Molnupiravir and Long COVID; Shortness of Breath After COVID Infection

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 molnupiravir and long COVID, who is at risk for shortness of breath following COVID infection, beta-blockers after heart attack, and community health workers and early childhood outcomes.

Program notes:

0:34 Molnupiravir and long COVID

1:35 Did turn out to reduce eight of 13 post-acute sequelae of COVID-19 (PASC)

2:35 Benefited all vaccination groups

3:19 Who is at risk for persistent shortness of breath after COVID

4:19 Compared with a non-COVID community cohort

5:18 Weight loss helps

5:50 Community health works and at risk kids

6:50 Insured by Medicaid

7:50 Meet needs proactively

8:50 Thought they would decrease ED visits

9:20 Beta-blockers post myocardial infarction (MI)

10:20 Preserved heart function after heart attack

11:54 End

Transcript:

Elizabeth: Molnupiravir and risk of long COVID.

Rick: Determinants of recovery in people that have shortness of breath after COVID infection.

Elizabeth: Can community health workers improve outcomes for young children?

Rick: Is the long-established treatment following heart attacks really helpful?

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, how about if we turn first to The BMJ. This is a look at a molnupiravir and the risk of post-acute sequelae or so called long COVID.

This is really a huge study. It’s a VA study where they had just shy of 230,000 participants who tested positive for SARS-CoV-2 between January 2022 and January 2023, and had at least one risk factor for progression to severe COVID-19, survived the first 30 days after testing positive. Of that number, they had 11,472 who received a prescription for molnupiravir within 5 days of a positive test result and the remainder did not. What they wanted to see was, “All right, what happens with this so-called long COVID — or PASC, as we’re abbreviating it these days — in these folks?”

They had a pre-specified set of 13 post-acute sequelae, including death, post-acute hospitalization, and other sequelae. It did turn out that taking molnupiravir did reduce 8 of these 13 post-acute sequelae in these folks who took it within 5 days of their positive test result.

Rick: It was pretty remarkable. I mean, this was a medication that was not given to prevent the post-acute sequelae, but actually to reduce the risk of hospitalizations acutely with infection, and also reduce the risk of death, which it does very well. But it also reduces, as you mentioned, the risk of post-acute sequelae by about 14%. There is a 38% lower risk of post-acute death and a 14% lower risk of post-acute hospital admission. This is between 30 days and 180 days after the infection. This medication actually decreases replication of the virus. There are many people that believe that the ongoing replication is what causes the post-acute sequelae.

Elizabeth: Well, among this 11,000 plus people they were also able to subdivide into different groups and found that it did reduce the risk of post-acute sequelae (PASC) in people who had not received a vaccine, had received one or two vaccine doses, those who had had a booster dose, and in people who had a primary SARS-CoV-2 infection or reinfection. Among all of those groups, it was still able to reduce the risk of these sequelae.

Rick: Pretty much everybody falls in those groups. One of the things it doesn’t address — again, these are people that had at least one risk factor for progression to severe COVID. What we don’t know is whether people that don’t have these risk factors, whether this medication would be helpful or not, so additional studies in the works concerning this.

While we’re talking about this, Elizabeth, you want to talk about our other article dealing with COVID? Let’s transition over to The Lancet and we’re going to ask ourselves what determines how people recover after they have COVID and subsequently have shortness of breath.

This is one of the long COVID symptoms. We’re referring to those individuals that have had symptoms 12 weeks or more, gosh, over 3 months afterwards. Specifically, the symptom of dyspnea or shortness of breath. That affects about a fifth of COVID-19 survivors who experience shortness of breath for more than 6 months after they have actually had an infection. These investigators became interested in that and they said, “Gosh, I wonder if we can determine what risk factors predict who will recover — or who won’t recover — with shortness of breath.”

They used data from the 2 UK studies that were going on simultaneously. One was of patients who were hospitalized with COVID between March of 2020 and April of 2021. They also had a community cohort that also presented with respiratory symptoms, some of whom who had shortness of breath but they did not have COVID. They compared the two groups and also tried to assess what could determine whether they recovered or not.

They had over a thousand patients in the COVID study and over 3,300 patients in the concomitant community studies. They observed a higher odds of improvement from 5 months to 1 year if you were a younger, male, if you didn’t have obesity, no preexisting anxiety or depression, no cardiovascular disease, and a shorter hospital admission. Conversely, that means you were less likely to recover if you were older, female, obese, have pre-existing anxiety or depression, or cardiovascular disease.

Elizabeth: This constellation of factors really makes a lot of sense to me. I’m wondering what your thoughts are on intervention.

Rick: Is it the same risk factors that the community individuals had that didn’t have COVID infection? The answer is yes, it does. The authors posit that therefore things that are beneficial for individuals who have shortness of breath in the community and get better, it would be helpful for COVID. That includes primarily two things. One is losing weight because we know that that increases your lung volumes. There are also some pulmonary function exercises that can improve shortness of breath in people that don’t have COVID.

Elizabeth: That’s really good news, because those are exercises that can be done at home at an individual’s own discretion.

Rick: They are. They are designed to increase the respiratory reserve or the lung volumes, or lung function.

Elizabeth: Let’s turn, since we’re talking about what can be done at home, to JAMA. This is a look at community health workers and their intervention in early childhood well-child care for Medicaid-insured children to see whether they can have a benefit during that time period of a child’s life.

This is part of a study that’s known as the PARENT intervention — that’s the Parent-focused Redesign for Encounters, Newborns to Toddlers. This is in children younger than 2 years of age. It was conducted between March 2019 and July 2022. There were 937 parents and their kids who were enrolled. They were in California and Washington.

This is a team-based approach that uses a community health worker in the role of a coach. This person turns up at well-child visits, talks with the parents, and elicits a number of questions, or answers to questions, about how the child’s growing and behaving, and if there any concerns. They had in this cohort 73% Latino ethnicity and 63% with an annual income of less than $30,000.

They were insured by Medicaid, the majority of them, and we know that this is an at-risk population. Eighty-six percent of these payers or these families completed that 12-month follow-up.

What they found was there was actually no difference in the two groups — those who received the community health worker intervention and those who didn’t — in emergency department use. However, among other secondary outcomes, including psychosocial assessments performed, parents who had their developmental or behavioral concerns elicited and addressed, increased attendance at well-child visits, and better parental experiences with care received, it did help to have a community health worker on board.

Rick: These are mixed results as far as I’m concerned. The major reason for using these unlicensed community health workers and adding them to the well-child care team was to anticipate what the needs may be, meet them proactively to offload some of this from the physician, and as a result there would be fewer emergency department visits. Unfortunately, that didn’t prove to be the case.

The rest of the endpoints I consider fairly soft. I mean, helpful, but a little bit softer. Here is one of the things I think that the study doesn’t address. Was it the fact that we use these unlicensed community health workers — in our community we call them promotores — or was it just the fact that people spent more time with the kid and its parents?

Elizabeth: I would point out that these community health workers were trained, even though they weren’t licensed. They did have specific training, and also their model was that this coach would meet individually with the family at the start of their well-child visit for 10 to 20 minutes, but they could also intervene via phone or telemedicine within 24 to 48 hours of the in-person or telemedicine well-child visit.

I agree with you. I think that these are somewhat lackluster results and they were not what they expected. I think they are a priori hypothesis was that they were going to decrease the ED visits in this population.

Rick: I do agree with you though, Elizabeth, as well. We don’t have enough licensed health care providers. We don’t have enough physicians, nurse practitioners, physician assistants, social workers, counselors, and so using trained but unlicensed coworkers to step into the gap may be very helpful. But unlike the pilot study, which showed a decrease in ED visits, they weren’t able to demonstrate it in this larger trial.

Elizabeth: I think there is more to come on this one. Let’s turn to your final one. Gosh, everybody is using beta-blockers. Maybe we ought to think about something else.

Rick: Beta-blockers have been around for decades now. They are usually medications that end in -ol like carvedilol or metoprolol, or an older one, propranolol. Their initial use was in people that have had heart attacks. Administering these medications to people that had heart attacks early decreased the risk of death and hospitalization. That was 30 or 40 years ago.

Fast-forward now, our treatments are much better and we’re opening arteries sooner. We have other agents that are designed to prevent future heart attacks. The question is, are beta blockers still really helpful? In people that have had a heart attack and don’t have heart failure or decreased function of their heart, we know that beta-blockers are clearly helpful in that group. But what if you had a heart attack and your heart function still remains relatively normal? Do beta-blockers actually provide a benefit?

To answer this particular question, they looked at over 43,000 patients in Sweden between the years of 2005 and 2016 who had a heart attack and had preserved heart function. About three-fourths of them got a beta-blocker and one-fourth didn’t. They compared the two groups. What they discovered was the addition of a beta-blocker following heart attack did not really improve survival long term, specifically a year after their heart attack. And following them for another 4½ years, the use of a beta blocker did not seem to be particularly helpful.

Elizabeth: Let’s just mention that this is in Heart and this is a BMJ journal. Talk to me about using a beta-blocker. What’s that feel like? What are the downsides of someone being on it?

Rick: Overall, it’s a safe medication, but about as many as a fourth of patients feel either fatigue; sometimes they get depressed; it can obviously affect the mood. It’s like most medications, you only want to give it if it’s beneficial in some way.

Elizabeth: Would you suggest then to people who are on them that it’s worth inquiring whether they really need them?

Rick: That’s a very fair question. Again, if the heart function is decreased at all, beta-blockers have been shown to be helpful. But for those with normal heart function, the individuals should talk to their physicians.

By the way, this is a practice I have been doing for years. I thought the data were really pretty weak and gathered in a time that was decades ago. I wasn’t sure it was relevant. This study for me confirmed that my clinical suspicion was right.

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.