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Ignacio Lopez Goni, Full Professor of Microbiology, University of Navarra, Spain.

Antigen testing against COVID-19: a tool to be interpreted in a clinical context

There is no perfect test. They all have their advantages and disadvantages. We have already explained what the three types of tests consist of: PCR, antibodies and antigens. The latter have become fashionable after the Community of Madrid announced their massive use.

Fri, 25 Sep 2020 09:45:00 +0000 Posted in The Conversation
Ignacio López-Goñi

The tests that allow the diagnosis of infection are those based on PCR and antigens because they directly detect the virus (the genome or its proteins). The fact that they are positive does not always imply that the virus is active and infective: we can detect its genome or its proteins, but the virus is not complete, only traces.

On the other hand, antibody tests detect molecules produced by our body when we are infected, so they serve to evaluate the disease. A positive test does not always mean that we are infectious or that we have active disease.

The diagnosis of a disease is not only based on a microbiological test. These are helpful, but the physician also takes into account other clinical aspects, symptoms and other analytical tests.

How an antigen test works
Antigen tests confirm the presence of the virus by detecting its proteins (antigens). With some difference, they all have more or less the same rationale.

Specific antibodies that will react against some protein of the virus are fixed on a support. The protein on the surface of the envelope (protein S), which projects outwards, is usually used. If viral particles are present at sample , they will be bound to the antibody. It is as if the virus or its proteins have been captured by the antibody.

A second antibody against the virus is then added in such a way as to form a sandwich: antibody-virus-antibody. This second antibody will be labeled or marked in some way to highlight the reaction. If the reaction is positive, it shows that virus proteins were present. That is, the person was infected.

The advantages of this test are its speed and simplicity. It does not require expensive reagents, machines, or qualified technicians staff . They are much cheaper than PCR. They are usually manufactured like a pregnancy test: a sample is taken from the nose with a swab or from saliva, a few drops of a reagent that extracts the virus antigens are added, placed in the device and less than 30 minutes are waited for the corresponding reactive bands to appear.

Its specificity (the probability that a healthy person will be result negative) is similar to that of PCR. This means that the issue false positive rate is low. But its sensitivity (the probability that an infected person is result positive) is lower than that of PCR.

This means that they can give more false negatives than PCR. PCR is much more sensitive than antigen detection: while with the PCR technique we can detect one viral RNA molecule per microliter, with antigen tests we need thousands or tens of thousands of virus proteins per microliter for the result to be positive.

So, why do we say that this subject of tests can be a good tool for diagnosis?

Having a lower sensitivity than PCR, antigen tests are positive at higher concentrations of virus and this may have an advantage. Although we do not know what viral load implies that a person is infectious or not, we can assume that the higher the viral load, the more likely one is infectious.

Antigen tests can be very useful early in the infection, when the viral load is highest: a few days before symptoms appear and a week later. The problem with PCR is that it is so sensitive that it can remain positive several weeks after the onset of symptoms because it detects even remnants of the non-active, non-infectious viral genome.

Antigen tests can be done much more frequently: it is better to do a test (cheap and simple) that we can do twice a week, for example, than another (more expensive and complex, such as PCR) that we do every two weeks.

Infection status should always be correlated with clinical history and other diagnostic information. The interpretation of a test should always be done within a clinical context.

For example, if the antigen test is negative but the person has some symptoms, it could be combined with the much more sensitive PCR. Antigen tests can be a very useful tool in primary care. As they can be repeated much more easily than PCR, they can be a good alternative for monitoring and follow-up in certain groups or collectives: residency program for the elderly, health centers, schools.

What is less clear to me is whether these tests are useful for mass screening of asymptomatic individuals.

Another topic to keep in mind is that there are several companies marketing antigen tests. Although the rationale is similar, the results need not be the same. The tests may vary in the subject of antibodies they use, the virus protein they detect or the way the reaction is revealed. Sensitivity and specificity may differ among them and should be evaluated first. Let us remember the fiasco of the famous Chinese rapid tests.

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