Coronavirus FAQ: I'm immunocompromised. Will pills, gargles and sprays fend off COVID?

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My husband is immuno-compromised. He scours the internet for products that can protect him against COVID – from mouthwashes to supplements. Is there any evidence that any of these products work?

Four years into the COVID pandemic,many people are relaxing their precautions. But it's still tough to be immunocompromised, perhaps even tougher than a year or two ago.

Back then, an immunocompromised person who caught COVID could get monoclonal antibody treatments, which were effective at lessening the severity of the disease and could even help prevent infection if taken prophylactically. But those treatments are now all gone. The Food and Drug Administration pulled them from the market as the virus evolved, rendering them ineffective.

Yes, we still have vaccines and effective antiviral treatments like paxlovid. But for some immunocompromised folks, vaccines are often less effective as their weakened immune systems fail to mount a sufficient response,and paxlovid can interfere with many commonly prescribed medications. Well-fitted, high quality masks work well, but aren't foolproof, especially in crowded indoor spaces where no one else is wearing one.

With so few options, many immunocompromised people — and other folks looking to avoid COVID and long COVID — are turning to treatments and products outside of official prevention and treatment guidelines. The dozens upon dozens of products purported to fight or prevent COVID can be overwhelming, ranging from vitamins and other supplements to anti-COVID nose sprays and mouthwashes.

"People, especially immunocompromised people, have a desire to take control of their health, particularly in the context of COVID," says Andrea Love, an immunologist and executive director of the American Lyme Disease Foundation who has studied the effectiveness of supplements. "The wellness industry kind of exploits that."

Naturally, the question arises: Do any of the products have merit? For this edition of the FAQ, we dove into the literature and asked experts whether any of the most common interventions are evidence-backed. We'll go category by category.

Can vitamins and supplements help fight COVID?

Walk down the supplement aisle of your grocery store and you'll be bombarded with products claiming to boost your immunity or immune system. "It's very appealing to feel like you're doing something proactive by taking them," says Love.

On a surface level, it makes sense. Vitamins and minerals, like vitamin C, vitamin D, zinc and copper, are crucial for maintaining a healthy immune system. If you hope to avoid catching COVID or reduce symptoms if you do, nutritional supplements seem like a reasonable option.

While there are some studies that suggest certain supplements could help certain people, it's far from clear that, on the whole, they do much goodwhen it comes to COVID.

"I'm not aware of any supplements that are available over the counter, herbal or otherwise, that are associated with a reduction of either the risk of acquisition of infection or a severe infection," says Dr. Marwan Azar, an immunologist at Yale University.

Love agrees. "When you look at the big ones — vitamin C, vitamin D, zinc, copper, iron — there's really no evidence to suggest that supplementation with any of those things improves outcomes related to COVID, reduces the risk of infection or illness severity," she says.

Vitamin C and zinc are among the most popular supplements, with labels that boast of their immunity-boosting powers. Both nutrients play important roles in maintaining a healthy immune system, and some studies suggest that taking vitamin C and zinc supplements might help reduce the duration of a cold or its severity, though the evidence is far from conclusive.

When it comes to COVID, the most robust studies — randomized clinical trials — don't show any significant benefit for some of the most common vitamin and mineral supplements. For example, a randomized clinical trial designed to study vitamin C and zinc supplementation for COVID found neither intervention made much difference in speeding recovery. Without conclusive evidence, these supplements aren't part of the National Institutes of Health's official treatment guidelines.

Vitamin D's picture is murky, too. Although several studies suggest people with lower levels of vitamin D are at higher risk of COVID infection and severe disease, existing studies (of which there are many) haven't clearly shown that supplementation reduces this risk, according to the NIH.

N-acetylcysteine, or NAC, is a supplement that acts as an antioxidant and can help reduce mucus along the respiratory tract in some circumstances. Given that profile, researchers started testing its efficacy against COVID early on in the pandemic, finding mixed results. Some studies suggested it reduced severity of illness in hospitalized patients, while others found no benefit.

Quercetin is a flavonoid found naturally in many vegetables, fruits, seeds, tea and even red wine. Some researchers suspect it may have antioxidant, antiviral and anti-inflammatory properties. Several small studies have found that quercetin might reduce the duration of COVID symptoms, though confounding factors in these studies (like the placebo group containing older patients than the treatment group) make it hard to draw definitive conclusions.

Why are all these vitamin and supplement studies so... inconclusive?

Measuring the impact of supplements is more challenging than, say, a new drug, because we get many of these same nutrients from our food.

"There are so many confounding variables," says Love, including diet and baseline levels of these nutrients. A well designed clinical trial can often try to control for those confounding variables, she says, "but that very often is just not the case with a lot of supplement trials."

As a result, it's difficult to get a clear picture

Still, what's the harm in trying if they might help?

For folks looking to take anything that might boost their resilience against COVID, supplements may seem like a low risk. "People may think, worst case it does nothing, best case it helps," says Love. "But the reality is that's not the case, there are a lot of potential harms associated with supplements because they are unregulated."

While multivitamins likely don't pose much risk, non-standard supplements, like proprietary herbal blends, can be more problematic. Herbal blends often contain long lists of ingredients of dubious origin and can sometimes get contaminated.

"Herbal medicines are often associated with liver injury," says Azar, and can contain ingredients that interfere with medications immunocompromised people might be taking, including paxlovid. "There's significant risk for interaction with something like that," he says, adding that immunocompromised people should consult with their physician before starting a supplement.

Can nitric oxide nose sprays make a difference?

COVID infections usually begin in the nose. Some nose sprays aim to stop or slow down the virus at this entry point, using the antimicrobial properties of nitric oxide, a compound our bodies naturally produces.

"The idea is, if we megadose [the nasal passages] with this chemical that's important for immune function, then maybe we'll improve outcomes," says Love. Such a spray might be useful as a short-term prophylactic, or reduce the chance of getting sick after an exposure.

Evidence for these nose sprays is limited. The best study — a randomized control trial of 80 adults with mild COVID in England — found that nasal sprays significantly knocked down the amount of virus in a patient's nose, compared to a saline placebo. But the study was sponsored by the company behind the nose spray, SaNOtize Research & Development Corporation, which "is a major caveat," says Love.

So far, the sprays seem relatively safe, though they've not been approved for use by the Food and Drug Administration. Several other countries, including Israel, India and Germany, have approved SaNOtize's nitric oxide spray, called Enovid, which isn't available on pharmacy shelves in the U.S. but can be purchased online.

Might mouthwash vanquish COVID pathogens?

COVID infections can also start in the mouth. Some mouthwashes, especially those with a chemical called cetylpyridinium chloride, or CPC, are useful in preventing bacterial infections in the mouth, as they break down cellular membranes. Several laboratory studies suggest CPC mouthwashes can do the same to SARS-CoV-2.

But the lab isn't an actual mouth. While one clinical trial found rinsing with CPC mouthwash reduced the amount of infectious virus in COVID patients' mouths, it's unclear whether this has any impact on symptoms. "You're really just addressing what happens to be in your mouth at a given point in time," says Love. "It's not actually dealing with the underlying pathology of the infection."

Can a diabetes drug reduce the odds of long COVID?

A generic diabetes medication is getting increased attention as a drug that might help prevent long COVID.

Metformin treats diabetes by reducing inflammation in the liver, but laboratory studies suggest that it has antiviral capabilities too. That anti-inflammatory, antiviral combination led some researchers to suspect it might be a useful COVID treatment, since inflammation contributes to severe disease, says Dr. Carolyn Bramante, a clinician and researcher at the University of Minnesota Medical School.

Bramante and colleagues published a randomized clinical trial study last year that showed that non-hospitalized overweight or obese patients who took metformin within a week of infection were 40% less likely to develop long COVID than those who got a placebo. Patients who started the medication less than four days from the onset of symptoms were 63% less likely to develop long COVID. "If you start it early in infection it works even more," says Bramante.

Those results were very promising, says Bramante, but she'd like to see the results replicated in different patient populations. Currently, researchers at the NIH are conducting a similar clinical trial (which you may be able to enroll in if you test positive for COVID). If evidence continues to build, metformin could start putting a real dent in the number of people who develop long COVID, especially since it's relatively inexpensive, accessible and doesn't interact with many other drugs, she says. "Metformin is probably available in every pharmacy in the world."

In the meanwhile, what's the best advice for the immunocompromised?

Unfortunately, there's still no silver bullet for avoiding COVID. But that doesn't mean immunocompromised people and those looking to avoid infection are helpless, even as much of society moves on from the pandemic.

The standard precautions are still the best defense, says Azar. "Vaccination is still a very important way to provide some protection and minimize risk of disease," he says, even if it's not as protective for some immunocompromised people. Some people with weakened immune systems may be able to get boosted more frequently to provide extra protection.

Beyond vaccination, Azar advises patients to modify their behavior based on transmission levels in the community and a person's individual risk level. When lots of people are sick, avoiding crowds can help minimize exposure, as can wearing high-quality, well-fitting masks in indoor spaces.

Improving indoor air quality at home or work can help too, by opening windows (if possible) or using personal HEPA air filters. At-home tests can still help you avoid catching the virus from close contacts too, says Love.

If you do happen to get sick, be sure to talk with your doctor straight away about taking paxlovid. "Paxlovid is really the workhorse for our outpatient management," says Azar, but it often isn't prescribed to many patients who might benefit because of worries about interactions with other drugs. Under physician supervision, patients taking medications that interact poorly with paxlovid can scale back or stop those drugs while on paxlovid.

And while there aren't monoclonal antibody treatments available now, several geared toward more recent SARS-CoV-2 strains are in the clinical trial pipeline.

"There's a possibility that there will be a new monoclonal on the market in the next few months," says Azar.

Jonathan Lambert is a Washington, D.C.-based freelance journalist who covers science, health and policy. He's been a staff writer at Grid and Science News and has contributed to NPR, Nature News, Quanta Magazine and the Dallas Morning News. He holds a Master's degree in evolutionary biology from Cornell University. Follow him on X @evolambert or on bluesky @jonlambert.bsky.social.