Ten months since the disease now known as COVID-19 first crept into the headlines, standard advice for avoiding it—such as wearing a mask, avoiding crowds, and washing hands well and often—has become familiar. But as winter approaches in the northern hemisphere, and with it an anticipated surge in cases, we sought out additional science-backed tactics to lower the chances of becoming infected, or of developing severe disease. The Scientist spoke with experts in virology, immunology, and medicine about the measures they’re taking themselves and recommending to others that may boost defenses against the novel coronavirus and other pathogens. None yet meet the gold standard for clinical evidence—a randomized controlled trial showing they reduce COVID-19 transmission or severity—but for each, there’s a scientific rationale for thinking they may provide some protection.

Get vaccinated 

As we anxiously await a proven vaccine for SARS-CoV-2, studies indicate that certain existing vaccines—namely, those made with live, attenuated pathogens—confer some degree of temporary protection against germs they weren’t designed to target. For example, a trial published last month in Cell found that 25 percent of elderly people randomized to receive the tuberculosis vaccine bacille Calmette-Guérin (BCG) developed any kind of infection over the following year, compared with 42 percent of those who got a placebo shot. The vaccine appeared to be most protective against viral respiratory infections. 

Trials are now underway to test whether BCG and two other live vaccines, oral polio and measles, mumps, and rubella (MMR), provide some protection against COVID-19. Robert Gallo, who directs the Institute of Human Virology at the University of Maryland School of Medicine and chairs the international scientific leadership board of the Global Virus Network, has advocated for testing oral polio in particular against the coronavirus. It’s cheap, easy to administer, and readily available, he says, adding that he expects other live vaccines would likewise provide bonus protections, including the intranasal flu vaccine, “which I’d love to take myself for the flu season.” He is unfortunately over the age limit—it’s only approved for people between 2 and 49 years old.

The conventional flu shot is not a live vaccine, but the protection any flu vaccine provides against influenza itself is particularly important this year, notes Rachel Roper, who studies SARS-CoV-1, SARS-CoV-2, and other viruses at Eastern Carolina University. You don’t want to get the flu and need medical attention at a time when the healthcare system may be overwhelmed with COVID-19 cases, she writes in an email to The Scientist. “If you get flu and have to go to the doctor, you may be exposed to people who have COVID and catch it yourself!” 

Get some sunshine (or a supplement)

Far from being only important for bone health, the hormone vitamin D “affects many, many, many systems and cells throughout the body,” including innate and adaptive immunity, says Carol Wagner, a neonatologist at the Medical University of South Carolina who studies the vitamin in clinical trials. “I, of course, have all my family members and friends taking vitamin D.” Wagner and others now have clinical trials underway to test whether supplements of vitamin D—which can also be obtained through sun exposure and some foods—reduces the risk of SARS-CoV-2 infection or of developing severe COVID-19. In the meantime, some observational studies have pointed to an effect, such as an analysis published last month that compared 191,779 US patients’ SARS-CoV-2 test results with a vitamin D blood test they’d undergone within the past 12 months. That study found an inverse relationship between levels of vitamin D in the blood and the chances of SARS-CoV-2 infection, which persisted after researchers adjusted their model for demographic factors.

Taking extremely high doses of vitamin D supplements can cause toxicity, but Wagner says that based on studies she’s done, it’s “very safe” at the doses she recommends, namely, 4,000–6,000 international units (IU) per day for adults, depending on their BMI. Children, she says, should take about 50 IU per kilogram of body weight until they’re big enough to take the adult dose. The goal for both is to get to a concentration of between 40–60 nanograms per microliter in the blood, Wagner says.

Fire up the humidifier 

Along with a drop in sun exposure, winter’s arrival tends to herald a decline in humidity levels both indoors and out. Studies have indicated that viruses can travel further through drier air and remain stable for longer than they would at humidity levels above 40 percent, says Akiko Iwasaki, an immunobiologist at Yale University. In her own lab, she’s looked at the other side of the story—how dry air affects host defenses—and has found it’s bad news there, too. Based on her studies in rodents, some of them partly supported by humidifier company Condair, and work she’s seen in human subjects, she says that drier air thins the aqueous layer that lines our airways, which impairs the movement of cilia that work to expel viral particles. This leads to a scenario in which “the virus particles remain longer in the airway and therefore they have a chance to infect the cells, more so than if you are inhaling moist air,” she says. 

Iwasaki uses humidifiers in her own home with the aim of hitting a relative humidity level between 40 percent and 60 percent, she says, and she recommends the same to friends and family. “Having a whole house humidified would be great, but that’s kind of expensive,” she says. “But having even a small humidifier in the rooms, especially where you sleep, I think makes a difference.”

Tamp down aerosols 

Another practice that appears to fortify the airways involves the mucus layer that sits under the aqueous layer. When we breathe, air rushing through our trachea and main bronchi breaks off bits of this layer, so that “when you breathe in, you generate little droplets in your upper airways that go deep. And when you breathe out, you breathe them out,” says David Edwards, a bioengineer who has studied the phenomenon for decades and is now the CEO of the company Sensory Cloud. Those droplets can in turn carry viruses into the lungs or out into the environment to potentially infect others. 

Edwards and his colleagues have found in a not-yet-published study that the number of smaller, aerosol-size exhaled droplets varies widely from person to person, with people who are older, have a high BMI, or are infected with COVID-19 tending to exhale more of them. “Typically, in a young person, there’s very few particles, which gets to the fact that the proper barrier function of mucus is such that it really resists that kind of breakup,” he says. 

In other work, such as a study published last week in Molecular Frontiers Journal, he and colleagues have found that inhaling a saline solution that contains calcium can reduce the number of aerosols a person exhales. That’s because, Edwards says, the positively charged calcium links negatively charged mucin proteins in the mucus, bolstering its surface tension and its resistance to sloughing off. That fortification should not only lower the number of small droplets a person exhales, but also reduce the chances that any virus that makes it into the upper airway will cause disease, he says. “If you can lower airborne movement of mucus in the upper airways, in the event that you’re infected, it lowers the probability that infection will spread to your deeper lungs where symptoms then arise.” He adds that using the calcium-fortified solution should complement wearing a surgical mask, with the treatment reducing exhalation of very small droplets and the mask catching larger ones. 

Sensory Cloud is now taking preorders for a $50 product, FEND, that delivers the calcium-containing solution; the company recommends that customers use it several times a day to cleanse their airways. The company hasn’t yet conducted clinical studies on whether FEND reduces SARS-CoV-2 transmission or infection rates, Edwards says, but he’s hoping to study the product’s use soon in a high-risk setting such as a nursing home or prison.