Viral Testing: Antigens, Antibodies, and PCR
There’s a lot of misinformation still floating around about the COVID pandemic, and while I don’t have the energy in my current state to keep doing updates to correct all the absurd claims going around, I thought maybe a little update diving into how we test for viruses in the lab will go a long way in helping people navigate some of the nonsense out there. I realize people lack a lot of the most basic medical knowledge to discern truth from imagination, so hopefully with this little piece you’ll understand a little more about what goes into the tests we do in the lab, and what that tells us about someone’s condition.
There are three main areas of testing that are relevant to this topic: antigen testing, antibody testing, and PCR testing. To understand what they each look at, it helps to have a little picture of a virus.
You can image a virus as a little piece of DNA inside a protein/lipid shell. Some viruses use RNA instead of DNA, but the end result is the same; it’s the virus’ genetic material enclosed in a little nanoparticle. A virus isn’t capable of replicating on its own; the only way it can reproduce itself is by infecting a living cell and using that cell’s ribosomes and polymerases to replicate its genes and proteins. The way it infects a cell is by using those proteins around the outside shell of the virus. One of those proteins will have a way to bind to a protein on the outside of the cell it wants to infect, and using that connection it will absorb into the cell and start replicating itself, eventually killing the cell and release more virus to infect more cells.
That brings us to the first way to test for a viral infection: antigen testing. Antigens are what we call those little proteins around the outside of the virus, and we have specific tests in the lab for different viruses that will detect them either in blood or saliva or other specimen samples. Since each virus has its own unique proteins around the outside, its easy to distinguish one virus from another. Additionally, these tests are very quick; only taking a matter of minutes to complete. The downside is they take a while to develop, because they work by creating an artificial antibody to that specific part of the virus and incorporating that antibody into an assay that produces a signal in response to the presence of the virus. Different antigen tests developed by different manufacturers will have different sensitivities and interferences, because each of the antibodies developed will be slightly different, although for the most part any good manufacturer is going to develop a test with sufficient accuracy for the lab to use.
Alternatively, you can test for the presence of the genetic material of the virus, which is PCR testing (also called “molecular testing” in the lab). The nice thing about PCR testing is you can develop the test very quickly; all you need to know is the genomic sequence of the virus and you can identify a portion of the genome that is unique to that particular virus. Then you just build two short genetic strands that match up to either side of that segment, package them together with a polymerase enzyme, and you can test a sample for the virus. Total it takes probably less than a week to develop the test. It also offers the benefit of being more sensitive than an antigen test, able to detect virus present at much lower levels. The downside is it’s a little more expensive and takes a little longer to run than an antigen test. In order to test for the genetic material, you need to collect the sample properly, break open the virus to release the genetic material inside, then go through dozens of cycles of amplifying the desired genetic sequence. Depending on the analyzer you’re using, this can take hours per sample, which isn’t ideal in an emergency care setting when you want your answer in 10–15 minutes. There are faster versions, but generally there’s always going to be a speed vs sensitivity tradeoff.
Now, both of these tests are looking for active presence of the virus in the person at the moment, but there is a catch. Just because you identify the presence of the virus doesn’t mean that virus is active and contagious. If your body has successfully fought off the virus, you may still detect the presence of fragments of the virus in your sample. One of the things we noticed early on in COVID testing was you could detect the presence of virus in someone using PCR for weeks after their infection, but you really couldn’t isolate functional, infectious virus from them more than a week after they initially presented with symptoms. We can test to see if the virus is functional by actually putting it in petri dish with cells and seeing if the cells start dying off. It’s the perfect test for determining if a person is contagious, but unfortunately It’s too involved to effective perform in the healthcare setting, and is primarily done for research purposes.
This is an important point I want to make here, because I feel like a lot of people are equating a positive test result with an infectious individual, and that isn’t necessarily the case. Rapid antigen testing will probably correlate a little better with whether a person is contagious, since those tests tend to be a little more specific to active, infectious virus, but a PCR test can turn up positive even if all that’s left in a person’s throat is broken, inactivated virus. All you need are some segments of RNA present; it doesn’t matter whether or not it’s in a form that can infect someone. Given the early studies we did on this kind of testing, it’s very likely that a lot of these positive PCR test results coming from vaccinated people really don’t represent an infectious person, but rather someone that has already fought off the virus and just has broken pieces of the virus left in them.
That brings us to antibody testing, also called serology testing. Antibodies are produced by the B cells of our immune system, and are only one aspect of how our immune system fights off disease. They are, however, the easiest thing to test for, and do a good job of representing our bodies ability to fight off a specific disease. Every time our body is exposed to a new disease, our immune system builds a specific defense against that disease in the form of T cells and B cells, a process that usually takes a few weeks to fully complete, so antibodies will be detectible after the infection or vaccination has run its course. This is what we refer to as the adaptive branch of the immune system. Antibodies will bind to the virus and both label it for destruction and physically prevent the virus from infecting cells. By testing for the antibodies produced by the B cells that target a particular virus, we can determine whether or not the person has been previously exposed to it either by having been infected or vaccinated. For some diseases we even test for the levels of antibodies present, called an antibody titer, which sometimes indicates the level of protection a person has from reinfection. As long as someone’s antibodies for a particular disease are above a certain titer, we say that person has immunity to the disease. This isn’t true for all viruses; for instance, no matter what your antibody levels are, the immune system isn’t capable of fighting off viruses like HIV or Hepatitis-C, but we do have determined target titer levels for a wide range of viruses that indicate sufficient immunity.
While we don’t technically know what that immunity titer is for COVID-19 quite yet, there is still some benefit in testing for antibodies. Doing a wide population test for antibodies will give you an idea of the percentage of the population that has been exposed to the virus already, either through infection or vaccination, and an individual can use the test to determine how long their immunity is lasting. It’s something I wish we were promoting and doing a little more of, because the more data we collect on antibody levels the better overall understanding we’ll have on long term immunity. It would also help us dispel some of these rumors about antibody levels dropping, because the reality is we see lasting immunity response in the vast, vast majority of people. I’ve had a chance to talk to doctors I’m connect with to get a feel for what kind of COVID patients they’re seeing, and they all tell me that the only problematic cases they have are unvaccinated, previously unexposed patients. Our immune system is clearly capable of fighting off this virus effectively, even the different variants, as long as it has a head start.
And those are the three main areas of testing when it comes to virology. Antigen tests will typically be the most representative of current infection, PCR testing will be a little more sensitive but also test positive for longer after the infection has run its course, and antibody testing will give you information on your body’s immune strength against a particular virus in question.
Now, a while ago I saw people jump on this CDC announcement saying they wanted our labs to start switching to analyzers that tested for multiple viruses at once, rather than using dedicated analyzers just for COVID. For some reason people interpreted that as meaning that our current testing couldn’t distinguish between different viruses. That is a ridiculous idea. Every time a hospital brings a new test online, we test it for accuracy and interferences. A lab would never use a test that couldn’t distinguish between viruses; antigen, PCR, antibody testing…those are all specific for specific viruses. Viruses would have to be almost identical to trigger a positive result.
What the CDC meant is they wanted us to stop using analyzers that were only testing for positive COVID cases, since we’re expecting diseases like flu and the common cold to start being more common again. We have analyzers that test for different viruses all at the same time, rather than just one after the other, and our labs are starting to rely on those more. I think dedicated COVID analyzers will still have a role to play in the public health setting, but as more and more people become immune to COVID they’ll probably be less useful than analyzers that are more versatile.
With that out of the way, I wanted to spend a little time addressing some of the other goofy things I’ve seen floating around. I don’t have the time to cover all of them or do my usual deep dive into the literature, but hopefully this can help you be better equipped to deal with some of the nonsense.
First of all, I saw this ridiculous meme floating around show mice talking to each other, saying the vaccines were being tested on the humans before them, trying to make the claim that these vaccines are still “experimental”. That’s completely absurd. These vaccines were very much tested for safety and efficacy in animals before they were tested in humans, and RNA vaccines were first tested in mice back in the 90s for viruses like influenza. 30 years ago they were experimental, but at some point you go from being experimental to having proven safety and clinical efficacy. Once something is done with phase three clinical trials and tested in hundreds of millions of people, they really are no longer experimental.
There have been goofy claims of toxicity of the spike protein produced by the RNA vaccines, I saw some nonsense about the vaccines somehow being magnetic, and all kinds of other things. In reality, if the spike proteins produced were actually triggering a toxic vascular inflammatory response, you’d see that immediately in just about everyone. It’s extremely noticeable. The only side effects from the vaccine that we’ve caught after hundreds of millions of doses are complications that you’re roughly 1000 times more likely to see in a COVID infection anyway, so no matter how you analyze the data it’s clear the benefits far outweigh the risks for the vast majority of the population. And seriously…magnetic? We’re storing these things in metal freezers, using metal needles to administer them…you’d see if they were magnetic.
There’s been a lot of hype over this Dr. Robert Malone guy, who gave himself the self-appointed title of the inventor of the RNA vaccine technology. Just to be clear, there is no single inventor of this technology; I’ve personally seen it presented by a wide range of researchers and labs over the last few decades. My guess is the guy just got jealous that he wasn’t receiving as much recognition as he thought he deserved, and is just trying to throw the technology under the bus. Normally he’s a smart guy, but I’ve seen him mistranslate articles, misrepresent the statistics, and generally mix and match numbers that really don’t go together. You might think it’s strange that a researcher can be that petty, but having worked in research labs for a very long time, and having interacted with a lot of researchers, I can tell you that they can be very petty and arrogant. They’re human just like everyone else, faults and all.
Another absurd claim I’ve seen is that wearing a mask to stop a virus is like using a chain-link fence to stop a mosquito, or that if you smell something through the mask that means it isn’t working. This claim gets a few points wrong. First of all, we use surgical masks in the hospital, in surgery rooms, and they’re very effective in preventing infections acquired during surgery. Every surgeon is wearing them. There have been a few experiments done to test mask effectiveness for preventing the spread of COVID, and they generally point to a roughly 75% reduction in the risk of infecting other when an infected, contagious person is wearing one properly. It isn’t perfect, but when our goal is to prevent a hospital from being overwhelmed with too many patients, it’s good enough.
And the reason they work is simply that we don’t need to filter out individual viral particles. The virus is suspended in respiratory droplets and saliva (which are thousands of times larger), it isn’t free floating, and those respiratory droplets absorb into the mask, trapping them and preventing them from becoming aerosolized. And that’s all we need to reduce the spread by a decent amount. There probably isn’t much of a benefit for a vaccinated person to be wearing one, given the likelihood of them getting infected and infecting others is extremely low; but masks are our easiest, lowest cost mitigation strategy, and sometimes it’s easier to tell everyone to wear a mask than to trust that unvaccinated people will be honest about wearing them. Given a virus that can put around 5% of the people it infects into the hospital, even if just 20 or 30% of you population is vulnerable, that’s still enough to overwhelm a hospital if you have a large event with hundreds of exposures.
Another weird fight going on is around ivermectin. For the life of me, I cannot figure out while studying potential treatments has become so controversial and politicized. There are a good number of studies published that suggest it can be a very effective treatment, although none of them are a clear home run; each study has its own flaws and issues. Meanwhile, there are a couple of high powered clinical trials in the works for it, which will hopefully give us a clearer picture of efficacy in the near future. There has been a significant uptick in ivermectin prescriptions being issued, so clearly doctors have started using it off label, and it is being included in standard of care in several countries, including India.
Then you have the media making this out to be some kind of super dangerous medication that is just for animals and has all kinds of side effects. While there are animal forms of the drug, which shouldn’t be taken by humans, this has been widely used in humans for decades. It’s simply not true that this is a dangerous medication to take as long as you are using the right dosage. So let’s wait for the trials to come through; I personally think this has a lot of promise, and I completely understand why doctors would want to use it off label given the data we have at this point.
There’s some much more misinformation that I could address, but I just don’t have the energy for it at the moment. Instead, I want to leave you with a few words from Jesus in Luke 12:22–26
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Then Jesus said to his disciples: “Therefore I tell you, do not worry about your life, what you will eat; or about your body, what you will wear. For life is more than food, and the body more than clothes. Consider the ravens: They do not sow or reap, they have no storeroom or barn; yet God feeds them. And how much more valuable you are than birds! Who of you by worrying can add a single hour to your life? Since you cannot do this very little thing, why do you worry about the rest?
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If there’s one thing the media has been good about over the last year and a half, it’s been driving unnecessary anxiety. Fear about the virus, fear about the economy, fear about treatments, fear about the vaccines…the list goes on and on. But anxiety and fear will get you nowhere. The truth is we don’t know what will happen tomorrow; life can flip on a dime. Going into this last summer, I never could have imagined I’d get another diagnosis of cancer, and it completely changed almost everything in my life in a matter of days. And no matter what plans I make, I don’t know what will happen in the months ahead, so all I can do is choose to be faithful and walk with God in all that I do. We look out for our neighbors, we care for the sick and hurting, and we try to be wise in each of our steps. In the end, that’s what really counts.
