NSAIDs and Severe COVID; New Asthma Antibody: It’s TTHealthWatch!

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 NSAIDs and COVID, neurological complications of COVID, use of antibiotics or tubes in middle ear infections, and a new antibody for severe asthma.

Program notes:

0:38 NSAIDs and severe COVID

1:38 Cohorts that did use NSAIDs compared with not

2:38 Should we continue in hospitalized?

3:35 Neurologic manifestations of COVID

4:35 Almost 6 times more likely to die

5:25 Acute asthma and a new monoclonal

6:29 Fewer exacerbations with monoclonal

7:30 Doesn’t require allergic type

7:45 Otitis media treatment

8:45 No difference in recurrent infections

9:45 Provide fodder for informed discussion

11:01 End

Transcript:

Elizabeth Tracey: Does use of NSAIDs lead to more severe COVID-19 disease?

Rick Lange, MD: How common are neurologic manifestations of people hospitalized with COVID?

Elizabeth: A new antibody for people with severe asthma.

Rick: For kids with inner ear infections, tubes or no tubes?

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, and also dean of the Paul L. Foster School of Medicine.

Elizabeth: Let’s do our COVID ones first, Rick. First, let’s turn to The Lancet Rheumatology. This is an ongoing issue of whether the use of NSAIDs actually results in more severe COVID-19 disease. People have been attempting to look at it in lots of different ways since, really, the pandemic began.

These, of course, are really, really important drugs for anybody who has an inflammatory disease, and I would say, “Hey, guess what? I use these things myself.” There was a concern about whether they resulted in more severe COVID-19 disease when people already were using them.

This is a study from the U.K. where they included patients of any age admitted to the hospital with confirmed or highly suspected COVID between January 17^th and August 10^th of last year, so pretty robust dataset.

Ultimately, they had 72,000-plus patients for whom death outcomes were available and then what they did was look at two different cohorts and they matched them, those who were taking systemic NSAIDs before the admission to the hospital and then those who were not.

Basically, they looked at a number of different outcomes, including invasive ventilation, non-invasive ventilation, supplementary oxygen, acute kidney injury, death, of course. They really, in this very extensive and attempting to correct for all these different variables study, found that this NSAID use was not associated with worse in-hospital mortality or any of these other secondary outcomes.

Rick: This is probably the largest prospective study of people admitted to the hospital with COVID-19 reported anywhere in the literature, so that’s of great value. As you mentioned, there was concern that people taking NSAIDs — non-steroidals — beforehand could have worsening infection and it appears not.

Here’s what it doesn’t answer. It doesn’t answer whether we should continue giving NSAIDs once people came in the hospital, so that’s going to require an ongoing study, but at least we can say that if you’re taking an NSAID now you don’t have to stop it if you’re going to be around somebody that’s been COVID-infected.

The great value of NSAIDs is they prevent opioid use if people have chronic pain syndromes and that’s why this is incredibly important, so this was a really good study. Again, large, almost 80,000 people who’d been hospitalized, but we need to do further studies to see whether NSAIDs can make COVID infection less severe because of the anti-inflammatory effects.

Elizabeth: Right, they mentioned that. They say that there’s an ongoing study right now that’s looking at the use of NSAIDs in people who are hospitalized. They also identified the most common ones that they use in the U.K., first of which was ibuprofen, but then the other ones, diclofenac, and then also COX-2 inhibitors, so they did examine those things. Things that I would ask questions about would be acetaminophen because so many people take that also.

Rick: Yep, so additional studies to be done. While we’re talking about hospitalized patients, can we go to the next study?

Elizabeth: Yes, of course.

Rick: This is in JAMA Network Open and it looked at the global incidence of neurologic manifestations among patients hospitalized with COVID-19. This is a consortium, and like your study, it’s a rather large study.

This was done at 28 centers at 13 countries in four continents. It was to identify how commonly neurologic manifestations occur and what are the most common ones, and then to ask the question, “Do they influence hospital mortality?”

Overall, there were about 4,000 patients included in this study. What they discovered was that a total of about 82% of these had some type of neurologic manifestation. The most common reported symptom was headache — about 37% of patients had headache — inability or loss of sense of smell or taste, and that was in 26% of individuals. The most prominent neurologic signs or syndromes were acute encephalopathy, which occurred in about 50% of individuals, coma in 17%, and stroke in 6%.

Those that had the neurologic signs or symptoms were almost six times more likely to suffer in-hospital mortality than individuals without neurologic manifestations. So Elizabeth, I’m surprised that the number was really quite that high.

Elizabeth: I guess one of my questions would be, what’s the relationship of the neurological complications to long COVID?

Rick: This particular one did not address that, but we know that there are individuals that do have ongoing neurologic manifestations. Some continue to have decrease or loss of sense of smell or taste; the headaches don’t usually persist for a long period of time, but we’ve talked about things like confusion — what people call COVID fog. This particular study couldn’t address whether these neurologic manifestations turned into some of these long-haul symptoms.

Elizabeth: Again, we’ll go back to that “more study needed” and undoubtedly somebody’s examining this. Let’s turn to the New England Journal of Medicine and our non-COVID material for this week. Acute asthma exacerbations are really an important cause of hospitalization and death, and worldwide, and we know that asthma’s actually increasing in incidence.

This is a report on a monoclonal antibody called tezepelumab and it blocks something called thymic stromal lymphopoietin, which is quite interesting. I was unaware of it previous to this, and this is a cytokine that’s implicated in the pathogenesis of asthma.

This is a phase III multicenter randomized international study, placebo controlled, including patients 12 to 80 years of age who had the tendency for these acute severe asthma exacerbations, and they were randomized to receive either tezepelumab or placebo subcutaneously every 4 weeks for a year. They also had a baseline blood eosinophil count. Overall, they had 529 assigned to receive the antibody, 532 to receive the placebo, and the great news is that those who got the monoclonal antibody experienced significantly fewer asthma exacerbations than those who got the placebo.

In the cohort who had the blood eosinophil count of less than 300 cells per microliter, they also experienced a benefit from the monoclonal antibody use. The frequencies and types of adverse events were not different, really, significantly between the two groups, although they did occur. So this looks like an important addition to the armamentarium for trying to help manage these people who have severe asthma exacerbations.

Rick: This monoclonal antibody, as you said, is directed against the cytokine. For those that may not be familiar, these are inflammatory proteins and this one’s not been targeted before. And about 10% of people with severe asthma have recurrence, despite all the things we’re throwing at them already, so it’s nice to have something else available.

As you mentioned, the monoclonal antibodies we have right now are really most effective in people that have a high number of eosinophils, those are the allergic white blood cells. This particular antibiotic doesn’t require a high number of eosinophils. It’s effective regardless of whether those particular allergic cells are around, so that’s good news as well.

Elizabeth: Right, a very important addition. Staying in the New England Journal of Medicine, let’s go to this issue of young children with recurrent middle ear infections, or otitis media, “Should we treat them with antibiotics or should we put the tubes in?”

Rick: This is an ongoing issue and it’s been controversial for a long period of time. This is done from a group that has done a lot of work with otitis medias.

We know that kids are most likely to get inner ear infections in the first couple years of life and they kind of outgrow it, but it’s those years where they’re developing their speech patterns and it’s important that their hearing is preserved. The issue is, when someone has recurrent otitis media, do you put in tubes or do you treat with just episodic antibiotics?

They randomized kids that were 6 to 35 months of age, and they had had at least 3 episodes of otitis media in the last 6 months or 4 episodes in the last year, so it was recurrent, and they randomized about 125 kids to have tubes put in, and 125 to continue episodic antibiotics and they followed them over the course of the next 2 years. What they discovered is in those two groups, that there was no difference with regard to recurrent infections.

OK. What are the caveats? Well, about 50% of the kids that were randomized to antibiotics ended up getting tubes placed, sometimes because the antibiotics failed to stop recurrent infections and sometimes because the parents just wanted it, so there was a lot of crossover.

Secondly, there were trade-offs. For example, the kids that had tubes in, they were more likely to have runny ears because there was fluid running out of their ears about 8 days over that 2-year period, but those that had antibiotics were more likely to have decreased hearing during that short period of time, more likely to have fluid in their ears as a result, so there is a trade-off.

In essence, I think what it boils down to is there’s no wrong therapy. If you decide you want to use episodic antibiotics, you can, and if they fail, then you can put tubes in. If you want to put tubes in, you can do that. You just need to know you’re going to have runny ears. What’s your take on it?

Elizabeth: Well, I did find the editorialist to be somewhat … I mean, the conclusion is somewhat lackluster, isn’t it, which is, this is going to provide fodder for an informed discussion between parents and providers. That’s really great. Having participated in many of those kinds of discussions for lots of other medical issues, I think parents have a high rate of anxiety, they want to do the best thing for their child, and I’m not really sure that this helps us to get to that conclusion.

Rick: You’re right. You want something definitive. You want to look the doctor in the eye and say, “What does the science show?” And the science says, “Well, it’s whatever you want to do is perfectly fine. There’s no wrong answer.”

I mean, if you want to avoid anesthesia in your child and don’t want to have scarring in the ear with tubes, then go ahead and put them on antibiotics. If you don’t want to have fluid behind the ear and you don’t mind runny ears, put the tubes in. You’re right. It’s not definitive.

In fact, he closes with the following statement, “Management decisions can be made jointly with a high degree of parental satisfaction.” I’m not sure there’s much satisfaction. I think there is a little bit of dissatisfaction because it’s not as definitive as parents would like. It’s “the data are what they are, and that’s what we are reporting.”

Elizabeth: Okay. On that note — and I think I’m betting that at some point we’re going to talk about this again — 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.