Basics of COVID-19 Testing

 

In the historic COVID-19 pandemic of 2020, the disease has affected all aspects of life, including how volleyball is practiced and played. These posts are meant to be explanatory about the basics of coronavirus biology and public health, and seeing the big picture before applying it to learning volleyball.

As with any kind of testing, we do it learn something that we didn’t know before. Many different kinds of tests exist in the context of COVID-19, and these often get lumped together during discussions, and can lead to confusion.

So, let’s understand the nature of the virus and infection, and why we need a test.

COVID-19 is a vexing disease because it has such a wide range of symptoms and a distressingly high rate of mortality – but the wrinkle in most any infectious disease is the transmission from person to person. A COVID-19 infection is contagious long before symptoms appear (and in fact, some people may not develop symptoms at all). Different testing technologies are being developed to try to detect the presence and production rate of viable virus from infected people, and it’s a very challenging problem. Ideally, we want a strong predictive power in the test – we want to know if a person is going to be contagious as early as possible. Likewise, we also want strong specificity – we want to be sure if someone is not going to be infectious.

So, let’s understand the problem.

We would like to detect the virus production early, which means finding vanishingly tiny amounts of it, but also being assured that if you didn’t see anything, that you weren’t too early in the infection period. Thus, developing a test is no small feat, while the clock is ticking, and needing to deploy it by the millions.

Believe it or not, all animals (humans included) are a galaxy of viruses, both in amount and diversity. A coronavirus is basically a piece of genetic material (RNA in this case – which will be worth an entire discussion on its own) covered by a shell that gives it a crown-like appearance under an electron microscope. The shell has components that seek out a compatible cell, latch onto it, and shuttle the genetic material into the cell. There are various coronaviruses that circulate in different animal species, but in this particular pandemic coronavirus (SARS-COV-2), the target cells seem to be the ones in the respiratory system. Once inside a host cell, the genetic material “takes over” the biological machinery to produce even more virus, a process that can result in the death of the cell. As the virus progeny are released from this infected cell, it can spread to infect the adjacent cells, in a logarithmic chain reaction, and eventually the infected person sheds virus outside – which is the basis of transmission. But not all viruses cause disease in this manner. How we tell is based on the information encoded in the genetic material.

Coronaviruses have very large genomes for viruses – about 30,000 letters. Optimizing the test is not only the sensitivity to detect it with as little starting material as possible, but also to correctly identify the virus. The main technique right now is an RT-PCR test, which uses a standardized method to detect a couple of small segments of the genome. This is more complicated than it sounds, because the results of one lab need to be directly comparable to the results of another lab, which may have different budgets and available equipment. And different centers around the world actually chose different segments to monitor, which is a product of the rush to get it out there. Note, however, that this particular test cannot tell the difference between infectious virus and just the genetic material fragments (which cannot infect cells). But it’s a reasonable marker for infectious material if it’s used on the proper samples.

Proper sampling is key, and need to be discussed in the context of testing. For example, genetic material can be recovered from swabbing surfaces where sick patients have been in contact with long after they’ve left (the basis for the reports that virus can survive on surfaces for 2 weeks or so), but this is probably not due to active virus. But if we are testing nasopharyngeal swabs – the Qtips that are stuck up the nose and feel like scraping the base of the brain – then it’s likely that a positive RT-PCR result is because of infectious virus. Detection technologies are still be refined, as sampling, processing and RT-PCR can be laborious, leading to the long lead times to getting results.

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