"Untouchables" - what are the reasons for the immunity of some people to SARS-CoV-2

"Untouchables" - what are the reasons for the immunity of some people to SARS-CoV-2
"Untouchables" - what are the reasons for the immunity of some people to SARS-CoV-2

Already in the first months of the COVID-19 pandemic, scientists noticed that there are "untouchables": for example, a person may not become infected while working in the "red zone", or the whole family is sick, but he is not.

Academician of the Russian Academy of Sciences, Director of the Pasteur Research Institute of Epidemiology and Microbiology Areg Totolyan spoke about the research carried out at the Institute of immunity to SARS-CoV-2, as a result of which three markers were discovered - interferon, cytokine and genetic.

The academician also explained how this knowledge can be applied in practice, why COVID-19 patients need rehabilitation and how scientists are developing ways to restore the immune system.

- Areg Artemovich, we know that you have been struggling for a long time with the mystery of people immune to SARS-CoV-2. Are there any research findings already?

- Experts have always been interested in the reasons for resistance to a particular infection. The new coronavirus infection is no exception. An intense scientific search led us to quite interesting findings: people with a high level of interferon alpha, with a high content of lymphocytes in the blood and carriers of some genetic markers have increased protection. There are other factors, but research on them is just beginning.

I must say right away that the reasons that I will list are not absolute. It resembles a balance: on one side there are sensitivity factors, on the other - resistance (a person's resistance to infection - Izvestia), and they need to be assessed comprehensively. In addition, today these scales can work like this, but six months or a year after the stress and other reasons, both with a plus sign and with a minus sign, it is already different. For example, a little stress is a plus, and chronic stress is a minus, and it leads to immunosuppression (suppression of the immune system). Against the background of chronic stress, you can safely pick up any disease, including an infectious one.

- Can you elaborate on the three factors that make some people immune to COVID-19?

- The first protective factor is the level of local protection. Coronavirus enters the body through the upper respiratory tract, through the mucous membrane, primarily the nose and throat. And if in the body a high level of interferon alpha is a molecule that is synthesized and produced by cells of the immune system and has a direct antiviral effect, then the risk of infection is reduced. It is no coincidence that interferon alpha exists as a drug and is used for the treatment and prevention of respiratory viral infections. In the case of SARS-CoV-2, it also works by neutralizing viral particles that have not yet entered the cell.

- How to determine if a person has a high level of interferon alpha?

- Such a study is carried out in specialized laboratories, this analysis is not for public access.

- If you cannot find out the level of your own interferon, then you have to rely on drugs. How to use them correctly during a pandemic?

- Interferon alpha preparations are indicated for prophylaxis if it is known that you have come into contact with an infected SARS-CoV-2 and are afraid that you may get sick. They are also indicated for the early treatment of COVID-19 during the first two to three days. Interferon will prevent the virus from actively multiplying. For interferon alpha, we can reach a virus that has not yet entered the cells.

- Is the use of interferon alfa appropriate for vaccination?

- Yes, within a week after vaccination, you can drip interferon alfa into your nose and not part with the mask for a week, observe the isolation regime as much as possible, since vaccination takes place against the background of an epidemic.

- Have you managed to find genetic markers of immunity to SARS-CoV-2?

- Yes, this is the second factor. They are found among the genes encoding the immune response in humans. We identified two protective alleles (different forms of the same gene - Izvestia) and one predisposing to disease. These are the very first results of the study; it continues, and in an active phase. I think we will get a more ambitious result by autumn.

I want to emphasize that the found genetic markers belong to the inhabitants of the Northwest, since the genes encoding the immune response depend on national, ethnic factors and, as a result, have regional characteristics.

- In the course of the study, the number of protective and predisposing genetic factors to COVID-19 can expand?

- Yes, there are a lot of such genes, and at least for the next year we are provided with work only in this direction.

- What else can prevent infection?

- We studied the levels of various cytokines (small proteins that are secreted on the surface of cell A and interact with the receptor of the nearby cell B. Thus, a signal is transmitted from cell A to cell B, which triggers further reactions in cell B. - Izvestia) plasma in patients with COVID-19 in the acute phase and after recovery. And they found that in the acute phase most of the cytokines in the blood plasma are significantly increased, while in the recovered people, on the contrary, the number of some cytokines is reduced. And these are the cytokines that regulate the maturation of lymphocytes - the main cells of the immune system, which provide humoral immunity, cellular immunity, and also regulate the activity of other types of cells.

As a result, we concluded that the transferred infection leads to the formation of certain defects. These defects are indicated by a reduced number of lymphocytes in the blood plasma. This finding provides a key explanation for a common problem where an active infection is gone but its effects remain. These effects can persist for a week, and for some, even a month.

Decreased lymphocyte count - lymphopenia - is one of the poor prognostic signs for COVID-19. Because patients in the acute phase with a reduced number of lymphocytes carry the infection in a more severe form. Conversely, a good lymphocyte count indicates that a person is less likely to get sick, and if he does get sick, there is less risk that the disease will be severe.

- Everyone can find out the level of lymphocytes, it is enough to pass a clinical blood test.

- Oh sure. Moreover, it is not so much their relative content that is important here, as their absolute. The percentage may be normal and the absolute may be reduced. This may be the reason for the greater sensitivity to infections.

Our institute has extensive professional contacts with many medical institutions of the city. And we know that after suffering COVID-19 with a reduced level of lymphocytes, liver damage, lung damage can develop, there is a risk of developing autoimmune diseases, existing autoimmune diseases (processes in the body associated with the production of killer cells that attack healthy tissues of its own the body, leading to inflammation).

- You named three factors of immunity. Is their number likely to grow as research progresses?

- Yes. We are only at the very beginning of the journey.

- How did you manage to identify these three factors?

- You know, when you fall asleep with the thought of the results obtained the day before, and wake up with the thought of these results, sooner or later an understanding arises that you need to do this and that.

- How about Newton's apple?

- You can compare this with Newton's apple and with the periodic table, it all depends on the degree of modesty and self-esteem. When you are immersed in a problem and live in it, you want to test various hypotheses. Many things are done in collaboration.

Scientific research consists of several stages.At the first stage, it is enough to take 10-15-20 people, look at some indicator, and it will be immediately clear whether it makes sense to “dig” in this direction or not. At the second stage, already on a more significant sample, you prove to yourself that the path is correct. To prove to others that the results are worthy of the attention of the epidemiological community, more evidence needs to be obtained.

- Now the need for post-ovarian medical examination and rehabilitation is being widely discussed. Do you have recommendations for clinicians on how to restore the immune system of patients after a SARS-CoV-2 attack?

- People who have undergone COVID-19 need clinical examination, active observation, and rehabilitation. And probably immune rehabilitation. Immune system problems are at the root of many diseases, and restoring the functioning of the immune system often helps to cope with all other symptoms.

Sooner or later, we will come to grips with such research. There are simply not enough free valences now. There are not enough hands.

- So, you need to stimulate the immune system?

- There is a subtle point here. Rehabilitation of the immune system in one way or another should be associated with its stimulation. And the immune system hates being stimulated all the time. Therefore, the existing hypotheses must be thoroughly tested. Take patients who have been ill who still have lymphopenia and other signs of suppression of the lymphocytic link a month after the illness, after two, after three. Conduct a rehabilitation course and see in which group of patients - receiving the course or in the control group - there are fewer adverse events in the form of recurrent diseases or complications in the form of autoimmune diseases. There can be completely different scenarios here.

- Among the consequences of COVID-19 there are other unpleasant violations - mental ones. There is no consensus among specialists whether they are reversible or not.

- What I had to face, everything is reversible, thank God. Then I would redirect this question to colleagues who specialize in this area. I cannot rule out that there is a risk that mental disorders in a certain proportion of people may be irreversible.

It is also known that the number of autoimmune diseases is increasing, that COVID-19 can lead to an exacerbation of existing autoimmune diseases, an increase in cases of perverse sense of smell and olfactory hallucinations. There are a lot of tasks for post-ovarian rehabilitation.

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