When should a serological test be done? How reliable are they? What do you gain if it comes out positive?

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With or without PCR, asymptomatic but with a test performed, symptomatic awaiting diagnosis, rapid or "normal" tests ... For weeks now, these and other terms, more typical of a laboratory than of casual conversation, have crept into any talk. But the ease with which experts refer to them in updating epidemiological data contrasts with the confusion of the uninitiated. What determines each test, when should you do it, if it is a good idea to order it on your own ... are some of the questions that are asked. These are the answers to these and other important questions to understand what serological tests are. that many joys are giving when they report that one has passed the virus, and on which the study of the Ministry of Health is based to determine how many Spaniards have SARS-CoV-2 antibodies.

The test reports on the body's immune response to the SARS-CoV-2 virus. A blood sample is enough to know if a person has antibodies. "With these tests two immunoglobulins are detected, which are two types of antibodies: IgM (immunoglobulin M), which is the first to develop and which gives us an indication of active or ongoing disease, and IgG (immunoglobulin G) , which is the antibody that is produced a little later and that reports on past illness, "explains Ignacio López-Goñi, professor of Microbiology at the University of Navarra. IgM appear, more or less, with the symptoms of covid-19, approximately 6 days after the beginning of the infection, and remain in the body for about two weeks. IgG antibodies appear approximately 15 days after the onset of symptoms, and their permanence in the blood is much longer.

"The main difference is that both the so-called rapid antigen tests and PCR (polymerase chain reaction) diagnose the presence of the SARS-CoV-2 virus. Specifically, rapid tests detect the existence of proteins or genetic material of the virus, while the PCR determines its presence from the beginning of the infection.The objective of the serological tests is not to identify if the person has the coronavirus or not , but to check if they have been in contact with it and the your body's response to it, "in the form of antibodies or defenses, explains occupational medicine specialist Javier Cotelo. Also, while the serological tests are blood, the antigen test and the PCR require a sample of cells taken from the nose or pharynx.

The extraction form and the technique used divide the serological tests into two types. On the one hand, there are those based on lateral immunochromatography or CSF (a technique similar to that used in pregnancy tests), which are also known as qualitative tests or "rapid antibody tests" because the result is generated in only 15 minutes. On the other hand, there are those based on more precise and developed laboratory techniques (ELISA, CLIO), which must be performed in specialized hospitals and laboratories, and which are known as quantitative tests.

"The 'rapid' serological tests have a monotest format: a drop of blood is obtained by a small prick on the finger and it is contacted with the reagent, testing positive or negative depending on the presence or absence of coronavirus antibodies. ELISA or CLIA tests require a blood sample to be taken from the patient's arm (just like in a blood test). The duration of this test is around 40 minutes, "says Cotelo Vila. Although both tests detect the presence of the two main antibodies (IgG and IgM), in the case of the ELISA or CLIA tests, the concentration and quantity of these antibodies can also be determined, "which translates into greater sensitivity and therefore it makes the results more reliable. "

Reliability is determined based on two parameters: sensitivity and specificity. The first refers to the ability to detect true positives (high sensitivity means few false negatives), while specificity is the ability to detect true negatives (if high it means there is little chance of false positives). As they are more sophisticated techniques, the ELISA / CLIA tests are considered more reliable than the rapid tests, but the pharmaceutical industry is working on improving the parameters of the monotest (which allow making large-scale diagnoses more quickly), increasing its reliability.

The levels of sensitivity and specificity of these tests vary according to the laboratory and the manufacturer, but in general, those currently being performed have a reliability very similar to the ELISA / CLIA. "The rapid tests we use in our laboratory have a sensitivity, according to the FDA [the agency competent to authorize drugs in the United States], of 95-99%, and a specificity of 99-100%," explains the Catlab microbiologist Emma Padilla.

According to the Spanish Society of Infectious Diseases and Clinical Microbiology in a document of recommendations, in the general population the test is indicated in three cases: in the emergency services of hospitals, as a complement to PCR in patients with an evolution of the infection longer than 7 days; when the PCR result has been repeatedly negative, but there are clear symptoms of covid-19; and to confirm that the infection has passed (since in some cases, clinical samples with remains of the inactive virus have been detected). It is also applied in the detection of antibodies in healthcare personnel, as a strategy to identify those who are already immune, allowing them to attend to infected patients and minimizing the risk of transmitting the virus to colleagues and people in their environment.

These are the recommended criteria in the case of patients seen in the emergency services . However, more and more clinics and medical centers offer the performance of these tests and, also, people who want to have them done, for example, return to work with the security of not being a possible contagious, due to the fact to be caring for or living with an older person or simply to resume the "new normal" with complete peace of mind.

"Indeed, we are receiving many requests in this regard in consultations, but it is important to make clear that for asymptomatic people, the usefulness of these tests is limited, in the sense that they can provide false security. In other words, these tests offer a 'photo' of your immunological condition at that specific moment, but this situation can be completely different after a few days, especially now that mobility has resumed. The most important thing is to respect and comply with preventive measures to avoid I spread it, even those people who, according to the results of the rapid tests, have antibodies, since this does not mean that they can lower their guard against the coronavirus, "explains Cotelo.

"This type of tests should be performed by professionals in clinical diagnostic laboratories, who are used to carrying out serological tests for infectious diseases ," says Imma Caballé, president of the Spanish Society of Laboratory Medicine.

It is difficult to give a concrete answer to this question, "since in the price of the test it is necessary to take into account the reagent, the time used, the laboratory tools, the extraction of the sample (nurse, displacement, material ...), the input of requests and the response of the result, as well as other factors, such as the structure of the laboratory or the ownership of it (if it is public or private), "responds Caballé. There is great variability depending on the centers, but the average cost of the rapid tests ranges between 36 and 60 euros, while the ELISA / CLIA tests cost between 80 and 90 euros.

Since the start of the pandemic, online sites offering rapid tests for coronavirus antibodies have proliferated (most of them are currently out of stock), an option that Caballé is not a supporter of: "It is recommended that serological tests have passed a validation process prior to use, in addition to FDA validation, something that cannot always be verified in products sold 'online'. In addition, they must be done in an expert laboratory accustomed to the diagnosis of infectious diseases " . Another important fact is that, up to now, the Spanish Agency of Medicines and Health Products has not authorized the sale in Spain of any covid-19 self-diagnosis health product.

This diagnostic test must always be indicated by a doctor , as stated in the BOE of April 14, 2020, in which it is explicitly stated that "the performance of diagnostic tests for Covid-19 is limited to those cases in which that there is a previous prescription by a doctor and they comply with criteria established by the competent health authority ".

Imma Caballé explains that, in these cases, if there has been risky contact, it is recommended to repeat the serology, and that "the indicated thing is to do it 3 or 4 weeks after the first determination."

"In case the serological tests have given negative but there are symptoms of the disease, it would be advisable to do a PCR to check if the virus is really present and, therefore, infection," he adds. For his part, Cotelo comments that PCR is also recommended in those situations in which IgM is positive in serology and the patient is asymptomatic, "with the aim of determining the possibility of virus transmission."

"It is a question that at this moment we do not know for sure," admits López-Goñi. And he adds: "It should be borne in mind that it has been a very short time since the virus erupted, which makes it difficult to know that data. It is known that infections caused by other coronaviruses produce immunity that lasts for some years (between two and three), but what will happen in this regard in the specific case of SARS-CoV-2 is something that we do not know today. "

"In studies with macaques infected with the coronavirus, it has been shown that they have developed an immune response, later proving that they were protected against an experimental infection. This indicates that the antibodies would protect against a second infection. But We must not lose sight of the fact that we are talking about an animal test, not a human one, "says López-Goñi. The professor of Microbiology at the University of Navarra explains that having IgG antibodies means that one can be positive IgG, "but that does not mean that these antibodies are neutralizing, that is, that they are capable of blocking the virus, since it is something we don't know yet. "

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