Along with PCR diagnostics, rapid testing has been organized today in all regions of the country to detect antibodies to the SARS-CoV-2 virus, which is the causative agent of COVID-19 disease. So far, such rapid immunochromatographic tests are used only in health facilities according to indications, and in the future, as expected, they will be available to everyone. How accurate they are and whether it makes sense in mass testing of the population, Tatyana Borisenko, candidate of medical sciences, head of the clinical diagnostic laboratory, doctor of the first qualification category of the 1st city clinical hospital in Minsk, told BelTA.

- In mid-April, Belarus received a test batch of rapid tests for antibodies to COVID-19. They were assigned to hospitals. Have such tests been carried out before this time in Minsk, in particular in your laboratory?

- Earlier, there were no rapid tests for antibodies to COVID-19 in the republic. The first diagnostic systems came from China. On May 11, another batch of the Dutch manufacturer arrived. In the near future, tests for semi-quantitative and quantitative determination of antibodies may appear on our market. They can show not only their presence or absence, but also a specific number.

Our laboratory received 60 tests from the first batch, this is a rather limited number. In the process of use, there were both positive and negative results. Tests have shown their effectiveness and a high degree of comparability with the results of PCR studies. Now we have 800 tests. We will test all categories of patients (for medical reasons) and medical workers, which are indicated in the regulatory documents of the Ministry of Health.

In the future, we plan to purchase at our own expense a certain number of tests for those analyzers that are in our centralized laboratory. It is equipped with equipment of leading world manufacturers, which today are actively entering the market with their test systems. 

- In what cases is it important to quantify antibodies to COVID-19?

- First of all, we are talking about plasma donation. Such tests make it possible to identify not only whether there are antibodies in the human blood, but also in how much they are contained. This figure also suggests how persistent immunity is in humans. If the indicator is high, the immunity is longer. And if the number is not very large, perhaps the antibodies will soon disappear from the blood.

- How is express testing different from PCR diagnostics? What is the principle of rapid tests?

- These are completely different principles for the diagnosis of COVID-19. With the PCR method, the causative agent of the disease, that is, the coronavirus RNA, is determined directly. According to the results of rapid testing, we can state the presence or absence of antibodies to this virus in the patient’s blood.

Rapid tests are a strip or cartridge where murine antibodies to human antibodies to the SARS-CoV-2 virus protein, i.e. the so-called antibodies, are adsorbed. The patient’s blood (serum, plasma or whole blood) and a buffer solution are placed in the hole, after 15 minutes the result is read. The control zone should definitely work - this indicates that the test was performed correctly. As a result, either one of the strips responsible for the presence of class M or class G immunoglobulins, or both at the same time, will appear. In the absence of antibodies there will be no additional strip.

Now, Covid19 Antibody tests are available easily in UK or other countries. Basically, tests are the same, as well as the methodology for their implementation. Blood can be taken from a vein or finger.

- How accurate are express tests?

- Each test is characterized by such concepts as diagnostic sensitivity and diagnostic specificity. The first concept implies the ability of a method to produce the correct, truly positive result. Simply put, this is the likelihood that a sick person will have a positive test. The sensitivity of tests received in the republic is 98%, which is considered a high indicator. Diagnostic specificity - the ability of the method not to give a false positive result in the absence of a disease. In other words, the probability that a healthy person will have a negative test is 97%.

Sensitivity and specificity are checked by comparing the express method with a more accurate reference method, for example, with PCR analysis. That is, compared with PCR, the sensitivity and specificity of the available immunochromatographic rapid tests are 98% and 97%, respectively.

- Why is PCR diagnostics still more accurate?

- This is due to the features of the method. PCR is such an accurate analysis that it doesn’t even catch the virus or bacterium, but the sections of their RNA or DNA in biological material. The patient’s blood or sputum may contain a microscopic amount of the pathogen, but it will still be determined. Rapid tests reveal antibodies. According to foreign authors, up to 25% of patients do not have antibodies to COVID-19 in their blood at all, in any case they cannot be detected by modern methods. People may have experienced coronavirus infection, but in 25% of cases they will not find antibodies.

- Is there a connection between how hard a person has had the infection and the amount of antibodies in the blood?

- I would say this: antibodies should not be many or few, they should be enough. An overly strong response of the immune system is clearly unfavorable when the so-called cytokine storm is launched - the release of a huge number of inflammatory mediators, leading to damage to all organs and systems, and in the long term to an unfavorable outcome. At the same time, with mild, erased forms of the disease and virus carriage, the body can cope with the infection only by launching the system of interferons, it doesn’t even reach antibodies, there is no need to develop them.

On the other hand, the highest antibody numbers are found in the blood of patients with severe COVID-19. After recovery, these are the most promising plasma donors for other severe patients.

- Does the production of antibodies indicate the presence of immunity to the virus?

- Some scientists hope that with infection of 70% of the population, collective immunity will form, which will prevent the further spread of the infection. Others believe that collective immunity will not naturally form, but a vaccine that will hit the market by 2021 will certainly help. She will stop the infection.

- Explain in simple words the mechanism of the formation of immunity in a person who has encountered a coronavirus infection.

- The first after infection - on the 5-7th day - class M immunoglobulins appear, on the 10-14th day - class G immunoglobulins. Then the first leave, and the second remain in the blood for quite a long time - up to eight weeks. They can persist and longer or gradually disappear from the blood.

After eight weeks, antibodies in the blood may not be detected at all. But this does not mean that a person does not have immunity. Since he had already encountered a coronavirus infection, a pool of so-called memory cells, or T-lymphocytes, formed in his body. They store information about a meeting with an antigen, and specifically with a coronavirus. If a person ever encounters a coronavirus infection again, T-lymphocytes will activate and trigger an immune response by acting on other cells, such as plasmocytes, which will begin to actively produce antibodies. As a result, the infectious process will not develop, the process will end at the initial stage due to the activation of immunity. Moreover, the immune response during repeated infection will be stronger and will begin to act in a shorter time.

Immunity as such remains, even if no antibodies are detected in the human blood after recovery. But how long in this case the immunity is long and stable, this remains to be seen. At the moment, there is not enough data, since the necessary time has not passed even after the first cases of recovery in China. Research is needed.

- Who should conduct express testing at the moment?

- Rapid tests have a wide range of applications. First of all, they are used for diagnostic purposes, for example, for testing contacts of the first level, patients with symptoms of the disease, as well as for examining health workers who directly serve patients with COVID-19. They can be used separately or as an addition to PCR diagnostics. This is a good help when monitoring the course of the disease, because they allow you to evaluate the healing process.

One of the most important uses of such tests is to determine the presence of antibodies in patients who have recovered from COVID-19 for surveillance. Thus, it is possible to determine the immune layer among the population, and this is important from a scientific point of view. Moreover, a person who has recovered from a coronavirus infection can become a plasma donor if there are antibodies in his blood. A person who has coped with the disease thanks to good immunity will help someone whose immunity is weaker and cannot cope with the infection himself.

- In your opinion, is there any sense in mass testing of the population with the help of rapid tests? If in the future they will be available to a wide circle, can they be carried out at home?

- Extensive testing of the population makes sense primarily for the purpose of surveillance to determine the immune layer. The more we know, the more effective we can help in the future. That is, first of all, we are talking about scientific research to determine collective immunity.

To sell such tests in pharmacies, in my opinion, is not worth it. Now they have entered all hospitals and clinics. The public has wide access to these tests. As a specialist in laboratory diagnostics, I believe that the test, despite the apparent simplicity of its use, should nevertheless be performed by a paramedic or laboratory diagnostics doctor with exact adherence to dosing and instructions. Only in this case can we get the correct result and interpret it adequately. In addition, at home, not every person is able to take blood from his finger. Diabetic patients do this to monitor glucose levels, but they are trained accordingly.

- Has the load on your laboratory increased in connection with COVID-19?

- Our centralized laboratory serves not only the 1st clinical hospital, but also 19 polyclinics, a number of hospitals and dispensaries in Minsk for certain types of studies. We always had a high load. I can’t say that in connection with the current epidemiological situation it has increased, rather, the emphasis has shifted. Now we diagnose COVID-19 infection using rapid tests and conduct laboratory tests that can help treat patients with coronavirus.

In routine laboratory indicators, there are specific changes that can suggest to the attending physician the presence of a coronavirus infection, for example, a low level of lymphocytes in the general blood test. With an already confirmed diagnosis, a series of laboratory tests are carried out, suggesting how a particular person will have an infection - in mild, moderate or severe form. For example, with high levels of D-dimers (a marker of thrombosis), the disease can have complications, antithrombotic therapy must be connected.

- You have already mentioned the high-tech equipment that is in your laboratory. Tell us what kind of cars.

- These are not even analyzers, but laboratory information and analytical systems of the world's leading manufacturers of relevant equipment. High-performance machines with a fully automated analysis process, operator intervention is minimal. All biomaterial test tubes entering the laboratory have barcodes. The laboratory assistant puts the test tube on board the analyzer, and it reads from the barcode what research is needed. Then a result is displayed on the computer screen, which is already evaluated by a laboratory diagnostics doctor. We send it to users via electronic network. As soon as we conducted a laboratory test on analyzers, almost immediately the doctor in the clinic or in the hospital sees the result of the patient’s blood test on his computer.

We have most of these machines now; they were purchased for the needs of a centralized laboratory. Today, not only patients of our hospital, but also all attached polyclinics, hospitals and dispensaries can take advantage of such laboratory analytical systems.