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 a nanoparticle vaccine for COVID, use of dexamethasone and surgical site infections, blood groups and disease propensity, and adverse events after vaccination for COVID.
0:38 Adverse events relative to the J&J vaccine
1:38 Syncope following injection
2:36 Primarily headaches
3:37 Clotting disorder after vaccination
4:37 Any neurological events
4:50 Dexamethasone and surgical site infection
5:51 Also had people with diabetes
6:53 Doesn't interfere with wound healing
7:09 A nanoparticle COVID vaccine
8:09 Two doses 21 days apart
9:09 Blood groups and disease propensity
10:09 No preset conceptions
11:07 49 associations with ABO and 1 with Rh
13:07 End
Transcript:
Elizabeth Tracey: Does blood type have anything to do with susceptibility to disease?
Rick Lange, MD: Is there an effective COVID vaccine against the South African variant?
Elizabeth: Can dexamethasone be used safely in people who are having surgery?
Rick: And complications related to the Johnson & Johnson COVID vaccine.
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 Texas Tech University Health Sciences Center in El Paso, where I'm also the dean of the Paul L. Foster School of Medicine.
Elizabeth: Rick, in view of the fact that we've resumed using the J&J vaccine, why don't we turn directly to that study first, along with the others that we're going to consider in that same realm?
Rick: Elizabeth, there are two issues related to the J&J vaccine that we'll talk about today. One is what's called anxiety-related adverse events and the other is the issue of particular clotting disorder associated with low platelet counts.
The first is addressed in the CDC MMWR -- that's the Morbidity and Mortality Weekly Report -- and it's related to five U.S. mass vaccination sites in April of 2021. They noticed an increased number of what are called anxiety-related complications associated with the deliverance of the COVID vaccines, and by the way, this was done before issues related to thrombosis or clotting were known about.
They were defining an anxiety-related event if anybody in the 15 minutes after the vaccine had things like fast heart rate, or rapid breathing, or difficulty breathing, or chest pain, but the thing they focused on primarily was syncope -- that is, fainting. What they discovered was these anxiety-related events, specifically fainting, was 164 times more likely to happen with the COVID vaccine than it was with the flu vaccine. The group that seemed to have the highest complication rate were those that were young, aged 18 to 29.
Now, by the way, none of these were serious, but they just mentioned the fact that we need to be aware of this, especially if we're going to be giving vaccine to younger individuals, so that's the first.
The second relates to more serious complications, the known incidence of what's called cavernous venous sinus thrombosis -- that is, clotting in the veins and the brain -- associated with low platelet counts in individuals that have received the J&J vaccine. This is a case report identifying 12 cases in over 7 million people that got the vaccine, so it's relatively uncommon but it's serious, and it's not associated with the other vaccines.
Of these 12 individuals, all 12 were women, mostly under the age of 50. They weren't taking oral contraceptives and they presented primarily with headaches, and that's about 6 to 15 days after they received the vaccine. It's always associated with low platelets, and it needs to be recognized and treated because about 25% of these women with this died.
Headaches can be common after the J&J vaccine. About 40% of people get them, but that occurs in the first 24 to 48 hours and it's just associated with the immune response, not with the thrombosis.
Elizabeth: A couple of things that I think I'd like to follow up on. One is with regard to this idea of syncope following vaccination. I mean, that's an extremely common phenomenon kind of all over the map. Why do you suspect it appears to be increased relative to the COVID vaccine?
Rick: Well, Elizabeth, that's a great question. I mean, they compared it to the flu. It may be just a reporting thing. Because of the newness of the vaccines for COVID and the reporting that's been done, it may be that people more vigilant about it. There may be heightened concern because it's not FDA-approved, but again, they do remind individuals that they need to be followed for 15 minutes afterward. But again, I don't think it's anything serious.
Elizabeth: Let's turn to the other serious side effect. I just saw in some of the reports that there was one male who's just been reported who experienced the same phenomenon. I guess the only thing I can take home from this is that if you're a week or so post-vaccination and you develop a headache, you ought to go and seek care.
Rick: Absolutely, Elizabeth. There are a couple of blood tests. These were individuals that had low platelets, so they needed to have their platelet counts, and they can look for what's called an antiplatelet antibody or a heparin platelet factor 4, a HIT antibody specifically, for our medical providers that are listening.
These are people that didn't receive heparin, but we know that there's a similar event that happens to people that receive heparin. They develop an antibody to the platelets that causes them to clump together and there may be something in the vaccine that produces the exact same antibody, because 11 of these 12 individuals had heparin platelet factor 4, HIT antibody.
If individuals do have a headache a week to two afterward, especially associated with nausea or vomiting, any neurologic events, they need to go be evaluated by their primary care physician and may also need to be seen by a neurologist or a hematologist. They certainly need to have their blood checked.
Elizabeth: Okay. Let's turn to the New England Journal of Medicine. This is a look at dexamethasone and surgical site infection. Of course, we've been hearing a lot about dexamethasone relative to COVID. This is, of course, a non-COVID indication.
There has been all kinds of conversation about the use of dexamethasone during surgery, or actually, administered right before surgery, because it helps to prevent nausea and vomiting afterward, but there's a concern about surgical site infections and whether it might predispose folks to get that.
This is a really big study, almost 8,900 people, international non-inferiority trial where they enrolled folks who were having non-urgent, non-cardiac surgery of at least 2 hours' duration with a predicted skin incision length longer than 5 cm and a post-operative overnight hospital stay to receive 8 mg of intravenous dexamethasone or matching placebo while they were under anesthesia.
They also had a subgroup, I'm going to call it in here, who had diabetes because there's a concern, of course, that those folks who have diabetes might be even more susceptible to adverse events relative to the use of dexamethasone, since they're already susceptible.
Post-operative nausea and vomiting in those first 24 hours after surgery occurred in about 42% of the patients who received dexamethasone and about 54% of those in the placebo group, so it seems like it was helpful.
With regard to hypoglycemic events in those without diabetes, that was very low, and with regard to this issue of infections, there was essentially not much in the way of difference, and so it looks like, "Hey, it's probably okay to use this."
Rick: Yeah. This is a good news report, Elizabeth. We know that long-term steroid use is associated with an increased risk of surgical site infection, and also where the wound fails to heal. The question is, will this one-time dose also have those same side effects? Dexamethasone is effective in helping preventing nausea and vomiting after surgery. By the way, those of us that have had surgery, we can appreciate that.
It's nice to know that this steroid, which has a half-life of up to 72 hours, really doesn't interfere with wound healing and it certainly doesn't increase wound site infection, so this is a great study.
Elizabeth: We love these things. Simple questions, great answers, and positive outcomes. Let's move on. Let's go. We're staying, of course, in the New England Journal of Medicine, and this is looking at an entirely different type of COVID-19 vaccine.
Rick: There are three approved in the United States -- obviously the Pfizer, the J&J, and the Moderna vaccine -- two mRNAs and one adenovirus vaccine. This is a new vaccine, a nanoparticle vaccine, which hasn't been approved in the United States yet. It's made by Novavax, but we know that in early phase I and phase II trials, it elicits a strong neutralizing antibody response and also T-cell responses that are effective in preventing disease.
This trial was conducted in South Africa. We know that the South African variant has become the most prevalent variant there and there's concern that vaccines, particularly the AstraZeneca, aren't effective in this particular variant. In this phase IIA/IIB trial, they looked at over 6,000 participants ages 18 to 84 -- most of which were HIV-negative, but there was a small group that were HIV-positive -- that received two doses of this particular vaccine 21 days apart.
A third of these individuals that were in the study were already seropositive for COVID, but they looked at those that hadn't had it, and in the individuals that received the vaccine compared to placebo, the vaccine was about 50% effective in preventing infection, with the vast majority of these -- 93% of them -- being the South African variant. By the way, when they looked at the individuals who are HIV-negative, the efficacy in the vaccine was about 61%.
Elizabeth: Potentially good news, of course. Among all these COVID-19 vaccines, this is something that has to be kept at super-cold temperatures, and then why do we need to have two administrations of the vaccine? What is the peculiarity of the nanoparticle formulation?
Rick: Like the mRNA vaccines, the first dose is the one that confers some immunity and the second one seems to confer durability. With regard to how this vaccine was stored, there wasn't any information in this particular study. I'm unable to answer that.
Elizabeth: Yeah. I guess I'm trending toward -- and I bet you are too -- really like these shelf-stable single-dose vaccines, if it's possible. More to come, no doubt.
Let's finally turn to a journal that I don't think either one of us ever heard of before. It's called eLife and it seems, to me anyway, to be part of this burgeoning bunch of journals that all have their purported objective of trying to reduce barriers to publication and get things out more quickly so that research can go forward with dispatch, and so I think that's a laudable goal.
In any case, what these folks did was they took a look at ABO and Rh blood groups and phenome-wide disease risk, and they call this an agnostic study of associations. I'd, before we even start talking about it, like you to define agnostic study.
Rick: This is the largest study that's investigated blood groups, A, and B, and O, and Rh factors, and disease occurrence in an effort to find novel and also to confirm previously known associations. They didn't do this based upon a specific preset conceptions of specific disease categories and looked at possible associations. They looked at all blood groups and all diseases. They were able to do that because this is a very large population studied. It represents one-third of the Swedish population. This effectively removed researcher bias, so that's why they called it agnostic, and by the way, all this data was collected prospectively.
Elizabeth: Really? I thought, "Agnostic, isn't that interesting?" It's unclear to me whether it really is possible to remove bias, and I'll just put that out there. We don't have to discuss that right now.
You're right, so they used this SCANDAT3-S, a comprehensive nationwide blood donation transfusion database. They modeled outcomes for over 1,200 disease categories, and that represented 70 million person-years of follow-up accruing from 5.1 million individuals. I'm always persuaded by these giant ns, and this is certainly one of those.
When they queried this whole thing and approached it exactly the way you've described, they discovered 49 associations with the ABO groups and one with the RH blood group that was disease propensity, if you will. As far as novelty was concerned, they really didn't come up with a lot of novelty, at least in my estimation. Did you have thoughts about that?
Rick: No, Elizabeth. Again, it's association. They also mentioned that the associations are relatively mild and you wonder whether some of this is driven by diseases that are associated with ABO in other ways. For example, if you identify that ischemic heart disease is associated with a blood group, well, anybody that has ischemic heart disease are more likely to be tested for diabetes, and high cholesterol, and things of that nature. Whether there actually is a causal association or not is really unknown. It's interesting, but where do you take this? That's really what's up in the air right now.
Elizabeth: I think one of the places where it's potentially practical is we certainly were examining blood groups and propensity to develop severe COVID-19 disease, for example. And so if there's some way that this could be translated into a higher vigilance relative to blood group for certain diseases or conditions, that might be a reasonable thing to do.
Rick: Okay. The other thing, obviously, is to validate this in other cohorts because this is a Swedish population. It's very limited in terms of racial and ethnic diversity. But also, if you identify an association, and use it to investigate whether there is some honest mechanistic approach or some causal and biologic interaction that people can identify.
Elizabeth: Yep, I agree, but still really interesting. You have to admire these folks for taking on this giant data crunch.
Rick: Agreed.
Elizabeth: On that note, 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.