It is well documented that the body's first encounter with SARS-CoV-2, the virus responsible for COVID-19, occurs in the throat, nasopharynx, or nose. Research suggests that the first responses in this preliminary battlefield play a crucial role in determining whether an individual will proceed with mild or no illness or will develop a severe reaction to the disease. Interestingly, a recent Cleveland Clinic study revealed that individuals who frequently use steroid-based nasal sprays are less likely to develop an extreme response to COVID-19. Likewise, a study in January by scientists from Northwestern University and Utah State University indicates an over-the-counter nasal spray is effective at dramatically reducing SARS-CoV-2.
SARS-CoV-2 can be transmitted by respiratory particles released from an infected subject. Droplets are large particles that commonly deposit within a few meters away from the emitting subject and are responsible for the infection of close individuals. Once entered in the airways, SARS-CoV-2 interacts with S protein to its receptor ACE2. The proteolytic cleavage of S, mediated by the cellular protease TMPRSS2, facilitates SARS-CoV-2 infection, which is followed by the release of viral nucleic acid, protein synthesis, and assembly of new viral particles.
The nose represents an essential part of the mucosal immunity in the upper airways (UA). Through both natural and acquired immunity, the nose and nasopharynx play a central role in the introduction of mucosal immune responses. Indeed, in evolutionary development, the nasal cavity and the nasopharynx constitute an ancient barrier system found in early bony vertebrates. In immediate physical contact with the external environment, the nasal mucosa consistently "filters, moistens, and warms the inhaled air to minimize the effects on lower airways."
Steroid-Based Nasal Sprays
Applying the hypothesis from early lab reports that steroid-based nasal sprays in vitro reduced the protein receptor ACE2—which allows the SARS-CoV-2 virus to enter the cell and spread COVID-19—the Cleveland Clinic study set out to determine the relationship between baseline intranasal corticosteroid (INCS) use and COVID-19 related outcomes. Specifically, if the nasal spray disrupts ACE2, it may present a more difficult challenge for the virus pathogen to penetrate and replicate within the cell.
Figure 1. Association of intranasal corticosteroids with COVID-19-related hospital admission, intensive care unit (ICU) admission, and hospital mortality among all patients who had a positive SARS-CoV-2 test and met inclusion criteria. CI, Confidence interval; COVID-19, coronavirus disease 2019; OR, odds ratio; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
The study, led by Cleveland Clinic's Drs. Joe Zein and Ronald A. Strauss, pointed out that intranasal corticosteroids fall under the category of steroid medicines. This medication classification is primarily used to mitigate cold or allergy symptoms, such as stuffy nose and allergies. From April 1, 2020, to March 31, 2021, the Cleveland Clinic study team tracked 72,147 COVID-19 positive individuals aged 18 and above across the clinic's health system. Of the total study population, 12,608 (17.5%) were hospitalized, 2,935 (4.1%) were admitted to the ICU, and 1,880 (2.6%) died during hospitalization. A significant portion, 10,187 (14.1%), were using INCS (steroid nasal spray) before SARS-CoV-2 infection.
Funded by the National Heart, Lung and Blood Institute and the National Institute of Neurological Disorders and Stroke (of the NIH), the study concluded that patients using the nasal spray before the COVID-19 infection were 22% less likely to be hospitalized, 23% less likely to be admitted to the intensive care unit, and 24% less likely to die from COVID-19 during hospitalization compared to patients not taking the nasal spray. Dr. Zein commented in the Cleveland Clinic Newsroom:
"This study shows the importance of the nose in COVID-19 infection. The nose, in this instance, is the gateway to our bodies, allowing the virus to enter and replicate within. The use of intranasal corticosteroids may help disrupt that gateway."
While not recommending that INCS be used to treat or prevent COVID-19, the study findings suggest that patients who regularly use intranasal corticosteroids should continue to do so. Given the economic potential of this affordable treatment, the implications for worldwide access are numerous. Dr. Strauss remarked:
“Our findings are particularly significant, as decreased COVID-19 hospitalizations, ICU admissions, and mortality could alleviate the strain on health care systems with limited resources across the globe, especially in developing countries where there is limited access to vaccines and where mutations in SARS-CoV-2 have emerged.”
Xylitol and Grapefruit Seed Extract Nasal Spray
In addition to the recent Cleveland Clinic study on steroid nasal sprays, Biospace published research on January 26, 2021 that suggested the over-the-counter nasal spray Xlear was effective at "significantly reducing and nearly eliminating SARS-CoV-2, the virus that causes COVID-19 after a single dose." The article states:
"An in vitro study conducted by scientists from Northwestern University and Utah State University concluded that components found within the Xlear nasal spray, particularly grapefruit seed extract (GSE) and Xylitol, were successful in statistically reducing the amount of SARS-CoV-2.
After a single blast, the researchers saw the nasal spray reduced virus from 4.2 to 1.7 log10 CCID50 per 0.1 mL, a statistically significant reduction of 2.5 log10 CCID50.” News of the study was announced by Xlear and the company said this is only the latest research that reaches a conclusion the over-the-counter spray is effective against the virus that causes COVID-19."
Mark Cannon, Feinberg School of Medicine at Northwestern University elaborated on the groundbreaking Xlear study in January, saying, "First, we conclude, in addition to countering SARS-CoV-2, Xlear is likely effective in preventing the spread of future H1N1 viruses, including the emerging SARS-CoV-2 variants, along with other viral epidemics. Given the more transmissible variants we now face, this is critical now.” Dr. Cannon remarked the study theorizes that Xylitol acts as a decoy for SARS-CoV-2, thus preventing virus attachment to the core protein on the cell wall. He added:
“Using electron microscopy, we have visual evidence showing that Xylitol and GSE counters the virus. The GSE kills the virus, while the Xylitol prevents the virus from attaching to the cell walls. The image shows SARS-CoV-2 viruses outside the cell and never attached, thereby preventing infection.”