More and more tests for the novel coronavirus are coming onto the market. By the end of July, there were already more than 350 different products worldwide. There are three main types: PCR tests, serological tests (ELISA) and antigen tests.
To check whether someone is currently infected and can also infect others, a test based on the polymerase chain reaction (PCR) method is usually used. Alternatively, there are also so-called isothermal DNA amplification tests, which, however, work very similarly to PCR tests.
In both cases, saliva is extracted from the patient's throat using a cotton swab. Sputum from the deeper lung is also suitable for detection. Afterward, a certain part of the genetic material — for example, a gene — is multiplied from the sample in numerous steps, and, finally, a biochemical method called agarose gel electrophoresis is used to determine whether the expected viral genetic material was contained in the sample.
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If the genetic material is found, the patient is considered infectious. If the genetic material is not found, however, this does not necessarily mean that the test person is not infected after all: It could still be that the viruses were not in the sample but are present elsewhere in the body.
This may also explain why in individual cases, COVID-19 patients who were considered cured turned out positive in PCR tests later on. Probably in these cases the viruses were present all the time but were not found in the test before the patients were declared to have recovered.
In a podcast with the German public broadcaster NDR, the infectious disease specialist Christian Drosten from Berlin's Charite Hospital compared this with an attempt to catch a goldfish in a tank with a hand net. If you pull the net out of the water and there is no fish in it, it does not mean that there are no fish in the tank.
PCR rapid tests
Traditional PCR tests are carried out in a laboratory. Mostly this is performed via high-throughput screening, in which thousands of samples can be tested simultaneously. This procedure usually takes several hours to produce results, and patients normally have to wait between half a day and a couple of days to receive results.
PCR rapid tests are one possible solution to this time-consuming process. In this case, the test is not carried out in a central laboratory, but can be performed on site using mobile equipment. These devices can produce a result within 45 minutes. The disadvantage is that the devices cannot manage more than 80 tests per day.
These novel rapid tests have only been on the market since this summer and are supposed to be as easy to use as a pregnancy test. The antigen test also involves taking a saliva sample. This approach detects viruses using the fluorescence immunoassay (FIA) method, and can usually determine whether a patient is acutely infected and contagious within 15 minutes.
Many of the tests now achieve a good sensitivity and, above all, a sufficiently high specificity of more than 98%. This means that there are relatively few false positive results. The research team of the virologist Christian Drosten from the Charité in Berlin compared seven different kinds of antigen tests. Only two of those failed - only achieving a specificity of between 88 and 94 percent. The results were published on MedRXiv on November 13 as an non-peer-reviewed preprint.
The major advantages, though, are quick results and the possibility to use it directly on site. Some tests require a special device for the analysis.
Influenza tests that work on the same principle achieve a sensitivity of slightly more than 50% and a specificity of about 99%. This would mean that only every second virus carrier is detected. One in 100 people tested would have a false positive result.
Nevertheless, a growing number of physicians are in favor of the widespread use of antigen tests because they hope that this will ultimately mean more infected people are detected.
They also argue that the sensitivity of the tests increases when the patients have a high viral load, which is when they are most contagious and, therefore, when they pose the greatest risk to the community.
In most countries, including Germany, these rapid tests are not freely available. As the Infection Protection Act stipulates that all SARS-CoV-2 diseases must be reported, only doctors may carry out the tests.
Evidence of infection in the past
Serological tests, also called enzyme-linked immunosorbent assays (ELISAs), detect antibodies that the immune system has mustered against the virus in the blood of the test persons. This means that the body has already shown an immune response to infection with a particular virus. For ELISAs, a person must give a small blood sample that is then tested in the laboratory.
Manufacturers now also offer rapid tests based on this principle, but these must still be performed by a practicing physician. All that is needed is for a few drops of blood — much as with a diabetes test — to be put into into a test cassette and for a buffer solution to be added.
If SARS-CoV-2 specific lgM and lgG immunoglobulins are present in the blood, the sample changes color. A positive result can mean that the test person has undergone a coronavirus infection and now has a certain immunity to it. But this is not necessarily the case. Almost all antibody tests "react crosswise," as Drosten emphasized in his podcast.
Some manufacturers claim that this is not the case with their products. However, it is conceivable that someone who has tested positive might have had a different coronavirus infection — a cold, for example — and not an infection with SARS-CoV-2.
When is a test useful and for whom?
PCR tests are important for finding out whether patients and their contacts are currently infectious and what form of quarantine they have to go into: Is it enough to impose a two-week stay-at-home order on a contact person, during which time he or she may still meet with members of the household, or does the person really have to be completely isolated?
ELISA tests are an important tool for epidemiologists to estimate how many people have gone through an infection undetected and whether a certain level of herd immunity might eventually be achieved. This can help politicians to decide whether to relax restrictions.
The test can also help to check the immunity of people who were definitely infected with COVID-19 or those who have received one of the newly developed vaccinations.
Various German university hospitals have started broad studies in which they use ELISA tests to check randomly selected participants for a possible undetected infection — partly to find out more about the behavior of the virus.
Test strategies in different countries
Countries around the world are taking very different approaches to coronavirus testing during the current pandemic. There are many reasons for this. Differences in the performance of health care systems, availability of tests and different laboratory capacities have played as great a role as the question of how seriously the threat was taken from the outset.
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For example, South Korea, which had learned from the experience of the SARS epidemic of 2002, was one of the countries that systematically tested large numbers of people at a very early stage, even those who had no symptoms and at a time when the number of cases was still comparatively low.
In terms of the total population, Germany is also one of the countries that test a great deal. But it tests mainly people who have had proven contact with infected persons and show symptoms. Other countries, such as the USA, are currently massively expanding their testing capacities, but the pandemic has also progressed more rapidly there and the case numbers are very high. This is in contrast to countries in Africa, where testing is almost non-existent.
Due to new developments, this article has been updated since original publication
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