Nasal drops of interferon alpha-2b (IFN-α2b) can protect against respiratory viruses, including COVID-19 and influenza. Over 90% of all acute respiratory infections are caused by viruses such as influenza, parainfluenza, respiratory syncytial virus, rhinovirus, adenovirus, and coronaviruses. IFN-α2b in nasal drop form reduces the risk of infection and alleviates symptoms of existing diseases.
Acute upper respiratory tract infections affect the nose, throat, larynx, trachea, ears, and sinuses. Respiratory viruses are transmitted from person to person through inhalation of droplets expelled by coughing and sneezing. Treatment of respiratory infections mainly focuses on symptom relief, as most antiviral drugs are ineffective. For example, oseltamivir is the most well-known antiviral drug used only against influenza.
Interferon alpha is a protein that helps the body fight viruses by activating the immune system. IFN-α binds to receptors on cell surfaces, triggering reactions that activate genes responsible for suppressing viral replication and enhancing immune response.
The mucosal lining of the upper respiratory tract contains numerous immune cells with receptors for interferon-alpha. These cells can effectively combat viral infections. Nasal drops of interferon-alpha exert a rapid antiviral effect by activating the mucosal immunity of the respiratory tract. Studies indicate that IFN-α can effectively prevent or mitigate symptoms of infections caused by respiratory viruses, including COVID-19.
Human recombinant IFN-α2b, produced in Cuba, has demonstrated antiviral efficacy and safety for over 37 years. In January 2021, the Cuban regulatory authority granted emergency use authorization for nasal drops of interferon alpha-2b. Cuban scientists recommend using nasal drops of IFN-α2b for COVID-19 prevention in high-risk individuals.
Efficacy and Safety of Nasal Interferon Alpha-2b: A Cuban Study
Pharmacodynamic Study
The study involved 91 healthy volunteers aged 19 to 85. Nasal drops were available in 2.5 million IU/ml, 5 million IU/ml, and 10 million IU/ml of IFN-α2b in 2 ml vials. Participants were administered one drop into each nostril, equivalent to 0.05 ml. The dose depended on the IU of IFN-α2b per drop.
The study was conducted in three phases:
- Phase one: A group of 24 participants received 1.0 million IU per application, once or twice daily for 3 consecutive days.
- Phase two: 40 participants received 1.0 million IU per application twice daily for 10 consecutive days.
- Phase three: Three groups of 9 participants received 0.25 million IU, 0.50 million IU, or 1.0 million IU once daily for 3 consecutive days.
During the three phases, participants were provided oropharyngeal swabs five times throughout the study before starting interferon use. In the first and second phases, blood samples were collected to check for the expression of several IFN-α gene biomarkers and innate immune effector activity.
Preventive Health Measures
In two Cuban cities, Havana and Cardenas, nasal drops of interferon alpha-2b were distributed to individuals engaging in international travel and their close contacts. The participants ranged in age from 19 to 80 years. Among the close contacts of each traveler, two or three individuals used IFN, while one person did not, forming the control group for this study. A similar intervention was conducted among hotel workers at the Varadero resort. The total number of participants in the survey exceeded 29,000.
Participants received nasal drops of IFN-α2b (10 million IU/ml in a 2 ml vial) in doses of one drop into each nostril twice daily (2 IU daily) for 10 consecutive days.
In both interventions, the success criteria included the daily absence of clinical and respiratory symptoms and the non-detection of SARS-CoV-2 infection during the 10-day preventive use of nasal IFN-α2b drops. A database of COVID-19 patients diagnosed by the Cuban national health system was monitored for 30 days after including the last participant in the study.
Study Results
Pharmacodynamic Study
IFN-α2b induces the activation of immune cells and increases the expression of genes responsible for innate immune responses. Over 50% of participants showed activation of IFN-α biomarkers and other immune proteins in the oropharyngeal mucosa and peripheral blood mononuclear cells (PBMC). Increased doses of IFN-α2b corresponded with heightened immune system activation.
Participants who received a dose of 1.0 million IU of IFN-α2b twice daily showed the most significant changes in the expression of immune genes compared to those who received lower doses or used interferon once a day. However, reducing the dose of IFN-α2b from 1.0 million IU to 0.5 million IU administered once daily did not diminish the expression of antiviral activity genes or the activation of the innate immune response. Reducing the application frequency from twice to once daily did not alter the effect of the nasal drops.
The expression of the OAS1 gene, crucial for antiviral defense, increased in 57.5% of participants throughout the observation period. OAS expression is a classic marker of IFN antiviral activity, typically indicating successful treatment. Maximum OAS1 expression peaked 72 hours after starting interferon use, increasing 65-fold compared to baseline levels. Expression in PBMC was 4-6 times lower than in the oropharyngeal mucosa.
87.5% of participants showed increased STAT1 and STAT3 expression levels in PBMC. These changes indicated the activation of the interferon signaling pathway and the body’s antiviral response.
Over 50% of participants showed increased TLR expression in the oropharynx and PBMC samples. Levels of β-2MG increased 50% of subjects but not as significantly as OAS1 or STAT.
The baseline level of IFN-α2b in serum increased in 6 out of 12 patients on the third day of using nasal drops of interferon alpha-2b.
Preventive Health Measures
Using nasal drops of interferon alpha-2b significantly reduced the risk of COVID-19 infection: incidence rates in Havana and Cardenas decreased by 46.8%. Among travelers and their close contacts receiving IFN-α2b, there were significantly fewer cases of COVID-19 compared to the control group (4 cases versus 1026 cases). Among hotel workers receiving IFN, no cases of infection were reported, while the control group had 39 cases (10.2%).
Nasal IFN-alpha-2b proved to be an effective measure for preventing COVID-19, particularly in confined populations such as hotel workers. The interferon preparation helped avert virus transmission and new cases of infection in 5.7 out of 100 instances, meaning that 1 in 18 people was protected.
Safety Profile Analysis
Adverse events (AEs) were reported in 10.2% of individuals. The most common AEs were headache (4.3%), rhinitis (1.5%), and rapid fatigue (1.3%). 92.8% of AEs were mild. No severe AEs were reported. All AEs were local, transient, and reversible, did not require additional treatment, and did not affect the continuation of IFN use.
Image source: https://www.liebertpub.com/doi/10.1089/jir.2023.0193
Conclusion
Interferon activates the body’s defense mechanisms aimed at destroying viral genomes. Nasal drops of IFN-α2b stimulate these mechanisms by enhancing the activity of genes responsible for antiviral protection.
IFN-α2b activates innate immunity receptors TLR3, TLR7, and TLR8, which help recognize and neutralize viral nucleic acids. The expression of the STAT1 and OAS1 genes confirms the active involvement of interferon in combating viruses at the mucosal level.
Nasal drops of IFN-α2b significantly reduced COVID-19 incidence in high-risk groups such as international travelers and tourism workers. The national Cuban protocol for COVID-19 treatment includes IFN-α2b as part of antiviral measures. Using nasal drops of IFN-α2b is a convenient and effective method that can be self-administered without disrupting daily activities.
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