Predicting COVID Outbreaks Via Wastewater; New Medicine for Menopause

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 myocarditis after COVID vaccination, a new medicine for menopausal symptoms, heat-related deaths in the U.S., and wastewater surveillance for predicting COVID outbreaks.

Program notes:

0:47 COVID vaccination and myocarditis

1:49 25 to 31 years of age, most of them male

2:49 Don’t be dissuaded from vaccination

3:01 Long-term care facilities and wastewater surveillance

4:01 Compared with clinical picture

5:03 Negative predictive value really good

6:06 Heat-related deaths in the U.S.

7:06 People who are employed where heat is an issue

8:07 Shifting the workday

8:26 Treating vasomotor symptoms in menopause

9:26 Took a long time to accrue

10:32 Fifty percent reduction

11:32 Benefits to hormone therapy

12:40 End

Transcript:

Elizabeth: A new agent for managing menopausal symptoms.

Rick: Heat-related deaths in the United States.

Elizabeth: Looking at wastewater to predict COVID-19 outbreaks.

Rick: And inflammation of the heart after COVID vaccine.

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 dean of the Paul L. Foster School of Medicine.

Elizabeth: Rick, in light of the fact that we have a COVID outbreak that’s racing through the country once again — and we haven’t talked about COVID in quite a while — why don’t we turn first to JAMA and look at this issue of, if you get a vaccine, is it going to compromise your heart if you’re a young guy?

Rick: COVID vaccination can result in myocarditis. Now, even though it’s a very rare event, it has been recorded to be 30-fold higher in individuals that have had COVID vaccine than those that didn’t. How do these individuals fare? We have got three different causes of myocarditis: routine cause, COVID infection, or COVID vaccination.

To investigate how individuals do following myocarditis after COVID vaccination, these investigators looked at all individuals who were 12 to 49 years of age hospitalized for myocarditis in France from 2020 to 2022. If they followed these individuals over 18 months, how do they do with regard to hospital readmission for ongoing cardiac issues, other cardiovascular events, death, or the combination — the composite endpoint of all of those?

They were able to identify over 4,600 individuals that had myocarditis: 558 of those were after vaccination, 298 were after COVID infection, and almost 3,800 with just convectional myocarditis. They are relatively young. They’re between the ages of 25 to 31. Most of these individuals with myocarditis regardless of the cause were male. Then when they followed them over 18 months, those who had myocarditis due to COVID vaccination did much better. They were 45% less likely to have any of the outcomes that I mentioned than individuals that either got myocarditis after COVID infection or after conventional myocarditis.

Elizabeth: Let’s talk about the development of myocarditis secondary to infection. What is the hypothesis relative to the etiology?

Rick: There must be some cross-reactivity with the immune system recognizing normal tissue — that is, specifically the heart as being foreign — and it begins to attack it. I want to stress this is really rare. The vaccines do prevent COVID infection and the complications associated with it. I don’t want this report to dissuade anybody from having a COVID vaccination. This vaccine, and all vaccines, have a small risk, but the overwhelming benefit of them makes them worthwhile.

Elizabeth: Turning to The Lancet, then, and in staying with COVID material, this is a look at long term care facilities, which as we know normally house older people, and early-warning COVID-19 outbreaks in those facilities using wastewater surveillance. They termed this WBS, wastewater-based surveillance. This technique, of course, really came to the fore in COVID as a means of discerning, “Well, it looks like there is a lot of infection going on. Can we corroborate that?” In this case, what they are wondering is is it possible to actually predict that there is an outbreak that’s about to take place in this very at-risk population?

This was a multisite, 28-month-long study that looked at wastewater samples that were collected 2 to 3 times per week and tested for COVID using PCR. They also looked at two different antibody categories relative to whether your antibodies were related to vaccination or previous infection, or if they were current. They compared that with what they saw in all of the folks who were at these long-term care facilities, including the staff.

What they basically found was that sure enough you could use this WBS as an effective early warning system that would help to say, “Yep, it looks like we have an outbreak that’s incipient here. Let’s start to ramp up all of our measures in order to protect folks.” It would enable, of course, public health outbreak management ahead of a peak of an infection.

Rick: They had to have site-specific wastewater collection. All of the wastewater that drained from a building into a single manhole, is this a leading or is this a lagging indicator? Can it predict infection before it’s recognized clinically, or does it happen afterwards or even concurrently? According to their study, they suggest that in 60% of the outbreaks this was a leading indicator. Therefore, you could use targeted testing of these individuals. In about 23% of the time, it was a lagging indicator and the rest of the time it happened concomitantly. The negative predictive value was really good. If there wasn’t anything in the wastewater, there really wasn’t any infection.

Elizabeth: One of the reasons that I’m intrigued by this study is because this whole notion of surveying wastewater seems to me extremely practical. I know that we are conducting this nationally in lots of places and not just for COVID, but for other pathogens that could gain an upper hand and create a lot of problems.

Rick: There are two ways to use this. One is as a population surveillance. This is unusual in that it was very site-specific.

Elizabeth: Right, and I’m guessing that it’s going to gain a lot more ascendancy in terms of public health.

Rick: I agree with you. One of the limitations is if you’re looking at long term care facilities, a lot of the individuals wear diapers and that wouldn’t be in the wastewater. The other thing is, even after people have been infected and they have been cleared, they continue to shed the virus. It’s just some caveats, but overall again I think for population surveillance, wastewater analysis can be very helpful.

Elizabeth: I think we are going to see more of it. Speaking of more of it, let’s turn back to JAMA, a look at heat-related deaths in the US.

Rick: Elizabeth, I was surprised to find out that the warmest average temperature recorded since 1950 occurred last year. Recent research suggests that heat-related mortality is also increasing globally, but they have never done a formal analysis of heat-related mortality trends in the United States. That’s what the investigator attempted to do, is to look at heat-related mortality rates in the U.S. from 1999 to 2023.

They used data from the CDC and another platform that would allow them to combine death counts with population estimates. What they discovered is that over that 24-year period, there were about 21,500 deaths recorded as heat-related. It increased 117% in the number of deaths and a 63% increase in the age-adjusted mortality rate, and then a steady increase of about 17% per year from 2016 to 2023.

Elizabeth: They are not just old people. They’re people who are employed where they are being exposed to high rates of heat. I just saw — I’m sure you did too — development of these higher-tech ice packs that people are utilizing when they need to be in places where it’s really hot and they’re working outside.

Rick: In fact, that’s why they use age-adjusted mortality because, as you mentioned, you say, “Well, we have an aging population. It’s getting hotter and maybe the absolute number of deaths is increasing because they are older patients.” When you look at the age-adjusted mortality, that increased 63%. If we identify high-risk areas, and that’s pretty easy to do, because we’ve got a thermometer — you can figure out where the high-risk areas are. We need to increase expansion to access for things like hydration, public cooling centers, or buildings that have air conditioning so that even individuals with limited or transportation needs can get to the places that are cooler throughout the day.

Elizabeth: It also sounds like something that has been underway for quite a while in the transportation industry with regard to construction on major roads shifting the work day so that it’s in the cooler hours versus being out in the thick of it.

Rick: You’re right. Changing hours, making sure that there are required breaks, and a lot of education to workers. This kind of thing kind of sneaks up on you. People develop signs or symptoms of heat stroke with relatively little warning.

Elizabeth: Finally, remaining in JAMA, let’s talk about a new medication for the treatment of vasomotor symptoms, a.k.a. hot flashes that are associated with menopause. This medication is called elinzanetant. It is a selective neurokinin-1,3 (NK-1,3) receptor antagonist — yikes, there is a mouthful! It turns out that research has demonstrated that there are certain neurons that are involved in the development and propagation of hot flashes in women who are in this whole menopausal transition. These particular receptors are found in those neurons and this medicine then helps to eliminate their hyperactivity so that they can help to improve some of the symptomatology.

This describes two studies, OASIS 1 and OASIS 2. It seems like it took them a long time to accumulate a proper number of participants for these studies. Their participants were women aged 40 to 65 years of age who were experiencing moderate to severe vasomotor symptoms in the U.S., Europe, and Israel, and in Canada and Europe. It seems like a really big catchment area, a very common condition. It’s curious to me that it wasn’t an instantaneous kind of accumulation of the participants.

In any case, they randomized them to receive either this medication or a placebo and then they took a look at using various techniques, “Hey, what about your hot flashes?” They also looked at sleep disturbance and a quality of life indicator. Sure enough, the elinzanetant improved both sleep disturbances and quality of life at 12 weeks. They also reduced the number of hot flashes or vasomotor symptoms.

Now, I have to say that I thought it was a fairly modest reduction and then I would also say that the safety profile was favorable.

Rick: I’m surprised you described it as “modest” because about two-thirds of the women realized at least a 50% reduction in vasomotor symptom frequency at week 4 and, by the way, that continued on. You’d like for them to go completely away, but that’s actually not so bad. Now, you’re asking a guy about that. These women not only had fewer vasomotor symptoms, but also better sleep as well. I actually think that this will make a significant impact if it’s routinely available and also cost-effective.

Elizabeth: Clearly, as somebody who has had this experience, a reduction of 50% is really great and it would be really great to have it go to 0 or a much more substantial reduction. I would also say I want to talk about the role of hormone therapy in this because we still have that tale of the Women’s Health Study that’s precluding many women stepping into the space of taking hormone therapy.

We know that hormone therapy is very effective. While I applaud the basic science that is underpinned, determining where these things arise and how we can ameliorate them, I also think that there are some benefits to hormone therapy that are pretty powerful and we know it works. It’s also not very expensive.

Rick: Your point is well taken. Unfortunately, the trial didn’t say whether these women had tried estrogen or not, because while estrogen therapy can be very helpful some individuals aren’t responsive to it. There is a small group of individuals in whom estrogen therapy isn’t provided because of an increased risk of cancer. Having an alternative available for women, I think it’s very important.

Elizabeth: Finally, let’s mention that with regard to side effects, a lot of women reported headaches and there were also those who reported fatigue.

Rick: Elizabeth, as you note, about 7% of women will experience a headache and 5% to 7% experience fatigue with elinzanetant.

Elizabeth: We’ll be watching as this one rolls out. 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.