A recent article posted to the Research Square* preprint server illustrated that early intervention with azelastine nasal spray therapy might lower the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) load among virus-infected patients.

Background

Since coronavirus disease 2019 (COVID-19) strongly impacts the daily lives of people, medications for treating early infections are urgently needed to stop their progression. The nose and nasopharynx typically have the highest viral titers during early SARS-CoV-2 infection.

Therefore, a nasal spray containing an active ingredient that prevents viral entry and replication might delay or stop the disease's progression to the lower respiratory tract and lessen transmission to non-infected people.

An approved medicinal product, azelastine hydrochloride nasal spray, is presently used for allergic rhinitis treatment at 0.1% w/v concentration. Azelastine hydrochloride, the active ingredient, is a histamine-1 receptor antagonist that exhibits anti-inflammatory actions by stabilizing mast cells and preventing the production of pro-inflammatory cytokines and leukotrienes.

Since the COVID-19 pandemic began, numerous independent research organizations demonstrated azelastine as a viable option for drug repurposing to lower SARS-CoV-2 viral load and infection frequencies.

About the study

In the present parallel, randomized, placebo-controlled, double-blind phase 2 study named CARVIN, the researchers aimed to verify the preclinical data demonstrating the antiviral efficacy of azelastine among SARS-CoV-2-positive patients.

The trial was performed at the Otorhinolaryngology Department of the University of Cologne in Germany. Outpatients who visited COVID-19 test centers were informed of the opportunity to participate in the study. Patients between 18 and 60 years were eligible for participation if they tested SARS-CoV-2-positive within 48 hours before enrollment and had to home quarantine under local health authority guidelines. The investigators, who were doctors with specialties in otorhinolaryngology, general medicine, or medical hygiene, regularly visited patients at home.

The team randomized 90 COVID-19-positive patients into one of three treatment groups, receiving placebo and azelastine nasal spray in varying concentrations, i.e., 0·02% or 0·1%, for 11 days (the treatment phase), during which time virus loads were measured using a quantitative polymerase chain reaction (qPCR). Scientists monitored the patients' conditions throughout the research, including during safety check-ups on days 16 and 60. Moreover, the symptoms were recorded in patient diaries.

Results

The study results indicated that the initial SARS-CoV-2 loads were log₁₀ 6·85 ± 1·31 copies/mL of open reading frame 1a/b (ORF 1a/b) gene. Based on a literature assessment conducted during research preparation in the 2020 autumn, this result was higher versus the predicted mean viral load of log₁₀ 5.5 ± 3.00 copies/mL. Additionally, the SARS-CoV-2 Alpha variant was present in most study participants.

From day 1 of the treatment (baseline) to day 11, the viral load decreased gradually in all three groups, resembling the two-week natural SARS-CoV-2 clearance period. Notably, the area under the curve (AUC) analysis illustrating the decline in viral load based on the ORF 1a/b gene detection throughout the 11-day treatment period revealed a considerably higher drop in viral load in the 0.1% azelastine cohort relative to the placebo.

Compared to the placebo arm, the viral load in the 0.1% group was significantly lower on day 4 in a subgroup of patients with an initial cycle threshold (Ct) value of less than 25. Negative PCR results came earlier and more often in the azelastine-treated cohorts: 21·43% and 18·52% in the 0·02% and 0·1% groups, respectively, relative to 0% for the placebo group on day 8. 

Besides, the frequency of adverse events was similar across all treatment cohorts, with no safety issues. Of note, just one patient complained about the well-known bitter taste of azelastine, and compliance across treatment groups was identical, suggesting that the taste had no negative impact on treatment adherence.

Overall, the authors noted that the study results indicate the antiviral potential of azelastine. 

Conclusions

Overall, the present proof-of-concept research sought to determine whether nasally administered azelastine might have the ability to decrease the viral load by preventing viral entrance and replication in COVID-19-positive patients and could have a significant effect on subsequent viral spread across the community. The trial revealed the first human evidence demonstrating that azelastine hydrochloride nasal spray could be beneficial in speeding the decrease of viral load inside the nasal cavity and alleviating symptoms experienced by COVID-19 patients.

Although the current findings are promising, additional investigations are required to support them. Indeed, the authors also mentioned that future studies should include people in various risk and age groups and those with varying degrees of symptom intensity. 

Despite the small sample size of the present trial, the researchers noted that the findings nonetheless provide a solid platform for a currently planned phase 3 investigation. Besides, how azelastine nasal spray impacts symptom severity and advancement to severe COVID-19 will be examined in a larger patient group during this phase 3 study.

*Important notice

Preprints with Research Square publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.