Frequently Asked Questions (FAQ)
Everything that you should know about SARS-CoV-2 rapid tests
Can it be detected if someone has been infected with the novel coronavirus?
Yes. There are two different methods.
- From several different types of human cells, the genetic matter (RNA) of the virus can be detected. This method is called PCR test (Polymerase Chain Reaction test). Obviously, it is impossible to spot the genetic matter of one single virus, but it is possible to detect multiple copies of it – the chain reaction is performed for producing the necessary amount of genetic matter.
- It is possible to detect the antibodies produced by the human body to the novel coronavirus. This method is called serological test, immunochromatography test, or rapid test – where the name refers to the fact that the assay can be done in 15 minutes.
How does a rapid test work?
The immune system is responsible for distinguish the “intruders” from the own cells and materials of the body. These “intruders” – also called antigens – can be several things, including bacteria and viruses.
When an antigen enters the body, the immune system starts producing multiple kinds of materials which are capable to fight off the bacteria and viruses (and the disease caused by them). These materials are called antibodies. This is happening in case of the novel coronavirus, too. There are antibodies which appear in the body only if the immune system meets a particular pathogen. The rapid tests thus detect the presence the antibodies which are produced only if the novel coronavirus is present in the body.
Who can perform a rapid test?
In Hungary, only qualified and licensed medical staff (doctors, nurses etc). Private persons are not allowed to use a rapid test kit – even if there are products sold on the internet whose description says the opposite! The rules may be different in other countries, therefore, we recommend you consult the local regulation.
Why cannot a rapid test be performed at home, on one’s own?
The regulation applied to in vitro diagnostic tests for non-professional use is different to the same products intended for professional use. Currently, there is no licensed product available in the European Union with which self-testing or home environment testing could be performed. More on the legal background can be found here (English summary below) .
Moreover, there are other reasons that make non-proffessional use strongly not recommended:
- In Hungary, only licensed institutions are allowed to perform immunological assays (even if the testing takes place on-the-spot, for example in a factory), since the efficient and safe use of these tests require proper specimen collecting environment, medical skills and knowledge. In other countries the regulation may be different but similar guidelines or rules are usually to be followed.
- Epidemic health regulations must be obeyed by those who are using the tests.
- Although finger prick blood samples may be used for testing, too, many institutions prefer using venous blood. From that, the plasma can be isolated, frozen and stored for later use (e.g. repeating the test).
- The materials, tools and specimens used during the testing count as hazardous waste.
Whom is the rapid test recommended?
- who have been in contact with confirmed infected people recently,
- in whose family/close relatives an illness of influenza-like symptoms has been or is present,
- who experience the mild form of the characteristic symptoms of COVID-19,
- who have recently been abroad or to a place where the risk of infection has been high,
- who experienced the typical symptoms of COVID-19 caused by the novel coronavirus and think they already came through the disease in the past – these people might be immune to the virus presently.
Whom is the rapid test NOT recommended?
For those who has had high temperature, severe cough or general sickness (may be related to COVID-19) in the last 7 days.
In this case, voluntary quarantine, or – if the symptoms are severe – hospitalization is strongly recommended in order to ensure the convalescence. This also prevents the spreading of COVID-19.
How is the rapid test performed?
The blood specimen is being taken from finger prick or from the vein (used generally in blood-taking). The test detects the presence of the antibodies in the blood (whole blood, serum or plasma). The interpretation of the results can take place on the spot or in a laboratory suitable for this process.
What is being detected?
The rapid test detects two antibodies produced by the human body exclusively to the novel coronavirus. These are called immunoglobulin G and immunoglobulin M, their common abbreviation are IgG and IgM, respectively.
IgM appears in the body in a detectable quantity on the 5–8th day after the infection. As the immune system fights off the virus, the amount of IgM decreases. In most cases, 4 weeks after the infection it cannot be detected anymore.
In contrast, IgG starts being produced typically 2 weeks after the infection. Its quantity peaks in the end of the first month, decreases afterwards – but it is detectable for a long time. (Currently there are insufficient data available but it is suspected that IgG is present in the blood for at least several months, maybe years.)
This is illustrated in the following figure:
How to interpret the results?
There are four possibilities.
(1) Neither IgM nor IgG is present in the specimen (IgM and IgG negative).
This means that neither antibodies can be found in the blood in detectable quantity.
This can indeed happen because of the tested person is not infected, but that is not the only possibility!
- In case of a very early phase of the disease the production of IgM has not been started yet, therefore there is nothing to be detected.
- Also, some people who are already infected do not produce a detectable amount of IgM for some reason.
For these reasons, if someone with a negative test result shows the typical syndromes of COVID-19 and/or has been to a place with a high risk of infection, it is recommended to repeat the test in the future!
(2) IgM is present in the specimen (IgM positive).
It is very likely the sign of the infection. The virus appeared in the body 5–21 days before the testing since this antigen is usually detectable in this time range.
The typical syndromes of COVID-19 may be present or develop later. It is worth noting that the novel coronavirus does not always causes symptoms – however, the percentage of symptomless cases is not known yet.
Regardless of the presence of the symptoms, IgM positive people can infect others. For this reason, these people must spend 2 weeks in voluntary quarantine!
(3) Both IgM and IgG are present (IgM and IgG positive).
It is very likely the sign of the infection. The virus appeared in the body 14–28 before the testing since both antigens are usually detectable in this time range. (The exact amount of time may be different.)
The typical symptoms of COVID-19 have already developed by this time – if it has not happened, the tested person must have a symptomless infection.
Still, IgM–IgG positive people can infect others, therefore they must spend 2 weeks in voluntary quarantine.
(4) IgG is present (IgG positive).
The person has already fought off the infection, with or without symptoms.
According to our current knowledge this also means that the tested person has become immune to COVID-19. (Even if they become infected in the future, their immune system will fight off the virus in a couple of hours or in 1–2 days; in many cases without any symptoms.)
However, the virus still may be present in the body – according to our knowledge, for 2 weeks –, therefore voluntary quarantine is recommended. After this period of time these people can go back to work safely: neither they can infect others nor they can become ill.
Why are there pages saying rapid tests are useless?
As always, “hot” topics make certain people posting content for increasing the panic, belittling the danger, spreading fake news, part-truth and statements taken out from their original context. It is the same for COVID-19. Unfortunately, it has not been without example that rapid tests have been used in a wrong way or the quality of the tests have been below standard. It is always recommended to check whether a test has the necessary certificates before using.
We think it is worth clearing certain things that are often misunderstood, misinterpreted or misrepresented.
Rapid tests generate a false sense of security since they give negative result for infected people, too.
As it was explained above, a negative result does not mean essentially that someone is not infected. That is why it is recommended to repeat the test later if the risk of being infected is high.
Nevertheless, safety precautions are to be followed regardless of the reason behind a negative result.
An interesting piece of information that there was a part the Hungarian high-school graduation of mathematics in 2017 which was about a fictional pandemic. The similarity between the example and the current situation is mere coincidence, obviously. However, it gives a valuable explanation regarding how the rapid tests in reality work. https://index.hu/techtud/2020/05/08/a_2017-es_matekerettsegi_megjosolta_a_jarvanyt
Tests are recommended only if someone has influenza-like symptoms.
On the contrary. Check the corresponding section about the recommendations.
Rapid tests can only detect the post-infection state.
Wrong. IgM can be detected 5–8 days after the infection. IgG indeed appears later in the body but it is usually present in the second half of the infection – and remains detectable for a long time.
This makes those people identifiable who have already fought off the virus, which is in itself a valuable piece of information regarding the ability for work.
Rapid tests are suitable neither for monitoring nor for emergency cases.
Moreover, rapid tests can be used for identifying a considerable portion of those who are infected. Isolating these people slows the spread of the novel coronavirus down.
If “emergency” is defined by the severe symptoms of COVID-19 – high temperature, serious breathing problems etc. –, the most urgent task is to treat the symptoms. Regardless of they are caused by the novel coronavirus or not.
Rapid tests are useless Chinese tools, there is neither evidence for their efficacy nor approval for their use. That is why plenty of countries have stopped using them.
These concerns are, unfortunately, real in certain cases – especially regarding a couple of products available at online shops. Sometimes there are indeed no data available about the manufacturer, the distributor or about any clinical trials performed on them.
In fact, only products with proper documentation, certificates and data about their efficacy can be marketed and sold in the European Union, which is independent of the manufacturing country.
The rapid test cassette imported by our company has Declaration of Conformity, it is registered in the European Union. It is also registered in the EUDAMED (European Database for Medical Devices; registration number: DE/CA05/IvD-238321-1330-00) and by the OGYÉI (National Institute of Pharmacy and Nutrition of Hungary; registration number: HU/CA01/17106/20).
Are PCR tests better than rapid tests?
Yes, they are, from two points of view.
(1) PCR tests detect the genetic material of the novel coronavirus, therefore they are able to detect the virus in an earlier phase than rapid tests. (Even PCR tests cannot detect the presence of the virus in the very first days, though.)
(2) Partly because they respond more quickly to the virus, partly because the production of antibodies can be different in people, the sensitivity of PCR tests is better.
However, there are several reasons why PCR tests cannot replace rapid tests in all cases.
- For performing a PCR test an instrument worth ten thousands of Euros is needed. The test itself and the other ingredients (used for e.g. isolating the genetic material of the virus) are expensive, too.
- Partly because of these financial reasons, partly because of the environment, instruments and licenses essential for performing a PCR test, much fewer institutions are able to perform them.
- The reaction which detects the presence of the virus RNA lasts for 1 hour or more, and the other steps of the protocol are time-consuming, too. Therefore, fewer PCR tests can be performed in the same amount of time than rapid tests.
- It is not difficult for qualified medical staff to use an immunochromatographic assay. However, running a PCR test properly requires skills relatively few healthcare personnel have.
- It is possible that no cells containing the virus are being collected even if the staff are skilled enough for collecting the specimen.
- Since PCR tests detect the virus itself, it is impossible to learn whether someone has not been infected yet or has been infected before but fought off the novel coronavirus.
According to some recent articles, the reliability of PCR test is questionable, too. Several researches have been done on these tests (for example: 1, 2), but the most thorough summary was published by the John Hopkins University (Baltimore), which is one of the most prestigious institutions of the USA. Seven articles and 1330 PCR tests were reviewed by their researchers, whose results were shocking.
It is known that the symptoms of COVID-19 usually appear 5 days after having been infected. During this time period, PCR tests were able to detect the virus only in 0–33% of the cases, depending on the day the test was actually taken on.
On the day of the onset of symptoms the performance of PCR tests was significantly better; their sensitivity was 62%. In the next 3 days it raised further, but only to a sensitivity rate of 80%. Afterwards – 9 days after having been infected, or 4 days after the onset – the proportion of false negatives started to raise again. Another 12 days later the sensitivity of PCR tests dropped to 34%.
Another summary which includes the opinion of 11 experts on the pandemic also emphasizes the high rate of false negatives of PCR tests: “They miss something like 30% of the infected people, and even more of those who are infected but not showing symptoms.”
Several conclusions can be drawn from these findings.
PCR tests are unable to detect the virus before the onset of symptoms either; thus, it is impossible to tell whether someone who contacted with a confirmed case of COVID-19 actually caught the virus or not.
It seems there is a time interval the sensitivity of PCR tests the best is in. It could be 1–7 days after the onset of symptoms.
Neither negative rapid test nor negative PCR test results are capable of confirming the absence of the virus if they are used as the only tool of diagnosing. Unfortunately, it has elready been reported, that two new infection clusters appeared because of a person who had been examined by PCR test twice – but both of the results had been negative!
The more time elapsed since the onset of symptoms, the less reliable the PCR tests are.
Although the reliability of rapid tests is often checked by performing PCR tests, this appears to be a questionable method.
According to the researchers of John Hopkins University, “Because antibodies appear later in the course of infection, a combination of antibody testing and RT-PCR might be the most useful for patients more remote from symptoms or exposure.”
The two methods seem to complement each other. In the early phase of the disease, RT-PCR tests are more reliable. About 2 weeks after the onset of symptoms it is worth using both tests. In the late phase of the infection, serological rapid tests appear to be more useful. However, whenever it is possible, as long as the symptoms are present, it seems to be the best to apply both tests so that COVID-19 could be diagnosed with the highest reliability.
Is there any Hungarian reference on the usefulness and advantages of applying rapid tests?
The Hungarian Academy of Sciences (MTA) released its commitment on COVID-19 on the 22nd of April, 2020. It says the following about testing:
„It is essential to test and survey those who are susceptible or immune to the virus by using internationally, uniformly validated tests.”
„Selective, well-aimed, proof-based (measurements able to detect both the virus and the immunization) epidemic actions are more cost-effective than general, “stop-and-go” actions.”
„What the most important for the short-term actions of the authorities is testing in a professional, validated way by using RT-PCR molecular diagnostic tests. […] It is, in itself, is not suitable for determining the long-term actions.”
„For estimating the possibilities of long-term actions of the authorities it is essential to assess the development of the immunological protection (immunity) to SARS-CoV-2 in the population. Two types of examinations of different frequency are needed. Firstly, the citizens must be widely tested by using scientifically grounded and representative sampling methods – to assess the level of antibody present in the blood, after the infection. Secondly, selective testing of tight-contact groups and/or groups of professionals working in high risk (e.g. healthcare professionals, nursing homes, schools) is necessary, too.”
„Both virus-testing [PCR testing] and serological testing must be applied thoroughly and regularly for people being in high risk of infection (healthcare professionals, nursing home residents, people returning to the society e.g. who are leaving hospital). This is the way how isolating and treating those who are infected is possible and necessary.”
Regarding the international references, the opinions about using rapid tests are mixed…
We cannot provide a full list of references, obviously – but we can provide a short list of authentic sources.
A New York Times , having asked several experts, is sceptic and cautious about rapid tests. Still, they admit that they have their own place.
„The tests are not reliable enough to guide policy on lockdowns and reopenings, experts said. But they can help model the spread of the virus.”
A CEBM (Center of Evidence-Based Medicine) has compared four different testing methods. Regarding rapid tests, they pointed out the following things:
Lateral flow assays are extremely quick per patient, giving results in just 15 minutes.
Testing levels of antibody in blood allows a single patient sample from one accessible part of the body where sampling is non-invasive to be tested for presence of virus.
These tests require very little training to perform and don’t rely on specialist laboratories or scientists to analyse.
The technology is new and the evidence for its accuracy in coronavirus diagnosis is still being evaluated.
So far, available lateral flow tests can only determine if a patient has at some point been infected with COVID-19. Further testing would be needed to check if a patient is currently infected. Future versions of this technology might allow clinicians to detect current infections.
Lateral flow tests are more expensive and time consuming for large batch testing than specialist laboratory based antibody tests such as ELISA.” (On the grounds of other references, ELISA has not been proven to be reliable yet.)
AsianScientist emphasizes the long-term benefits. Their argument is based on a rapid test of other manufacturer which has appeared to be unreliable, though
„That is not to say that antibody-based tests are not useful. On the contrary, antibody-based tests have proven to be crucial in linking clusters of infection, by detecting people who were infected but discovered too late to test positive via RT-PCR. As RT-PCR looks for virus RNA, it will only give a positive test result if there is an ongoing infection. On the other hand, antibodies can persist for months or years, allowing tests to identify anyone who has ever been infected.”
A diazyme.com to diazyme.com, it is important how the specimen are being collected. They state it is best to use both PCR and serological tests simultaneously.
„IgG/IgM serological tests offer some advantages over RT-qPCR. Firstly, serological tests detect human antibodies (proteins belonging to the immunoglobulin class) which are known to be much more stable than viral RNA. As a result, IgM/IgG serological specimens are less sensitive to spoilage during collection, transport, storage and testing than RT-qPCR specimens. Secondly, because antibodies are typically uniformly distributed in the blood, serological specimens have much less variations than nasopharyngeal viral RNA specimens […]. Thirdly, unlike RT-qPCR, serological tests can detect past infection […]”
„IgM/IgG serological tests also have some limitations, mainly related to the slow pace of the human antibody response to SARS-CoV-2. Although, several studies are still on-going, SARS-CoV-2 antibodies may not be detectable before 3 days after onset of symptoms (or at least 7 to 10 days after infection).”
„While IgM/IgG serological tests alone may not be enough to diagnose COVID-19, they can be a valuable diagnostic tool when combined with RT-qPCR […]. In addition, because of their scalability, serological assays can be used in large-scale, whole-population, testing to assess the overall immune response to the virus and identify asymptomatic carriers of the virus. Indeed, 20-80% of COVID-19 cases are estimated to be asymptomatic.”
How can the results of a rapid test and a PCR test be compared?
A diazyme.com summarizes the possible results in a clear and concise way:
Patient may be in the window period of infection. [When the rapid tests cannot detect any antibodies.
Patient may be in the early stage of infection.
Patient may be in the active [middle] phase of infection.
Patient may be in the late or recurrent stage of infection.
Patient may be in the early stage of infection. RT-qPCR result may be false-negative.
Patient may have had a past infection, and has recovered.
Patient may be in the recovery stage of an infection, or RT-qPCR result may be false-negative.
It is said on the Internet that more often than not, positive results of a rapid test belong to people who are not infected at all!
It is true, in itself. However, for explaining this phenomenon a couple of concepts need to be explained. (In this section, we ignore the fact that rapid tests detect two kind of antibodies, for better understanding.)
The reliability of a test can be described with two different values. Sensitivity shows with what percentage a test can detect the event we search for (in our case, the antibody produced to SARS-CoV-2). Specificity shows what the chance is that the ground of a positive result is the event we search for (the antibody is actually present in the body and it is being produced because of the virus; again, in percentage form).
We need another concept, too. Prevalence gives us how many people have been infected in a certain area (e.g. a city or a country).
In the following example, imagine that a test works with 90% specificity and sensitivity, and the prevalence is 2%.
Using these data, if we examine a random sample of 1,000 people, there will be 20 infected persons, on average. 18 persons will be detected by the rapid test (2 of them will not – sensitivity is 90% - these 2 results are called false negatives). There are, on the other hand, 980 people who are not infected. The test will confirm the lack of the infection in 882 cases – but will give in 98 cases a positive result for healthy people, too (specificity is 90% – when the result shows infection by mistake, it is called false positive). Thus, the chance that a positive result belongs to an infected person is the following: 18(18+98)×100%, which is merely 15.52%. This value is called positive predictive value, counted by dividing the true positive cases with the sum of the true and false positive cases (multiplied by 100%).
The test will give a negative result for the 90% of the non-infected people, which is 882, plus for 2 of the infected ones. The chance that a negative value means the actual lack of infection is called negative predictive value. In our example, it is 884/(884+2)×100% - 99.77% (the true negatives divided by the sum of the true and false negatives, multiplied by 100%).
At first sight, this appears to be devastatingly bad: the chance of getting a false positive – the test shows the presence of the infection when there is no infection at all – is 84.48%! However, this happens because of statistical reasons and has nothing to do with the particular rapid test. Whenever the prevalence is low, sensitivity and specificity have very little impact on the predictive values – the 10% “specificity error” is paired with a huge amount of data (after all, most people are not infected), whereas the 90% sensitivity belongs to very few (the infected minority).
Without elaborating the deduction, it is worth looking at the following numbers, as well:
If both specificity and sensitivity is raised to 95% and the prevalence is unchanged, the positive predictive value is still only 27.94%. The negative predictive value is 99.89%.
If specificity and sensitivity remain 90% and we raise the prevalence to 4%, the positive predictive value is 27.27%, the negative predictive value is 99.53%.
With specificity and sensitivity of 95% each, at 4% prevalence, these predictive values are 44.19% and 99.78%, respectively.
If we raise the prevalence to 10%, with specificity and sensitivity of 90% each we get 50.00% for the positive predictive value and 98.78% for the negative predictive value. In case of specificity and sensitivity of 95% each, these values are 67.86% and 99.42%, respectively.
What we can see is the positive predictive value is affected by the prevalence at least as much as by the specificity and sensitivity of a test – in contrast, the negative predictive value changes very little as long as the prevalence is low. (The positive predictive value changes almost as much if we raise the prevalence to 4% as if we raise sensitivity and specificity to 95%!)
This is something that can be experienced regardless of COVID-19. Whichever serological test we examine, the positive predictive value will be low if the prevalence is low, too. Actually, the same applies for any test which has false positive and false negative results.
Still, this does not mean that rapid tests are useless!
Shortly said, there are three factors that are not taken into consideration at all in the deduction above.
1. In case of an epidemic and/or a disease which causes severe symptoms, the primary objective is to detect those who are affected. Even if there are several healthy people who get positive results. Regarding COVID-19, it would be a bigger risk not to find the infected (whose condition can become critical any time, and who can spread the virus, too) than to have a number of people examined thoroughly unnecessarily. Moreover, most SARS-CoV-2 rapid tests detect two types of antibodies – IgM and IgG –, which alone lowers the risk of remaining undetected. (Even if these antibodies are being produced in a different time interval.)
2. Even if the positive predictive value of the rapid tests is low, using them narrows the amount of people who need to be examined further. The method is cheap and quick, it is easy to test a lot of people with these tests. Therefore, only those are to be examined thoroughly who may be infected. In this way, fewer PCR test need to be made – these are more reliable, but, unfortunately, slower, more expensive and complicated, too. It must be pointed out that the safest way to diagnose those who are suspected to be infected is medical examination and history. If it is known that the subject has been in contact with infected people recently and he or she shows the typical symptoms of COVID-19, the chance of being infected is much higher than in case of a “mere” positive test result. Obviously, it would be the most efficient if every single person were examined thoroughly – but the capacity of the healthcare system is insufficient for this. Not only in Hungary, but also everywhere in the world.
3. In case of an epidemic, prevalence is mostly theoretical. Again, considering a prevalence of 2%, we can say the following: choosing 100 persons randomly we will find 2 infected on average. However, if we want to know how many infected are there in an institution of 100 people (e.g. a nursing home), we are definitely not choosing that 100 people randomly! If the virus has already appeared in that place, most likely there will be more than 2 infected persons – if not, prevalence will be exactly 0%. If we apply rapid testing to all these 100 people, the sheer amount of positive results will give us information on the presence or the absence of the virus – even if there are false positives and false negatives, too. That said, if 25% of the test results are positive, it is worth monitoring and confirming the infection with other methods too, for all the people. On the other hand, if there are only 1–2 positives, that might be because of false results; especially if no one shows the typical symptoms of COVID-19 currently, or in the near future.
Finally, we should not forget. There is no test which is 100% reliable. Thus, it is impossible to detect all the infected, nor to detect only the infected. The risk must be lowered to an acceptable rate, though, and that is what rapid tests are for.