The demand for drugs to treat and prevent COVID-19 has increased the number of immunological studies. Study the mechanisms of penetration of the virus into healthy cells. Various types of vaccines are being developed that use different fragments of the coronavirus to achieve the desired immune response of the body. The features of immune responses that cause severe forms of the disease are studied. The influence of individual immune cells on the course of the disease is studied. A significant part of the research related to SARS-CoV-2 is devoted to the study of the natural mechanism of antiviral protection-interferons.

Interferons – a basis of antiviral protection

Interferons are signalling proteins that trigger and regulate the immune response to the virus entering the body’s cells. Interferons activate genes that produce antiviral defence cells. Interferons attract immune cells to the site of infection. Interferons signal healthy cells about the danger of infection.

However, some viruses (SARS-CoV, SARS-CoV-2, MERS) can counteract the antiviral work of interferons. As a result, the regulation of the immune system is disrupted, and the disease causes severe complications and leads to death. The COVID-19 pandemic has provided an abundance of research material and has allowed for the intensification of a comprehensive study of antiviral protection associated with interferons.

Insufficient production and interferons activity

Influence of SARS-CoV-2

Studies aimed at studying the development of the body’s interferon during viral invasion have revealed the suppression of antiviral protection.

Interferon production and activity decreased under the influence of SARS-CoV-2, and production of chemokines – signalling proteins that attract distant immune cells-increased. There was a hyperinflammatory immune reaction that was not controlled by interferons. It led to the destruction of vital organs and tissues: blood vessels, lungs, kidneys, and bronchi.

The results of these studies showed similar trends for both humans and animals (mice, monkeys).

Inherited genetic mutations

Researchers have studied the characteristics of children who had severe flu. Genetic analysis revealed a complex heterozygous IRF-7 mutation, in which the body’s cells produced very few interferons of types I and III.

The mutation affected the immune system. Interferon production by lymphocytes and dendritic cells is significantly reducing. This same genetic feature led to the fact that tissue cells-dermal fibroblasts and pulmonary epithelial cells – also produced a reduced amount of interferon.

Researchers have suggested that a severe form of flu may be the result of inborn errors in genes. And to protect such people from primary infection with the flu virus, scientists believe that IRF7-dependent amplification of interferons of types I and III are necessary.

Interferon level recovery

The next step was to study ways to maintain the level of the body’s interferons throughout the disease without damaging the body.

Systemic interferon drugs have been developed for a long time and are highly effective drugs. They have been used to treat cancer and hepatitis C for several decades. Side effects occur if you take the medication for several months, as required by the course of treatment. Individual calculation of the dose of the drug can reduce the intensity of side effects: vomiting, headache, and depression.

Interferon preparations for local treatment and prevention of respiratory diseases are just beginning to gain popularity in the world. That is due to current research on their effectiveness and lack of side effects. Its use is limited to days and weeks, but not months, as in the case of cancer and hepatitis C.

The main feature of drugs for local use is the ability of exogenous (coming from outside) interferon to stimulate the production of endogenous (self-produced) interferon. That’s, on the one hand, requires lower doses, and on the other – ensures that the drug enters the respiratory system, without affecting other systems of the body.

Prevention of COVID-19 with nasal forms of interferon-alpha-2b

The pandemic has affected people in all countries. Each country has developed guidelines for the treatment and prevention of COVID-19.

For drug prevention of the population and doctors, nasal forms of interferon-alpha-2b are often used.

In the Wuhan, a study was conducted on the incidence of COVID-19 among doctors using this form for daily prevention. Result: none of the 2415 doctors who worked in the “red zone” was ill during the month.

In studies on mouse cells, it is seen that pretreatment with interferon has a protective effect when infected with SARS-CoV-2. Similar positive effects were observed from the early administration of interferon when mice were infected with SARS-CoV and MERS viruses.

Treating COVID-19 with nebulized interferon-alpha-2b

The first studies of interferon-alpha-2b therapy were conducted in mice.

A general trend is to use the drugs in the early stages of the disease to reduce the disease severity. When interferon was administered at late stages, the therapy only increased uncontrolled inflammation and led to severe consequences. It has also been observed that using interferon in the later stage of infection slows down the recovery of the lungs.

Clinical studies in humans have shown the effectiveness of early therapy with nebulized interferon-alpha-2b. The severity of the disease and mortality significantly decreased. The patients did not develop a cytokine storm.

Conclusion

Numerous studies show the effectiveness of the prevention and treatment of respiratory diseases using interferon preparations for topical use.

The most crucial thing about this form of therapy is the time of its beginning. It is essential to start treatment within 5 days of the onset of symptoms. During this period, the body’s resources for the production of interferons are not yet exhausted so that exogenous interferon will contribute to the full output of endogenous. This therapy will allow the patient’s body to control the systemic inflammatory response and prevent the development of a severe form of the disease.

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