The surprising way melatonin may block COVID-19

We recently wrote about how melatonin is being considered as a possible treatment for COVID-19. The Cleveland Clinic-led study cited in that article showed using melatonin led to a 30 percent reduced likelihood of testing positive for SARS-CoV-2. However, at that time the researchers could only theorize as to why melatonin may have that effect.

A more recent study has shed light on why some people are not infected with SARS-CoV-2 or have no symptoms of COVID-19 even when testing positive for the virus — and the reason is directly connected to melatonin…

Melatonin in the lungs: a potential barrier to SARS-CoV-2

Researchers at the University of São Paulo (USP) in Brazil have discovered when melatonin is made in the lungs, it can block SARS-CoV-2 at several entry points for the virus.

Melatonin stops the expression of genes that encode the proteins in cells such as resident macrophages in the nose and in the alveoli of the lungs, as well as in the epithelial cells lining the alveoli. Thus, the hormone prevents SARS-CoV-2 from infecting these cells. Melatonin also inhibits the immune response, causing the virus to stay in the respiratory tract for a few days before leaving to find a new host.

The study presents the option of administrating melatonin via nasal drops or spray to prevent COVID-19 from developing in patients who don’t yet have symptoms. This use will need to be studied in preclinical and clinical trials to determine melatonin’s therapeutic effectiveness against SARS-CoV-2, the researchers caution.

“We showed that melatonin produced in the lung acts as a barrier against SARS-CoV-2, preventing the virus from entering the epithelium, activating the immune system and triggering the production of antibodies,” says Regina Pekelmann Markus, a professor at USP’s Institute of Biosciences (IB) and principal investigator for the project.

“This action mechanism by pulmonary melatonin must also involve other respiratory viruses such as influenza,” she added.

Melatonin is produced at night by the brain’s pineal gland to signal the body that daylight is done and it’s time to prepare for sleep. Markus began researching melatonin in the 1990s, showing in animal studies that the hormone can be produced in other organs, such as the lungs.

In a more recent study also involving rodents, she and her collaborators demonstrated that when resident macrophages in the pulmonary tract absorb particles of pollution, it spurs the macrophages to produce melatonin and other molecules. These molecules then engulf the particles and trigger mucous formation, coughing and expectoration to eject the particles from the respiratory tract. When this melatonin production was blocked, the particles entered the bloodstream and spread throughout the body, even reaching the brain.

The researchers then decided to explore whether melatonin produced in the lungs would alter the entry points for SARS-CoV-2 the way it did for air pollution particles. “If so, the virus wouldn’t be able to bind to the ACE-2 receptor on cells, enter the epithelium and infect the organism,” Markus says.

Analyzing genes and lung melatonin production

To test their theory, the researchers selected genes involved in viral cell entry, intracellular traffic, mitochondrial activity and transcription and post-translation processes to create a physiological signature of COVID-19. Next, they used RNA sequencing data to quantify the level of expression of the COVID-19 signature genes in 288 samples from healthy human lungs.

They then correlated these gene expression levels with a gene index that estimates lung melatonin synthesis capacity (MEL-Index) based on their analysis of lungs in healthy rodents. What they found was a low index reading correlated with a high level of expression of genes that encode proteins for resident macrophages and epithelial cells.

The index also negatively correlates with genes that modify proteins in cell receptor CD147, a viral entry point in immune cells like macrophages. This indicates that normal lung melatonin production may naturally protect against SARS-CoV-2.

“We found that when MEL-Index was high the entry points for the virus in the lungs were closed, and when it was low these ‘doors’ were open,” Markus says. “When the doors are shut, the virus wanders around for a time in the pulmonary airspace and then tries to escape in search of another host.”

Besides potentially using direct application of melatonin to the lungs to stop SARS-CoV-2, another idea could be to use the MEL-Index as a predictive biomarker to detect asymptomatic carriers of the virus.

Optimizing your body’s melatonin

While it’s still not guaranteed that taking melatonin pills or nasal sprays can help protect against COVID-19, they can definitely help with getting good sleep, which will strengthen your immune system. If you have trouble getting to sleeping, doctors recommend taking 1 mg to 3 mg of melatonin two hours before bedtime.

There are also steps you can take to optimize your body’s own production of melatonin. About two hours before bedtime, try lowering the lights in your home to signal to your body that the day is ending. If you’re watching television, make sure the screen is at least 6 feet away. And if there are bright lights like streetlamps shining in through your bedroom window, consider installing blackout curtains or using a sleep mask.

Also, it’s important to put away computers, tablets and smartphones because the blue and green light from these devices can cancel out the effects of melatonin. If you absolutely can’t avoid using these devices before bed, set your devices to emit yellow light instead of blue or use special glasses that filter out the blue and green wavelengths of light.

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Sources:

Melatonin produced in the lungs prevents infection by novel coronavirus — Agência FAPESP

Melatonin-Index as a biomarker for predicting the distribution of presymptomatic and asymptomatic SARS-CoV-2 carriers — Melatonin Research

Melatonin for Sleep: Does It Work? — Johns Hopkins Medicine

Limit Your Exposure to the Wrong Kind of Light and Live Healthier — The Better Sleep Council