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, Apgar score utility in preterm infants, triple inhaled therapy in chronic obstructive pulmonary disease (COPD), and multisystem inflammatory syndrome in children (MIS-C) following COVID-19 infection in kids.
Program notes:
0:42 Looking at antibody tests for COVID-19
1:45 How sensitive are they?
2:45 Point of care most unreliable
3:43 Haven't been adequately validated
4:20 Apgar scores in preterm infants
5:20 1.8% mortality
6:20 Score of 10 is perfect
7:15 MIS-C
8:15 Average 8 years of age
9:15 Fever in 2 to 4 weeks
10:22 Triple inhaled therapy in COPD
11:23 Two combinations worked best
12:25 Some increase in pneumonia
13:24 End
Transcript:
Elizabeth Tracey: Can Apgar scores help us to identify at-risk preterm infants?
Rick Lange: The sequelae of COVID infection in children and adolescents.
Elizabeth: How about triple therapy in people with COPD?
Rick: And is antibody testing for COVID ready for primetime?
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: I'm Rick Lange, President of Texas Tech University Health Sciences Center in El Paso, where I'm also Dean of the Paul L. Foster School of Medicine.
Elizabeth: Rick, in light of current events, of course, I think that we should turn to some of the COVID material first. My personal fave would be in the British Medical Journal, a look at, "Hey, what about these antibody tests?"
Rick: Elizabeth, the title of this -- and it summarizes what they looked at -- it's called "The Diagnostic Accuracy of Serologic Tests for COVID-19." It's both a systematic review and a meta-analysis. I will remind our listeners is there's two types of tests for COVID. One is the antigen test. One gets a nasopharyngeal swab and looks for evidence of viral particles in that specimen and it would detect active infection. The second test is the antibody test. After someone has become infected, 1 to 2 weeks after that they begin to develop antibodies. Serologic tests identify somebody that has been infected. There are a number of antibody tests that are available. How reliable are they?
There are three different types of serologic testing: one called an enzyme-linked immunosorbent assay, called an ELISA, one called a lateral flow immunoassay, or an LFIA, or a chemiluminescent immunoassay, called a CLIA. What they discovered, first of all, is how sensitive they are -- that is, if you have it, are these tests sensitive enough to determine whether that's true or not? It ranged as low as 66% for the LFIA test to the highest of 97.8% in CLIA. Then they looked at also the specificity -- that is, if it says it's positive, is it truly positive? There was a variety among those as well.
Also, by the way, it determines on when you get the test. If you get the test within the first 2 weeks of infection, you're not likely to detect it. You have to wait for at least 3 weeks after the infection. In essence, what they concluded is that the current available evidence does not support continued use of existing point-of-care serologic testing.
Elizabeth: This is just such a big problem because we cannot confirm any of our assertions relative to, hey, who's had it, who's safe, who is not -- any of that -- if we don't have adequate testing.
Rick: Right, and what happens is they misclassify individuals. Their recommendations are -- and especially the ones that are really unreliable -- are those at point of care. As you walk in, they say, "We can give you an answer within minutes." Those are the most unreliable tests.
Elizabeth: And so, we were talking, of course, before we started to record about the FDA actually allowing all of these tests to get out there and just how inexplicable I find that. You, of course, were defending the agency.
Rick: What happened early on, as you know, there was not adequate testing. There were a number of companies that proposed tests, so the FDA gave emergency use authorization. It didn't say that they had validated the test, but in order to get the test out quickly, the FDA allowed that. But they made it clear they had not approved the test. Now that we're having more time to look back -- and that's what this study does -- it shows they're not as reliable as we'd like for them to be.
Had the FDA not done that and we had inadequate testing, people would be pointing a finger to the FDA and be saying, "Well, we have all these tests available. You're just not allowing the public to use them." I think what the FDA found was that middle ground, saying, "We'll allow it to be out there, but we can't endorse them because they haven't been adequately validated."
Elizabeth: If you were a betting guy, what would you say about when we're going to have validated tests that are going to have adequate sensitivity and specificity?
Rick: Elizabeth, I think that there are some on the market. Part of it depends upon what the prevalence is. The more people that have in the baseline population, the more likely a positive test really means it's positive. When the seroprevalence is very low -- that is a few people do -- you're more likely to have false positives. The tests are getting better. The trouble is most of the populace does not know which tests those are.
Elizabeth: More to come, no doubt. Let us totally flip gears. Let us go to the New England Journal of Medicine and take a look at this study that was looking at the utility of the Apgar score to help identify the risk of neonatal death among those babies who are born preterm.
This is a study that was conducted in Sweden and they identified 113,300 preterm infants from 1992 through 2016. Preterm was defined by 22 weeks to 36 weeks 6 days of gestation. That was further subdivided into 22 to 24 weeks, 25 to 27, 28 to 31, 32 to 34, and 35 or 36.
They performed Apgar scores on these infants at 5 and 10 minutes, and they also calculated the change in the Apgar score in that 5-to-10-minute assessment. There were 1,986 neonatal deaths, 1.8% of this group, of this cohort.
Here is what they showed. Not surprisingly, those infants who were earlier in that preterm group had a higher rate of mortality and that was pretty predictable. Then they also showed something interesting, which was an increase in the Apgar score between 5 and 10 minutes was associated with lower neonatal mortality than an Apgar score that stayed the same. So these authors say that this is really the first time that anyone has looked at this particular aspect of the Apgar score and tried to use it to prognosticate what a likely outcome for these infants might be.
Rick: For those of our listeners who may not know what an Apgar score is, it was developed by Dr. Virginia Apgar in the 1950s and it was a way to assess whether children would need to be resuscitated. She looked at five very simple things. When the child's born, you assess their heart rate, their respiratory effort, their muscle tone, their reflex irritability, and their color. They gave a score from 0 to 2 for each of those five things. So an Apgar score of 10 meant everything looked terrific.
That's clearly been shown to predict resuscitation and survival in normal term births. But the question is with preterms -- because reflexes may not be as good, their muscle tone may not be as good -- was the Apgar score still predictive? That's why this study was done. As you mention, Elizabeth, it does have prognostic value, but this is the first test to show it, especially in this large population. If the Apgar score is very low, 0 to 3 at 5 minutes and 10 minutes, the chance of meaningful survival, even in preterm infants, is extremely low.
Elizabeth: I also thought that it was very interesting, this idea that the change, if it improved over that time period, was also associated with an improved prognosis.
Rick: What that would mean is probably there were some measures taken between 5 and 10 minutes that the baby responded to, and if they do, any of those give things get better, it indicates the child will continue to improve.
Elizabeth: Let's turn back to our COVID material, this time in the New England Journal of Medicine, talking about children. What about that rare complication in children who are COVID-19 infected?
Rick: That rare complication you're referring to is called MIS or the multisystem inflammatory syndrome. For the most part, the acute complications are relatively rare in children. But what was noticed was that there were infants and adolescents who would develop infection and they'd be fine. Then about a month later, they would develop a multi-inflammatory syndrome characterized by high fever and evidence of inflammation in multiple organ systems.
There are two studies in the New England Journal of Medicine. One of them was conducted in New York City. The other is a surveillance that was done in pediatric health centers across the United States, the first one about 95 patients, and the second one 186 patients in 26 different states. Here's what they found out.
The vast majority of these kids either had active virus or antibody, more commonly antibody. The average age of individuals who got this MIS was 8 years old. They usually got it about 2 to 4 weeks after the active infection. It affected the GI tract in about 90% of individuals, the cardiovascular system in about 80% of kids and infants, the hematologic system in about 76%, mucocutaneous manifestations -- skin manifestations -- in 74%, and respiratory in about 70%.
It looks like it occurs in about 2 per 100,000 individuals under the age of 21. When it happens, the mortality is about 2%. About 80% of those kids end up in an ICU and about 20% on a ventilator, with only about 2% dying. Their average hospitalization is about 6 to 7 days.
Elizabeth: One of the things that I had heard about even previous to these two articles was the idea that if you have a child you suspect has had COVID-19 and they develop a rash, that that might be a time when you want to seek care, or at least assessment.
Rick: Right. In fact, even before then, Elizabeth, it looks like about 97% of these kids have a fever. So if the child has recovered from COVID manifestations and then 2 to 4 weeks later they develop a fever again -- or, again, GI symptoms, cardiovascular symptoms -- then the child needs to be brought to attention of the pediatrician.
By the way, it's a clinical diagnosis. There's no single test. But if you measured lab tests, you'd find markers of inflammation are very high -- they're through the roof -- and about 50% of these kids will have some heart manifestations as well, elevated troponin, for example.
These kids seem to recover from the acute events. Now, are there long-term sequelae? We don't know the answer. There does seem to be a higher prevalence in African American and Hispanic kids than there are in whites, for example, but there are many things that we just don't know about it yet.
Elizabeth: I guess the other thing I'm wondering about is the utility of dexamethasone in this population. Certainly, we don't have any data on that, but it seems like it would make sense.
Rick: Yeah. Elizabeth, I'm glad you mention this because almost all of these kids were treated with some sort of immunomodulating agents, whether that could be they get an immunoglobulin infusion, whether they get an interleukin inhibitor, or whether they get dexamethasone, or some combination. We don't know which works best, but the vast majority of these kids did receive some type of treatment for their inflammation.
Elizabeth: Staying in the New England Journal of Medicine, let's take a look at this population that internationally is growing all the time, and that's folks with chronic obstructive pulmonary disease or COPD.
It's taking a look at triple inhaled therapy at 2 glucocorticoid doses in folks who have this moderate to severe COPD. They used an inhaled glucocorticoid, a long-acting muscarinic antagonist, or LAMA, and a long-acting beta 2 agonist, a LABA. It's been studied previously at single doses, but this study takes a look at two doses.
The study took place over a year. It's a phase III study and randomized, included people with, as I said, moderate to severe COPD who had had at least one exacerbation in the previous year. There were four study groups. There were different combinations that were in each of these and I'm not going to go through every single one of them. The ultimate population that was treated was 8,500 patients plus and what they found was that the combination of either 320 mcg of budesonide or 160 mcg of budesonide, with all of these other meds, resulted in the best outcomes.
Rick: This is, I would say, kind of a moving target because the current recommendations are that there's kind of a stepwise approach that you start with one medication. If it doesn't work, you add a second medication. If it doesn't work, then you work your way to a glucocorticoid or a steroid. The reason why they reserve steroids to last is because inhaled steroids are associated with some complications, like pneumonia, bone fractures, and even cataracts.
What this study shows is that the use of triple therapy was more effective both at two things: at reducing exacerbations and improving mortality at the higher dose. That's the new swing. Because if you use two instead of three agents, you don't get the benefit of that.
Now, was there an increased risk of pneumonia? There was. It was a slight increased risk of pneumonia. Overall, it seemed to translate into an improved mortality in these individuals, again, with moderate or severe COPD.
Elizabeth: Another part of this that I thought was noteworthy was that over 80% of the patients at enrollment had already been on glucocorticoids previously and also the incidence of serious adverse events was about 20% in the people who were taking this therapy, any of these therapies.
Rick: Elizabeth, your point is well-taken because normally you wouldn't include people like that in a study because you think, "Well, maybe they wouldn't receive a benefit." But this study would suggest even if they have been treated otherwise that this triple therapy can still be beneficial in those individuals, so that's an important point.
Elizabeth: All right. On that note then, 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.