Feb 18, 2021
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Non-specific prevention of ARVI: the experience of an infectious disease specialist

Zhanna Betovna, coronavirus belongs to respiratory viruses, and yet it is clear that COVID-19 can have much more serious consequences than a common cold. Why?

Zhanna Ponezheva: As we already understand, the severe course of COVID-19 is not just an acute respiratory infection and pneumonia, but a systemic infectious vascular disease with impaired hemostasis. The disease caused by SARS-CoV-2 is largely unpredictable, with a number of unknown parameters for predicting the course and outcomes, since there is still no clarity and certainty in understanding the immunopathogenesis of this infection. According to many national health services, 45% of those who recover from hospital have a significantly reduced quality of life and patients may need medical care and rehabilitation for a long time.

Much has already been written about the routes of transmission of the virus and clinical manifestations. Still, I would like to hear the opinion of an infectious disease specialist: what accents would you place?

Zhanna Ponezheva: The transmission of infection is carried out by airborne droplets, when the virus is transmitted by coughing, sneezing, talking. The contact-household route is realized through objects contaminated with the pathogen. The fecal-oral mechanism is possible, and this is confirmed by the detection of the pathogen in the fecal samples of patients.

COVID-19 can be asymptomatic, the most common complication is viral pneumonia, the development of acute respiratory distress syndrome was noted in no more than 5% of all cases of the total number of infected. The entrance gate of the pathogen is the epithelium of the upper respiratory tract and epithelial cells of the gastrointestinal tract. When the virus enters the respiratory tract of a person, suppression of the activity of mucociliary clearance and death of epithelial cells are observed, which makes it possible for the virus to penetrate into the peripheral blood with subsequent damage to target organs (lungs, digestive tract, heart, kidneys).

Who is at risk for a severe course, what is the mortality rate for such patients?

Zhanna Ponezheva: According to the data available in the world, persons aged 60 years and older are at risk for a severe course of COVID-19, as well as patients with concomitant diseases: pathologies of the cardiovascular system (coronary heart disease, hypertension), kidney, liver, metabolic syndrome (hypertension, obesity, Diabetes mellitus, lipid metabolism disorder), chronic diseases of the bronchopulmonary system, malignant neoplasms. Mortality in the risk group ranges from 50 to 80%, according to different countries. In addition to age and chronic illness, there are additional risk factors. First of all, these are bad habits: taking drugs, smoking, alcohol abuse reduce local and systemic immunity, which facilitates the possibility of infection. It must not be forgotten that the risk of infection and severe illness or death affects everyone and exists in all age groups.

Doctors have an additional risk of contracting COVID-19 while on duty. Is this confirmed by official statistics?

Zhanna Ponezheva: Indeed, the professional activity of doctors working with a new coronavirus infection, especially in the red zone, is associated with an increased risk of infection. This is facilitated by working conditions, stress, constant high loads and contact with patients. Official statistics confirm the high risks of infection of medical personnel. At the beginning of the epidemic, the number of infected health workers was significantly higher than in the general population, and, according to various sources, their share reached 12-15% of the total number of infected at the end of April. This was due to the real shortage of personal protective equipment among medical personnel in the red zone around the world. In the Russian Federation, at the beginning of July, about 14 thousand medical workers were officially confirmed infected. And the “Memory List,” which lists doctors, nurses, orderlies, laboratory technicians, and other health workers who have died from COVID-19, lists 484 names. The official death toll of health workers infected during the provision of medical care to patients with COVID-19 is currently unknown. To clarify the cause of death of each medical worker, a special commission works, which establishes all the circumstances during the investigation.

It is no secret that at the beginning of the pandemic, doctors did not have enough personal protective equipment. What is the situation with ensuring the safety of medical personnel today?

Zhanna Ponezheva: Today in the Russian Federation all medical and preventive institutions are provided with the necessary protective equipment. It is important to follow absolutely simple rules to prevent the spread of infection (mask mode, distancing, sanitary and hygienic rules) and reduce active communication. This actually reduces the spread of infection during the incubation period and in asymptomatic, mild course, when the infected person does not make complaints. Simple rules save lives!

Let’s talk about what probably everyone cares about today – about prevention. How can an infection be prevented?

Zhanna Ponezheva: High hopes for a vaccine. At least nine vaccines are currently being developed in the world. We have two registered in our country: “Gam-COVIDVac” (FSBI “NITsEM named after NF Gamaleya” of the Ministry of Health of Russia) and “EpiVacCorona” (FBUN SSC VB “Vector” of Rospotrebnadzor). In the future, mass specific vaccine prophylaxis for a new coronavirus infection will be available. And, of course, the possibility of non-specific prophylaxis of the disease, in particular with interferon preparations, has been widely studied and continues to be studied. Previous studies on the preventive and therapeutic efficacy of interferon preparations during the epidemiological season have established that therapy with interferon preparations effectively prevents re-hospitalizations for ARI within a three-month follow-up. Studies investigating the combined use of nasal and rectal forms of interferon-α-2b with antioxidants confirm the pronounced clinical and immunological efficacy of these drugs.

What is the theoretical basis for non-specific prophylaxis with interferon-α-2b?

Zhanna Ponezheva: It is known that the tropism for type II angiotensin-converting enzyme (ACE-2), which is a receptor on the surface of many cells of the body, is of particular importance in the process of penetration of the virus into target cells. The main target of the new coronavirus is primarily type II alveolar cells, which contain a large amount of ACE-2. Type I interferon deficiency (alpha interferons) is believed to play a key role in the pathogenesis of SARS-CoV-2. Delayed signaling of type I interferon (IFN-1) has been shown to be associated with persistent viral replication and serious complications. The SARS-CoV-2 virus inhibits the production of its own interferon, which reduces the activation of regulatory cells, triggers the hyperactivation of macrophages with overproduction of cytokines and causes an imbalance in the immune system (cytokine storm). According to some authors, in vitro studies carried out suggest that SARS-CoV-2 may be significantly more sensitive to type I interferons than other respiratory viruses and coronaviruses. Prophylactic intranasal administration or systemic administration of recombinant interferons can limit viral replication. Employees of the clinical department of infectious pathology studied the preventive efficacy of recombinant interferon-α-2b in a pandemic. Taking into account the clinical and experimental data on the possible therapeutic potential of interferons in a new coronavirus infection and experience in the prevention and treatment of acute respiratory viral infections in the epidemic season, we, researchers of the clinical department, proposed a preventive course for medical workers in a pandemic. Due to the absence of other etiotropic drugs at the beginning of the pandemic, the VIFERON® drug, which was successfully used for the prevention and treatment of acute respiratory viral infections, was chosen for our study for a long time, the main active ingredient of which is recombinant interferon-α-2b.

Please tell us more about this study.

Zhanna Ponezheva: All medical workers were offered a prophylactic course of combination therapy with recombinant IFN-α2-b. The control group consisted of 75 medical workers of the specialized hospital who received, for prophylactic purposes, a course of interferon-α-2b (VIFERON®) for 10 days. The comparison group consisted of 34 health workers who refused the preventive course. The observation continued for a month. All participants underwent a weekly nasopharyngeal and oropharyngeal smear test to detect SARS-CoV-2 RNA by PCR. Depending on the scheme used, after interviewing medical workers with a preventive course, three groups were identified:

  • 15 people (20%) used only VIFERON® Gel for topical application intranasally 2 times a day;
  • 45 medical workers (60%) used a combination of interferon-α-2b in the form of a gel 2 times a day intranasally and a suppository 1 million IU rectally 1 time a day on weekdays;
  • 15 (20%) health workers received intranasally in the form of VIFERON® gel 2 times a day and on every day of duty VIFERON® suppository 3 million IU rectally once.

The results were very impressive: in the group of the preventive course of interferon-α-2b (all three regimens), four (5.3%) cases of COVID-19 were identified, while in the comparison group, the proportion of infected was 32.4% (11 health workers from 34). At the same time, three participants infected with SARSCoV-2 during prophylactic therapy with interferon-α-2b were asymptomatic, and one suffered a mild illness.

Which interferon prophylaxis regimen was most effective?

Zhanna Ponezheva: We revealed a pronounced prophylactic efficacy of interferon-α-2b in various regimens: both in the form of a gel for topical application, and in a combination of rectal and topical forms in comparison with the control group. Most of the study participants nevertheless used the following scheme: VIFERON® Gel in combination with a single use of VIFERON® Suppositories 1,000,000 IU. The risk of infection in the group with the prophylactic course of VIFERON® was 6 times lower than that of physicians who did not take the drug. The only case of infection during therapy with VIFERON® was mild.

The results obtained convincingly show the high preventive efficacy and feasibility of using the VIFERON® drug for the prevention of COVID-19 in a pandemic, especially for emergency post-exposure drug prevention of COVID-19.

Is it possible, based on the results obtained, to recommend similar prevention regimens for other risk groups? Elderly people, for example, or the family of a covid-positive patient?

Zhanna Ponezheva: Interferon drugs have been well researched and have already proven their safety in clinical trials, therefore, in all of the listed risk groups, prophylaxis with recombinant interferon-α-2b drugs, such as VIFERON® Gel and Suppositories, is quite appropriate.

Zhanna Betovna, what can you wish doctors at this difficult time?

Zhanna Ponezheva: Patience, endurance and health! We will definitely stand and cope. Set an example of prudence and calm caution to your patients and relatives, take care of yourself – this is the best we can do.

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