the Lille Neuroscience & Cognition Inserm Research Center at the University of Lille, the team delved into how COVID-19 affects hormones in patients. Published in the journal “eBioMedicine,” in order to avoid variability due to the menstrual cycle in women, they examined hormone levels in blood samples from male patients who had contracted COVID-19. They also studied brain tissues from patients who passed away due to COVID-19, focusing on areas such as the hypothalamus that are key for hormone control and the communication between the brain and other organs. Additionally, they looked at tissue samples from developing human brains to understand how the virus could impact brain development.

“We found that persistent low testosterone levels in some men might actually originate from the brain, contributing to ongoing cognitive or neurological symptoms after COVID, and that these hormone levels and body weight changes over time were closely related,” Dr. Prevot explains. Their study suggests that long-lasting cognitive issues and changes in reproductive hormones in men, and presumably women, could be due to the damage of specific brain cells responsible for releasing a vital hormone that regulates reproduction as well as cognition.

To gain more insights, the researchers also performed experiments on human brain cell cultures. These experiments allowed them to see firsthand the virus’s effects on cells. They used special labeling techniques to observe the virus’s presence and effects in brain tissues and employed advanced cell analysis methods to study infected cells in greater detail.

The team identified two main ways the virus might enter the brain – via the smell-sensing neurons and special cells in the brain called tanycytes. “We found evidence of the virus infecting smell-sensing neurons and tanycytes, indicating at least two possible pathways for the virus to invade the brain,” Dr. Prevot  notes. Alarmingly, they found that the brain cells that produce the key reproductive hormone were dying in all the patient brains they studied, significantly reducing hormone production.

Furthermore, they discovered that the birthplace of these brain cells during development, closely linked to the parts responsible for smell, were also susceptible to infection, indicating that fetuses or babies might be particularly vulnerable. This finding raises concerns about how the COVID-19 virus might affect brain development in children as well as brain aging in adults, potentially leading to serious reproductive, metabolic, and mental health issues in those with long-COVID.

In conclusion, this significant study establishes an important connection between lingering COVID-19 symptoms and neuroendocrine dysfunction, using men as an example. It emphasizes the need for more research in this area to fully understand COVID-19’s impact on mental functions, cognitive health, and reproductive health. As we continue to confront the pandemic, these findings could lead to new treatments to help those experiencing long-term effects of the virus.

Figure. Drawing. SARS-CoV-2, the virus causing COVID-19 may enter the hypothalamus either via the blood or the olfactory route. Fluorescent microscopy Images. A neuron producing the gonadotrophin-releasing hormone (GnRH), the neurohormone controlling reproduction (identified by its expression of GnRH, red) in the brain of a patient who died following infection. The neuron expresses the molecule ACE2 (white) used by the virus to enter most target cells. The presence of the viral spike protein (green), a protein on the surface of the virus that attaches to the target cell, in the same cell indicates that it is infected and producing more viruses. In blue, the nuclei of this and surrounding brain cells.

Journal Reference

Sauve F, Nampoothiri S, Clarke SA, Fernandois D, Ferreira Coêlho CF, Dewisme J, Mills EG, Ternier G, Cotellessa L, Iglesias-Garcia C, Mueller-Fielitz H, Lebouvier T, Perbet R, Florent V, Baroncini M, Sharif A, Ereño-Orbea J, Mercado-Gómez M, Palazon A, Mattot V, Pasquier F, Catteau-Jonard S, Martinez-Chantar M, Hrabovszky E, Jourdain M, Deplanque D, Morelli A, Guarnieri G, Storme L, Robil C, Trottein F, Nogueiras R, Schwaninger M, Pigny P, Poissy J, Chachlaki K, Maurage CA, Giacobini P, Dhillo W, Rasika S, Prevot V. Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death. EBioMedicine. 2023 Oct;96:104784. doi: 10.1016/j.ebiom.2023.104784.