There are three types of Covid-19 tests:
- Antibody, and
- Antigen Test
But how do they work? And what’s the difference? We’ve heard sort of test, test, and test. What does it mean? What are we testing?
Covid-19 is a disease caused by the SARS-CoV-2 virus, which stands for Severe Acute Respiratory Syndrome Coronavirus 2. It’s related to the almost 50 other coronavirus species. And right now there are over 630 SARS-CoV-2 tests commercially available or in the development phase.
Types of Covid-19 Tests
Among them, molecular tests are the gold standard for Covid-19 testing and are the ones you’ve probably been hearing about. They’re both the most reliable and the kind that was first developed. They involve looking for genetic material from the virus itself.
You need to get some of the viruses and some cells. And that’s done by putting a swap right to the back of somebody’s nose and then taking a scrape. Then scientists take that sample and run it through a process called amplification.
If SARS-CoV-2 is present in the sample, it’s not enough to accurately study. So this step copies the virus’s genetic material over and over until there are millions of times more of it and it can be conclusively identified.
The technique most tests used to do that amplification is called a polymerase chain reaction, or PCR, which has been around since 1985. So it’s not a new technique, but to do it with a new type of virus, you need that new virus’s genetic sequence.
And on January 12, China sequenced SARS-CoV-2 and released that data publicly, which meant that scientists had all they needed to make a test for it.
As soon as you know the viral RNA you can develop a test for it. So the first plus is you can develop the test very quickly, almost overnight.
And that happened with SARS-CoV-2. Tests were developed within days of the virus’s sequencing in January.
The question that I think everybody has in their mind is if it’s that easy to develop a molecular test, why are we still talking about inadequate testing?
The development of the tests is just one part of it. The whole system that needs to be in place to be able to receive these tests, use them and so on, is a much larger issue that goes beyond just the actual physical test. So even though every country and leaders of every country have promised volumes of tests and all these things, often they’re looking at it from a perspective of, oh I have access to XYZ manufacturer and, you know, so many tests and so on. But it takes a lot more than just the actual test.
In the United States, there still working to catch up when it comes to getting sufficient tests out there.
But hundreds of these kinds of tests exist. Some of the biggest producers include companies like Roche, Thermo Fisher, LabCorp, and Abbott, as well as the CDC.
If you think you have Covid-19 right now and you have symptoms, you should take the molecular test. And if you’re in the symptomatic stage you should certainly have a virus that’s enough there to detect. And there are also genetic tests that use this same basic process but in a miniaturized form.
What we’re seeing now is some extensions to that kind of test, which is taking all of the machinery that you would normally use in a lab and kind of using a miniaturized version so that instead of in a lab where we can look at thousands of samples at a time, it’s doing it just on small numbers of samples, maybe even one at a time.
One such rapid test that has received significant attention is a SARS-CoV-2 test made by Abbott to work with the company’s existing ID NOW system, which was already being used to test for other infectious diseases.
ID NOW is set up for point of care right at the site of the patient. That instrument is designed to use, for example, a nasal swab or oral swab and then directly put the swab into the instrument and perform the test.
It’s meant to be used at urgent care clinics, physicians’ office labs, emergency departments, and retail settings; and tests one sample at a time in five to 13 minutes. This is great if you’re one person needing results quickly, but much less efficient if you have a large group of people who all need to be tested.
And there are a couple of studies that have yet to be peer-reviewed but suggest ID NOW’s accuracy may be as low as 48%, something that Abbott disputes. The more standard lab-based counterpart to Abbott’s ID NOW system is the company’s m2000 Real-Time system.
A laboratory instrument, you can process many more samples. For an m2000 platform, run at optimal efficiency for 24 hours, you can analyze 470 specimens. So, much higher throughput.
So it’s not like one size fits all. And just because there’s one test that seems on the surface of it that they are going to solve every problem, they’re not.
The other kind of test that you’ve likely heard about is an antibody test. When a harmful virus is introduced into your body, your body reacts. Studying that reaction is another way to detect SARS-CoV-2. Symptoms or not, if your body has been fighting the virus, there should be evidence of that in the form of antibodies. This kind of test uses your blood instead of a swab from your throat.
So this is not directly measuring the presence of the virus in your nose or nasal cavity. What you’re doing is measuring through a finger prick or a blood draw, you’re trying to say is an antibody response present in a particular individual?
Two types of antibodies are produced after an infection. One, IgM, shows up in about a week and then tapers off. And the second, IgG, shows up after about two weeks and sticks around for much longer. This adds to the difficulty in making a consistently accurate antibody test.
You could be either too early in the infection for the IgM to pick up or you could be in the bit between your IgM and your IgG being detected. Or you could be somebody who isn’t making those particular antibodies and won’t be detected at all.
We don’t know enough of this particular virus and genetics and so on whether it lasts a month, six months, a year, two years, we don’t know that.
All of this means that it’s tricky to develop these tests, especially during a pandemic when they’re needed much more quickly than usual.
In the case of the IgG test, this was an unbelievably compressed development cycle. Under normal circumstances our development cycles are years. In this case, the IgG test was developed in a span of about 30 days. So how do you get a supply chain, determine methods to be able to scale and ramp to go to millions of tests? Because we could have the best test in the world and if we can’t produce it, it isn’t getting the job done.
Abbott says it will ship nearly 30 million tests this month and will have the capacity to ship 60 million in June. We also don’t yet know what the consequences of having SARS-CoV-2 antibodies are. It could mean a resistance or immunity to Covid-19, or it could mean neither.
We know from other coronaviruses that it is very likely that as soon as you have gone through an infection, you will also acquire immunity. But this still nevertheless has to be proven over time.
The antibody tests become much more useful on a population level later to find out how many people were likely infected in the first place. They’re not a great way of going, you as an individual are okay to go back to work or you’re protected or something, because that’s just based on stuff we just don’t even know about yet.
And the FDA recently tightened its guidelines for companies wanting to sell antibody tests after initially allowing them to be sold without evidence they worked. Ongoing research into these early tests, which has not yet been peer-reviewed, has shown a troubling lack of accuracy. But there are more than 120 antibody tests already on the market.
One of them is a pinprick test that can be taken and results received in about 15 minutes without an instrument. Having said that, it is not approved by the FDA, per say.
But we also know that some people don’t make any antibodies. People can test negative so they don’t have antibodies, but they could still be infectious. Spain and the UK in particular, were going to roll out millions of these tests and they’ve ended up having to abandon all of them.
Finally, there are antigen tests. The sample comes from a throat swab, just like the genetic test. But you’re looking for evidence of the virus via a completely different method. A rapid strep test that you would do in a doctor’s office is an example of an antigen test.
As the virus secretes proteins called antigens, you can detect those also.
While the end product could potentially be very simple, developing them comes with obstacles you don’t have when developing a more straightforward genetic test.
First, you need to have access to the right patient population, get the antigens. You need to then have a way of immunizing some other animal to develop antibodies, because the antibody ultimately is what goes on the plastic that you have and what you’ll see even today is that there are very few true antigen-based tests that are available for Covid-19.
The advantage molecular has is that you can amplify the genome. So in any of these molecular tests, we might go from a few virus particles to billions of virus particles after the amplification step. Antigen assays don’t have that advantage.
But if they can be worked out, antigen tests could be one important tool among many in the fight against Covid-19. Just last week, the FDA granted emergency authorization to Quidel Corporation for a new antigen test that only takes about 15 minutes.
This test tests for antigens that the virus produces in the blood. So it has antibodies effectively on a stick and you swab someone with that stick. And then you put it in a little machine called a Sofia that’s about a thousand dollars. The test itself probably is going to cost about five dollars. Now, the problem with it is it’s only about 85% sensitive. So that means if you have 100 patients with COVID come into your office, you’re only going to catch 85 of them with this test.
Testing the Tests
The biggest obstacle in developing any of these tests has been how quickly it had to be done. So while there are hundreds of tests already available, it’s unclear how well many of them work. The Foundation for Innovative New Diagnostics, or FIND, is a global nonprofit based in Geneva working to bring clarity to exactly that.
What we set out to do was set up a platform where we can uniformly address the tests and see how well do they actually perform compared to each other and also in terms of what the needs are. That way we can inform the countries when they look for different tests and how good they are, essentially.
FIND currently lists over 600 SARS-CoV-2 tests as commercially available or in development. But not all of those are being made by established companies like Abbott. And new tests are coming out all the time, including at-home tests that you would then send off to a lab like Quest Diagnostics’ recently announced at home antibody test. LabCorp also has an at-home test.
According to the CEO of LabCorp, Adam Schechter, “we announced expanding access to our Pixel at-home kit. We have over 200,000 kits available and we announced that it’s available for anybody that meets the CDC criteria.”
Conclusion: So what’s the next?
This is truly an unprecedented situation in terms of how rapidly the virus expanded. One of the challenges is that we were in the midst of the outbreak and then confronted with the reality that one needs to develop tests. It’s one thing to develop a test. It’s another to scale it to the quantities that we’re talking about. I mean, we’re talking millions and millions of tests.
Early on, the U.S. focused on using new tests developed by the CDC that were revealed to be faulty instead of using tests already established elsewhere.
It’s completely unclear to me why the U.S. screwed up the test approach because the test was available. There was something that could have been used and was used by lots of different countries. So it’s unclear why the U.S. in particular took a different route to try and develop something of their own. Because everyone else had something that worked and was using it.
Along with shortages of actual tests, there have been shortages of materials like swabs and protective gear that we need to safely perform them.
We’ve just chronically had problems getting tests out there to people. And it’s been a real bungling of this response.
But it wasn’t like that everywhere.
The development of a test and the rolling out that test has not been a disaster in many, many countries. They took the tests that had been developed and they got it working up in their diagnostic labs and their academic labs to the level that they needed to use to get Covid-19 under control in their country. Some countries decided not to take that route for whatever reason, but that meant that they lost weeks compared to those countries that brought them in really fast. And what we’re seeing with Covid-19 is that every day counts.
On May 7, the head of the National Institutes of Health said that the U.S. will work with companies to make millions of accurate and easy to use coronavirus tests by the end of the summer, a timeline that NIH Director Francis Collins said was beyond what most experts think will be possible. Nonetheless, as time passes, testing will remain critical for knowing not only who is currently infected, but also who has been previously infected.
It’s only when there are not enough people left to infect that viruses will start to disappear. And so the point, I guess, is that for this particular virus, that’s probably such a large number of people that this is going to continue to go on for some time. So even those countries that look like they are peaking now may well end up seeing more waves of the virus if there are still more susceptible people around.
These antibody tests will give us critical, it’ll be critical in determining the country’s approach to reopening markets and safely returning employees to work.