“There is still so much that we do not know about SARS-CoV-2, the virus that causes COVID-19.”
Recently, COVID-19 threw a curve-ball. There were reports that patients who had previously tested negative were testing positive again. This would go against the expectation of the scientific community that once a person recovered from the disease, they would have some form of immunity from the disease. So why is this happening?
There are three possible explanations for this observation, and no, none of them considers a re-infection as the underlying reason:
- How PCR works and what it tests
- Sensitivity of the COVID-19 tests
- The type of test whether PCR or antibody
PCR works by amplifying and identifying the genetic make-up of an organism. In other words, it looks for genetic material in the sample and returns a positive result if found. This is by far the most reliable test across diseases as it looks for the actual presence of the causative agent. The problem is, it doesn’t distinguish between viable and non-viable (“dead”) genetic material. The leading theory around those who turn positive after turning negative is that what is being picked are non-viable genetic remnants of the SARS-CoV-2 virus. In this case, there is no relapse and the persons are not expected to be contagious. Attempts to grow the virus from such persons in the lab have been unsuccessful supporting the argument that the material is non-viable and non-infectious.
The second possible reason bears an inherent worry: the sensitivity of medical tests. Sensitivity, in simple terms, is the likelihood of a test returning a positive result in a situation in which what it is testing for is present in the sample being tested. Doctors know that tests are rarely absolutely sensitive. In-fact, separate from COVID-19, this one property of tests has been a common cause of friction between patients and doctors for decades: talk of “misdiagnosis” and wrong treatment come to mind. Anyway, several factors affect the sensitivity of tests: the test itself, the stage of the disease (are there many viruses or few viruses in the body), the sample used, the technique of collecting the sample, the handling of the sample and many other factors. In the context of COVID-19, samples may be obtained from the nose or from the lungs. The sensitivity of the COVID-19 RT-PCR testing is reported to range from 55% and 70% for nasal samples, while lung samples bear sensitivities of between 77% and 90%. What this means is that between 10% and 45% of those tested will return a negative result while in fact they are positive. This is what is called a false negative. WHO has issued a guideline requiring that to be declared negative, a person recovering from COVID-19 must undergo two PCR tests done at least 24 hours apart.
Unfortunately, a patient with a false-negative test can still spread the virus.
The third possibility is the least likely. This is a situation in which testing agencies mix PCR tests (usually from nasal swabs and lung secretions) and antibody tests (usually from blood). I say this is least likely because I trust that all testing agencies around the world know enough not to do this. Whereas PCR tests looks for material from the virus, the antibody tests looks for the body’s response to the virus. Antibodies are what the body produces to fight infection and these often persist for years after the infection has cleared. A positive antibody test shows that one has ever been exposed to the virus but does not confirm that one has an actual ongoing infection (there are complexities around IgG and IgM but that’s technical stuff for doctors). Therefore, performing an antibody test on a patient who has recovered from COVID-19 is most likely to return a positive result even when the patient doesn’t have the disease.
A key point to note is that most rapid tests and home-testing kits are antibody tests. It means that those who will have recovered from the disease should brace themselves for a positive test all the time every time. The good news is that such a positive test is actually a test of immunity. Bear in mind that the value and longevity of such immunity is still under study. A patient with a positive antibody test but two negative PCR tests at least 24 hours apart is unlikely to be infectious.
I hope this information helps. Do share and leave a comment. You have my permission to copy, paste, publish, any or all of this material provided you accurately cite the source.
Dr. Victor Ng’ani