Assessing Host Response for Sepsis Through Early Detection

April 28, 2020

Hollis O’Neal, MD, the national primary investigator for the Cytovale early sepsis detection system, discusses sepsis and COVID-19 and provides an overview of his pilot study.

Segment description: Hollis O’Neal, MD, pulmonary-critical care expert, Our Lady of the Lake, and the national primary investigator for the Cytovale early sepsis detection system, discusses sepsis and COVID-19 and provides an overview of his pilot study.

Interview transcript (modified slightly for readability):

Contagion®: Thanks for joining us today for another coronavirus video with Contagion. Today we're joined by Dr. Hollis O'Neal, who is a pulmonary and critical care expert at Our Lady of the Lake in Baton Rouge. He is the national primary investigator for the Cytovale early sepsis detection system. Thanks so much for joining us this morning.

O’Neal: Happy to be here.

Contagion®: Great. So why don't we get started. What is the current burden of sepsis in the United States?

O’Neal: Sepsis has gotten a lot of press over the last several years in United States for a lot of reasons. Number 1, the economic burden is really astronomical. Yearly sepsis costs tens of billions of dollars and rapidly outpaces the other costs of inpatient conditions that we have in the United States, I believe. Osteoarthritis, so hip, knee replacements and things like that would be probably a number 2 and really sepsis massively outpaces that. The other burden that we've seen with sepsis are a couple of things that aren't really captured in monetary cost. One is the intellectual burden it places on emergency medicine providers. It's something that they screen for constantly.

There are sepsis alerts because the government has in place the SEP-1 bundle that requires rapid identification and treatment. It really places a large, I would say intellectual burden, on the emergency department staff to identify the disease. There are frequent notifications from the electronic health record that requires them to intervene. The other burden that it places on us that is also not accounted for in costs--and the Infectious Disease Society of America has made a good point of looking at this-- is the fact that because sepsis is a disease that requires emergent and aggressive intervention, the thought that it requires early and aggressive and almost indiscriminate use of broad spectrum antibiotics. We don't know what the organism are going to be until sometimes several days after the patient's admitted.

It runs the risk of promoting one of the things that we try to prevent, which is antibiotic resistance and now, the development of multidrug resistant organisms because of our indiscriminate use of broad-spectrum antibiotics and the resource utilization that it requires. When we think a patient has sepsis, we often go down a pathway of early and aggressive IV fluid resuscitation, admission to the intensive care unit, and this places yet more burden on the health care system.

Contagion®: So how can sepsis come into play in patients with COVID-19?

O’Neal: COVID-19 has presented to us a little bit of a challenge in that traditionally, we always thought of sepsis as being predominantly a disease caused by bacterial pathogens and then occasionally fungal pathogens in certain populations. What COVID-19 has really shown us is that viral pathogens can also cause a sepsis syndrome as well. It's a little bit different in that there's no great treatment for it. There's no proven therapeutic option for COVID-19 right now, or, for that matter, most forms of viral sepsis. But this is, to my understanding, the first time, probably in history where a viral pathogen has become the overwhelming cause of sepsis, or at least concern for the overwhelming cause of sepsis in our health care system.

It's really provided quite the challenge for us in discerning those patients who do have the disease. I think that one of the things that providers have a hard time understanding sometimes is that COVID-19 tends to be a "plus one" disease not an "instead of" disease. In other words, patients will come in with all of the other things that they typically come in with and they could have COVID-19. It's not a mutually exclusive disease. So, when they come in with a disease, it's not necessarily the only thing they have, they can still have all of their other conditions and complications.

COVID-19 has really provided quite the challenge there. The other thing that it's done to us is really pressed our resource utilization. It was a disease, a pathogen that humans had never seen before, and a disease course in the natural history that was unknown to the treating clinicians. There was a lot of uncertainty upfront in how to treat the patients. There's a lot of concern with communicability of the disease that places a large burden on the use of personal protective equipment, and also disposition. These patients deteriorate rapidly. They often are placed in intensive care units, probably earlier than most patients would be and for good reason, because they do deteriorate and decline so rapidly. For example, an institution like ours, we increased our ICU bed capacity from 80 something beds to over 170 beds within just a week or 2 to accommodate the massive influx of critically ill COVID-19 patients that we have.

Contagion®: Dr. O'Neal, can you tell us a little bit more about the pilot study that you're launching?

O’Neal: One of the things that we've noticed, and through my work with Cytovale over the last 5 to 6 years that we've seen, is that the signature that occurs in viral sepsis does appear to be very similar to the signature that appears in bacterial sepsis. Our largest experience with viral sepsis over the last several years has been influenza, because that does tend to be the viral pathogen that we understand the best with regards to causing multisystem organ failure. We found there are studies that influenza-related sepsis does have a similar signature to other bacteria-related sepsis. As we're thinking through this, one of the important things that we have to do in the emergency department is risk stratify patients and find those patients who are at risk for deterioration for admission to the hospital admission to the ICU versus finding those patients who are at lower risk for deterioration, and those patients can go home and self-quarantine, and treat themselves at home since there is no specific therapy for disease.

We've designed this pilot to be placed very early in the course of an emergency department setting. So most patients who come into the emergency department with some suspicion that they may have COVID-related disease are going to be triaged and at some point, they'll probably have a purple top tube draw for what would be a typical of a CBC. We've designed this pilot to take the remnants of that CBC, and then observe those patients over time, and then determine if they have any infection, including COVID-19. Because remember, COVID-19 is just 1 more of a number of pathogens that these patients could have. But we're looking to see if they have an infection such as COVID-19, and to see if the results of the test will correlate with the severity of illness that the patient has. Where they're admitted to, how long they're in the hospital, do they survive? What kind of treatment do they require? What kind of IV fluids do they require? The goal of this study is to identify those patients rapidly and see if the results of the assay could help in risk stratification of these patients very early in the course of the disease, so that the emergency department can then rapidly work through this massive population of patients that they're seeing every day, and appropriately triage them to treatment.

Contagion®: Now, are there any other goals or objectives that you're looking at in this trial specifically?

O’Neal: Yeah, there are a number. Number 1 is appropriate risk stratification pf these patients. But number 2 is looking at the results of the essay with regards to the severity of illness, predicting certain things like organ dysfunction, organ failures over the first 3 to 4 days of hospitalization in these patients, disposition where they're where they're discharged, to, obviously, length of stay in survival. Those are all secondary end points that we're looking at.

Contagion®: So, you're conducting the study in Louisiana, which is becoming quite a hot spot for COVID-19. How could this rapid diagnostic help hotspot communities in this pandemic that we're seeing right now?

Louisiana really has become one of the hotspots for this disease. If you look at it, per capita, we are probably in the top 3 or so with regards to states in the United States with being affected by this disease. Actually, if you drill down in Louisiana, New Orleans and Baton Rouge are the areas where the predominance of these cases are. One of the things that we're hopeful for is that if we can employ this and in our facilities and see that that this assay, which can be performed in under 10 minutes, can provide our emergency department clinicians with the information they need to appropriately triage these patients, determine who needs more aggressive therapy versus determining who may need to go home, then since we're leading the country in this, as other communities begin to see more and more of this, we could deploy this technology to those communities and help them avoid some of the burden that we've seen with regards to admissions of patients who stay in the hospital for just a day or 2 because we're concerned about what they may or may not have, and then are discharged back resource utilization.

The biggest thing that we see, the biggest problem that we have with regards to resources are really 2. Number 1 nursing and support staff. There just aren't enough nurses and our health care providers do sometimes get sick and so there aren't enough nurses and support staff to take care of the patient. It's much better when we can to have a patient self-quarantine at home. Then, the never-ending shortage of personal protective equipment that we have. Every patient that goes home and is able to self-quarantine is a patient that we don't consume, at least 23 sets of PPE per day as the nurses are going in and out of their rooms to care for the patients. Those are things I think we could help the rest of the country with. If we could use our experience here to educate and help technology and provide technology to help those other locations more efficiently move through their patients in the emergency department. I think that that would be a huge win to the medical community overall.

Contagion®: Absolutely. Is there anything else that you want to add about your study or anything in general?

Yeah, I think the important thing to understand about the Cytovale assay that makes it a little bit unique with regards to this is that a lot of attention has been focused, not only in COVID 19, but in other forms of sepsis that we see is that there's been a lot of attention placed on early pathogen identification. A lot of technology out there and diagnostics [focus on] finding out what the pathogen is. That is not our intent and we should not be not be confused with early pathogen identification. We are a test that assesses the host response. What we say is that we're about the patient not the pathogen. We're looking at how the patient's host response is affecting that patient, and how that immune response might impact that patient's outcome. We'll leave it to the pathogen identification experts to tell us what pathogen that is. We feel that it's our job to appropriately risk stratify these patients because it may be that if you have relatively mild disease and you can go home, it may not be necessary for at least treatment of that specific patient. It may not be necessary to find out what the pathogen is if they're going to be fine at home. Now for epidemiologic purposes, I think that that's a different question. But at least with regards to treatment of the individual patient, we are looking at host response to determine if we can help the patient's outcome.

Contagion®: Fantastic, well Dr. O'Neal, thanks so much for taking the time to join me today. We really appreciate hearing more about your study, and we wish you luck.

O’Neal: All right, thank you so much.