TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week. A transcript of the podcast is below the summary.
This week's topics include antibody testing for COVID-19, EVALI deaths, NIH guidelines on COVID-19 treatment, and RT-PCR for SARS-CoV2.
Program notes:
0:35 NIH guidelines for treatment of COVID-19
1:35 Against HIV protease inhibitors
2:32 Number of anecdotes
3:22 Two assays for SARS-CoV2
4:22 Slips that happen in testing
5:09 Antibody testing in California
6:09 Early outbreak
7:09 Not much confidence in the results
8:09 Antibody testing and following
8:18 EVALI deaths
9:18 In light of COVID-19
10:18 Half the fatal cases
11:15 How it should be used
12:09 End
Transcript:
Elizabeth Tracey: NIH treatment guidelines for COVID-19.
Rick Lange: Detecting antibodies to coronavirus in California.
Elizabeth: What do we know about deaths from EVALI?
Rick: And comparing two tests that detect the coronavirus.
Elizabeth: That's what we're talking about this week on TT HealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I'm Elizabeth Tracey, a Baltimore-based medical journalist.
Rick: And I'm Rick Lange, President of the Texas Tech University Health Sciences Center in El Paso, where I'm also Dean of the Paul L. Foster School of Medicine.
Elizabeth: Rick, this just came over the transom late last evening and so we're going to headline with this. The NIH has published COVID-19 treatment guidelines and of course these are things that everybody who's got a single patient with COVID-19 really wants to hear about. Some of the highlights of this were that the panel does not recommend any drug for pre- or post-exposure prophylaxis outside of clinical trials. It does not make a recommendation for specific antiviral or immunomodulatory treatments, saying that no drug has been proven to be safe and effective. It does provide a rationale for the use of certain therapies under investigation and a summary of studies to this point on these particular treatments.
It comes out against the use of hydroxychloroquine plus azithromycin outside of clinical trials because we know that there's a toxicity risk related to this and also against lopinavir, ritonavir, or other HIV protease inhibitors because of negative clinical trial results and unfavorable pharmacodynamics. They also recommend against interferons and Janus kinase inhibitors.
Again, in the "against" group, against the use of systemic corticosteroids for those folks who are mechanically ventilated with COVID-19 who don't have ARDS, acute respiratory distress syndrome. And finally, it prefers low-dose corticosteroids over no corticosteroids in patients with refractory shock.
When I take a look at these particular guidelines, the thing that I'm struck by is this. There's really nothing that we think the evidence is supporting its use of. This, in spite of many anecdotal reports relative to efficacy, and also this huge emphasis on clinical trials.
Rick: Elizabeth, I think you hit the nail on the head. There were a number of non-randomized observational trials and sometimes anecdotes that suggested particular therapies might be useful. And people ran with that information without actually proper verification that those treatments could be effective. Not only could they be effective, but in fact that they weren't harmful. The NIH has taken a very strong stance. These treatment guidelines are just that. They're guidelines now and they will likely evolve as some of these randomized trial results become available.
Elizabeth: I just have to reflect -- and I know this is likely to be your clinical experience also -- that many clinicians I talk to about this are concerned because it's one thing to know what the black and white guidelines are and it's another to be faced with a patient, or a patient's family, who really feel like, "Gosh, isn't there something we can try?"
Rick: We all want to try something, but we want to try something that works. We want to avoid something that is particularly harmful.
Elizabeth: Let's turn to the Journal of Clinical Microbiology. This is a study that's taking a look at a couple different assays for detecting SARS-CoV-2 and we're going to frame this, of course, within the larger issue of testing.
Rick: This looks at two different tests that allow rapid testing for the SARS-CoV-2. When an individual is exposed it takes about 5 days, on average, before they develop symptoms, but one can actually detect virus 2.5 days before that. And so they're potentially infectious during that time period, called presymptomatic transmission of the virus.
These are two different techniques that use RT-PCR. One is the Cepheid Xpert Xpress method. The other is from Roche. It's called the Roche cobas. These can both deliver results within hours. When they looked at over 103 specimens and compared these two tests, there was agreement 99% of the time. There was only one patient in which there was some disagreement between the tests.
Elizabeth: Clearly, this underscores our need to be able to do this and then there are a number of other sort of slips that happen in the midst of this testing. For example, collection of the specimen has to be adequate.
Rick: Right. First of all, it has to be a collection. It's put into a viral transport medium. Then you have to get it to the test. So all along the way, interruption of any of those steps interrupts our ability to get fast results.
Elizabeth: This problem with testing has been a problem since the pandemic began. And there are all kinds of other technologies that are on the horizon, this saliva test that doesn't require that fairly uncomfortable collection of the specimen. But when we take a look at some of the sensitivities and specificities of those tests, they're not very good.
Rick: No, and you're right. Each test is a little bit different.
Elizabeth: Pointing to a problem with that. Let's turn to your other one and break with our tradition because this is one that's taking a look at antibody testing. Of course, this is the great hope with regard to reopening the country and allowing hospitals to do routine procedures again, and whatever, to take a look at, "Gosh, do you have antibodies? Have you been exposed and are you protected?"
Rick: One can detect the virus as early as 2.5 days after someone's been infected, but antibodies take several days to weeks. The initial antibody is what's called IgM (immunoglobulin M) and it appears usually between 5 and 14 days, if it does appear. Following that is IgG (immunoglobulin G) that appears weeks to months and may last for years.
Part of the issue with antibody testing is making sure that the antibodies we're testing for are specific for coronavirus, and secondly is, are they protective long-term? We'll circle back around to that, but I just want to talk about this particular trial. This was conducted in Santa Clara, California, where they had an early outbreak, and they just did testing for the antibody in the general population.
What they determined was in people without known symptoms, they could detect coronavirus antibody in about 1.5% of the individuals. Then they realized that the testing wasn't very perfect -- this is not an FDA-approved test -- and they tried to adjust for that in the demographics. And based upon that, they concluded that the prevalence of COVID-19 infection in the population ranged between 2.5% and 4%.
First of all, although there were 100 antibody tests proposed out there, there are only four that are approved by the FDA, and this is not one of them. These need to have rigorous testing and controls. That wasn't done in this particular trial. It's not clear that the antibody they tested to is specific for COVID-19 coronavirus as opposed to others. So this particular journal is not a peer review journal. It allows rapid access to publication, but not necessarily peer review.
Do I think the results are right that 2.5% to 4% of the population was infected with COVID-19 without symptoms? I have grave doubts about that, but it does allow us to talk about antibody testing in general.
Elizabeth: This is in the preprint server medRxiv. One thing that's garnered media attention about this study has been the idea that, in fact, exposures are much higher than are being reported because, again, we're in that situation where we don't have adequate testing and the testing that we do have is pretty pathetic by and large. It's hopeful, though, the idea that there are way more people who are seropositive for having been exposed to the virus because it suggests that the denominator is much bigger and that the lethality is probably much smaller.
Rick: This trial, I don't think one can reliably say that the infection rate is much higher. The second issue, though, is does antibody confer long-term immunity? We don't know whether the antibodies to COVID-19 infection will in fact confer long-term immunity.
The antibodies that one really wants to know about are the neutralizing antibodies and this doesn't make any mention at all. The only way we're going to get that information is to do antibody testing in a large group of individuals and follow them over a period of time to see whether those antibodies actually confer immunity.
Elizabeth: Finally, let's turn to the New England Journal of Medicine. This is a look at EVALI -- that is the vaping-associated lung injury -- the acronym EVALI for that. This is a retrospective analysis of just under 2,600 hospitalized patients with non-fatal cases of EVALI and 60 patients with fatal cases of lung injury due to their e-cigarette or vaping use. They were trying to analyze what are the factors that are different between the folks who succumbed to their lung injury versus those who didn't?
Basically they found that the fatal cases, compared with the non-fatal cases, more of them had a history of asthma, cardiac disease, and mental health conditions. A little bit greater than 50% of these fatal cases of lung injury were obese. And finally, the majority of the fatal cases were associated with vaping THC products versus nicotine-containing products. I think this is kind of interesting in light of COVID-19 because a lot of the pre-existing conditions are similar, as well as the obesity, with regard to more severe consequences.
Rick: So Elizabeth, one of the disconcerting things was the number of individuals that were reported to the CDC to have vaping-related lung disease. These individuals that had vaping-related death were more likely to have a lot of chronic conditions. They were more likely to be a little bit older as well. The mean age was about 50 years old. In those that were non-fatal, about 23. There were individuals that were only vaping nicotine.
One of the things that I found interesting is they looked at frequency of vaping and the vast majority of individuals, regardless of whether they were vaping THC or nicotine, were doing it on a daily basis.
Elizabeth: I thought that was interesting. Also, the piece of data relative to those who were also former or current combustible cigarette smokers also had a predictive value with regard to who was going to end up with fatal injury.
Rick: I'm glad that we're talking about this particular study. Half the cases that were fatal presented to an outpatient setting. There was an opportunity then to recognize what was going on and initiate treatment and follow-up. That didn't happen, and so the patient was sent home, and subsequently hospitalized and died soon thereafter.
One of the things as healthcare providers we need to be doing is -- when someone presents with some lung injury -- is making sure that we inquire about it because people oftentimes won't volunteer that information because they may be embarrassed about it, or they may not want to be admitting that they're vaping THC-containing compounds.
Elizabeth: Finally, I would note that in the discussion the authors say because traditional mechanical ventilation can worsen lung injury in patients with acute lung injury or ARDS, they really need to consider evidence-based principles on whether they should use mechanical ventilation. We're seeing this same thing coming out with this COVID-19.
Rick: Well, not only whether it should be used, but exactly how it should be used. It's different for these patients than it is for other types of patients.
Elizabeth: On that note then, why don't you give us a little update on Texas Tech and how you guys are doing?
Rick: We're dealing with the health aspects of COVID-19 infections pretty well. The economic impact, though, is pretty substantial. We, as in many places around the country, are trying to decide when do we release some of the strict restrictions to allow the economy to come back, but at the same time to preserve the health of the community. We'll be wrestling with that over the next several days and weeks, not only here in the city, but across the state, and I'd say across the nation as well.
Elizabeth: That's a look at this week's medical headlines from Texas Tech. I'm Elizabeth Tracey.
Rick: And I'm Rick Lange. Y'all listen up and make healthy choices.