While the pandemic still lingers, vaccination programs and the natural course of pandemics is reducing the risk of getting COVID-19 and the severity of illness if you do get infected. The WHO has now ended the public health emergency of concern for COVID-19. Many people have stopped wearing masks routinely. Risk of transmission is fairly low this summer.
COVID is still out there, however, and the long term health risks from a COVID infection are potentially serious. People are often left in a gray zone, wondering if masks are still a good idea and how much they should do to protect themselves. (Short answer – wear a mask if you have symptoms or are around people with symptoms.) One increasingly popular option being heavily marketed is various nasal sprays. They are offered as an option to masking, providing hours of protection from getting infected with COVID. But do they work?
No nasal spray currently on the market has proven efficacy in preventing or treating infection from COVID-19, and there are no FDA approved products in the US. But the idea is plausible and there is some preliminary research. The problem for now is that research is scant, while the marketing is getting heavy and way ahead of the science.
A nasal spray approach to preventing or treating COVID makes sense from the point of view that the nasal cavity is often the first line of defense against COVID, and a common point of entry of the virus. Nasal sprays are easy to use, and can be administered at home. They could potentially provide an extra layer of protection, and even if the duration of effect is relatively short, it could cover an outing in public or a plane trip. There are also several nasal spray vaccines under development, and these could provide a useful alternative to injectable vaccines.
The state of the science for the non-vaccine and non-antibody nasal sprays, however, is distressingly preliminary. I could find very few studies on PubMed, and they are mostly either pre-clinical or case series. First, of course, we need to consider what substance was being studied. There are several that are most promising and marketed – nitric oxide (NO), xylitol, and Iota-Carrageenan (I-C), which is a sulfate polysaccharide.
NO has demonstrated anti-viral effects, including against SARS-CoV-2. A 2021 pilot study found that NO nasal spray decreased viral shedding of SARS-CoV-2 but it did not track clinical outcomes. There is a large clinical trial underway, with initial results anticipated in 2024.
Xylitol is a sugar alcohol that may have antiviral activity. Preliminary studies find that xylitol may have activity against SARS-CoV-2. Another pilot study found the time to negativization of viral titers was shorter using xylitol NS. However, there are currently no clinical trials of xylitol nasal spray and COVID.
The use of NS with Iota-Carrageenan was tested in one clinical trial, using it four times a day in a setting where health care workers were treating COVD positive patients. They found:
A total of 394 individuals were randomly assigned to receive I-C or placebo. Both treatment groups had similar baseline characteristics. The incidence of COVID-19 differs significantly between subjects receiving the nasal spray with I-C (2 of 196 [1.0%]) and those receiving placebo (10 of 198 [5.0%]). Relative risk reduction: 79.8% (95% CI 5.3 to 95.4; p=0.03). Absolute risk reduction: 4% (95% CI 0.6 to 7.4).
These preliminary results are just that – preliminary. They are enough to justify a hypothesis of potential clinical efficacy and to execute full phase 3 type clinical trials, but not enough to justify clinical claims. The FTC agrees. In 2021 they sued Xlear, inc, for marketing a product with xylitol with claims that it could prevent or treat COVID. (Case status is still listed as pending.)
It is well-established that outcomes from pre-clinical and preliminary research are poor predictors of ultimate clinical efficacy demonstrated in rigorous clinical trials. The existing research on the above three types of nasal sprays for COVID, while plausible, are extremely thin. They are insufficient as a basis for making any health claims. But what about a risk-vs-benefit analysis – even if the probability of benefit is low, the nasal sprays to appear to be relatively benign?
The big problem here is that these products are partly being marketed as an alternative to proven preventive methods, such as wearing an effective mask and social distancing. The concern is that use of a nasal spray, if they turn out to be ineffective (completely or in the dose and method of use), will essentially give people permission not to use a more effective preventive method, or to take excessive infection risks. An ineffective nasal spray can provide a false sense of security, and increase the overall risk and spread of COVID.
Ideally clinical research will test each specific nasal spray formula not just to see if it has preventive efficacy, but also in comparison to other established preventive methods. One or more of these products may prove ultimately effective. The problem is that we currently just don’t know, the research is far too scant.
