Why cold weather makes it harder for the body to fight respiratory infections

The winter surge in COVID-19 is due to more than merely spending time indoors.

“For the coming on of winter resolves the diseases of summer, and the coming on of summer removes those of winter,” wrote the father of medicine, the Greek physician and philosopher Hippocrates, in 400 B.C.

This account is considered the earliest recorded study of the seasonal variability of a disease, namely influenza. Why some conditions are periodic, however, was a mystery that puzzled scientists until the modern era.

We still haven’t totally figured it out, but researchers now understand that as the seasons cycle, germs, their hosts, and the environments they inhabit change together in complicated ways that make people more or less prone to catching a disease.

“If you asked five flu epidemiologists what they thought the relative contributions are, you'd have a decent chance of getting five different answers,” Dylan Morris, a postdoctoral researcher at UCLA studying the ecology and evolution of viruses, says with a laugh.

That said, scientists have discovered how the changing seasons affect not only the physical structures of viruses, but also our body’s natural barriers against disease. In the winter in particular, the cold, dry air and lack of sunlight negatively affect our ability to stave off respiratory infections like the flu or the SARS-CoV-2 coronavirus.

Coronavirus thrives in winter conditions

Based on past experiences with seasonal colds and flu, public health experts have been warning of a possible surge of coronavirus cases in the winter, as cold weather forces people to move indoors where airborne transmission thrives. This prediction has sadly come to pass as cases, hospitalizations, and deaths in the United States hit record highs in recent weeks, with no sign of abating.

Morris and his colleagues recently posted a preprint study examining one of the factors that could have led to this surge: how the stability of the coronavirus changes with temperature and air moisture.

They found that lower temperatures and extreme humidities—both high and low—keep the virus stable and infectious for longer. Lower temperatures slow down chemical reactions, like the ones that cause viruses to break down. That means the coronavirus can float around in respiratory droplets unencumbered for longer.

Lower humidity evaporates droplets to a smaller size, making it easier for the virus to bump into other chemicals in the droplet and inactivate–but only up to a point. If the droplets get too small, the naturally occurring salts in the fluids we exhale crystallize and trap the virus, preserving it for awakening when the drop gets dissolved in a new host’s airway.

Unfortunately, low temperature and humidity are exactly what we get in the winter months. Other variables, like folks staying indoors and not getting enough sunlight, aren’t looking too rosy either.

“You've got all these factors that are all sort of pointing in the same direction, multiple reasons to expect respiratory viruses to be more of a challenge in the winter,” Morris says.

These winter conditions can also affect the other half of the infection equation—the bodies being infected.

That brisk, winter air

Breathing colder, drier air actually changes how the immune system operates, says Akiko Iwasaki, an immunologist at Yale University and an investigator with Howard Hughes Medical Institute.

In a 2015 paper, Iwasaki and her colleagues showed that cells lining the airways of mice produced fewer molecules called interferons when they were colder. Interferons are a class of proteins that sound the alarm of a viral crime, calling immune cells to the scene and hopefully stopping it in progress.

“Since that study came out, I've been telling my children to wear a scarf around the nose—and currently, obviously, masks—because that allows for the temperature to remain warmer in the nose,” Iwasaki says.

More recently, Iwasaki and her team found that low humidity can also dampen the body’s sticky first line of defense: mucus. Your airways are lined with the gooey substance and, below that, with cilia, tiny fingerlike paddles used across the animal kingdom for movement. These two components work together like a conveyor belt: The mucus traps gunk, and the cilia beat together to move the mucus back out through the nose and mouth. Anyone need a handkerchief?

This process is called mucociliary clearance, and cold, dry air is not its friend. As low humidity dries out the mucus layers in our faces and throats, it disrupts the movement of the cilia, making it harder for the body to kick out any invaders.

“So, these things are happening when we inhale dry air, and then combined with the cold air, we're really taxing the host immune response so that we're no longer able to fight these viral infections well,” Iwasaki says.

Iwasaki recommends getting a humidifier and keeping your home at 40 to 60 percent humidity. “That way, we are not only helping our immune response to the pathogens, but also, in humid air, the viral-containing particles accumulate water,” she says. “Instead of being airborne, they drop to the floor.”

Sunny delight

More people staying all day indoors because of the pandemic exacerbates another downside of winter: reduced vitamin D. You might be familiar with vitamin D from its ever-present mention on milk cartons. But aside from fortifying bones, vitamin D plays an important role in modulating our immune responses, affecting at least 200 chemical pathways involved with these essential defenses, says Annelise Barron, a bioengineer at Stanford University who designs synthetic versions of natural molecules.

She’s particularly interested in replicating the peptide (or small protein) called LL-37, a potent antiviral, antibacterial, and antifungal molecule that naturally occurs in humans. That’s because primates are the only subgroup of mammals that depend on the body’s ability to absorb sunlight and make vitamin D to produce this antimicrobial peptide.

Our skin manufactures vitamin D by using ultraviolet-B rays from the sun to break open one of the carbon rings of a chemical precursor of cholesterol. Though foods like fatty fishes or fortified milk can supply some of our vitamin D, sunlight boosts our levels—and that’s a problem for people who live farther from the Equator.

“All around the world, during these more sunny months, around half of people are low on vitamin D,” Barron says. “Now, you go to the dead of winter, and on average, that percentage of people being low on vitamin D will be more like 80 percent.”

Appropriate vitamin D levels are associated with lower risks for inflammatory diseases like type 1 diabetes and multiple sclerosis, as well as lower incidence of acute respiratory infections. Though Barron says the full health impacts remain unclear, surveys continuously show deficiencies in vitamin D across U.S. populations that live above 35 degrees latitude, an area that includes cities as far south as Las Vegas.

During the COVID-19 pandemic especially, people are staying indoors a lot—good for curbing transmission, but bad for soaking up vitamin D-producing sunlight. Some research is also starting to show that many severe COVID-19 patients are vitamin D deficient. For example, a study published in late November found vitamin D-deficient COVID-19 patients had a death rate almost four times higher than those in the study with normal vitamin D levels. Whether this is truly causative remains to be explored: Early studies of administering vitamin D for COVID-19 treatment have shown positive and neutral results.

Darker skin can sometimes restrict vitamin D production, which has been pointed to as a possible genetic explanation for the higher impact of COVID-19 on African Americans and other communities of color. However, less efficient production doesn’t always translate to lower levels of vitamin D in people of color versus white communities because other molecules that neutralize vitamin D are also present in different concentrations between populations. Moreover, numerous social determinants to health appear to play a more considerable role with regards to COVID-19 outcomes in minority communities.

Still, taking vitamin D supplements can help upregulate the body’s natural defenses, says Barron, pointing to a recent study that showed supplementation improved LL-37 activity during the winter. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, says that he takes a daily supplement of vitamin D to boost his immune system.

Barron recommends 2,000 international units—the standard measure of substances—of vitamin D supplement a day. That’s higher than the National Institutes of Health guidance of 400 to 800 IUs, but in line with the upper end of recommendations from the Endocrine Society, and far below the 4,000 IU daily dose at which vitamin D becomes toxic for adults.

The long reach of seasons

Vitamin D production is not the only bodily function affected by seasonal variability in sunlight, says Micaela Martinez, an infectious disease ecologist at Columbia University, who studies biological rhythms and seasonal disease.

Some researchers are already proposing studying how disrupted sleep affects health care workers’ vulnerability to the coronavirus and what time of day is best for administering dexamethasone, a treatment for severe COVID-19 patients.

“Pretty much all the aspects of our body—metabolism, hormones, immunity—change with the day-night cycle,” she says.

Some of the earliest disease-focused research in chronobiology was done on the day-night cycle and melatonin. And a 2015 study in Nature found seasonal variability in the expression of about a quarter of human genes, though the group did not show how or if this variance in gene expression affected the immune system’s ability to fight invaders.

“It's not that you would have more infections in the winter and less in the summer. No, it's for every infectious disease, there is a season,” says Martinez, whose lab is currently working to show how seasonal changes affect the ability of the immune system to ward off different pathogens. Historically, she points out that measles epidemics were widespread in the spring, and polio hit hardest in summer.

No matter the season, Martinez worries that people are not getting enough sunlight to help our bodies keep functioning consistently, as more of us spend our days inside. In a preprint study released in October, her team demonstrated how study participants outfitted with light sensors in New York City had low natural light exposure throughout the year and little variability between seasons.

“We have washed out the majority of our seasonal changes in light just because we are staying inside so much,” Martinez says.

She recommends soaking up a burst of morning sunlight to help transition into daytime mode and regulate vital functions, including, hopefully, keeping your body primed to fight respiratory pathogens like SARS-CoV-2.

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