Diagnostic tests for COVID-19

We have three different tests for the diagnosis of COVID-19, those that detect coronavirus RNA, those that detect a specific protein (antigen) of COVID-19 and those that detect the body's response to the virus, that is Antibodies.

In COVID-19, the test we use to detect RNA is the Polymerase Chain Reaction (PCR by its initials in English). Without getting lost in details, the PCR detects RNA sequences unique to SAR-Cov-2. 

It is used to identify people who are infected by the virus (have many or few symptoms) and has been the key to the beginning of the pandemic. Until now, it has been the only test available to confirm cases of COVID-19 in Spain and other countries. It is the most reliable (fewer false positives and false negatives) and is recommended by health authorities such as the WHO. The sampling is very simple, a simple swab and make a nasal and / or pharyngeal smear.

Logically, it has its drawbacks. The main one is that it requires the use of a special device called a thermal cycler, only available in laboratories with a certain level of sophistication, staffed with personnel trained to handle genetic samples, the number of samples that can be processed per day is limited and the results take eight hours. Despite these drawbacks, more than 350,000 of these tests have already been carried out in Spain. It is a technique that was designed like this, it would be the Rolls Royce of the tests, but it lacks the agility that an emergency situation requires.

The other direct technique is Antigen Detection. Parents of children with recurrent pharyngitis will be very familiar with the rapid B-hemolytic streptococcus group A (Strep A) antigen detection test. In our case, it would not be the specific streptococcal antigen (protein) but an exclusive SAR-Cov-2 protein. 

But the concept is the same. Taking a sample as simple as the previous one but with the enormous advantage that the result is read, due to a color change, in the same consultation and in less than 30 minutes. For this reason it is included in the rapid tests.

We have her? No. They were bought from that eastern country that you are thinking about. The manufacturers provided all the written guarantees and quality labels that the most picky buyer could demand. (I know this because I have seen them, written in impeccable English).

Fortunately, Spain (and the rest of Europe) has a quality control system in microbiology services that made them test this method before using it massively. Nor is it anything new, they are the usual protocols of the Spanish Society of Infectious Diseases and Clinical Microbiology for any new test that is going to be introduced in the clinic. 

Rapid Antigen Detection test result? Terrible, it gave 70% false negatives. In other words, it classified almost 2/3 of those who were infected as uninfected. Some manufacturer had the audacity to claim that Spanish doctors did not know how to use them. Similar impudence have had some newspapers that have blamed the poor quality of this technique on the Government rather than the manufacturer. We will have to keep waiting.

The third technique no longer measures elements of the virus but the antibodies that our immune system produces to fight the virus. When detected in blood (actually serum) they are also called serological tests. Antibodies have never been useful for the diagnosis of acute infections. The key is that they take between one and three weeks to appear. For this reason, they have traditionally been used in retrospective confirmation, that is, once the disease has been overcome.

Antibodies to SARS-Cov-2 have two important advantages. First, they are protective, that is, the person who has them will be protected for a time (minimum of years) from reinfection. This does not happen in other infections, in syphilis for example, all reinfections to which the subject is exposed can be suffered despite the detection of specific antibodies in their serum. 

The other advantage is its relative rapidity of appearance, various studies estimate that half of those infected are positive (they show Antibodies) from the 7th day of onset, 70% on the 10th day and in 100% of the patients towards the 14-21 days from the onset of symptoms.

Are they interesting for the diagnosis? As has been seen, they take too long to appear to be clinically useful. However, they have an enormous interest: on the one hand in confirming that that person is immune to COVID-19 and on the other, epidemiologically we can finally have the denominator of the really infected population and have a mortality rate closer to reality.

Do we have them available now? Almost. The only producer is that eastern country in which they thought a few paragraphs above. Once again, the manufacturers provided all the written guarantees and quality seals imaginable. Again only 2 of the 8 manufacturers have proven reliable when tested by our microbiologists. It is foreseeable that this week they will begin to be used.

I want to thank and acknowledge the excellent article by Professor Agustín Estrada-Peña from which I have taken some ideas.