COVID-19: Nasal sprays reduce viral load and speed recovery

The mucous membranes of the nose and throat are the main access routes for the corona virus. They contain a particularly large number of ACE2 receptors, which the virus uses as a docking point. In addition, the immune system takes longer before it can funnel antibodies to the mucous membranes. However, if the viral load, i.e. the number of pathogens, in the mucous membranes can be kept low at the onset of infection, this has two main advantages: viruses can spread less in the body, the disease is often less severe, and people infected spread significantly fewer viruses. This in turn can reduce the risk of infection and the severity of the disease in contacts.

Therefore, the sprayable active ingredients should protect the nasal mucosa and throat and prevent the attachment and multiplication of SARS-Cov2. The agents tested include, for example, iota-carragelose which inhibits the red algae virus. A combined antiviral spray based on povidone iodine and ammonium glycyrrhizinate also showed good results in a randomized, placebo-controlled study with 200 test subjects.

When the PCR-positive subjects sprayed the combination in their nose and throat six times a day since diagnosis, they recovered statistically significantly faster than subjects in the placebo group. Her general symptoms disappeared after 7.6 vs.8.9 days, while her sense of smell and taste returned after just 5.6 vs.11 days. This is what Egyptian researchers around Hazem Elsersy of the University of Menoufia write in the journal “Frontiers in Medicine”.

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At the same time, the overall PCR-determined positivity rate in the treatment group decreased very rapidly and much more rapidly than in the placebo group. While the fourth day was only 70 percent versus 99 percent, it had already dropped to 20 percent (versus 65 percent) on the seventh day and was only one percent (versus ten percent) on the tenth day.

At the same time, only four percent of family members in the treatment group that received the spray were infected. In the placebo group, on the other hand, 76 percent of relatives became infected. However, they were only tested if they showed symptoms.

Both components of the spray had previously shown an antiviral effect against SARS-Cov2 in laboratory tests. Povidone iodine is a water-soluble disinfectant that the authors say is safe to use at the 0.5 percent dose used. Derived from licorice root, the glycyrrhizic acid derivative has two other benefits. Relieves the sometimes irritating effect of the iodine solution and prevents infection-related inflammation through various mechanisms. Among other things, it inhibits the formation of reactive oxygen radicals and pro-inflammatory immune messengers (interleukins).

Fighting corona infections with antiseptics like iodine as soon as the first symptoms appear on the mucous membranes makes perfect sense, says Peter Meiser, head of Ursapharm’s medical-scientific department of general medicine. However, the effect of antiseptics is relatively nonspecific. The Saarbrücken-based drug manufacturer wants to reduce SARS-Cov2 viral load in a more targeted way and is testing a nasal spray containing azelastine in clinical trials.

The advantage of this approach is that such nasal sprays have been available on the market for years as antiallergic drugs such as Pollival (Ursapharm) or Allergodil (MEDA Pharma). The idea was born during the evaluation of patient records in the United States, which also took into account the dressing of the infected and documented a reduction in positive tests after the use of azelastine.

According to preliminary results from a double-blind phase 2 study called CARVIN, which has not yet gone through the peer review process, azelastine can lower viral load faster than placebo. 90 subjects were divided into three groups and received the drug at a higher or lower dose, or received a placebo nasal spray. Additionally, six and eight subjects in the two drug groups tested negative before the end of the eleven-day testing phase, which did not occur in the placebo group.

The results published as a preprint have not yet shown any statistical significance, so the effect has not yet been clearly demonstrated. “However, if you look at viral load during the entire treatment phase in the final evaluation, you can see less than 0.1% statistical significance of azelastine compared to placebo therapy,” says Meiser. As soon as the final results of the final evaluation have been submitted for publication, Ursapharm intends to publish this preprint.

“Ultimately, it’s a sticking point that we only had 30 patients per group,” Meiser says. The next phase 3 study, which is expected to begin in the fall, will include several hundred subjects. In addition to the viral load, it will primarily address clinical symptoms, Meiser says. So it comes down to whether and how strong the azelastine-containing nasal spray can prevent symptoms and hospital stays in the most current variants. At the time of the phase 2 study, the alpha variant was still predominant.

The possible efficacy of azelastine is likely based on several mechanisms that go beyond “addressing the spike protein, like many of the current approaches, including vaccinations,” Meiser says. On the one hand, azelastine makes it more difficult for the SARS-Cov2 virus to penetrate cells by deforming the handle on the cell door, so to speak: it changes the spatial arrangement (conformation) of the ACE2 receptor, which the virus needs to dock.

Second, azelastine also blocks the sigma-1 receptors that the virus needs to replicate. And thirdly, the active ingredient also inhibits the viral enzyme called the main protease, with which the pathogen otherwise assembles new viral particles. According to Meiser, it has not yet been studied whether the nasal spray may also have a preventive effect.


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