Nasal Sprays for Respiratory Infections; Paxlovid in COVID Prevention – Medpage Today

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 nasal sprays and upper respiratory infections (URIs), nirmatrelvir/ritonavir (Paxlovid) in prevention, endometriosis and ovarian cancer, and diabetes after COVID.

Program notes:

0:53 COVID infection and nirmatrelvir/ritonavir

1:49 Did not reduce infection risk

2:51 Not noticed a difference with variants

3:14 Nasal sprays, behavioral interventions for URI

4:14 Stress management might help

5:14 Reduced antibiotic use

6:14 Stress reduction makes us less susceptible

6:35 Type 1 diabetes and COVID infection

7:32 Attacks pancreas and accelerates progression

8:32 Same thing in adults?

8:42 Endometriosis and ovarian cancer risk

9:44 597 women with ovarian cancer

10:45 If they have same origin it might provide insight

11:45 Arises in the fallopian tubes

12:35 End

Transcript:

Elizabeth: Can nasal sprays reduce the duration of colds?

Rick: Diabetes after COVID infection.

Elizabeth: The relationship between ovarian cancer and endometriosis.

Rick: Can Paxlovid prevent COVID infection for someone who has been exposed?

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, it's been a bit since we have talked much at all about COVID. Our habit, of course, during the pandemic was to feature that material first. Now that we are having a pretty significant amount of COVID spreading around the country, why don't we turn to one of your two?

Rick: Yeah, Elizabeth, and I'm actually surprised that the infection rate has gone up, especially during the summer. It's interesting to note that initially if someone had COVID, the rate of a secondary attack among their household contacts was about 10% to 12%. But now with the new variants, it's as much as 60% to 80%.

All right. If we take Paxlovid, nirmatrelvir, and ritonavir -- because we know that that can be effective in high-risk individuals in reducing the severity of infection -- can we prevent infection in people that have been exposed to household contacts? [The study] took about 2,700 participants that did not have COVID at baseline, but they had a post-contact, someone in the household that did develop COVID.

They randomized them to receive either placebo or they received Paxlovid -- a typical dose -- either for 5 days or for 10 days, and what they discovered was statistically those who received Paxlovid did not have a decrease in the incidence of subsequent development of COVID. Those individuals that received placebo, only 3.9% developed COVID. For those that received 5 to 10 days of Paxlovid, the rate was about 2.4%.

You might ask why is the rate so low? Well, 90% of these individuals were already seropositive. They either received vaccines in the past or they had a previous infection. There were some side effects from taking the Paxlovid. They are relatively mild. The major one is dysgeusia -- that means an abnormal taste in your mouth. But the fact that it didn't significantly reduce the rate tempers our enthusiasm for giving it to a large population.

Elizabeth: Nobody wants to take anything that isn't really going to work. Let's mention that this is in the New England Journal of Medicine. Would this also suggest to you that maybe this variant is less susceptible to the machinations of Paxlovid?

Rick: That's certainly a possibility, because we know that the antibodies that we administered with the very early variants haven't been subsequently beneficial with the most recent ones. When we talk about Paxlovid in the treatment of individuals, we have not noticed a difference with variants. I'm not sure that explains it. Again, I think one of the major reasons is, so many people have been exposed or have been vaccinated that their risk of developing COVID after being exposed is relatively low and we can't get any lower with Paxlovid.

Elizabeth: Let's turn from here to The Lancet. This is sort of a corollary and maybe it could help as far as COVID is concerned. In fact, some of their populations did get COVID. It's nasal sprays and behavioral interventions compared with usual care for acute respiratory illness in a big primary care setting. This was in the U.K.

This randomized, controlled, open-label parallel-group trial of 332 general practitioner practices, and they enrolled adults who were older than 18 years of age with at least one comorbidity or risk factor that would increase their risk of adverse outcomes due to respiratory disease.

These folks were randomized 1:1:1:1, and they were either given 1) a gel-based spray of this material called carrageenan. This was 2 sprays per nostril at the first sight of an infection or after potential exposure up to 6 times a day; 2) saline spray, same behavior; or 3) a brief behavioral intervention where they were given access to a website that would promote physical activity and stress management. This is based on previous information from studies that suggested that those might reduce one's severity of upper respiratory infections; then 4) usual care. There were just shy of 12,000 who had complete data.

Compared with the usual care group, who had a mean of 8.2 days of illness, the folks in both the gel-based and the saline group had 6.5 days of illness. I would take that reduction, no problem. Then as far as the behavioral website, 7.4 days, so slightly less. That was kind of protective, rather than treating what was going on. That's their speculation. Then they did say that their most common adverse event was headache or sinus pain in the gel-based group.

The other thing that happened that was really great in this study was that everybody who participated in any intervention used fewer antibiotics. This sounds like this is a pretty quick and easy way to try to reduce symptomatology to make people feel better, and reduce antibiotic use when it comes to URIs.

Rick: Elizabeth, this was a really well-done study where they used a really low cost -- I mean, we're talking about saline -- nasal spray that's easy to administer and effective. If you have upper respiratory tract symptoms -- by the way, almost all of us have a cold every year -- it reduced the duration of the symptoms by 3 days. It reduced antibiotic use by 25% and I think it ought to modify how we treat individuals. It's one of those common reasons people visit their general practitioner, and they won't leave unless they get an antibiotic prescription. We know that contributes to antibiotic resistance. I think this is a really well-done study.

Elizabeth: I will say two other things about it. Their speculation, of course, is that what happens with the stuff in the nose, whether that's the carrageenan-based or the saline-based nasal spray, is that it mechanically removes the virus rather than allowing it to adhere and then do all of its stuff after that. They also note that this advice to use a physical activity and stress management website resulted in a modest reduction in the incidence of disease. Their speculation, of course, is that stress reduction relative to increased physical activity makes us less susceptible. That clearly is something I would like to see followed up and studied in a more robust way.

Rick: Yep. No, there are clear advantages to obviously keep your immune state healthy.

Elizabeth: Let's move on, then, back to COVID, and that's in JAMA.

Rick: We have previously reported that the incidence of type 1 diabetes seemed to increase during the COVID pandemic. Type 1 diabetes is an autoimmune disease. Something has triggered an immune response that attacks the pancreas. It's no longer able to secrete insulin, so we have to administer it. Based upon that information, what these investigators wanted to know is, if we have kids and they have presymptomatic type 1 diabetes, does COVID infection accelerate that where they will develop clinical diabetes over the next 3 to 6 months?

There were 509 kids, the average age was 4 years old, but it included individuals that were 1 to 6 years of age. What they were able to determine was that from February of 2015 to 2020 is that the incidence per 100 person-years of developing type 1 diabetes was about 6.4 for every 100 person-years. For those who developed COVID infection, that rate doubled.

This viral infection with the COVID virus somehow stimulates an immune response that attacks the pancreas and accelerates the progression to type 1 diabetes. When kids get a viral infection and their body attacks that, they also develop antibodies to their own pancreas. The fact that this occurs with COVID shouldn't be terribly surprising, but it's not really been proven in a way until this particular study was done.

Elizabeth: One of the things I have a question about is, what in the world is prediabetes and how do you identify that?

Rick: These were kids that had had blood tests that showed that they had autoantibodies to their pancreas.

Elizabeth: Why would you look for that?

Rick: This particular study was done in Germany. It was part of a screening program, Elizabeth, so we wouldn't typically do that, for example, in the routine clinical setting.

Elizabeth: What would you say are the practical implications of this observation?

Rick: We certainly need to be aware of this so that in kids that develop this or other viral infections, we certainly should be aware that they could develop diabetes. The other question you have to ask, is the same thing true in adults? The other implication is, do vaccines help prevent this? We can use this as a launching pad to see whether vaccines help prevent this and also to identify this condition in adults.

Elizabeth: Remaining in JAMA, let's turn to a study about endometriosis typology and ovarian cancer risk. I think that this whole picture of ovarian cancer has really been changing a whole lot. Most of the folks I talked to are saying that, gosh, in fact, it's not ovarian cancer at all. It's fallopian tube cancer that ultimately migrates its way to the ovaries and that in women who are at risk, or who have risk factors like BRCA1 or 2 mutations, prophylaxis and removing the fallopian tubes might be a good idea.

This study was informative to me in a lot of ways, this notion that endometriosis has a bunch of types and also that ovarian cancer does too. This is using data from the Utah Population Database (UPDB). They matched almost 79,000 women with endometriosis in a 1:5 ratio to women without endometriosis.

Their mean age at first diagnosis of endometriosis was 36 years. They had 597 women who developed ovarian cancer. It was higher in those women with endometriosis compared to those without, almost 4 times higher. Their risk of what is called type 1 ovarian cancer was especially high, 7 times higher.

The ovarian cancer risk is highest in women with two types of endometriosis: what's called deep infiltrating and/or ovarian endometriomas. For all ovarian cancers, we really need to carefully assess types of endometriosis and then subsequently potentially counsel women who have it that their index of suspicion with regard to developing ovarian cancer is also way higher.

Rick: Women that have endometriosis -- and about a third of them may -- it's associated with an increased risk of ovarian cancer. You said type 1 and type 2. The type 1 is generally slow-growing, less likely to spread, and more responsive to estrogen. The type 2 is faster-growing and it doesn't respond to estrogen. If they have the same origin, then the endometriosis may give us some insight into ovarian cancer, either prevention or treatment.

Ultimately, we would like to be able to screen for it. We know that if you just screen the general population, you don't do a very good job of identifying ovarian cancer early enough to treat it. But maybe if we take these high-risk individuals, maybe they are the ones that the cancer screening should be offered to and maybe it will be effective in that circumstance. For those reasons, I think this is a study that requires further follow-up.

Elizabeth: No question about that. I think that there are a couple of things that are noteworthy. This notion that endometriosis, which is often associated with cramping and really painful menses, could be, I'm going to call it, almost a masking against some of the early symptoms of ovarian cancer, which, as we know, are extremely nonspecific. I am wondering if women become accustomed to that feeling during their menstrual cycle if that's something that causes them to not be that tuned in to some changes that might predict ovarian cancer.

Then the other thing is that this idea that it really arises in the fallopian tubes has a lot of traction, and removing the fallopian tubes is fairly benign if you're finished with childbearing, and sounds like it could be something that would be a useful strategy.

Rick: If in fact the ovarian endometriosis is a risk factor for ovarian cancer, then maybe just removing the fallopian tube alone may not prevent that. The ovaries may have to be addressed as well.

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.

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Nasal Sprays for Respiratory Infections; Paxlovid in COVID Prevention - Medpage Today