Coronavirus Tests: what you need to know

This blog post will focus on the tests that have been offered for the coronavirus pandemia in order to evaluate individually and in geolocations how the virus is spreading. I am writing this post since most people do not really understand how these tests work, their differences, specificity, efficacy and also what means to have a positive and/or negative test depending on the technology used. I would say that 99% of people is “blind” when it comes to information on the tests and how to proceed after receiving a result. Well, since I am a researcher and have been reading a lot about the types of test, I will try to describe the ones in the market in an easy way to understand with no technical jargons. The main problem, like everything related to this coronavirus pandemia is misinformation or lack of it; this is expected since people in general know nothing about virology and the technologies used in research and clinical laboratories. In addition, most governments are not helping at all with confusing guidelines. There are two main ways to detect viral infections: immunoassays and by the PCR technique. Immunoassays are the widespread ones since they are cheaper and need just a droplet of blood or body fluids. PCR which means “Polymerase Chain Reaction” is a classic technique used in molecular biology since the 1990s. It was invented in 1989 and I have been using it since my undergraduate academic studies; this is not new at all. However, the way it is used and the type of it can impact the results. I will start with the immunoassay tests and then discuss PCR. Lastly, I will give my take home message with some guidelines and remarks on how people should proceed.

Immunoassays

Immunoassays have been used in laboratories for a while. I will not discuss the types of tests but how it works. These assays will detect an immune reaction caused by a pathogen, such as the virus, since our immune system generates what we call antibodies against the pathogen and a cellular “memory” against it in some cases.  One of the problems with this coronavirus is that we still do not know how long the immune cells will “remember” the virus and generate a better response in a second infection (the base to develop an efficient vaccine). This is still open to discussion. There are several ways to do immunoassays, but the best way is to detect indirectly the presence of these antibodies. Most antibodies are created against proteins in the outside part of the viruses. Thus, this type of test is indirect and will detect a response against the virus. Here that the problem happens. Most tests are binary: yes or no for the presence of antibodies against that specific virus (in this case the coronavirus). Just to make sure people understand: these tests are not measuring the virus, but a body response to it which will vary individually. The main problems that can happen are what we call false positives and false negatives. False positives happen when even without coronavirus infection you have a positive test. The main explanation for this is a cross-reaction with other viruses that the person was infected in the past that are very similar to the current virus. Another important point is that immunoassays will only detect the reaction of the body to the virus after the infection when the body was able to create antibodies after getting in contact with the virus. So, if you do these tests early in the timeline of the infection you can get what we call false negative. Finally, the pros to these tests is that they are fast, cheap and need just a few people and reagents. These are the ones that most people are doing now globally.

PCR and qPCR

The basic steps of the PCR test start with sticking a long swab far into a person’s nose (body fluid) or getting the person’s blood. To clean up the starting material, most test protocols then call for performing an assay that extracts out just the genetic material, clearing away all the debris and inconsequential bits. This requires time and specific reagents, which can be in short supply. PCR, like I wrote before, is not a new technology. However, in this case PCR will measure directly the presence of the viral particles (the nucleic acids or genetic material of the coronavirus) in the blood and/or body fluids. Thus, this test is mainly indicated during the infection period timeline since it will measure directly if the viral particles are circulating in the body. If you do the PCR test before the infection or after it, most likely it will be a negative test. The “upgrade” so to speak of the PCR is the qPCR or quantitative PCR, which can measure the number of viral particles per volume of blood and body fluid. For example, this is the test used to detect and to administer HIV viral infections in AIDS patients. That is the “state of the art” method indicated to detect the virus, even in small amounts. In this case a false negative will be very unlikely since it is designed for that specific virus. False positives could happen if the PCR test was badly designed and gets the genetic material of other viral particles infecting the person. These types of test have lots of pros since they are very specific; false positives and false negatives will be almost impossible. The cons are mainly the time it takes to get a result (generally days to a week), it is laborious, involves more people, reagents and it is expensive to be used for big populations. Moreover, most health insurance companies probably will not cover it, especially in the US. Recently, new technologies based in PCR were improved to decrease the costs, increase the specificity and efficacy making it more accessible (see this article for more information).

Take home message

The main message for the readers of this post is that there is no test that is 100% efficient and reliable, however as shown above in a very clear way qPCR is the best test if you are looking for a reliable result. However, be careful, the PCR tests should be used during the timeline of the viral infection since it will measure the viral particles directly. On the other hand, the immunoassays (there are several fast tests based in immunoassays) will measure indirectly the response of the body to the infection. Thus, these tests would be indicated maybe in the end of the timeline of the infection and after some time to see how long we can detect antibodies against the virus. All this information is very complex to understand but I believe these simple tips I am giving here are important to the general population and even governments to make decisions. Last, but not least, independent on the test you did or will do please do it at least 3 times, especially the immunoassays. For the PCR if you got a positive test it means you have an infection by the coronavirus at that moment. Then protect yourself and others and stay alert to symptoms. The tips I am giving here could be helpful so you won’t be confused by all this deluge of information (most times “fake news”) about tests and their results. Be aware and good luck – to all of us. We are in this together.

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