Alternative COVID-19 Testing Strategies

Expert Profile

Section 1: The Current Treatment Landscape

1.1. What are the current testing practices we have in place?

The key to understanding this is, that testing is one tool of what should be a much broader containment strategy or public health strategy for addressing the COVID pandemic. So, the testing strategy or the testing system, to the extent that it exists, is divided up between clinical uses and then public health uses, and there are some subcategories there.

The focus is on diagnostic testing, which means identifying people who are currently infected and carrying the virus. Those are the tests that are used to determine if someone is currently infected with the virus, because diagnostically, it is looking to identify the presence of the virus in a clinical specimen.

The two main categories of testing are; genetic testing, which looks for specific sequences in the virus and is a somewhat more complex method of diagnosis because it requires breaking up the virus and looking for the genetic sequences. The other is antigen testing, which looks at proteins that are contained within the virus, is rather than look at the genes in the virus.

This is a type of diagnostic test that can be done more quickly, and in theory can be done at the point of care essentially, without having to send a specimen to the laboratory and have it run on a machine in a laboratory setting.

1.2. Why do we have this testing system?

The genetic and the antigen tests could both be used for public health purposes. For clinical purposes, for someone who is showing symptoms, for someone who presents to the healthcare system, you want to use the genetic testing, the PCR type diagnostic testing, because that test is much more sensitive and specific. Obviously, it’s critical to know if someone who’s presenting for healthcare is, or is not infected with COVID. For public health purposes, you have somewhat more latitude.

For a clinical purpose, you’re dealing with a single patient, and it’s critical then to know the diagnosis in that individual patient; because it impacts not only the care of that patient, how that patient’s going to be treated, but it’s critical for understanding the risk to anyone in the healthcare system that, that individual may pose for transmission.

For public health purposes, you’re dealing with a very large population. You may be dealing with anywhere from 30 to 300 to 3000, you’re dealing with large populations. In that sense, you have somewhat more latitude because you’re trying to control transmission or understand the epidemiology of the epidemic. You have in this sense of latitude, that the criticality of each individual diagnosis is less important than your ability to get the big picture for that population.
The concern or the criticism has been that the public health system has been relying on the genetic testing, on the PCR. And the difficulties have been supply chain problems; with being able to get the supplies to do the test, the delays in getting the results back of the test, which could run anywhere from 3 – 14 days.

The criticism has been that, it is inadequate for testing large populations thus it has prompted this interest in antigen testing, particularly the so-called point-of-care testing, which can be done by report in 15 minutes. The FDA has been slow to approve those tests for diagnostic use other than perhaps for research purposes, because those tests are not as accurate. In particular, they’re not as sensitive, and so, depending on the report that you read, those tests could miss anywhere from 30 – 50% of all the patients who actually are infected with the virus. Just to clarify that in saying that the FDA has been slow, it’s not necessarily a criticism of the FDA. It’s indicating that the standards that are being used for approval, these tests are not meeting those standards.

1.2.1. Do you think these standards will change?

The larger problem that is coloring all of this, is the absence of a coherent public health strategy in the United States at the very least for containing the epidemic. So the determination of which test to use, when you use it, and the determination even of approving a test for a certain type of use, would be dependent on where the test fits in to this overall strategy.

If you don’t have a strategy, if you don’t have a coherent national strategy, you can’t then determine how best to use certain tests. Therefore, you can’t determine when the performance characteristics of a test would allow it to be used for a specific circumstance as part of that larger strategy. You have to use the standards that exist, simply because in the absence of any larger coherent strategy, you can’t tweak those standards for a specific purpose.

1.3. What is the value of this testing approach?

The genetic tests are very accurate. The debate in the press, is very pro of this broader antigen strategy. We’re in this situation because we have existing, a very accurate test; and because no one understands what the broader strategy is, that’s all you’re left with. We will always default to accuracy, and we will always default toward a better diagnostic test for the individual patient, because that’s our orientation, which is to look at how to do the best for the individual patient. A public health approach requires a different type of mindset, and because we haven’t been oriented to that, we can’t alter our approach.

The PCR test tells you the virus is either present in the body, or it’s not present in the body. The criticism being, that it may detect viral pieces of the viral DNA, excuse me, the viral RNA, even in patients who are no longer infectious, that’s been one of the criticisms, but it is accurate.

1.4. What are its drawbacks?

The difficulty is having very high throughput, given the complexity of these tests. It requires a number of steps; obtaining the sample, proper handling of the sample, sending the sample to a laboratory that has the appropriate equipment, and then processing the sample using a variety of chemicals and reagents, and then putting through a machine that it was a fairly expensive piece of equipment. So, the criticism is that doing a high throughput with that kind of testing can be upended or impeded by problems anywhere along that chain.

If you don’t have enough supplies to either do the test, if you don’t have the logistics to send the samples in, if you don’t have the supplies to run the test in the laboratory, if you don’t have enough personnel, trained personnel to run it, the machines can only process so many samples an hour or a day. So anywhere along that line, anywhere along that chain, you can be impeded. And that has been the problem all along, because there have been problems at each individual point in that chain.

Supplies, personnel, time, the machines, all of that has posed problems. That’s been the major problem, and that’s why the argument has been, “We can’t get enough tests done, and even when we get the test done, the turnaround time is so long that they’re essentially useless.”

1.4.1. Has the supply chain improved? Can it meet the demand?

Yes, the supply chain has improved. It has been somewhat difficult to get consistent data on how much it’s been improved, because again, in the absence of a coherent national strategy, each state is doing something different. Each health department is doing something different, everyone is scrambling for supplies. There have been a number of entrepreneurial groups springing up doing these tests through drive-ins. There’s no centralization of supply management, there’s no centralization of logistics, there’s no centralization of reporting. All of which would have been possible early on.

It’s still not impossible, but obviously with the growth of all these entrepreneurial and disconnected ways of doing the test, it’s much more difficult to get a handle on.

Section 2: Alternative Testing Strategies

2.1. What are some of the different testing options?

There has been this drum beat about we need more testing, we need several thousand tests a day, we need several tens of thousands of tests a day, we need millions of tests a week. It has devolved at times into testing for the sake of testing. Again, testing is a tool, and so its relevance and its significance is as part of a larger strategy that tells you which test to use, on which populations, under which circumstances.

As part of the broader question of preventive measures, whether that’s masks and physical distancing, whether it’s the identification, contact tracing, isolation and quarantine and all of these sorts of things. So testing It itself is only a tool, and we’ve been approaching the analogy of bringing a whole bunch of hammers and lumber to a construction site, but having no plans for building the house.

So it would be great to have all this testing, but it’s the same as having the tools and the lumber and having absolutely no architectural drawings.

Having said that, there are a number of different ways of using these tests. One certainly would be to ramp up the PCR testing, that could have been done all along. It could still be done if supplies were made more readily available, the distribution of those supplies and someone was monitoring in a centralized way, how to maximize the utility of those tests.

The antigen tests, even with their limited sensitivity, meaning that they could miss 30 – 50% of the true positives. Potentially there is value for using those tests on a large population basis, but the key would be where are you using them and how are you managing the other aspects of your containment strategy? For example, the big issue in the USA has been opening colleges and universities, as well as the schools for children in kindergarten through 12th grade in the United States primary and secondary education for children.

The proposals have included doing the antigen tests. People are coming up with schemes that test them every day, test them at the point of contact, twice a week, three times a week, all these different sorts of approaches. If you’re combining that with the masks and some type of physical distancing or what people are calling a POD approach in which they’re keeping smaller groups of children physically separated so that if you have a case, it’s contained within a smaller group. To do the PCR testing on a school with 600 or 800 kids, would be extremely problematic.

If you could get the antigen tests up and running and you were combining it with these other measures, in theory you could achieve some level of containment, even if you’re missing some number of cases. And the reason for that is because you’re reducing spread through these other measures, and by containing any clusters into these PODS or smaller groupings.

The concept there is, it goes to this issue of the so-called R-naught or the R0, which is a concept I’m not in love with, that tries to describe how the virus spreads within a population and this question of clustering. If each person who is infected infects one other person, that’s an R of one. If you get it below that, you’re still having a low level of transmission, but you’re not having these outbreaks or an epidemic spread. As soon as you get to the point where each infected person is infecting one and a half, or two, or three people, that’s where you get these so-called super spreader events.

That’s where you get these clusters or this explosive spread within a community. Consequently, what the antigen tests could do, if you were combining it with these other measures is to drive this R number, the R-naught, to the level where you would still have spread, but it wouldn’t become explosive.

It wouldn’t become an outbreak or an epidemic and that would be your goal. You wouldn’t eliminate spread and you wouldn’t eliminate cases, but it would be controllable and containable and that is the point which you could use your contact tracing and isolation strategy to further mitigate spread. So that would be the value.

2.2. How can more PCR tests be supplied? How feasible is it?

Early on, people were talking about using the Defense Production Act in the United States. This is where the federal government essentially takes over or mandates the production and the management of the supply chain. It would also require centralized coordination of setting up testing sites, setting up centralized reporting. Conceptually, the idea was that the federal government has the authority to mandate private industry manufacturing supplies.

Whether that would have worked in practice, we don’t know because it wasn’t tried, but theoretically, with a strong centralized operations and logistics capacity, at least in theory, that could have ramped up. It turned out that, that was done, we believe to some extent with producing these ventilators, which in the end turned out perhaps not to be necessary, but people didn’t know that at the time. In theory, that could have been done, but it was left to, the free market approach so we don’t know if the other would have succeeded.

We do know that the approach that was taken for all intents and purposes, didn’t succeed.

2.3. Are there any key learning points we can gain from other nations?

This has become very controversial, and anytime anyone in the United States says, “Well, in East Asia they’ve done this or in parts of Western Europe they’ve done that.” Someone else comes back and says, “Well, now look, they’re having spikes here, or they’re having spikes there.”

No one likes to compare themselves to other countries, but certainly in South Korea, in Taiwan, in Germany, in other countries, what’s happening in these places, particularly for their success early on, and what appears to be their ability to address these spikes and these clusters as they come up, is this more comprehensive strategy.

It’s much closer to universal mask wearing. It’s the ability to track people using cell phones. It’s the ability to do much more accurate contact tracing and isolation. Yes, they were using testing, but they were able to put those tests to use as part of the national comprehensive coherent strategy to control epidemic spread. So whatever testing strategy they used, and it often was the PCR and genetic testing, they didn’t need to do as much. They were able to track it much more closely, and they were able to use the testing as part of a strategy where they were able to contain the epidemic. That’s the difference, that they used testing as a tool, not as an end in itself.

Within the United States, the clinical rule that one is always taught in medical school, one of the first things you’re taught is, “Don’t order a test unless you know exactly how you’re going to use it.” And it’s very clear that tests are being done here very often without a plan for how to use the result of the test.

2.4. What is the future outlook for testing strategies in the USA?

Without getting into things that are overtly controversial, we are going to be having an election in the United States. Either those who are currently in charge will continue to be in charge; or we’ll have a different group of people in charge starting shortly after the first of the year. I think the election will be very determinative in terms of the overall approach, clearly if you change all of your leadership, something is going to change. Everything will be determined by who’s making the decisions, how much funding there is for those decisions to carry them out, and how the population at large reacts.

The last key point here about public health is, in all these debates and all these discussions about what to do about the virus, the key point is that we know a tremendous amount about the virus now. We’ve learned a great deal. We’ll continue to do research, but we know as much about the virus right now as we need to, to control it; and the virus is not changing.

What’s uncontrolled is human behavior. It’s the way human beings are behaving, that leads to these differences between India, Brazil, and the United States, or Taiwan, Germany, or Sweden, or South Korea. It’s what the human beings are doing. The virus is the same everywhere, but the way human beings are doing it from the way the population behaves, the way the leaders of those countries behave, that’s what’s determining the end point of this epidemic. It’s not the virus, it’s the way that people are handling it.