Interferon alpha-2b (IFN-α2b) is one of the effective agents against respiratory infections: COVID-19, influenza, ARVI (acute respiratory viral infection). The COVID-19 pandemic has accelerated research on IFN-α2b to protect against infection and reduce disease severity.

This article summarizes the world’s experience with interferon alpha-2b to prevent and treat COVID-19 and other inflammatory diseases of the respiratory tract. Further in the article:

  • reviews of medical research conducted in different countries of the world (China, Cuba, Russia, India);
  • recommendations of state health authorities (China, Cuba, Russia, India, UAE);
  • links to articles in scientific journals and documents on the websites of government organizations.

Content

Prevention of COVID-19 and Other Acute Respiratory Viral Infections with Interferon Alpha-2b

For the prevention of COVID-19 and other acute respiratory viral infections, only the nasal form of interferon alpha-2b is used. The drug protects the nasal mucosa – the part of the body that receives the brunt of a viral attack. Through the nasal mucosa, the virus spreads through the respiratory tract, and in severe cases, throughout the body.

For more than 30 years, IFN-α2b nasal preparations have been used to prevent inflammatory airway diseases. The action of the drugs is well studied, and the dosage is carefully selected. In nasal preparations, low doses of interferon alfa-2b are used, which increase the antiviral protection of the nasal mucosa, but do not affect the entire body. Therefore, nasal drugs are approved by state health authorities to prevent COVID-19 and other acute respiratory viral infections, even in particular groups of the population: pregnant women, people with weakened immunity, children.

Clinical researches


China

The world’s first study on preventing coronavirus infection with nasal interferon-alpha-2b was conducted in China. This country was the first to face the new coronavirus SARS-CoV-2, which causes severe respiratory syndrome COVID-19. At an early stage of the epidemic, high mortality and infectiousness of the new disease were recorded. The risk of infection among medical personnel reached 90% at the epicenter of the epidemic.

Even following the COVID-19 physical protection standard did not fully protect doctors. Since the pandemic began, 3,062 doctors at the epidemic’s epicenter have become infected in less than a month. Funds were urgently needed for drug prevention of the disease.

The Medical Ethics Committee of Taihe Hospital in Shiyang City, Hubei Province, has approved a pilot study of the efficacy and safety of IFN-α2b nasal drops in healthy medical personnel for the prevention of COVID-19. As a result, during the survey from January 21 to February 23, 2020 (28 days), none of the 2944 study participants contracted coronavirus infection. At the time of publication of the study results, March 6, 2020, there were still no cases in the group of participants.

For comparison, among the doctors of Hubei province who were not involved in the study, 2,035 people fell ill with a new coronavirus infection during the same period – from January 21 to February 23, 2020 (28 days). For more details, see the study overview. Bentham Science Publisher published the details of the study.

The background to this study was a field trial conducted in 2003 and 2004 with an IFN-α2b nasal spray to prevent respiratory viral infections. The test involved 14,391 people. According to the test results, the prophylactic efficacy of the drug was 50.27%. The trial details are described in Chinese, but the purpose, methods, and results are published in English in the National Library of Medicine.

Intensive Chinese studies of interferon alpha-2b began in 2003 when a joint Chinese-Cuban plant for interferon preparations was built using Cuban technology. The official Twitter of the President of Cuba reports that the Chinese Health Commission has approved this particular interferon to fight the coronavirus:


Cuba

Cuban specialists have been producing, researching, and using interferon preparations for 40 years – since 1981.

During the COVID-19 pandemic, Cuban scientists were among the first in the world to receive samples of SARS-CoV-2 coronavirus strains from their Chinese colleagues and learned the details of a study of nasal interferon alpha-2b for the prevention of disease in healthy medical personnel. As a result, 3 studies have already been conducted in Cuba on the prevention of COVID-19 using nasal IFN-α2b (Nasalferon) in people at risk:

  • doctors;
  • pensioners;
  • people with concomitant diseases and weakened immunity;
  • tourists returning from abroad and their family members.

From May 4 to June 4, 2020, the first study was conducted on volunteers from among doctors (17,241 people), retirees, and people with concomitant diseases (1,105 people). As a result, the preventive effect of the drug was 99.85%. During the study period (1 month), when doctors received prophylactic treatment with IFN-α2b nasal drops, only 27 people became infected with coronavirus infection – 0.15% of the number of subjects. The Cuban Academy of Sciences reported the details of the study.

In the following study, Cuban doctors examined the efficacy and safety of the nasal drug IFN-α2b to prevent COVID-19 in immunocompromised and immunosuppressed people. The study involved 15 people with end-stage chronic kidney disease. Three times a week, these people received hemodialysis (blood purification) at medical centers and therefore could not meet the requirements of social isolation. In addition to kidney damage, the participants had other comorbidities: hepatitis C, cancer, hypertension.

The study was conducted over 45 days. During this period, there was no single case of COVID-19 among the participants, and PCR tests did not reveal a single infection issue with the SARS-CoV-2 coronavirus. For more details, see the study overview. Details of the study are published in the Journal of Renal Endocrinology.

This research is essential to prevent the emergence of new strains of coronavirus. Scientists suggest that, for example, in the UK, a new strain arose due to months of the evolution of the virus in the body of one single immunosuppressed patient who developed a chronic form of COVID-19. Doctors register cases when the chronic condition of COVID-19 in people with immunodeficiency and immunosuppression lasts 2 to 4 months. When viral loads are high, these people have prescribed plasma transfusions from recovering people. Sometimes this procedure is performed several times. The viral particles that survived after the first procedure become resistant to antibodies. Sequencing of the viral genome from immunocompromised COVID-19 patients reveals an unusually high number of mutations. Cuban experts have demonstrated that immunosuppressed people can be effectively protected from COVID-19 with nasal interferon alfa-2b.

In another study, Cuban specialists studied nasal interferon alpha-2b to limit the spread of COVID-19 across the state border and the importation of new strains of the SARS-CoV-2 coronavirus into Cuba. The study involved 103 tourists returning to Cuba and 317 family members. All participants used IFN-α2b twice daily for 15 days. As a result, during the study period, none of the participants was found to be infected with COVID-19 by PCR tests or clinical examinations. Details of the study are published in MEDICC Review.

This study is part of a more extensive study on the use of nasal IFN-α2b by travel workers in the Varadero Beach region to prevent coronavirus infection. The drug was used by employees of three hotels and one camping. The country’s leadership plans to scale the successful experience gained in the study to the entire tourism industry in the country. The prerequisite for the study was mathematical modeling carried out at the University of Havana. The dean of the Faculty of Mathematics and Computer Science reported on the successful completion of the simulation to the President of Cuba.


Russia

In Russia, interferons have been produced, studied, and used since 1969.

In the COVID-19 pandemic, Russian experts have studied the prophylactic efficacy of interferon alfa-2b nasal spray (Grippferon) to protect medical personnel from coronavirus infection. A preliminary statistical analysis showed that the risk of disease of medical workers with coronavirus infection in Russia is 4 times higher than the general population. Doctors are at the highest risk of infection: 266 cases per 1000 people. The risk of COVID-19 in nurses and nurses is significantly lower: 82 cases and 61 cases per 1000 people, respectively.

The study involved 561 medical professionals. 348 people used IFN-α2b spray for emergency prevention of COVID-19. The control group consisted of 213 people, did not use the study drug.

Study result: Interferon alpha-2b spray reduces the risk of infection for healthcare workers by 67%. The incidence of people in the control group was 3 times higher than in the group receiving the drug. The best preventive effect was in the group of doctors: the chance of being infected with the SARS-CoV-2 coronavirus was 9 times lower if the doctor used an IFN-α2b spray. In the nurses and nursing staff groups, the drug reduced the chance of infection by 1.9 and 1.4 times, respectively. Details of the study are published in the Infectious Diseases journal.

Another critical study is devoted to preventing acute respiratory viral infections using the nasal spray IFN-α2b (Grippferon) in children with reduced immunity due to tuberculosis. Acute respiratory diseases lessen the body’s overall resistance to infections and aggravate the severity of the tuberculosis process. Prevention of ARVI in children with tuberculosis is an integral part of comprehensive treatment. The study involved 156 children aged 3 to 17 years. Of these, 106 children received treatment with IFN-α2b, and the remaining 50 children were included in the control group that did not receive IFN-α2b. The duration of the study was 6 months (from January to June 2016), and the period of the drug intake was 3 months.

According to the study results, it turned out that 92.9% of children receiving the drug had never had respiratory viral infections. In the control group, this indicator was almost 3 times lower – 34%. In the case of a child’s illness with ARVI, the use of interferon alfa-2b continued. In this case, the researchers evaluated the therapeutic effect of the IFN-α2b nasal spray in ARVI, which is described later in this article. Details of the study are published in the journal Infectious Diseases: News, Opinions, Learning.

In 2022, Russian scientists investigated the effectiveness of COVID-19 prevention methods in pregnant women. Among the prevention methods are intranasal interferon–α in drops or spray and IFN-α in rectal suppositories.

The study involved 125 pregnant women with confirmed coronavirus infection of moderate and severe forms and 175 healthy pregnant women. Both groups were recruited in September-November 2021.

Intranasal interferon-alpha was most effective with systematic use – once in the morning for 3000 ME with an interval of 24-48 hours. However, when interferon was administered only after contact with the patient, a high risk of infection remained. At the same time, most pregnant women were infected by family members and at work without assuming they had been in contact with the patient and without using emergency prevention with interferon.

Rectal suppositories of interferon-alpha increased the risk of coronavirus infection by three times with short–term drug administration after contact with the patient.

The study details are in the article “Prevention of COVID-19 in Pregnant Women“. The study was published in the “Issues of Gynecology, Obstetrics and Perinatology” journal.

In 2023, Russian scientists demonstrated that intranasal interferon alpha-2b enhances protection against the Omicron coronavirus variant among vaccinated individuals.

Due to the evolving nature of the coronavirus, vaccines cannot offer complete protection against Omicron and its subvariants. In comparison to the original Wuhan strain, neutralizing antibody levels against the Omicron variant decreased by 8.1 times for the “Gam-Covid-Vac.”

The research on the effectiveness of IFN-α2b against Omicron involved 170 healthy healthcare workers who had been vaccinated with “Gam-Covid-Vac”:

  • 108 participants used intranasal IFN-α2b nasal drops at the beginning and end of their work shifts, with a dosage of 3000 International Units (IU). The daily dosage amounted to 6000 IU.
  • 62 participants were part of the control group.

Intranasal IFN-α2b reduced the incidence of Omicron infection by a factor of 2.6. The combined effectiveness of “Gam-Covid-Vac” and interferon amounted to 64.5%.

For further details on the research, you can refer to the article titled “Interferon Alpha-2b Enhances Protection Against Omicron in Vaccinated Individuals.” This study has been published in the “Infectious Diseases” journal.

Recommendations from National Health Authorities


China

The Standards for the Diagnosis and Treatment of Novel Coronavirus Infectious Pneumonia prepared by the National Health Committee of China describes the prevention of COVID-19 for people at high risk who are in close contact with patients. One of the recommended means of drug protection for this group of people is interferon alfa-2b nasal spray. That was reported in a consensus statement by Chinese experts published in the World Journal of Pediatrics.


Cuba

The Cuban Journal of Public Health publishes Cuban Public Health Principles during the COVID-19 pandemic. The section on the prevention of coronavirus infection (page 3) recommends using a nasal form of IFN-α2b (Nasalferon) to protect people at risk from SARS-CoV-2 coronavirus infection.

The preventive action of IFN-α2b (Nasalferon) is mentioned in the first part of the Cuban Government’s National Report of 2021 in the chapter “Cuba against COVID-19”. The drug is recommended for use by the entire healthy population. A separate recommendation for medical personnel is highlighted: to use nasal forms of IFN-α2b to protect against infection.

The Pan American Health Organization, in a report on the COVID-19 situation in Cuba, notes the importance of preventing coronavirus infection with nasal IFN-α2b (page 37).


Russia

For drug prevention of COVID-19 in adults, the Ministry of Health of the Russian Federation recommends the use of nasal interferon alfa (section 7.3 “Drug prevention of COVID-19 in adults” of the “Temporary guidelines. Prevention, diagnosis and treatment of new coronavirus infection (COVID-19)”, version 11, dated May 7, 2021).

Also, in section 7.3, there is a recommendation for pregnant women – they can only use nasal recombinant interferon alfa-2b. Experts emphasize that pregnant women are prescribed only nasal recombinant IFN-α2b. Recombinant interferon is produced genetically and not from blood components, so it is safe.

In the same document, in section 5.7, “Special patient groups,” there is a particular recommendation for people with diabetes: “… should carefully follow the recommendations for the prevention of COVID-19 disease. The use of interferon-alpha preparations is recommended as a specific prophylaxis”.

National, Municipal, and Corporate COVID-19 Prevention Programs with IFN-α2b Nasal Drugs


Cuba

Residents of Havana who have been in contact with COVID-19 patients will be provided with a nasal preparation of interferon alfa-2b (Nasalferon) to prevent coronavirus infection. The same drug will be provided to people in contact, family doctors, and nurses. It was announced on his personal Twitter by Cuban President Miguel Mario Diaz-Canel Bermudez. The President’s words are quoted by the Pan American Health Organization in a report on the COVID-19 situation in Cuba (page 37). The same message from the President indicates that this practice will be extended to the rest of the country in the future:

Medical staff are most at risk of contracting COVID-19 and will be provided with IFN-α2b nasal drops (Nasalferon). Thфе was announced by the chief epidemiologist of the Cuban Ministry of Health. The expert emphasized that this measure is preventive and aimed at healthy people to protect them from coronavirus infection. This message was posted on the website of the Ministry of Foreign Affairs of Cuba.

Later, the National Center for Health Information reported that 499 health workers in one of the provinces where the COVID-19 outbreak occurred were using nasal interferon alfa-2b (Nasalferon) under experts’ supervision of the capital. At the end of 2020, the Minister of Health of Cuba, speaking before the National Assembly, announced that the prevention of coronavirus infection in risk groups, including among employees of covid departments, is carried out with IFN-α2b.

People arriving in Cuba will use nasal IFN-α2b (Nasalferon) as a preventive measure against COVID-19. The drug will also be provided to residents of houses in which travelers will settle. That was reported on the website of the Latin American School of Medicine. The Pan American Health Organization, in a report on the situation with coronavirus infection in Cuba, confirms this report (page 37).

Russia

Families with at least one COVID-19 case in one of the oil provinces of Russia will be provided with a nasal preparation of interferon alfa-2b (Grippferon) to prevent coronavirus infection in healthy people. The regional government thus strengthens anti-epidemic measures and seeks to extinguish the outbreak.

Employees of enterprises working during the height of the coronavirus pandemic were provided with antiviral protection kits or received recommendations for the prevention of coronavirus infection. The management of several enterprises purchased a nasal preparation IFN-α2b (Grippferon) for employees and their family members or recommended using this drug for drug prophylaxis of the disease.

Treatment of COVID-19 and Other Acute Respiratory Viral Infections with Interferon Alpha-2b

Interferon alfa-2b is usually used to treat COVID-19 as part of combination therapy. Different countries use different pharmaceutical forms of IFN-α2b, but in total, all available options are used all over the world:

  • nasal (intranasal, nasal) drugs: for asymptomatic infections and mild cases of the disease, to reduce the viral load in the nasal passages of patients with COVID-19 and to reduce the risk of infection of others;
  • aerosol preparations received through a nebulizer: in case of damage to the lungs by a coronavirus, to prevent severe forms of the disease;
  • injectables and lyophilized powder for injections: for the prevention of extreme conditions of the disease and in case of lung damage;
  • suppositories (suppositories): for the intestinal form of coronavirus infection and the prevention of severe forms of the disease.

An important feature of treating COVID-19 with interferon drugs, including interferon alpha-2b, is that they are best used in the first 5 days from the onset of symptoms. If they are used later or in severe forms of the disease, such treatment can complicate the course of the illness and aggravate the cytokine storm.

Clinical Researches


China

The first study examining the link between interferon alpha-2b treatment and clinical outcomes in COVID-19 patients was retrospective. Chinese experts analyzed 446 medical records of patients with coronavirus infection hospitalized between January 15 and March 31, 2020.

All patients were divided into 3 groups. Patients of the first group began to receive IFN-α2b treatment early in the first 5 days of hospitalization. Patients of the second group received IFN-α2b treatment with a delay after 5 days of hospitalization. Patients of the third group did not receive IFN-α2b treatment, and a nebulized form of interferon alpha-2b was used for treatment.

Study result: early initiation of treatment with IFN-α2b reduces mortality in patients with severe and critical forms of coronavirus infection. In the early treatment group, mortality was 0.9%, without interferon treatment – 4.9%. In the group of a late start of treatment, the result was 15.4%. Chinese experts suggested that with late initiation of therapy, interferon alfa-2b amplifies the cytokine storm in patients with severe and critical COVID-19. For more details, see the study overview. The details of the study are published in the journal Cell Host & Microbe.

In a similar but larger retrospective study, Chinese scientists have analyzed 1,401 medical records of patients with coronavirus infection hospitalized between January 17 and February 19, 2020. 852 patients received nebulized IFN-α2b, and 549 patients with coronavirus infection made up the control group.

Study result: therapy with interferon alpha-2b reduces the incidence of clinical complications by 64%. Moreover, if the start of treatment began later than 5 days after the onset of symptoms, this increased the likelihood of aggravating the patient’s condition. Patients had the best results if treatment with IFN-α2b was started within two days of the onset of symptoms. For more details, see the study overview. Details of the study are published in the British Journal of Clinical Pharmacology.

Scientists note: Studies have shown that early initiation of interferon alpha-2b therapy is an essential clinical factor in successful treatment.

In another study, Chinese doctors used nebulized interferon alpha-2b (Tianjin Sinbobioway Biology) as an experimental treatment for COVID-19. The study involved 77 hospitalized patients. All participants were divided into 3 groups. The first group received treatment with IFN-α2b, the second group – with arbidol, the third group – with IFN-α2b and arbidol.

As a result, the recovery period for patients who received:

  • IFN-α2b – 21.1 days;
  • arbidol – 27.9 days;
  • IFN-α2b and arbidol – 20.3 days.

For more details, see the study overview. Details of the study are published in the journal Frontiers in Immunology.

A systematic review of five Chinese studies involving 541 patients with COVID-19 found that interferon-alpha in combination with antivirals:

  • Accelerated the clearance of the virus. With early treatment with IFN-alpha, the clearance of the virus was 5.13 days faster than in the control group: 27.3 versus 32.43 days.
  • Reduced time to negative PCR test.
  • Reduced the duration of hospitalization: 16±9.7 versus 23±10.5 days in the control group. In the IFN-alpha early treatment group, the duration of hospital stay decreased from 25±8.5 to 10±2 days.

The average age of patients is over 41 years. The control group received standard antiviral treatment (lopinavir/ritonavir/arbidol), and the intervention group received antiviral treatment in combination with IFN-alpha.

In most studies, 5 µg/mL (12 million IU/mL) IFN-alpha was administered twice daily for two consecutive weeks or until discharge. IFN-alpha was administered subcutaneously or by aerosol inhalation. There was no significant difference in side effects between the intervention and control groups.

Details of the study can be found in the article “Interferon-alpha in COVID-19: a systematic review”. The study was published in the Journal of Medical Virology.

Chinese scientists have shown that interferon-alpha-2b spray shortens the infectious period of the Omicron coronavirus. The study included 871 patients with mild or asymptomatic coronavirus. All participants received symptomatic treatment, including non-steroidal anti-inflammatory drugs, cough medicines, and traditional Chinese medicine. Patients were divided into groups:

  • 413 received IFN-α-2b spray;
  • 458 received standard treatment only.

In the experimental group, recombinant IFN-α-2b was sprayed onto the posterior pharyngeal wall, tonsils and oral lesions every 6 hours for 7 days – 3 spray doses per day, about 1.2 million IU/day. Patients abstained from food and water for 15 minutes after applying the spray.

Interferon-α-2b spray reduced virus isolation time by 2 days when administered within 3 days of the first positive coronavirus test. However, delayed administration of IFN increased the infectious period.

The best effect of interferon-α-2b spray was in vaccinated patients. The timing of vaccination did not play a role. IFN did not cause side effects.

Details of the study are in the article “Interferon-alpha-2b spray reduces the infectious period of Omicron“. The study was published in the journal Frontiers in Immunology.

Interferon-alpha is effective and safe for infants with respiratory syncytial virus (RSV) pneumonia. RSV pneumonia is the leading cause of hospitalization and neonatal death worldwide. At present, there are no specific clinical treatments for RSV.

In 2020, scientists at Chongqing Medical University showed that IFN-α injections, in addition to standard treatment, significantly reduced the duration of symptoms and maintenance therapy. Moreover, the frequency of side effects is less than 1%, and the results are easily stopped and occur without relapses.

The study involved 286 full-term newborns under 28 days old. Each participant had been diagnosed with neonatal RSV pneumonia. The diagnosis was confirmed by laboratory analysis of the tracheal mucosa – antibodies of the respiratory syncytial virus were found. The most common clinical symptoms were:

  • cough – 93% of cases;
  • tachypnea – rapid breathing due to a decrease in the level of oxygen in the blood – 90%;
  • blue lips due to reduced oxygen levels in the blood – 68%;
  • choking milk – 62%;
  • wheezing – 58%.

In 67% of cases, an associated bacterial infection was observed: E. coli, staphylococcus, and streptococcus.

The participants were split into two groups:

  • standard care – 160 infants;
  • injections of interferon-alpha for three days in addition to usual care – 126 infants.

In the IFN-α group, the need for additional oxygen support was significantly reduced; the symptoms of lack of oxygen passed faster – blue lips, tachypnea; the duration of coughing, wheezing, and milk choking decreased. However, the time of hospitalization did not reduce significantly.

In the IFN-α group, two out of 126 cases reported a side effect of fever approximately 2 hours after injection. The patient’s temperature returned to normal after a 5-minute warm water bath. Special treatment was not required, and there were no relapses of fever.

The article “Efficacy and Safety of Interferon-Alpha for the Treatment of RSV Pneumonia in Infants.” The study was published in the Experimental and Therapeutic Medicine journal.


Cuba

Cuban experts investigated injectable interferon alpha-2b (Heberon Alpha R) therapeutic efficacy for coronavirus infection. Scientists have chosen this particular form of the drug because it is well studied compared to nebulized. The study was conducted from March 11 to April 14, 2020.

The study involved 814 patients with COVID-19. Of these, 761 people (93.4%) received intramuscular injections of IFN-α2b, and the rest received standard treatment. IFN-α2b treatment began on the fifth day of symptom onset. If the disease progressed to a critical condition, the doctors stopped injecting the drug.

As a result, scientists found that IFN-α2b injections reduced mortality to 0.92% versus 2.95% in people who received standard treatment. The need for intensive care in people in the interferon group was 2 times lower than in the standard treatment group. Details of the study are published in the Journal of Interferon & Cytokine Research.

Russia

Russian scientists have investigated the joint use of interferon alfa-2b (Viferon) preparations in the form of suppositories and IFN-α2b nasal gel as part of the complex therapy of COVID-19. The study involved 140 patients with coronavirus infection. Of these, 70 people received, in addition to standard treatment, rectal suppositories of IFN-α2b and IFN-α2b gel, which were used to treat the nasal mucosa and palatine tonsils. The second group, 70 people, received only standard treatment.

Study results. In the group receiving additional treatment with interferon alpha-2b, recovery occurred 7 days earlier than the standard treatment. Details of the study are published in the journal Infectious Diseases, News, Opinions, Education.


Another study by Russian scientists is devoted to treating ARVI with a nasal spray of interferon alfa-2b (Grippferon) in children with weakened immunity due to tuberculosis. SARS reduces the overall resistance of the body to infections and aggravates the severity of the tuberculous process. The study involved 156 children aged 3 to 17 years. Of these, 106 children received treatment with IFN-α2b, and the remaining 50 children were included in the control group that did not receive IFN-α2b. The duration of the study was 6 months (from January to June 2016), and the period of the drug intake was 3 months.

Study results: In the group treated with interferon alpha-2b, the duration of ARVI was almost 3 days less than in the control group: 5.4 days versus 8.2 days. Moreover, in the IFN-α2b group, there was not a single repeated case of respiratory disease. In the control group, two had ARVI twice.

In the same group of children, the prophylactic efficacy of the nasal preparation IFN-α2b from ARVI, described earlier, was studied. Details of the study are published in the journal Infectious Diseases, News, Opinions, Education.

India

Indian scientists investigated the efficacy of a single injection of pegylated interferon alfa-2b (Virafin) for the treatment of COVID-19 in moderate outpatients. Pegylated IFN-α2b (PEG IFN-α2b) has a more significant therapeutic effect than IFN-α2b since it remains in the body longer. Patients have been receiving injections at an early stage of the disease.

The study involved 250 patients with coronavirus infection. 130 people received standard treatment. In addition to standard therapy, 120 people received an injection of PEG IFN-α2b.

Study results. In the group that received an injection of pegylated interferon alpha-2b and standard treatment, the viral load decreased faster: in 91.2% of participants, the coronavirus was no longer detected on day 7. In the group that received only standard treatment, on day 7, the coronavirus was no longer detected in 78.9% of participants. The PEG IFN-α2b group experienced faster clinical improvement. On the 8th day, 80.4% of the group participants improved their clinical condition by two points on the 7 point scale established by the World Health Organization. In the group that received only standard treatment – in 68.2% of participants. Injection with pegylated interferon alfa-2b reduced the need for supplemental oxygen from 84 hours in the standard treatment group to 56 hours in the interferon group.

The review provides details of Phases 2 and 3 of the study. Details of the study are published in the International Journal of Infectious Diseases.

Recommendations and Guidelines from National Health Authorities


China

China has 100 guidelines (74 national and 26 regional) covering nearly all aspects of COVID-19. Of these, 15 are devoted to the pharmacological treatment of patients. The Standards for the Diagnosis and Treatment of Novel Coronavirus Infectious Pneumonia, prepared by the National Health Committee of China, states that patients with COVID-19 and upper respiratory tract symptoms only at an early stage of the disease should use interferon alfa-2b spray for the nasal cavity and the oropharynx. That was reported in a consensus statement by Chinese experts published in the World Journal of Pediatrics.

Cuba

Intramuscular and subcutaneous injections of interferon alpha-2b (HeberFERON, Heberon Alfa R) form the basis of the treatment for coronavirus infection described in the National COVID-19 Action Protocol (Version 1.6, Cuban Ministry of Health, January 2021). The drugs are used to treat the following groups of patients with a positive PCR test for coronavirus:

  • adults: asymptomatic, with mild disease, moderate disease (severe respiratory symptoms and signs of lung damage);
  • adults with comorbidities: cancer, HIV, chronic kidney disease, cardiovascular disease, Parkinson’s disease;
  • children over 3 years old: asymptomatic, with a mild form of the disease, a disease of moderate severity.

Adults are injected intramuscularly, children – subcutaneously. Treatment is stopped after a negative test for the SARS-CoV-2 coronavirus or if the disease develops to a severe form.

The same document states that interferon alfa-2b preparations are contraindicated in patients:

  • with an autoimmune disease;
  • with multiple sclerosis;
  • with a severe form of COVID-19;
  • children under 3 years old.

When treating pregnant women, the decision to use IFN-α2b is made on a case-by-case basis if the expected benefit outweighs the risk. In this case, low doses of the drug are used.


Russia

The Ministry of Health of the Russian Federation recommends recombinant interferon alpha-2b for the treatment of COVID-19 in pregnant women (section 5.1. “Etiotropic treatment” of the “Temporary guidelines. Prevention, diagnosis and treatment of new coronavirus infection (COVID-19)”, version 11, from May 7, 2021). Recombinant interferon is produced genetically and not from blood components, so it is safe.

In the same document, in Appendix 5, “List of possible drugs for the treatment of COVID-19 in adults”, there is a clarification that intranasal forms of interferon alfa-2b are used:

  • spray;
  • drops;
  • solution;
  • lyophilisate for solution preparation;
  • gel;
  • ointment.


India

In April 2021, the Comptroller General of India approved using subcutaneous injections of pegylated interferon alfa-2b (Virafin) in emergencies to treat moderate adult patients with COVID-19. PEG IFN-α2b is approved for use in healthcare settings as directed by a physician.

Posted by the Department of Biotechnology, Ministry of Science and Technology of India.

United Arab Emirates (UAE)

The UAE Ministry of Health and Prevention recommends using nebulized interferon alfa-2b (Bioferon) to treat patients with coronavirus infection. The national guidelines for the clinical management and treatment of COVID-19 (version 4.0, dated June 1, 2020) indicate that treatment with IFN-α2b is possible in the following patient groups:

  • adults with severe pneumonia or severe illness (section “Therapeutic regimens for adults,” page 12);
  • Children (section “Treatment Options for Pediatric Patients with COVID-19,” page 19);
  • pregnant women (section “Pregnant patients,” page 23).

Treatment regimens for children are based on experience in other countries, and drug doses have been extrapolated from data from adult studies. Moreover, the treatment of children in the intensive care unit with the help of IFN-α2b is carried out only in exceptional cases.

Treatment of pregnant women with interferon alpha-2b follows the same scheme as for other adults (section “Therapeutic regimens for adults,” page 12).

Interferon-α Actions Against Respiratory Viruses

A viral attack causes the infected cell to synthesize interferons “What Types of Interferon are Effective for Coronavirus Infection“, in particular, interferon-alpha. After synthesis, IFN-α molecules leave the cell and bind to neighboring cells or the same cell membranes. This compound activates antiviral defense in healthy and infected cells.

Preventive Action

In healthy cells, under the influence of interferon-alpha, antiviral proteins are produced, which:

  • prevent the virus from attaching to the cellular receptor on the membrane and entering the cell;

  • prevent the penetration of the virus into the cell, increased rigidity of the cell membrane, and regulate its curvature;

  • stimulate intracellular receptors, actively search for foreign proteins;

  • delay the processes of cell infection so that in case of disease, the virus multiplies, as it uses the cell infrastructure for its replication.

If the virus nevertheless enters a cell pretreated with IFN-α, then the cell is already ready to suppress the multiplication of the virus. Thanks to this mechanism, the spread of infection are slowed down.

A study by German scientists has shown the preventive efficacy of IFN-α from the SARS-CoV-2 coronavirus. Specialists treat cells of different cultures with doses of interferon-alpha 16 before infection. In 24 hours after illness, scientists estimated the number of viral particles. The best results were obtained when treated with a dose of 1000 IU / ml – the number of viral particles was about 10,000 times less than in untreated cells. Details are published in the Journal of Biological Chemistry.

Therapeutic Action

In infected cells, interferon-alpha initiates more antiviral processes than in healthy cells. In an infected cell, in addition to protecting against the penetration of the virus and slowing down life, proteins are produced that fight the virus at other stages of the life cycle – entering the cell, reproducing, exiting the cell:

  • neutralize the proteins of the viral capsid when, after entering the cell, the viral genome frees it from the protective envelope;

  • bind to the viral genome, preventing it from starting the process of copying itself;

  • cause hypermutation in the viral genome, cause the viral part to be non-infectious;

  • block the two-stage process of viral DNA reproduction: prevent the reading (transcription) of viral DNA or RNA, and then interfere with the synthesis (translation) of new viral DNA / RNA following the read;

  • prevent the release of new viral particles from the cell, which reduces the fluidity of the cell membrane;

  • expose viral proteins outside the cell membrane so that immune cells learn to recognize the enemy and quickly destroy the infected cell;

  • activate programmed cell death (apoptosis) so that the multiplying new viral particles do not have time to escape and infect other cells.

The biochemistry of the antiviral activity of interferon is described in detail in the American Library of Medicine.

Treatment with interferon-alpha is effective at the initial stage of developing a respiratory viral infection – when the virus is actively multiplying and the acquired immunity has not yet been formed. At the following stages of the development of the disease, when the pulmonary form of hyper inflammation develops, treatment with IFN-α may not work or make the condition of the patients worse.

Systemic Effect

Interferon-alpha preparations have a systemic effect, as the interferon molecule only briefly connects to the cell membrane. After the connection is broken, the same molecule can interact with other people. The magnitude of the systemic effect depends on the dose.

In nasal preparations of interferon alfa-2b, as a rule, small doses are used that are below the detection threshold. Low doses do not cause side effects.

In inhalation and injectable preparations, high doses are used. They cause side effects: fever, chills, fatigue, headache, mood deterioration. Side effects disappear quickly after stopping treatment.

Interferon Alpha-2b Preparations for The Prevention and Treatment of ARVI: Manuals, Release Forms, Storage Rules

Nasal drugs

Grippferon (Russia)

A drug for the prevention and treatment of coronavirus infections, influenza, and ARVI. Method of production: nasal drops, nasal spray, ointment.

Key features:

  • contains a low dose of interferon alfa-2b, an over-the-counter drug;

  • contains components that lengthen the time of drug fixation on the nasal mucosa and promote the penetration of IFN-α2b into the intercellular space;

  • relieves swelling of the nasal mucosa and has a dehydrating effect; therefore, it is not recommended to use vasoconstrictor drugs jointly;

  • allowed for pregnant women and newborns;

  • according to the WHO scale, it is classified as a non-toxic, harmless substance.

The drug is used according to the manufacturer’s instructions. There are additional schemes for the prevention and treatment of the drug

Prevention

Treatment

Viferon (Russia)

The drug is used for the prevention and treatment of coronavirus infections, influenza, and ARVI. Method of production: gel, ointment.

Key features:

  • contains a low dose of interferon alfa-2b, an over-the-counter drug;

  • the gel form provides a long-term effect of the drug;

  • contains antioxidants that have anti-inflammatory and regenerative effects;

  • allowed for pregnant women, newborns, and women during breastfeeding;

  • interaction with other drugs has not been identified.

The drug is used according to the manufacturer’s instructions. Additional schemes for the prevention and treatment of the drug are in the descriptions of clinical trials:

Prevention:

Treatment:

Nasalferon (Cuba)

The drug is used to prevent COVID-19. The release form is a solution for nasal administration.

Key features:

  • contains a high dose of interferon alpha-2b, is used as directed by a doctor;

  • causes moderate side effects that can potentially interfere with driving vehicles and mechanisms: dizziness, confusion, drowsiness, or fatigue;

  • not used in pediatrics due to high dosage;

  • no studies have been conducted on the safety of the drug for pregnant women. The doctor in each case, before use, performs risk and benefit analysis;

  • interaction with other medicinal products has not been identified.

The drug is used according to the manufacturer’s instructions.

Injection Forms

HeberFERON (Cuba)

The drug has been repurposed for the treatment of COVID-19. It was initially developed to treat cancer. The release form is lyophilisate for subcutaneous and intramuscular injections.

Key features:

  • contains high doses of interferon, is used as directed by a doctor;

  • includes 2 types of interferon: alpha and gamma. IFN-α2b provides antiviral effect, IFN-gamma – immunomodulatory;

  • a wide range of contraindications and side effects.

The drug regimens are described in the Cuban National COVID-19 Protocol of Action. The instructions for the drug are published on the manufacturer’s website.

Heberon Alfa R (Cuba)

The drug has been repurposed for the treatment of COVID-19. It was initially developed for the treatment of hepatitis, HIV, and oncological diseases. The release form is lyophilisate or solution for subcutaneous and intramuscular injections.

Key features:

  • contains a high dose of IFN-α2b, is used as directed by a doctor;

  • a wide range of contraindications and side effects.

The drug regimens are described in the Cuban National COVID-19 Protocol of Action. The instructions for the drug are published on the manufacturer’s website.

Virafin (India)

The drug has been repurposed for the treatment of COVID-19. It was initially developed for the treatment of hepatitis. Release form – injection solution.

Key features:

  • contains a high dose of IFN-α2b, is used as directed by a doctor;

  • contains pegylated interferon alpha-2b. It is a compound of IFN-α2b with polyethylene glycol, which increases the duration of the drug’s action;

  • a wide range of contraindications and side effects.

The drug is used according to the scheme described in phase 3 clinical trials: Efficacy and safety of pegylated interferon-α2b in moderate COVID-19: a phase 3, randomized, comparator-controlled, open-label study.

Storage rules

All preparations of interferon-alpha should be stored in the refrigerator at a temperature of +2 to +8 ° C. You cannot freeze.

Conclusions

Interferon alpha-2b drugs are used worldwide to prevent and treat COVID-19 and other respiratory viral infections. Based on the results of clinical studies showing the effectiveness of IFN-α2b, national health authorities recommend using these drugs for coronavirus infection and SARS.

The most effective use of interferon alpha-2b to prevent COVID-19 and other acute respiratory viral infections is as part of a set of protective measures. The intranasal form of IFN-α2b stimulates local immunity in the epithelial cells of the nose, where the infection is most common. The primary prevention directions are doctors, people with immunodeficiency, the elderly, pregnant women, and families with sick people.

When treating COVID-19 and other acute respiratory viral infections, interferon alpha-2b preparations prevent the development of severe forms of the disease, accelerate recovery and protect people caring for patients. Early (up to 5 days from the onset of symptoms) initiation of interferon alpha-2b therapy is an essential clinical factor in the successful treatment of coronavirus infection.

For treatment, the entire spectrum of forms of IFN-α2b is used:

  • nasal preparations – drops, sprays, ointments, gels, solutions;
  • aerosol preparations received through a nebulizer;
  • injectables and lyophilized powder for injection;
  • suppositories (candles).

Treatment with interferon alpha-2b drugs is carried out only by qualified medical personnel.

Sources

Our Telegram channel:

Related posts: