TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, 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.
This week's topics include examining the risk for clots and heart attack after COVID vaccination, predicting how bad COVID might be based on blood proteins, traumatic brain injury (TBI) and markers of severity, and looking in sewage for COVID variants.
Program notes:
0:43 Looking at sewage for emerging COVID variants
1:42 Capture all the viruses magnetically
2:42 Capture cryptic transmission
3:42 Detection 14 days earlier
4:30 Increased risk for heart attack, stroke or PE after COVID vaccination
5:31 30% increased risk with adenovirus vaccine
6:01 Plasma antigens and clinical course of hospitalized patients with COVID
7:01 Elevated baseline antigen levels and worse outcomes
8:03 Many patients already treated
9:10 Predictors of outcomes related to TBI
10:15 Measured proteins seen after CNS injury
11:15 If we can predict outcome we can apply therapy
12:03 End
Transcript:
Elizabeth: Looking in sewage for variants of SARS-CoV-2.
Rick: Is there an increased risk for a stroke or a heart attack after you've had a COVID vaccine?
Elizabeth: Can plasma antigens tell us how bad somebody's COVID infection might be?
Rick: And can we use proteins in the blood to assess whether someone is going to recover after a traumatic brain injury?
Elizabeth: That's what we're talking about this week on TTHealthWatch, 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 Texas Tech University Health Sciences Center in El Paso, where I'm also the dean of the Paul L. Foster School of Medicine.
Elizabeth: Okay, Rick, we've got three out of four back to our COVID stuff this week. Let's turn first to Nature. This was just an unbelievably information- and science-dense paper that was taking a look at detecting emerging variants early by looking at wastewater, specifically looking at RNA concentration in wastewater and a number of really impressive innovations relative to how to do that so that this could actually become a whole lot more practical than it is right now.
And just as a little bit of background, we are both aware that there are all kinds of wastewater testing that's already going on all over the world, in fact, to try to discern when SARS-CoV-2 is present, which variant is there, how many people might have it, and all of that.
In this case, they were looking in San Diego. They developed a technique using nanomagnetic beads with a high affinity for viral particles of all types. These are added to raw sewage samples. They capture the virus -- and all of the viruses, not just SARS-CoV-2 -- and then a robot with a magnetic head extracts the virus-bound beads in less than an hour.
They also developed a computational model that they call "Freyja," and Freyja is able to better identify multiple variants in a virally diverse wastewater sample and then estimate how these are related to other SARS-CoV-2 viruses that are hanging out or sublineages.
Very elegantly, they can do this not just with full-length RNAs and viral particles, but even little bits and with lots of confounders that of course are present in wastewater. What they were able to show was that they could find things way earlier. They say that they could detect emerging variants of concern up to 14 days earlier in these wastewater samples and that they can also identify cryptic transmission -- transmission that's not necessarily discernible clinically. They admit that one of the limitations of their study is that getting everybody all over the world up to speed on this is going to be a pretty big uphill battle.
Rick: Let's contrast that with how typically we detect it. Someone comes in, presents with symptoms, a nasal swab is done, it's submitted to a lab, and they look for specific variants. That already has a bias. There are a lot of people that won't get tested, they don't want to know or they don't have access. This goes against all those biases. It tests wastewater and, by the way, we all contribute to wastewater.
The thing that was really most remarkable to me was how they did his very fine analysis, looking at the whole genome, looking at all of the viruses and the different variants, and they were able to detect very small viral quantities.
I have to admit when they talked about doing this several months ago I thought, "There is no way they are going to be able to pull this off," because there is so much stuff in the wastewater and there is very low concentration of virus. But they have done both a special sequencing, a special analysis, and it's real. As you said, Elizabeth, they could detect special variants 14 days earlier than they could just by waiting for people to present with symptoms and testing a nasal swab.
Elizabeth: Clearly, it's something that the CDC has advocated. I'm just wondering, though, what the clinical utility of knowing 2 weeks previous to a variant presenting clinically might be.
Rick: You can geographically locate things to various parts of the city. You can identify variants that may or may not be responsive to previous vaccines and/or particular therapies, so you can make sure that either the vaccines that you would need or the therapies you would need are in the appropriate locations. This would be easier in some aspects than just doing nasal swab testing on thousands of different individuals. Also for other things, for example, can we detect monkeypox or can we detect measles?
Elizabeth: More to come. Let us turn to yours. You pose this question. Go ahead, pose it again.
Rick: Is there an increased risk for a heart attack or stroke, or even a clot in the lung -- pulmonary embolism -- following COVID vaccine in adults? Is it hard to tease out? Because we know that COVID itself is associated with an increased risk of clotting.
This is 46.5 million adults in France -- they were younger than age 75 -- who were hospitalized for either a stroke or a heart attack or a pulmonary embolism. There were over 73,000 of these events. They asked a simple question -- how many of these had the vaccine within 3 weeks of having that event -- and comparing it to individuals that did not have vaccination. They looked at, by the way, at four different vaccines, two mRNA vaccines with two doses, and two adenovirus vaccines, one with one dose and one with two doses.
What they determined is there was no association at all with the mRNA vaccines and the risk of any of those. However, with the first dose of one of the adenovirus vaccines, the Oxford AstraZeneca, there was a 30% [higher] chance of having a heart attack or a stroke within the second week after that vaccination. With the other adenovirus vaccine, there was an increased risk as well. This particular article is in the Annals of Internal Medicine.
Elizabeth: So really no action point here, other than high index of suspicion.
Rick: Right. But if someone has received an adenovirus vaccine, it needs to at least be on the forefront of some that's presenting with chest pain or shortness of breath or neurologic symptoms.
Elizabeth: OK. Let's stay in Annals of Internal Medicine. This is a study that's taking a look at plasma antigens and whether they are important biomarkers in predicting the clinical course for patients who are hospitalized with COVID-19 infection.
This is a really enormous study. In fact, pages of authors were cited. What they did was look at these plasma antigen levels from 2,540 participants who were enrolled in the Therapeutics for Inpatients with COVID-19 (TICO) platform from August 2020 to November 2021 with additional data on day 5 and time to discharge. The participants were all adults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms.
Basically, what they looked at was this plasma viral antigen level. That was all measured at a central laboratory, so there was no variation relative to these measurements. They basically found an association between elevated baseline antigen levels, which they drew these when they came in for hospitalization -- 1,000 ng/l or greater -- and outcomes including worsening of pulmonary function and an increase in time to hospital discharge.
They found a couple other things. All of this was much more common among men than among women. The severity of their pulmonary illness was associated with this plasma antigen level.
Rick: The more virus you have in the body or the more antigen, viral antigen, the more likely you were to have pulmonary issues.
And I agree with you, there were so many authors on this. This was conducted in 114 hospitals in 10 different countries. I thought they were listing all the people that got COVID infection. I have never seen that many authors before.
While it's intriguing, there are a couple of things you have to take a step back. First of all, there is just a single sample drawn. That was drawn at the time where the person was actually entered into the study. It's also mostly individuals that did not get vaccines, and then a large number of these individuals that had actually received remdesivir, so they already had been treated.
I wouldn't put all my money in the bank on this particular one saying, "Yes, more virus means in fact you're worse off," because we know that some of this is actually due to the inflammation associated, not the virus itself, but the inflammation that occurs. That's why anti-inflammatory agents are helpful in those with the most severe disease. But I do think it's intriguing and I think it needs to be followed up with additional studies.
Elizabeth: I'm very interested in this notion of how much viral replication may be taking place in your blood and how that might be impacting on your clinical course. Also, as we well noted, this biphasic nature of COVID infection and what exactly is happening at different times.
Rick: Elizabeth, they have actually measured the viral antigen levels in the lungs because that's the organ that's most severely affected and there is no correlation between that and pulmonary status. Again, it's an intriguing study, but I think there is a lot more needs to be done before we can clearly say, "Yes the more virus you have in your body the worse off you are." By the way, we need to track that over time.
Elizabeth: Finally, let us turn to your last one. What's that in?
Rick: It is in Lancet Neurology. This is individuals that have traumatic brain injury. Are there things that we can use to predict how well they are going to recover?
First of all, when someone has traumatic brain injury, we grade it based on what's called the Glasgow Coma Scale -- how their eyes respond, what their verbal response is, what their motor response is -- and we give them a score of 3 to 15 based upon that. 3 means you're comatose. 15 means you're actually in pretty good shape. Then we try to predict who is going to recover or who might not recover at all, or who might die.
There is a score used called the IMPACT score. You actually put those numbers into a calculator. It looks at your age, your motor score, your pupils, and it's somewhat good. But what we have noticed is that when you have brain injury there are proteins that were released into the blood as some of the neurons die. The two proteins that were released from damage in the brain, do they provide additional information over this calculator that we use?
They took a number of individuals, 2,552, that had traumatic brain injury. They did the usual score with a calculator and then they measured the protein as well and said, "Do these one-time measurements provide any information regarding whether someone's going to die or they were going to recover?"
That's exactly the case. Drawing these one-time blood samples do provide additional insight into mortality within 6 months. By the way, most of the patients die within 1 month. It also gave insight into whether the person would have an unfavorable outcome or not, but it didn't tell you who is going to have complete or incomplete recovery, so it does provide additional information -- by the way, only in the people that are most severely affected. If you have very mild traumatic brain injuries -- a Glasgow Score of 13, 14, or 15 -- it didn't really help.
Elizabeth: I think that this is clearly a useful thing to be able to prognosticate better. What about anything actionable?
Rick: Well, that's a great question, Elizabeth. If you're going to do studies to say whether something is effective or not, you need to have some predictor of what you think their outcome will be. Otherwise, you've got to have a randomized controlled trial.
But if we can accurately predict what we think their outcome will be, then we can apply therapy to everybody. It gives them a way to provide studies that might provide beneficial outcomes in smaller numbers of individuals.
Elizabeth: Let's just review. I mean, this is of course an extremely common phenomenon, TBI.
Rick: It is. In fact, I was looking at information from our hospital and saying, "Gosh, where are most of our traumatic brain injuries coming from?" They often come from motor vehicle accidents or falls. We're close to a military base and obviously people suffered traumatic brain injuries after being exposed to IEDs [improvised explosive devices] or explosions as well. Traumatic brain injury is fairly common.
Elizabeth: 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.