We are in a moment of great confusion regarding the application of PCR and serological tests, also called "rapid" tests. The general population does not distinguish between them. Sometimes they even think that these two tests are opposed to each other.

Adding to the confusion is the fact that the rapid tests available are not as good as we would like them to be. What we all agree on -society, physicians and researchers- is the importance of finding a system that allows us to take the pulse of SARS-CoV-2 in order to avoid new waves of the pandemic.

One of the first steps to achieve this is to identify the presence of the virus -PCR- and the immune response -rapid test- in both symptomatic and asymptomatic populations. Simplistically, the PCR reaction amplifies a fragment of the viral genome so that, by means of fluorescence, it can be identified and quantified. Serological or rapid tests identify the presence of antibodies in the blood.

As with any infection caused by a new intruder, it is important to understand the biology of the virus and how the immune system tries to fight it. As this is the first time the immune system has seen this virus, it lacks specific antibodies against it and, therefore, the battle is relentless. A person can have the virus in the pharynx - one of the main sites of viral replication - and not yet have developed antibodies ready to respond to the infection.

Innate immunity

At this very early stage the only defense we have is what we call "innate immunity": the infected cells themselves emit signals that alert the immune system, but there has not yet been time to identify the "weak points" of the virus that the army of lymphocytes (a subject of immune cells) will attack in a specific way.

We already have evidence that during the first five days of COVID-19 disease patients may be asymptomatic, without having developed antibodies - negative rapid test - and yet have a high viral load in their pharynxes - positive PCR - and may be carriers of the virus and highly contagious. In the asymptomatically infected person the virus behaves in a benign way.

However, for the general population, it means a danger of rapid spread of the virus and a pandemic. By the time a carrier is identified, he or she has been able to transmit the virus to others, especially the less symptomatic or the longer the incubation period.

As the infection progresses, the immune system is activated against the virus, reaching a stage where patients - who still have the virus in the pharynx - already have antibodies.

In this phase, even with the presence of antibodies -positive rapid test-, patients have viral particles in the pharynx -positive PCR- and also in other organs where the virus may have reached. These patients are also potentially contagious.

Finally, when the disease process is favorable, the infected person is cured. At this point, he no longer has virus in his pharynx -PCR negative- and instead has high levels of antibodies -rapid test positive-.

It is important to know that viral genome PCR is the only system we currently have to identify, at any given time, the presence of the pathogen. Therefore, this diagnostic test informs whether the person, even if asymptomatic, may be contagious.

On the other hand, the serology or rapid test allows to know if a person has antibodies against the virus, that is, if his organism has reacted against it, has already fought it. IgM antibodies appear initially and last for a short time -weeks-, while IgG antibodies appear a little later and remain high for a long time, providing protection against that strain of virus.

Further testing in some geographic areas during de-escalation

Thus, in countries or geographical areas where there may be many people potentially carrying the virus without having symptoms, it is very important to perform a general or massive PCR.

This was particularly relevant in the first weeks of the pandemic - as WHO advised on several occasions - but it is also relevant in a de-escalation of confinement and especially where there may be many people carrying the virus asymptomatically, such as residences or other gated communities where transmission may have been difficult to control until a few weeks ago.

The PCR can have false negatives, because the sample (from nasopharyngeal swab) was not taken properly. Therefore, if suspicion remains, it should be repeated after a few days.

In a few months, when there are very few people capable of carrying the virus in the population, the most important test will be the serology at the population level. That will give us an idea of how many people have passed the disease and have antibodies. It is epidemiological information that will help us make better policy decisions in the future.

The best: combining both types of test

Sometimes there are doubts as to whether people with antibodies -positive rapid test- are protected against new SARS-CoV-2 infections. It must be said that we still do not have any evidence and that it will probably be difficult to obtain it.

The only experiment that would answer this question would be to expose people with antibodies to the virus and determine what level of antibody is protective. This would obviously be unethical.

Therefore, we will only know if individuals with antibodies can be re-infected when this happens for natural reasons during a new outbreak, which hopefully will not occur, although it is possible, considering the low percentage of individuals with high levels of antibodies against SARS-CoV-2 in the population analyses performed.

Until a new wave of the pandemic arrives, it is desirable at this time to combine both types of test, PCR and rapid tests, especially in regions and groups severely hit by this health crisis. This would allow a safer, more accurate and effective de-escalation. And it would give a lot of peace of mind to individuals, families, communities and companies.

This article was originally published in The Conversation. Read the original.