Brad Puffer: Welcome, everyone, to this episode of Field Notes. I'm Brad Puffer on the Medical Office Communications team at Fresenius Medical Care North America and your host for this discussion today. Here, we interview the experts, researchers, physicians, and caregivers who bring experience, compassion, and insight into the work we do every day.

A new mathematical model published in the Network Open Journal of the American Medical Association suggests that pool testing for COVID-19 offers potential advantages over individual testing in certain cases. Through this method, samples from many individuals are grouped together into one diagnostic test. A negative result quickly eliminates everyone in the larger group. Well, this model was developed by a team at the Renal Research Institute, which is the division of Fresenius Medical Care. This group is a mission to improve the outcomes for people living with kidney failure by furthering our understanding of new technology.

Just a few days later after the publication in the Journal in late June, members of the White House Coronavirus Task Force said they were considering this pooling strategy to improve testing capabilities. And finally on July 18, the FDA approved the first authorized test for pooling. So why did the Renal Research Institute develop a model for COVID-19 pool testing? And how else is this important research division helping us better understand ways we can, perhaps, better detect the virus and treat the disease?

Here to answer these questions and explore this topic with me more is one of the co-authors of the study and research director of the Renal Research Institute. Dr. Peter Kotanko has led the Institute for the past decade and previously served as vice chair of the Department of Internal Medicine and Graz, Austria. Dr. Kotanko, thanks for being here, and welcome to Field Notes.

Dr. Peter Kotanko: Thank you for having me.

Brad Puffer: Well, I explain a little bit about what pool testing is, but maybe you can explain further the actual process. How does this work?

Dr. Peter Kotanko: The essence of pool testing is actually known for quite a while. In the 1990s, it was used for hepatitis B and HIV, but these were all various special use cases. Now, how does it actually work? So I'll give you just an example. Say you have 20 people, and you would want to know if they suffer from COVID-19. One way to do this is to collect one sample per person and then test every sample individually. In other words, this group of 20 people will result in 20 tests. Alternative approach that's pool testing is to do the following, to put all these samples into one batch or pool, and then test the pool. Now if the pool test is negative, then within the limits of the test sensitivity and specificity, you can conclude that all these 20 subjects are free of COVID.

Brad Puffer: If you have 20 samples and it's negative, you eliminate 20 people, but what happens if it comes back positive? Now, you don't know which one. How do you deal with that?

Dr. Peter Kotanko: If that pool test comes back positive, then you would test each individual sample. That's the simplest form of pool testing. It's called two-stage pool testing.

Brad Puffer: Do you already have that extra sample in hand?

Dr. Peter Kotanko: Right, so ideally, you would not want to go back to these 20 people, because you have an extra sample set aside in the event that the pool tests positive.

Brad  Puffer: How does that offer advantages? I could see how you would eliminate a lot of people very quickly. Is that the point? Is this really best for large groups of people?

Dr. Peter Kotanko: Yes, so it's really good for a large group of people, where the prevalence of the disease is low. Say if you know based on epidemiology that in the given population, the prevalence is less than 20%, 25%, 30%, then pool testing offers a higher efficacy. If the prevalence goes beyond 30%, then pool testing is not efficient. So what's the prevalence of the disease in the population of interest? And we have some good data around that.

For example in school classes, where there have been, say, one case of one of COVID-19 in the entire school, then you could assume that the prevalence is less than 20% to a30%. This would be a scenario for pool testing or in a nursing home, where one case has been diagnosed, but there are 200, 300, 500 residents. Then again pool testing could be a very, very efficient method.

Brad Puffer: And as we're all looking to see how we might be able to reopen schools in the fall or have some semblance of normal, it seems like pool testing is potentially a way to start addressing this demand in this issue? How exciting was it for you to see just a few weeks after your study was published, the FDA approved the first test for use in pool testing?

Dr. Peter Kotanko: I was just so surprised, I have to say. Pool testing has been around for three decades. In hindsight, it's almost a no brainer to do it. It was used already in some countries like in China, Israel, Germany, and a few other places, but I was so surprised. I would have thought it might take much, much longer. I guess, that's why it's called an Emergency Use Authorization, the FDA, and other Federal agencies. And well, the politics have understood that we just need to do more testing, and it's not just one test per person. It will be, I would think, repeated tests longitudinally.

From my home country of Austria, for example, that certain groups in the hospitality business, they undergo now weekly tests. So, I would think that something like this can also be implemented in some specific populations here in the country. And then you have to have tools that make testing highly efficient and economic acceptable.

Brad Puffer: How did the Renal Research Institute see a link between potential pool testing, and the work you do to advance technology, and understanding for people with kidney failure? What was the tie?

Dr. Peter Kotanko: We are responsible for a large number of patients. We, as a company-- RRI is part of Fresenius Medical Care. We are responsible for close to 200,000 dialysis patients, and dialysis patients are particular vulnerable population because they have immune deficiency. They have comorbidity. They are much more vulnerable than the general population to COVID-19.

We were really thinking hard, what could we do to improve patient outcomes on multiple levels? And one of those levels is, of course, the whole area of diagnostics. What can we do to speed up diagnoses in our patient populations?

Of course, we are also working on several other projects related to COVID-19. Pool testing is actually attractive, I think, to dialysis clinics because patients are organized in dialysis shifts. Say, a dialysis shift of 10 patients, 15 patients, 20 patients, lends itself naturally to pool testing setting provided that the prevalence is, as I said earlier, are low.

Brad Puffer: It sounds like you had the right team to gather, to create this mathematical model. The collaboration was quite extraordinary across your team.

Dr. Peter Kotanko: That's just RRI's modus operandi. We have such a diverse workforce here at RRI. Be it MDs, nephrologists, of course, epidemiologists, mathematicians, biochemists, engineers, and so on, and so forth. It's just our usual modus operandi that when there is a problem at hand that colleagues from different backgrounds look at the problem, and everybody contributes. In this specific case, it was very clear that fundamental problem is a mathematical one-- how to find this sweet spot for optimal pool testing.

And the other question was, of course, yeah, but somehow we have to operationalize it. This was a clear question for people versed in laboratory medicine and biochemistry. So, this team formed very naturally overnight, literally because there was a flurry of emails and text messages happening between-- I don't know-- 7 PM and 2 AM in the morning. And then the next day, this group was consolidated, and we knew what the path forward would look like.

Brad Puffer: Well, you mentioned a little bit earlier, this is not the only thing you're researching related to COVID-19. Tell us a little bit about some of your other research. I understand that you have a study you're working on right now around arterial oxygen saturation in COVID.

Dr. Peter Kotanko: RRI clinics and also some FKC clinics are equipped with a device that's called Crit-Line. And the Crit-Line-- it's an amazing device actually that measures hundreds of times per minute hematocrit and also their oxygen saturation. In a patient, who has an arteriovenous fistula or an arteriovenous graft, this oxygen saturation resembles the arterial oxygen saturation. So, this is one piece of important information. We have a way to get hearing a treatment data on the arterial oxygen saturation in certain patients.

It's also recognized that COVID-19 affects, in a number of patients, their lungs, and it causes inflammation in the lungs. And this inflammation impedes their uptake of oxygen from the air. And as a consequence, the oxygen level in the blood drops, and a very good way to assess this oxygen level in the blood is to measure what's called oxygen saturation. In a health that subject here living at sea level, this oxygen saturation would be something like 97%, 98%.

Now, what we've found actually is that in something like 10%, 15% of patients, the oxygen saturation starts dropping, and in some cases, dramatically dropping before COVID-19 was even diagnosed. So, it would drop, say, from levels of 92%, 93%, 94% within two days to levels of 85%, 80%, even 75%, which is a dramatic decline. But it's of course a highly alarming signal. And because we have all those data collected through Crit-Line anyway, it provides actually a terrific opportunity to follow the arterial oxygen saturation throughout the treatment but also between treatments.

Brad Puffer: The bottom line, if you could detect oxygen drop in some of our patients before they have COVID, what does that tell you, and how do you use this information? This is pretty exciting.

Dr. Peter Kotanko: We are now very careful when a patient's arterial oxygen saturation drops below 90% or declines for more than 5% point. In this case, our recommendation would be to test the patient for COVID-19, if there are no other clear reasons why the patient may have had this decline in arterial oxygen saturation.

Brad Puffer: As we talk about this various research that the Renal Research Institute is doing, whether it's pool testing or oxygen saturation, what do you hope will come out of all of these efforts?

Dr. Peter Kotanko: In a few months from now, we will be in a better spot when it comes to testing. Testing, in my mind, will comprise of a whole tool box. It will comprise RT-PCR testing,  [INAUDIBLE] patients, pool testing. It will comprise serology testing in certain situations. This is one aspect to really increase the capabilities for testing, not just quantitatively, but also qualitatively. The second hope is, of course, that we are able to identify patients at increased risk for severe COVID-19 illness, and oxygen saturation may provide the means here.

At The end of the day, I mean, it's really all about, can we keep our patients and staff safe? And if they contract COVID-19, I'll be in the position to diagnose this swiftly because early intervention helps. This is in my mind, the overarching goal here, and I think that the research we are doing here at the Renal Research Institute may contribute to achieving that goal.

Brad Puffer: Well, Dr. Kotanko, it's been really fascinating talking to you. And I wish you best of luck in all of this research in its effort to help our patient population and our employees, as you say, be ahead of this pandemic. Thank you so much for taking the time.

Dr. Peter Kotanko: Well, thank you. It was a real pleasure talking to you about this. And I hope that at the end of the day, in a few months from those, I said, we will be in a better spot.

Brad Puffer: Well, thank you. And to our audience, you can find Field Notes on the Apple Store, or Google Play, right here at fmcna.com, where you can also find our Annual Medical Report and other feature articles. We hope you'll be back and join us as we discuss more issues in the weeks ahead. Until next time, I'm Brad Puffer, and you've been listening to Field Notes by Fresenius Medical Care. Take care, everyone.