| Publicerad 14 maj, 2025

The science behind ColdZyme – Insights from professors

A study involving athletes has shown that Enzymatica’s oral spray, ColdZyme, significantly shortens the duration of upper respiratory tract infections and reduces symptom severity. These results are likely explained by a reduced viral load, which was also shown in a recent in vitro study with ColdZyme. To gain deeper insights, BioStock spoke with the principal investigators of both studies, Professor Glen Davison and Professor Doris Wilflingseder.

Enzymatica has developed ColdZyme, a medical device designed to protect against viruses causing common cold and flu-like symptoms in the upper respiratory tract. The spray works by forming a protective barrier in the throat, preventing viruses from attaching to, and infecting, cells, while also limiting their spread. This mechanism may help reduce both the severity and duration of cold symptoms.

Following its CE certification ColdZyme’s efficacy has continued to be evaluated. Recently, results from two separate studies were published in an article in The Journal of Physiology.

ColdZyme proven to shorten cold duration and reduce symptoms

The first study involved athletes with naturally acquired upper respiratory tract infections (URTI) and was led by Glen Davison, Professor of Sport and Exercise Sciences at the University of Kent, UK. The  endurance athletes were enrolled and randomised to use either ColdZyme or a placebo spray at the first signs of infection. The study included data from 154 athletes.

The study showed a significantly shorter duration of symptoms in the ColdZyme group, who also presented notably less severe symptoms, as measured by the Jackson score. As a result, the treatment cohort experienced fewer lost training days due to their cold, compared to the placebo group.

A significantly lower viral load was also observed in the ColdZyme group, which likely contributes to the reduced disease burden.

Professor Glen Davison comments on the findings

Glen Davison

BioStock reached out to professor Glen Davison to learn more about these.

ColdZyme users experienced a significantly shorter duration of illness, milder symptoms, and fewer missed training days. Can these results be directly transitioned to the general population?

– Yes, most definitely. Our interest in, and choice of, athletes for this study is not because they are any different in terms of how they are infected, nor how they respond to the infection or interventions like ColdZyme. We were confident that we would get a sufficient number of illness episodes in this population, and this is a population I am particularly interested in, as a Sports Scientist. However, there is no reason why the effects we have seen, in terms of symptom duration and viral load reduction, would be any different in any other populations.

Based on your findings, what would be your recommendations for when and how ColdZyme should be used?

– Definitely at the first signs of a cold (i.e. when symptoms are first noticed). Importantly, participants need to use it regularly (i.e. 6 times per day) in accordance with the manufacturer instructions for use (IFU) to get the most benefit. ‘Protective use’ (i.e. at times of increased risk (e.g. being around infected people, or in crowded places) would also be prudent.

The study also showed a significantly lower viral load in the ColdZyme group. How important is this finding in terms of understanding how the product works?

– This is incredibly important, as it helps us better understand the underlying mechanisms, specifically why it works. We know that some of the symptoms of URTIs are related to the tissue damage and inflammation, caused by the viral infection of  the airway cells when they are infected. So the lower viral loads, points towards a reduction in this damage and inflammation, which helps to explain these findings. This also likely means that it is easier for the immune system to clear the infection, leading to faster resolution of the illness and associated symptoms. Together, this helps to explain why the symptoms were less severe, and why the illness duration was significantly shorter with ColdZyme use.

The study is based on self-reported data. How does this impact the reliability of the results?

– First of all, a major strength of our study is that we also collected swabs to screen for URTI-causing pathogens to help us confirm illness in our participants. However, arguably self-report data is the most valid measure in this context, because that is how people experience URTIs in the real world. The most important things for studies like this, is to ensure that an appropriate reporting tool (like the Jackson questionnaire) is used. In addition, we need to employ stringent and robust methods to analyse these responses to ensure reliability (i.e. make sure we only count episodes that are highly likely a true, real URTI episode). Together, this combination of self-report and swab analysis makes our data very reliable.

Could you tell us more about the process of getting the study published, and the significance of having it accepted in the Journal of Physiology?

– This is a highly regarded, very prestigious journal, so we are very proud that it was accepted for publication in this journal. This is a peer-reviewed scientific journal, that has been around as the flagship journal for the Physiological Society for nearly 150 years.

– To be considered for publication, you must first submit the manuscript, which is assigned to an associate editor, or group of editors. They will perform a preliminary review to determine if it is suitable for further consideration. If it passes this initial test, it is then sent for review, where 2 or 3 recognised experts in the field are sought to review it.

– They critique all aspects of the study to make a recommendation to the editors as to whether the study should be rejected or is ‘potentially acceptable’ for publication. As part of this process, the reviewers usually have some suggestions for revisions, clarifications, or further improvements. So, if we get a decision of ‘potentially acceptable’, we then have to address any queries, or comments etc from the reviewers.

– The reviewers were very tough- of course we would expect nothing less for such a prestigious journal. However, they did believe it was a good quality study and through the above process, we were able to satisfy the reviewers and the editors, who agreed that it was worthy of publication, and that is how it is ultimately accepted for publication. This is essentially the “peer-review” process.

– Since publication in February, we have been really pleased with the attention that the article has received. For example, it has already exceeded 2,000 full text views and downloads from the publisher’s website. The Altmetric Attention Score is also performing well (this is a measure of the quality and quantity of online attention that an article has received. See: https://www.altmetric.com/about-us/our-data/donut-and-altmetric-attention-score/). The Altmetric score for our article as of 10 April 2025 places it in the top 5% of all research outputs ever tracked by Altmetric; and in the top 3% of all outputs of a similar age (as obviously the longer they have been available, the more time they have had to accumulate attention). Unsurprisingly, a lot of the attention for this article seems to be coming from Sweden.

Lower viral load

The second study included in the recent scientific publication confirmed a reduced viral load when ColdZyme was used on cell culture models containing human airway epithelial cells. These models simulated various parts of the upper respiratory tract, such as the nose and throat, and were infected with rhinovirus.

The results showed that the epithelial cells pre-treated with ColdZyme suffered less damage and inflammation. Tissue cultures treated with ColdZyme showed minimal signs of infection, preserved cell structures, and significantly fewer virus particles compared to those treated with a saline solution.

Professor Wilflingseder explains lab findings

Doris Wilflingseder

The in vitro study was led by Doris Wilflingseder, professor of infectious diseases at the Ignaz Semmelweis Institute and the Vetmeduni Vienna. BioStock reached out to Professor Wilflingseder to learn more about the results.

What motivated you to investigate ColdZyme’s effect in airway epithelial in vitro models?

– In the first wave of the COVID-19 pandemics, when no treatment or vaccination were available, we were interested, on whether antiviral medical devices that are commercially available are effective against this new challenge. Since we had a standardized airway model at hand due to working on Aspergillus fumigatus for a long time, we tested ColdZyme within our 3D human airway model and found that it is highly effective. And that is, how it started.

Can you elaborate on how the epithelial cell models simulate the human upper respiratory tract, and how closely they mimic real-life infection scenarios?

– Our models are closely resembling real-life infection scenarios. The tissue model has ciliated and mucus-producing cells as well as stem cells that are renewing the other cell types; moreover, the cells are of primary origin. To provide the cells a scaffold as they have in our body (which is called extracellular matrix), we mix cells and an artificial matrix prior seeding, so that the architecture is also similar compared to the real-life. After a 4-week differentiation period in air-liquid interphase the cells are ready to go for infecting these with the respiratory pathogen of interest.

In what ways do your in vitro findings support or complement the results observed in the in vivo study?

– In my opinion, in vivo and in vitro study complement each other and strengthen the data of each other. We found a reduction in viral load in both scenarios, which were associated with shorter duration on symptoms in the in vivo study and maintenance of tissue integrity in vitro, which goes hand in hand – the lower the viral load, the less tissue destruction, the shorter the symptom duration.

What are the next steps in terms of research or trials to confirm these results?

– We are right now in planning further combined in vitro and in vivo studies to also mechanistically explain our findings.