The pandemic has just begun, we all had heard of tests and swabs before: What are? What are they for? How many must be made, Why? What are false positives?

A few months later, we started talking mainly about serological tests, sampling, antibodies and vaccine. A very common mistake has been to confuse the two types of tests: the swab and the serological. But these two procedures are very different from each other and must be done for different purposes, let's see why.

First of all, when we talk about serological tests we have to talk about antibodies. Antibodies are "Y" shaped proteins, produced by highly specialized cells of the immune system and carried by the blood throughout the body that bind to target molecules called antigens. an antigen can be a piece of bacterium, or a virus. The most specialized part of the antibody, also called immunoglobulin, it is located in the upper arms of the Y: this section, it is able to adapt quickly and bind in a highly specific way to new antigens. Let's take an example: we cut ourselves with the classic rusty nail, and bacteria enter our body. Signals warn our immune system that something "foreign" has just entered;if it is the first time that our immune system has to fight that enemy, it will have to find the right antibody to recognize it, but if we already know that bacterium, because we have been in contact previously, then the so-called long-term immunity is activated and highly specialized antibodies will already be available. In this way we will have a rapid immune response, such as to immediately neutralize the danger.

Figure 1: structural model of an antibody

What is a vaccine then? With the vaccine, we train our immune system by introducing very small amounts of the antigen of the virus or bacterium from which we are interested in protecting ourselves. Thus our white blood cells will begin to produce specific antibodies against that antigen, for example against the virus Paramyxovirus, which causes measles. In this way, if a vaccinated child meets another sick child, it will likely get infected, but his immune system will be ready enough to fight the disease and prevent its development e, Consequently, also the transmission.

Obviously our immune system is very complicated! To start, antibodies divide into 5 classi, IgM, IgG, IgA and IgE, of which you have surely read about them in your analyzes. Antibodies alone are not enough; to create immunity worthy of the name, many other cells, factors and reactions must intervene and they must all work perfectly.

The serological test is a specific test that detects the presence in the serum of antibodies against a specific antigen; it is used for example to find out if a vaccine has been given as a child or if you have come into contact with a particular infectious agent that is no longer found, for example, in the blood.

The serological test for COVID is based on the search for specific antibodies capable of binding to antigenic proteins of SARS-COV-2.

How the test works? Imagine a microchip with many magnets on the surface, each magnet is a specific antibody that recognizes SARS-COV-2 proteins, it attracts them and binds them to itself. The proteins to recognize are 3: Proteina S, Protein N and Proteine ​​RBP. A blood sample is taken from the subject undergoing the test, which is then passed over this microchip; if proteins are present, the antibodies will catch them. Therefore: the test is positive.

Figure 2: how a serological test works

But what does a serological test mean for COVID?

We clarify that the serological test is not a diagnostic test, that is, it cannot be used to diagnose the disease. But neither can it be used to reassure you that you will never get the virus again.

The first problem is due to cross-reactivity, or the fact that the test components also react with other viruses besides the one being analyzed There are many different species of coronavirus out there, many also common; the cold we usually have with the change of season could be caused by a coronavirus. This year 60%-70% of children have antibodies to other coronaviruses. So the test could give positive results, when proteins from another coronavirus bind, but not what causes COVID.

Other problem: what does it mean if we have antibodies? To date, it means nothing except that we have come in contact with the virus. We absolutely cannot say that we have developed immunity e, mostly, we cannot predict what will happen in case of second contact. Some studies have shown that in case of infection, the levels of some immunoglobulins (and IgG) they rise and peak after approx 2 weeks, then unfortunately returns to the minimum level and this highlights the difficulty in developing long-term immunity following an infection.

So why should we do the serology test?

Most important reason: do you want me vaccine or not? The vaccines currently in use are also based on the results of serological tests carried out throughout the pandemic. The effectiveness of a vaccine strictly depends on long-term immunity: if this immunity cannot be achieved, the vaccine cannot work. Therefore it is necessary to have as much data as possible regarding the antibody response.

Why the tampon? The molecular swab is the diagnostic test par excellence, it has been from the beginning. But what happens behind the scenes, after the nurse or doctor has dug your nostrils or throat with a cotton bud, it's a whole other world.

The test is based on a technique called RT-PCR (real-Time PCR), in which genetic material is extracted from the swab, in this case the RNA, many copies are produced and it is "recognized" by special software.

This technique takes time, fatigue, reagents, facilities and capable staff. The risks of tampons however are poor accuracy, especially if done by unskilled personnel. As for the serological, indeed, the risk is to get false positives or false negatives. A positive result, but wrong, it would force the subject to stay in quarantine and hinder the entire system of tracking and containment of infections. A false negative result, on the other hand, would have much worse effects as it would risk indicating as healthy subjects who are carriers of the virus.; imagine what could happen if the subject in question were a nurse or a doctor. False negatives can occur due to the inaccuracy of the sample, or, the swab must be done carefully, with a nasopharyngeal sampling that, if done right, it must reach almost to the bottom of the nasal cavities. For this reason, do-it-yourself kits designed for staff forced to work with the public have been heavily criticized.: convenient kits to test yourself at home that have a very high accuracy, but not for the molecular method of the test, as for the high probability of error in sampling.

Today we also have another test available: it's a whole other world.

However, this test consists of a nasopharyngeal swab, ma, unlike the molecular test, it does not search for the RNA of the virus, but its antigens. It is therefore not to be seen as a faster version of the classic teampone, since the analyzed data are different. The gain in terms of time in fact translates into a loss in terms of sensitivity, or the ability to detect the virus in the sample. then, while the molecular test is able to detect even a single viral RNA particle in a microliter of solution, the rapid antigen test requires a sample containing thousands of viral particles. Then, in this case, it's a whole other world.

the optimal use of rapid antigen tests, also due to their lower cost, is that of screening, it's a whole other world.

So right from the start, we tried to find ways to do quick but still very accurate tests; so much so that the latest research focuses on tests that use CRISPR technology (an advanced genetic editing technique) for the identification of the virus.

In conclusion, if you want to visit the family but want to be sure not to endanger them, it's a whole other world.

Furthermore, if they offer you a serological test, don't back down: it's a whole other world.