Get pricked and not get infected

"The decrease in immunity lasts one and a half to two months after COVID-19"

Natalia Mikhalchenko, Izvestia

In different regions of the country, the number of COVID-19 cases varies from 21% to 60%, judging by the presence of antibodies in patients. Moreover, the largest megacities with the highest average daily morbidity – Moscow and St. Petersburg - are by no means in the leaders, but in the middle, Areg Totolyan, an immunologist, academician of the Russian Academy of Sciences, director of the Pasteur Research Institute of Epidemiology and Microbiology of Rospotrebnadzor, told Izvestia. In addition, during the study, experts found markers of a decrease in general immunity in patients with COVID-19, he said. According to the immunologist, this condition lasts two months. The scientist also spoke about what is more dangerous: first to get vaccinated, and then to get infected, or vice versa.

– Areg Artemovich, mass vaccination has begun. It takes place at the peak of the pandemic, and the risk of infection remains high during the formation of immunity. What is safer: for example, if the virus has already entered the body, but without knowing about it, a person will be vaccinated, or if infection occurs after the first or second injection, when immunity to SARS-CoV-2 is still being formed?

– The question is correct and fair. If there was contact with the virus, but there is no clinical picture, that is, the virus does not multiply in the respiratory tract, there is no need to be afraid of this situation. In this case, the vaccine cannot cause harm.

Another situation is if there is a certain clinical picture: signs of acute respiratory infections, the temperature is even at the level of subfebrile values (37.1–38 degrees. – "Izvestia"), there are more specific symptoms – loss of sense of smell, it is necessary to refrain from vaccination, to postpone it to a later period. If you lose your sense of smell, you should wait with vaccination even in the absence of other signs of the disease. I would recommend everyone to remember that permission or "admission" for vaccination should be given by a doctor, a specialist in vaccination prevention. So in any case, decisions should not be made independently.

– Is everything like with the flu vaccine?

– Of course! Against the background of an active infection, any vaccination is contraindicated. We are not dealing with therapeutic vaccines, but with preventive ones.

Today we have two vaccines approved for mass use. They have not been studied as therapeutic drugs. The studies that were conducted for registration and post-registration studies were devoted specifically to the preventive effect of the vaccine, not the therapeutic one.

– And if contact with the infection occurred after vaccination, but before immunity was formed?

– Yes, there may be such a situation that after vaccination a person fell under a high viral load, no one is immune from this. It's scarier to get vaccinated if a person is already sick. But let's divide: what we can influence, and what we can't influence. We can postpone vaccination at the signs of the disease.

It must be remembered that immunity does not develop immediately, the very fact of injection does not yet provide protection. In the case of the introduction of the Sputnik-V and EpiVacCorona vaccines, two injections are provided at intervals of three weeks. The total observation period is 42 days (six weeks, or a month and a half), during this time it is necessary to continue to observe all measures of social distancing, use personal protective equipment. Otherwise, it is necessary to sit down on self-isolation, but I think it is unlikely that anyone will follow such a scenario.

If the human immune system has responded normally to vaccination, the level of antibodies has become high enough, then you can feel protected.

– Some are just trying to sit out the pandemic. In which cases is this strategy correct?

– For super-strong people under 90 or 90+. We have a large country, there are also people aged 130 years, most of whom have chronic diseases, and this is a relative contraindication for vaccination. Some diseases are absolute contraindications to vaccination – primary immunodeficiency. In such patients, whole links of the immune system are turned off from functioning. They should wait for a situation when collective immunity is formed, this is quite a correct tactic. I would urge people aged 18 to 70-75 not to follow the path of rigid self-isolation.

The best protection

– What protects better – antibodies formed in the case of a previous illness or as a result of vaccination? Are they the same?

– Different. In relation to most vaccine-controlled infections, the rule applies: immunity, which is produced naturally, is more resistant, it persists for a longer period than post-vaccination immunity. I would not extend this rule to today's current infection. Firstly, we see that after a coronavirus infection, not everyone develops neutralizing antibodies. Some have antibodies, but not of the specificity that allows them to protect themselves from re-infection.

Secondly, both the Sputnik–V and EpiVacCorona vaccines are aimed at interacting with the S-protein. Sputnik-V is directed to the site that is responsible for the neutralizing activity of antibodies, and the EpiVacCorone uses peptides that are fragments of S-protein. Therefore, in the case of vaccination with both Russian vaccines, it is more likely to receive antibodies that will protect than in the case of passively transmitted infection, if we are talking about mild and asymptomatic forms of the disease. In the case of a moderate infection, both the level of antibodies and the quality of antibodies are significantly higher.

– What does the coronavirus "attack" in the body first of all?

– First of all, it disables the epithelial cells of the nasopharynx. They are the first to encounter the virus, and the interferon system is blocked inside the cells. They become defective due to the reproduction of the virus in them. This is important because the quality of the humoral immune response depends, among other things, on the functional usefulness of epithelial cells. Damage to epithelial cells is one of the causes of the body's defective immune response to the effects of the SARS–CoV-2 virus.

– Is the inhibition of the immune response by the virus a distinctive feature of SARS–CoV-2? Are other viruses not capable of this?

– Yes, this is the specifics of the new coronavirus infection.

Biomarkers

– How quickly does the normal immune response to infection recover in those who have been ill?

– We conduct an immunological examination of both patients and those who have been ill, who belong to the category of convolescents (they are in such a period of recovery when the obvious signs of the disease have ended, but there is still no complete restoration of the previous state of the body. – "Izvestia") on different dates, and there are already the first results. We found biomarkers of some immunological insufficiency, immune depression. Such a decrease in immunity lasts one and a half to two months after the COVID-19 and is reversible. Clinically, this manifests itself as asthenization syndrome. People suffer from increased fatigue, drowsiness, a person copes with loads worse, cognitive functions suffer. We investigated the immunological consequences of COVID-19 and identified immunological markers of these consequences. I can't tell you more about it yet. These data are now being prepared for publication in the scientific press.

– Is this your most interesting finding in the process of researching a new coronavirus infection?

– At the moment, yes. I will be able to tell you more later, when the work is completed. But perhaps the most interesting and most difficult task is another one. We want to find biomarkers in those who are not sick, even working in red zones. It takes a long process of observation, and we are conducting it.

– An article was recently published, the authors of which say that the virus can hide in exosomes in those who have been ill. Can you explain how this happens and does this mean that COVID-19 should be considered a chronic disease?

– When the virus destroys epithelial cells, they do not disappear without a trace. Microvesicles remain from them, and the virus can persist there. Experimental data allow us to speak about the validity of such a model. But this assumption requires evidence on clinical material, it is necessary to conduct an examination of patients and those who have been ill. So far, I have not seen such data in the scientific literature.

When we talk about the chronization of infection, it means that the virus has remained in the human body, it constantly exists there in some organs and cells, multiplies and eliminates (completely expel. – "Izvestia") it is impossible to get it out of the body. This is what happens with viral hepatitis B, with HIV, which lives in lymphocytes. There is no evidence yet that SARS-CoV-2 lives permanently in some organs or cells. Until this is proven, COVID-19 cannot be considered a chronic disease, although in some cases COVID-19 has the character of a prolonged infection. For example, in immunocompromised patients, in cancer patients who are on long-term or permanent immunosuppression.

Mosaic of population immunity

– For more than six months, scientists of the Pasteur Research Institute have been conducting a study of population immunity, and in dynamics. 75 thousand people in 26 regions of the country who take tests for antibodies to SARS-CoV-2 are covered. Please tell us how the picture is changing, what are the latest data?

– This is a large program of Rospotrebnadzor, in which eight research institutes and 20 territorial administrations and hygiene centers of Rospotrebnadzor take part. In total, more than 167 thousand studies have been conducted. Three stages of the program have already been implemented, the last one in December. The first stage began in June and lasted until mid-August. We got a very diverse picture in the whole country: in different regions of seropositive individuals (having antibodies to SASRS-CoV-2. – "Izvestia") it was from 4% to 51%. This is due to the fact that different regions were part of the epidemic at different times. For the second stage of research, we chose the beginning of the academic year – September-October, examined the same volunteers. The cohort is expected to have narrowed from 75 thousand to 50 thousand people, and as a result, we did not see much dynamics: the range slightly decreased from 5.5% to the same 51%. But we saw that the largest proportion of seropositive persons were children of preschool and primary school age. They have antibodies.

– There is no vaccination option for children yet, but it turns out that this particular age group was the most immunized?

- Yes. There really is no vaccine for children, but, fortunately, it is not as relevant for them as for adults and the elderly. In most cases, children carry the infection either asymptomatically or in a mild form. And indeed, children are immunized faster than other groups of the population. Even with minimal clinical manifestations or their complete absence, antibodies are produced in children and protection appears. In the course of the study, we clearly saw this.

– Is the third stage completed?

– Yes, it took place in December, the data were processed and mostly analyzed. Here we have already seen significant dynamics: there is a gradual leveling of the situation in different regions. The range of individuals with antibodies ranges from 21% to 60%.

– Are Moscow and St. Petersburg in the lead?

- no. Moscow and St. Petersburg are in the middle classes.

– After all, it is in the two largest megacities of the country that the average daily increase in cases is the largest. How can this be explained?

– The system of formation of population immunity is very multifactorial, and we do not see a direct relationship between the recorded level of morbidity and the level of collective immunity. However, we do not yet have a definitive answer to the question of why this is so.

– Will the research be continued? If so, how will it change due to the added vaccination factor?

– The fourth stage of research is scheduled for March. It will have a number of features compared to the previous three stages. The previous three stages took place in the conditions of acquiring population immunity naturally, we dealt only with those who were ill. At the fourth stage, we will already have a certain proportion of those vaccinated, and with different vaccines, who are at different stages of vaccination. The data will be very heterogeneous, and a more detailed analysis will be required.

Our strategic task is to continue the study of population immunity. After all, mass vaccination is carried out in order for us to reach the level of collective immunity, which will protect the entire population as a whole, the entire population. Until we reach such a situation, we will continue to investigate. According to my forecasts, it will take the whole of 2021.

– What do you think if in