Coronavirus infection and negative test result – how is this possible? WE EXPLAIN

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There have been many myths surrounding the tests for the diagnosis of SARS-CoV-2. One of them concerns a negative result and the belief that it gives one hundred percent confidence in the absence of coronavirus infection. This is not only deceptive, but also dangerous thinking. It turns out you can be infected, but your test won’t show you, and infect others. In what situations does this happen?

1. In some cases, tests for the coronavirus are negative even though the body is infected
2. The quality of the test, laboratory work and the analyzed sample are of great importance for the test result
3. According to American scientists, the test performed just after infection, before the onset of symptoms, will be 100 percent. false negative cases
4. In the second week of infection, a more reliable result may be obtained when examining material taken not from the nasopharynx, but from the bronchi
5. You can find more about the coronavirus on the TvoiLokony home page

Coronavirus tests – types, action

The increase in coronavirus infections has entailed not only better access to diagnostics, but also greater interest in performing a test for the presence of the pathogen in the body. The tests are applied not only to people who show the characteristic symptoms of COVID-19, but also those with less typical symptoms (to determine whether it is SARS-CoV-2 or another infection, such as a cold or flu) or completely asymptomatic (because they had contact with an infected person with a positive test result). A separate group consists of patients who decide to check whether their body is already producing antibodies against the coronavirus, suspecting that they may have already suffered the disease caused by it without experiencing any symptoms.

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This is possible thanks to the increasingly broader COVID-19 diagnosis. Currently, there are three types of disease diagnosis tests available on the market. The most important is a molecular test, performed with the RT-PCR method, which examines the presence of coronavirus genetic material in a swab taken, usually from the nasopharynx. The test is performed at special points, and its result is known several or several dozen hours after the material was obtained.

Equally helpful in detecting an infection is an antigen test that allows you to recognize antigens, i.e. particles of a microbial protein. It differs from the RT-PCR test in the waiting time for the result (it is shorter), but at the same time it is lower in sensitivity, so the swab must be taken at the right time of the infection to detect the virus.

The third type of test that is gaining popularity is the serological test – for the presence of anti-SARS-CoV-2 antibodies. It makes it possible to identify the antibodies in the body that have developed after contact with the virus. Importantly, however, these tests do not confirm or exclude coronavirus infection. However, a positive result may indicate that the patient has had an infection or is currently having an infection.

Sensitivity and specificity of tests for COVID-19

While the test results, no matter what their type, seem obvious, they can actually be misleading. These situations less often concern the cases of receiving a positive test despite being healthy, and more often the opposite – when we are infected with the coronavirus, although the test result is negative. There can be many reasons – ranging from the quality of the test, through the quality of the laboratory performing it, to the quality of the test sample.

– This is a new virus and many tests have been approved for use only conditionally – they do not have full documentation in the field of validation and qualification, i.e. their suitability for clinical evaluation of patients – explains Prof. Marek Jutel, MD, PhD, president of the European Academy of Allergology and Clinical Immunology (EAACI), Head of the Chair and Department of Clinical Immunology at the Medical University of Wroclaw.

But it’s not just the tests that are the problem. Procedures in laboratories, such as the cleanliness and accuracy of employees, turn out to be equally important. As a result, results from different laboratories may differ, even when the same test is used and the same sample is tested.

Regardless of the technical aspects, the parameters of the tests themselves are important, i.e. their sensitivity and specificity.

– In the case of tests for SARS-CoV-2, the so-called molecular, assessing the presence of viral genetic material, the sensitivity ranges from 60 to 80 percent. This means that the test is negative in 20 – 40 percent. infected people. Tests for the presence of virus antigens show 50 percent. sensitivity, i.e. they are negative in half of the tested patients infected with the virus. You can increase the sensitivity of the tests by adjusting their parameters differently, but then the test becomes less specific, that is, we will have more false-positive results and diagnose an infection in patients who do not have it. Therefore, in practice, no test is 100 percent. sensitive and specific. A compromise is needed. For this reason, it is very important to interpret the test by an experienced physician who will confirm, on the basis of the patient’s examination, whether the obtained result is reliable or not, explains Prof. Jutel.

Coronavirus: When to Test?

While we have no influence on the type of test and the work of the lab technicians, we do indirectly on the quality of the sample. To increase the likelihood of receiving a reliable test result for the presence of coronavirus, you need to come to the test in time. Such a “window” in the case of “covid” tests does not have a fixed width and is an individual matter, depending on many factors that researchers from around the world are still analyzing.

1. Scientists of the Polish Academy of Sciences: the situation has become critical, it is necessary to change the method of testing for the presence of SARS-CoV-2

So far, it has been established that in most patients, the first symptoms of COVID-19 appear on average about the fifth day after contact with an infected person. At the same time, the infected person most effectively infects two days earlier (i.e. on average three days after exposure to SARS-COV-2) and two days after the first symptoms appear. This is confirmed by the results of analyzes of the American Centers for Disease Control and Prevention (CDC), which indicate that in almost half of COVID-19 cases, the virus was transmitted before the infected person first developed symptoms.

These observations would suggest that the test to diagnose coronavirus infection is best performed in the first days after contact with an infected person. Meanwhile, this is not always a good lead. Researchers at The Johns Hopkins Hospital and Johns Hopkins School of Medicine in Baltimore (Maryland, USA) took a closer look at patients who tested negative despite infection. The results of the research, published in the journal “Annals of Internal Medicine”, show how the time of the test has a significant influence on the results of the test.

The probability of receiving a negative (unreliable) test, performed during the first days after infection, and before the onset of coronavirus symptoms, was estimated at 100%. Interestingly, the test performed on the day of the first symptoms reduced the probability by over 60%. (it was 38%), and after the next three days it was even lower – 20%. In the following days, the risk of receiving a false-negative result increased again – from 21%. on the ninth day of exposure to the virus, up to 66 percent. three weeks after potential infection.

1. What do the Ministry of Health’s COVID-19 statistics tell us? [COMMENT]

– We assume that if the minimum number of viruses to cause an infection enter the body, i.e. about a hundred, several infected cells begin to produce a virus after 12-24 hours. Then the process is repeated in other infected cells, and from then on you can think about performing molecular tests. So not earlier than about 48-72 hours from contact with an infected person – confirms prof. Marek Jutel, MD, PhD.

Where is the best place to get a swab for the PCR test?

Another condition for obtaining a reliable test result for coronavirus diagnosis is to take a swab from the right place. The virus accumulates in different amounts in different parts of the body depending on the stage of the infection. Standard material for research is taken from the throat, nose or mouth, but this does not exhaust the diagnostic possibilities. The presence of the virus can also be tested in the bronchi (bronchial lavage is then obtained using a bronchoscope) and the trachea, as well as in the epithelium of the digestive system, because SARS-COV-2 can be excreted from the body for up to two weeks after infection.

As prof. Jutel, the sensitivity of molecular methods (RT-PCR) varies depending on both the site of material collection and the stage of infection.

– In the first week it is around 60 percent. in the case of a nasal swab, 30 percent. from the throat, 50 percent from feces, 70-75 percent when collecting sputum and 93 – 95 percent. from bronchoalveolar lavage obtained in bronchoscopy. However, already in the second week, the amount of viruses in the nose and throat decreases and increases in the lungs. This causes a decrease in the sensitivity of tests made of nasal and throat swabs, while tests made of bronchial material are more reliable – he adds.

The above data is of particular importance for asymptomatic people for whom the diagnosis of the appropriate time to perform the examination may be quite a challenge. Some of them then give up testing and after quarantine, they are more willing to take tests for anti-coronavirus antibodies. Experts agree, however, against jumping to conclusions. Such a test may give a negative result, because the body is not yet outside the so-called window, which means that it has not been long enough after infection for the body to make antibodies.

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– Antibody testing should not be used to diagnose a current COVID-19 infection. They do not confirm ongoing SARS-CoV-2 infection as the body produces antibodies 2-3 weeks after infection. However, they are very useful for confirming whether a patient has had an infection and for assessing acquired immunity to the virus – confirms Prof. Jutel.

Therefore, caution is necessary – both when choosing the time and interpreting the result, which requires consultation with a doctor. It is he who has the knowledge to determine whether the result of the COVID-19 diagnosis is reliable and – in case of any doubts – advise against treating a negative result as a basis for abandoning precautionary measures aimed at preventing further contamination.

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