COVID-19 screening tests: How does it all work?

On the one hand, there are tests that directly detect the virus, which are currently used in every Canadian province. These tests detect the presence of the virus’ nucleic acid (RNA) in the body using nasal, oral and pharyngeal secretions. If the test is positive, the individual is contagious, whether symptomatic or not. This is currently the most reliable diagnostic method, but it is long and complex.

Tests that directly detect the virus allow health care professionals to detect COVID-19 very soon after infection and to recommend appropriate measures, such as isolation.

On the other hand, there will soon be many serological tests available, one was approved on May 13th by Health Canada. This type of test does not detect the virus as such. Instead, through a blood sample, it detects the presence of antibodies that an individual infected with the virus has developed. Serological tests are simple to perform and certain applications produce results in less than 15 minutes. However, since antibodies are only detectable about a week or two (sometimes more) after infection, a negative result does not necessarily mean that a person is not infected and, more importantly, not infectious.

Serological tests can detect antibodies that show that a person has been exposed to COVID-19 at some point.

You will find online a growing number of serological tests that promise “100% guaranteed” results in 15 minutes from a single drop of blood. We strongly advise against ordering these test kits, as none of them have been approved by Health Canada (as of May 15, 2020). To find out which tests are approved, please see Health Canada’s web page on this topic.

One drawback of the serological test is that it can take two to three weeks after you contract the virus for it to show that you have been infected. If you take the test within the first week of infection, a negative result could give you the false impression that you are not infected and, more importantly, that you are not contagious! By letting your guard down, you become a perfect vector for spreading the virus.

Tests that confirm the presence of the virus in nasopharyngeal/oropharyngeal (nose, mouth and pharynx) secretions, which are collected using a long swab, are definitely the most reliable screening technique. The virus is identified by its chromosome (RNA) using the PCR (polymerase chain reaction) technique, also known as NAAT (nucleic acid amplification technique). This is the approach currently used in Quebec laboratories.

Another more advanced technique, called viral RNA sequencing, provides confirmation of the diagnosis (referred to as true positive), but it is available only at very few laboratories in Canada, including the National Microbiology Laboratory in Winnipeg. At the beginning of the pandemic, all tests had to be confirmed in Winnipeg, which took a few more days to get results. Due to the high rate of concordance with tests done on the front lines, public health authorities in Quebec have cancelled this confirmation step to speed up the process.

However, there is no hiding the fact that the procedure remains cumbersome, and the time needed to do the test in a laboratory is long (several hours). PCR testing requires sophisticated and expensive equipment that is found only in specialized laboratories, such as the Laboratoire de santé publique du Québec, university hospital laboratories and some private laboratories. It also requires two types of reagents: one to extract RNA from the virus and one to detect the virus.

The health care community quickly became concerned about the scarcity of these reagents, particularly the one for extracting RNA from the virus. Due to the risk of shortages, public health authorities severely limited access to the test, to the dismay of many people. However, on April 8, French company Biomérieux announced that it would give the recipe for this precious reagent to the National Microbiology Laboratory in Winnipeg, and this has improved the situation.[2] However, the risk of a shortage of equipment, such as swabs or of trained staff, also has an impact on the number of tests performed.

The PCR test is not perfect either, as the false negative rate reported in a recent study has shown. The definitive false negative rate is not yet known with certainty, but in the only study done in China, it could be as high as 30%![3] This means that one in three infected individuals could test negative and not be quarantined! However, these false negatives are thought to be due to the samples (e.g. low virus levels at the onset of the disease, insufficient collection of secretions, transportation and storage problems) rather than to the test itself.

To address these various issues, there is a rapid version of PCR test that provides results in under 30 minutes and can be done away from traditional laboratories. Two of these devices are approved by Health Canada, one of which approved for research use only, the Spartan Cube, is manufactured in Ontario.[4] These devices will be especially useful in remote areas or any situation where an “immediate” result is preferred, such as in long-term care facilities and other seniors’ residences. However, these devices produce only one result at a time and therefore cannot be used to test large numbers of people.

Another promising avenue is antigen testing, which also uses samples collected from the nose, mouth or pharynx to identify proteins specific to the virus (viral antigens). These tests can detect individuals carrying the virus, but are less complex and less expensive than PCR tests. They can be performed away from large university laboratories, sometimes directly at the patient’s bedside, and results are available in a very short time, often about 15 minutes. It remains to be seen whether their rates of false negatives and false positives are low enough to justify their widespread use.

Public health authorities are placing great hope in serological tests, to complete the arsenal in the fight against COVID-19. Unlike tests that identify the virus, these tests measure the antibodies produced by the immune system in response to infection by the virus. As a result, it is possible to tell if a person has already been exposed to the virus and has developed antibodies.

In addition, serological tests are simple and can be done in laboratories of any level and, under proper supervision, even at clinics or in other health care settings. In some countries, individuals can get kits to test themselves at home using a drop of blood. However, many public health authorities advise against this method.

Serological tests are not new. They have been used for decades to confirm certain bacterial and viral infections both new and old, such as hepatitis (A, B and C), HIV, rubella, measles, etc. They work in a simple way. A few days after the infection begins, the body first produces IgM antibodies specific to the virus or bacteria, followed by IgG antibodies, which will be present for several weeks after infection.

According to a Chinese study[5], the serological test detected IgM in 29% of individuals infected with COVID-19 in the first seven days of infection, and this percentage increased to 73% in the following week. For IgG, results are reported to be positive for 19% of infections in the first week and 54% in the second week.

Due to the unreliability of serological tests in the early stage of infection, they are not recommended for diagnosing COVID-19 in the first two weeks after symptoms appear. Eventually, reliable quantitative tests that detect antibodies to COVID-19 will be able to confirm that a person has indeed produced enough antibodies to confirm that the infection was successfully cured and that the individual is immunized against contracting the virus again for a certain period of time (actually undefined).

The low cost of these tests, along with simplified analysis and specimen collection (often a drop of blood from the finger), and above all, the ability to conduct millions of automated tests, are all major advantages in efforts to screen the public for COVID-19. For this reason, public health authorities eagerly awaited their approval.[6]

These tests will probably prove to be valuable allies in containing the pandemic and, of course, in the gradual resumption of social and business activities. They would provide a better understanding of how the pandemic is spreading, how long the antibodies provide protection against the virus and, when a vaccine becomes available, help identify individuals who are already immune, so that we can better target the people who should be vaccinated first.

Until then, no laboratory test can replace the protective measures recommended by public health authorities: self-isolation, physical distancing, frequent handwashing, and wearing a homemade mask when you cannot maintain the two-meter distancing such as when you are grocery shopping or taking public transit.[7]

Biron offers molecular screening test for COVID-19. Unlike the serological tests, the molecular screening does not require a doctor’s prescription. For more details, click here.