What We Know About the Currently Available SARS-CoV-2 Tests
Their accuracy and power of detection
In all the craziness going on right now, the only thing we can hope for is for this pandemic to end soon with as little collateral damage as possible. Until this happens, we will still be introduced on a weekly, if not a daily, basis to the new detection tests for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Well, not all those tests are the way they are marketed on the media more specifically when it comes to their diagnostic or screening power. Some are better than what we think and others are not as much. Despite the fact that there is still a lot to learn, we know enough about the ones currently available to dig into their pros, cons, and accuracy.
According to the Foundation for Innovative New Diagnostics (FIND), we currently have two main methods for SARS-CoV-2 testing: 249 of which are commercialized immunoassays with only 6 approved by the U.S. Food & Drugs Administration (FDA), and another 250 commercialized molecular assays with only 18 approved by the FDA.
It is true that both types of tests detect the same virus; still, they bear many differences especially in the way their results are interpreted.
Immunoassays
These assays are of two types. The first is based on the detection of an antigen, which is a protein that is either part of the virus or released by body cells infected by it, and which in our case is a protein released by the infected cells. The second is based on the detection of an antibody, which is a molecule produced by the immune system against the virus, aka the antigen, to stabilize and eventually terminate it.
Think of it as a lock and a key. We search for a lock compatible with the key we are using. If we have a match, the test shows a positive result and eventually a positively infected patient.
Those assays, however, can detect two types of human antibodies. Immunoglobulin G (IgG) which indicates a previous encounter with the virus and recovery from it. It composes about 85% of our immunoglobulins and is easy to spot. The other Immunoglobulin is Immunoglobulin M (IgM) which indicates that an individual has had the virus for at least a few days or as the World Health Organization (WHO) classifies it an acute or early infection. In other words, it would be less common for these tests to identify a positively infected patient in the early stages of the disease.
All developed assays are based on scientific data and thorough studies; still, every technique has its own limitations. Based on an interactive algorithmic program created by FIND, immunoassays based on detection of anti-SARS-CoV-2 antibodies which included 29 manufacturers and 34 tests showed the following:
- None of the tests had a 100% accuracy in early (1–7 days) infections
- Only 1 test had a 100% accuracy in intermediate (8–14 days) infections
- None of the tests had a 100% accuracy in late (>14 days) infections
Molecular assays
These assays are based on what we call a real-time reverse-transcription polymerase chain reaction (RT-q-PCR) which can detect specific genes of the virus by detecting its ribonucleic acid (RNA), the genetic material of the virus, after transforming it to the more known form, deoxyribonucleic acid (DNA), and making many copies of its sequence through a specific automated process. Currently, three different gene sequences are being detected, the reason there currently exists double detection kits or triple detection ones. The three genes detected are:
- The N gene indicates the sequence of the virus’s capsid. A recent article published on Korea Biomedical Review Newspaper website claims that this gene is highly mutated, so if a test does not detect this gene, it does not mean that the person tested does not carry the virus.
- The E gene indicates the sequence of the envelope small membrane protein. This gene according to the study conducted by Dr. Lee Hyuk-min, the director of infection control affairs at the Korean Society for Laboratory Medicine, is less susceptible to mutation than the N gene, hence can lead to a more accurate diagnosis.
- The RdRp gene indicates the RNA-dependent RNA polymerase sequence of the virus. This gene is the most stable of all as per the testing protocol published by Institut Pasteur, Paris. In other words, the test you are taking should always look for this gene.
In conclusion, molecular assays can detect the viral gene as soon as the virus enters the body, the reason why it has been relied upon as the primary testing method against the SARS-CoV-2.
Taking into consideration what is mentioned in the section about immunoassays, every technique has its own limitations and molecular assays are no exception. Based on the same program explained above (interactive algorithmic program created by FIND) molecular assays based on viral RNA extraction which included 26 manufacturers and 28 tests showed the following:
- 3 tests had a 100% accuracy in early infections
- The same 3 tests showed a consistent 100% accuracy in intermediate and late infections
Takeaway message
We can conclude from all the above that in the early stages of an infection, it is better to go for molecular assays when one is asymptomatic, especially that it is well known that our immune system needs several days to produce an immune response to the pathogen. In addition to this, we might go for immunoassays to detect if one has undergone recovery and is immune to the virus. Keeping all this in mind, the above-discussed results showed that many authorized tests do not attain 100% accuracy, and therefore, might result in a false positive (a non-infected patient with a positive result) or a false negative (an infected patient with a negative result); still, the above referred to program undergoes a live update and therefore, results are constantly updated and may change.
On the other hand, guidelines and procedures recommended by medical facilities and international authorizations should always be followed. Unauthorized tests should never be a resolution. However, one thing is for sure. Prevention is always better than treatment so guidelines to protect ourselves and others published by the Center for Disease Control and Prevention (CDC) shall be serving as a front line defender.
