Answering Your Questions About Treating COVID-19 With Blood Filters

Stan Bunger
June 19, 2020 - 1:40 pm

    As we continue to navigate these unprecedented times, KCBS Radio is getting the answers to your questions about the coronavirus pandemic. Every morning at 9:20 a.m. Monday-Friday we're doing an "Ask An Expert" segment with a focus on a different aspect of this situation each day, sponsored by Sierra Pacific Financial Advisors. 

    Today we're focusing on the role of medical technology in treating COVID-19 with Dr. Keith McCrea, chief science officer and VP of research and development for Ex-Thera Medical Corporation, based in Martinez.

    For those who may not have heard of Ex-Thera or your machine, the Seraph 100, can you explain what the technology is?

    Sure. It's a blood filter. It looks very similar to a hemodialysis cartridge - so this is what patients will get when they have limited kidney function, they'll go in the hospital and go through routine treatments. So it's a very well known procedure, but what we've done is take a filter and design it specifically to remove pathogens, various other markers of disease and such. So it's a very straightforward blood filter.

    And at this point it's not just science fiction, it's been in use?

    That's correct. We don't have all the cases documented but we figure that we're well over 40 cases of COVID throughout the world right now.

    And this was not invented specifically for COVID, is that correct?

    That's right, originally the primary purpose of it was to address the significant drug resistance problem we have with bacteria. It was kind of designed for that, to treat the major issue of drug resistance. But we always expected, due to the mechanism, that it would be a therapeutic that would be ready for something like COVID-19. And once COVID-19 did hit Europe, it started to be deployed in Italy followed by Germany and France and Spain.

    Can you tell us a little about the specifics of the cartridge? In other words, what has to be done to attack or grab a specific pathogen?

    We identified a molecule that a very large number of pathogens - and this includes bacteria, viruses, parasites and fungi - utilize to attach to our blood vessels, blood cells. And it's a very straightforward molecule, it's readily available on that molecule. It's heparin, it's one of the anticoagulants that's been in use the longest, clinically since the 1940's. So what we've done is simply attach this onto a high surface area blood filter and it acts, essentially, as a bridge to grab these pathogens and other molecules that are circulating throughout the body.

    Let's get to the questions which have been sent in to First: how do you administer a blood filter to a patient? Does the patient feel anything during the treatment?

    Yes, as I previously mentioned this is very similar in form/function to a dialyzer. So we build the filter and there are other companies that build blood pumps, and a patient receives a catheter, which can pull blood out of the body. The blood is then circulated through our device and then returned back to the body. And this is an extremely standard procedure, there's over 600,000 hemodialysis patients in the United States alone and therefore on any one day there's 300,000 patients who receive a treatment very similar to what we're doing. It's very well tolerated and if anything, the feedback when patients are on our device, they seem to actually do better in terms of the ease of the treatment and the fact that there seems to be less complications that occur when our device is also being used.

    Is it a one shot deal, or is daily, weekly? What's the typical way that it would be used in a COVID case?

    Most patients have needed only a single treatment in order to see a sustained effect. There's been a few patients where they've used two devices, but there's been no more than that. The effects are very rapid. A typical treatment is between four and eight hours, although some have gone up to 24 hours. We've been able to see plots of how patients responded and anywhere from two to six hours show a pretty dramatic improvement in clinical symptoms. So right now, at least for a DoD-sponsored trial that's going to occur later this year, they're going to be focused on roughly an eight hour treatment.

    How receptive are doctors to novel technologies like this?

    That's a great question. This is interesting, obviously nephrologists or doctors who treat kidney disease, they're very receptive to it. They do this type of therapy all the time and they understand that patients need to have their blood treated and augmented with ex-corporal devices. So they get it really quickly.

    Other doctors who are used to typically just providing a drug, either orally or intravenously, they basically are a little bit more hesitant until they see the data. Then it seems like once they see the response, they're more interested and willing to try the device.

    I thought COVID-19 was a respiratory infection. How does filtering the blood help that?

    That's another great question. It is primarily respiratory, initially. During, let's say, the mild to moderate cases it is contained within the lungs. As you approach the severe cases, there's definite evidence that viral RNA, or the building blocks of the viruses, are found throughout the body in kidney cells, in heart cells, in the blood vessels themselves. So the only way that can get there is through the blood system. There are publications coming out more and more that seem to indicate that there is a correlation between disease severity and the amount of virus that is in the blood.

    Let me ask you this as kind of a side question: the lungs are obviously the respiratory center and there's a lot of blood there, so in theory anybody who's got the virus in their lungs will wind up with it somewhere else. The question is, what does it do?

    That's correct. Part of the response by the immune system is to attack the virus. So if the virus is circulating through the blood and it does attach to the endothelium and enter cells, our immune system is going to try to get to those. And that can actually cause part of the degradation of the endothelium that leads to these hyper clotting issues that many of these patients experience; the very high sustained inflammation that is preventing the body from being able to heal itself. So that's exactly right, it does get into the blood.

    If I get COVID-19, can my doctor get this device? Sounds like they're asking about the status with the FDA of this device.

    Yes, we had a very good experience with a hospital in the United States - a military hospital - and they treated two patients under an emergency process in which doctors can use unapproved devices on patients if they feel like there's no other option to save that patient. So this was done twice in the United States and the only requirement is the doctors have to report to the FDA that they did this. The FDA saw the results and the next thing we know, we got invited into the emergency use authorization program, which allows us to submit an application that provides the safety and efficacy data we have to date. They perform an evaluation to determine whether there's merits to allow approval, and that's exactly what happened. So about two weeks after we received the invite from the FDA, they gave us emergency use authorization, which essentially means any doctor who has a confirmed COVID patient can get devices from Ex-Thera Medical and treat patients. 

    What are the side effects or potential dangers?

    We have not seen any side effects yet of this device. And I think a major part of that is due to the bio-memetic nature. We are simply mimicking the native chemistry of our blood vessels and in these severe cases, that chemistry is degraded within our system. We're kind of augmenting that by providing a fresh chemistry, or surface. So we haven't seen any side effects yet.

    Another nice thing about an ex-corporal technique like this, as opposed to a drug - a drug can stay in the system for days, a very long time and have extended side effects or toxicities. This device, if there were ever a problem, you simply turn off the system and it's removed and there's no more exposure. So right now we haven't seen any issues with safety.

    Does this process also remove some of the good stuff in our blood that should not be removed? And does it beat up and shred the rest of the stuff in the blood that's not removed but returned to the body? 

    That's yet another great question. The easiest way to answer that question is that because we are mimicking what the body is basically missing in these severe cases, there really isn't anything that you would expect to remove. And we have performed many tests, such as antibodies and drugs and other important blood proteins and demonstrated very minimal removal. 

    We specifically designed the device so it has very low turbulence through it and it's very kind to the blood. We've performed tests to look specifically to see if we're harming blood cells - red blood cells or white blood cells - or activating platelets, which can all contribute to illness and inflammation. And all these tests have shown that there's almost negligible effects. The other thing, too, that's very interesting about this is because we are mimicking what the pathogens want to attach too, they don't die on our surface. They just grab on and they're happy and then we can throw them away. And this is an important difference from antibiotics that actually can kill bacteria and leave the byproducts of dead bacteria. The byproducts of dead bacteria can actually contribute to disease severity, and they can stay for a very long time - up to two weeks. And that contributes to a sustained inflammation.

    Does it remove only COVID-19 in its current configuration, or other coronaviruses or other viruses as well?

    We've tested a variety of viruses. We have tested Zika - that was obviously in the news several years ago - we've tested Ebola and these do bind, herpes simplex virus. And then we've got cytomegalovirus and adenovirus, these are viruses that many of us carry around but our immune system keeps them at bay. And if you're immunocompromised - such as a cancer patient or HIV patient - then these viruses are opportunistic and cause many problems. And so all of these have been demonstrated to bind. We've seen literature that would support that many important diseases such as dengue and other filoviruses like Ebola and flaviviruses will bind to the device as well. 

    Can we do this with HIV? Any possibilities for rheumatoid arthritis or other autoimmune disorders?

    We believe so. Right now the company is small, we have a great team of roughly 25 people between Martinez and Europe and we're focused obviously on COVID right now but we are doing sepsis research in Europe, starting a very large clinical trial there. For the systemic inflammation of immune disorders, we do believe that we can have an effect there as well and we do hope to be able to start pursuing those types of studies within a year or two.

    Are there other blood filters out there? How is this different? And how does the news of the success of dexamethasone impact the need for technologies like a blood filter?

    There are other blood filters out there. Primarily the ones that are also approved under EUA, they remove inflammatory mediators. So this is not a foreign concept, obviously, because there are companies that we're amongst. So those devices will remove the inflammation, potentially, but they don't deal with other sources of the disease. Our device, we have evidence that we can remove the virus very efficiently. We have evidence that we remove the inflammatory mediators. But then we're also removing the clotting parameters. And all these things are contributing to the disease severity. So I think we've got a multi-mobile effect that provides us with a very strong value proposition in these patients.

    And speaking of that, one of the questioners wanted to know how expensive are these machines?

    To be clear, we're building a filter. There's other companies, dialysis companies, that build the machines. They're obviously very expensive, and we just build the filter. So we're kind of like the razorblades that fill the blades to the razor manufacturers. The device is relatively inexpensive compared to a single day in the ICU. So we performed studies and indicated that again, there's a very strong value proposition to use our device quickly and try to get patients out of the ICU quickly.

    By removing the virus RNA, can you prevent the cytokine storms? And this of course is a phrase we've all learned about, something that seems to occur in really severe COVID-19 cases.

    That's exactly right. We've got a great medical advisor who basically gave us the analogy that if you've got a fire and all you do is remove the smoke - which is like the cytokines - and the fire's still burning below, you're not going to be able to do anything. You've got to take care of the source of inflammation. And that's what we're doing. So if you remove the source of the inflammation then you can not only get rid of the fire, but clear the smoke.

    I've heard people with blood Type A do not do well if they get COVID. Does that have anything to do with this technology?

    No, it doesn't matter what type blood will be circulated through. We're just targeting things in the blood that shouldn't be there, and we can efficiently remove them.

    Can your machines be used in an outpatient environment? I'm thinking of places like surgicenters or even small standalone medical clinics. Or do they need to be in a full-blown hospital environment?

    No, we do think there is going to be a role for this device down the road. And I'm going to go back to the hemodialysis population; roughly 600,000 hemodialysis patients in the United States and roughly 20% of those will get a bloodstream infection any single year. So it is very conceivable that as we gather more clinical data on treating bloodstream infections, that this could be rolled into the outpatient hemodialysis clinic and be used to treat patients very quickly prior to the need to go to the hospital and potentially the ICU. With any sort of antiviral or antibiotic treatment, the quicker you can treat a patient with an adequate therapy, the better off they will be. So right now these dialysis patients, the second highest cause of death is infection. And we really strongly believe that when we can get back to our main mission, that we're going to have a very significant impact on the health of these patients.

    And so just as a follow-up then, specific to COVID-19, the thinking might be then that this could be used early on in the course rather than at crisis time?

    That's exactly right. We want it to be used as quickly as possible, probably in the severe COVID cases. Severe COVID cases is when a patient starts needing some sort of supplemental oxygen prior to the ventilation. We do have several cases now in Europe in which the device was used in these patients sometimes when ventilators weren't available. Our device was deployed instead, and the patient response was very positive. 

    This interview has been edited for clarity.