The objective of this paper is to make an assessment of the different tests available for the diagnosis of COVID-19 infection, in order to provide clarity to the general population about their validity in different situations and moments of the disease.
Everyone knows that the airway is the main route of contagion in COVID-19 infection, so that there is a high number of viruses in the nasopharyngeal area from the first hours after said infection. This means that the ideal sample for diagnosis is the exudate from the nasopharyngeal area, collected with a swab.
Existing trials can be divided into two categories:
-Assays that detect the virus itself:
o PCR test (Polymersae Chain Reaction): detects the RNA of the virus in nasopharyngeal exudate.
o Rapid antigen detection test: detects virus proteins in nasopharyngeal exudate.
– Tests that detect the defenses (antibodies) generated against the virus:
o Antibody detection test: qualitatively or quantitatively detect antibodies in blood. They will be of the Immunoglobulin M (IgM) type in the most acute phase of the disease and of the Immunoglobulin G (IgG) type in its later phase.
The validity of these tests depends fundamentally on two variables: the sensitivity of the assay, that is, its ability to report a positive sample as positive, and the stage of the disease in which the patient is.
Assessment from the point of view of sensitivity
The PCR tests, which are the ones that have been used to date, are the most sensitive of all those available, detecting up to 20 copies of RNA of the virus/ml of exudate. For this reason, it is currently the reference test for diagnosis.
Antigen tests, known as “rapid tests”, have low sensitivities that, in some cases, are as low as 30%, which means that they would only be able to report as positive 30% of truly positive cases. . This implies that these tests will generate many false negatives, that is, negative results in patients who are actually positive.
Finally, blood antibody detection assays do have greater sensitivity, which could be between 80% and 90%, depending on published or ongoing studies to date. Its limitation has to do with the time it takes for these antibodies to appear in the blood.
Assessment from the point of view of the stage of the disease
The natural process of COVID-19 infection implies the existence of viruses in the nasopharyngeal area from the beginning of the infection, so tests based on virus detection (PCR and antigen detection) are ideal for early detection of the infection.
However, tests that detect antibodies would only be valid in more advanced stages of the disease, since these antibodies can delay their appearance in the blood between one and four weeks from the start of the infection.
For all of the above, it can be concluded that the most valid test for an early diagnosis of COVID-19 infection is PCR in nasopharyngeal exudate samples given its high sensitivity for detecting viruses from the first days after infection. Its limitation lies in the execution time of the test, which implies several hours from the time the sample enters the laboratory.
The so-called “rapid tests” for antigen detection, despite their low sensitivity, can be useful for the preliminary screening of a percentage of the population, due to the speed of obtaining results (15-30 minutes). Thus, those people with positive results in this test would be isolated immediately, while those with negative results, but with suspicious symptoms of infection, should be confirmed later by means of the PCR test.
Finally, tests for the detection and quantification of antibodies in blood may be useful for diagnosis in advanced stages of infection, in which the viral load is no longer detectable in nasopharyngeal samples by antigen or PCR tests. Likewise, they can be used together with antigenic tests as complementary tests in situations in which PCR is not widely available.
In short, determination by PCR in nasopharyngeal samples remains the reference test due to its sensitivity and ability to detect the virus early, but rapid antigen and antibody tests are valid in certain circumstances, as complementary to the first and always assessed in the context of the patient’s clinical picture.