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.
This week’s topics include protection from COVID-19 vaccines versus from prior infection, effectiveness of a third vaccine dose, maternal use of antidepressants during pregnancy and childhood outcomes, and a new agent to treat COVID infection.
Program notes:
0:41 Vaccination versus infection
1:41 Makes intuitive sense
2:45 Infectivity of vaccinated people
3:19 Third dose of Covid vaccine impact
4:20 Very large dataset
5:20 Using an existing vaccine
6:04 A new monoclonal antibody for Covid
7:02 Attaches to a site that doesn’t mutate
8:03 If this is a part that doesn’t mutate why not vaccine target?
8:45 Impact of maternal antidepressant use
9:43 10,000 children born to moms who filled antidepressant scripts
10:34 9% of women develop depression during pregnancy
12:00 End
Transcript:
Elizabeth Tracey: What happens when moms take antidepressants during pregnancy?
Rick Lange, MD: Does past infection provide as much protection against COVID as vaccination?
Elizabeth: How about a third dose of a COVID vaccine?
Rick: And why do we need a new antibody to treat COVID infection?
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: 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: Ahhh, a return to COVID, Rick. I am going to let you go first. Which of those that we are talking about would you like to start with?
Rick: Elizabeth, let’s talk about vaccination versus getting an infection. Because I hear a lot of people say, “Well, I have had a COVID infection, therefore I don’t need a vaccination.” This is a report from MMWR, from the Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report, where they collected data from 187 hospitals across nine states of people that were hospitalized with COVID-like symptoms, so upper respiratory tract symptoms, pneumonia, and shortness of breath. They went on to test them to see whether they were COVID-positive or not.
They were able to divide these individuals into people that had previously been COVID infected — and therefore you think that they would be somewhat protected — and those that have received vaccination with one of the mRNA vaccines. They went on to say how often do these individuals with COVID-like symptoms actually end up being COVID positive.
What they discovered was that unvaccinated individuals who had previously been infected and recovered from their coronavirus infection were five times more likely to get COVID as people who had received both shots of either the Pfizer or the Moderna vaccines.
Elizabeth: I think this makes some intuitive sense. I can certainly hypothesize on why we think this would be the case. That’s because of the vaccines eliciting a multitude of antibodies, not just ones against a specific strain that someone might be infected with.
Rick: Not only that, Elizabeth, but a higher antibody titer as well, as it appears to be more-long lasting. The key to our listeners is although being previously infected does provide some protection, if you want to be maximally protected — even if you’ve been infected previously — is to receive the vaccine. Now, we usually recommend that you wait 90 days after you’ve been infected before you receive the full vaccine doses, but it appears to be more protective.
Elizabeth: I guess there is always this concern, though, about the availability of vaccines and how we’re rolling them out worldwide, and if we’re vaccinating people who have already been infected, that’s taking them away from places that don’t have them.
Rick: The vaccine, unfortunately, distribution is not uniform around the world. I don’t think it’s a choice — you have to do either or. I think you do both. That is, you want to receive maximum protection for everybody around the world, and infection alone just doesn’t do it.
Elizabeth: Were we going to mention also that brief piece in The BMJ?
Rick: Kind of a follow-up report, this is a short report from the British Medical Journal and it shows that individuals that have received vaccination and unfortunately they have a breakthrough infection — which happens rarely, but it does happen in at least 5% of individuals that have been previously affected — they are just as able to spread the infection to others as people that have been unvaccinated. That is, they have the same high viral titers. Now, they don’t last quite as long, so they are just as infectious as individuals that have not been vaccinated.
Elizabeth: More to watch out for. Let’s turn to The Lancet since we’re talking about the COVID stuff. This is looking at the third dose of a COVID-19 vaccine for preventing severe outcomes in Israel. Of course, we have all been watching Israel all along because it’s a small country, it’s had a very high rate of vaccination, they got out there early, so it’s very informative what’s going on there.
They employed a third dose of an mRNA vaccine. This was administered between July 30th of 2020 and September 23rd of 2021. They were matched, all of the folks who got the vaccine, to those who did not receive a third dose. They got it at least 5 months after their second dose.
So, their outcome measure was, of course, COVID-19 related admission to hospital, severe disease, and death. They just have, again, one of these ginormous data sets. After they were matched, the third dose and control groups each included almost 800,000 individuals, mean age of 52 years.
The effectiveness was evaluated at least 7 days after receipt of the third dose. I think that’s a really short follow-up period. But what they were able to show was that it was extremely effective. The efficacy was estimated to be 93% for admission to hospital, 92% for severe disease, and 81% for death related to COVID-19. So some powerful evidence that that third dose is a good thing to do.
Rick: Israel as a country got out in front of vaccinations more than most other countries around the world. They were able to get over 55% of their population vaccinated. Then what happened is they recently had their fourth pandemic and it stemmed from probably two things: the initial immunity beginning to wane a bit, and also the emergence of the Delta variant, which was more infectious.
What this shows is this third Pfizer dose was effective in protecting individuals who have a waning immunity and those exposed to the Delta virus as well. It’s pretty astounding — over 90% effective at preventing these severe infections, using an existing vaccine, not one that’s tailored to the new variant.
Elizabeth: As we have talked about before, I think what’s going to become apparent as we examine all of this retrospectively is that the true vaccination schedule, if you will, likely has to include a third dose some months after the second one.
Rick: And when they looked at subtypes, Elizabeth, it was just as effective in males as females, in individuals between 40 and 70 and those over the age of 70. Now, there were a few severe infections under the age of 40, so they weren’t able to comment on that, but it appears to be equally effective across these various subgroups. As you said, it’s likely going to become a component that we are going to routinely recommend.
Elizabeth: And I think we are also going to see some data emerge about mix and match, which is going to be really interesting too. Let’s turn to the New England Journal of Medicine. You posed this as, “Wow, do we really need another antibody against COVID-19?” That says to me, “Hmm, how is he interpreting this paper?”
Rick: Elizabeth, the monoclonal antibodies are one of the few treatments we have available for people that are actively infected. We give it early on in terms of infection and it binds to the receptor site of the virus, where it binds to the cells in the respiratory tract. We know that it prevents severe infection in individuals that are treated early. However, here’s the rub: that receptor site is the site that’s most likely to have genetic variances. So there has been concern that these monoclonal antibodies aren’t as effective as these new variants that make their way into circulation.
This is a really interesting study. It’s a neutralizing antibody called sotrovimab. It is an antibody that was actually made from somebody who had been infected with SARS-CoV-1 — that’s the original SARS virus, not the SARS-CoV-2 that causes COVID — and it doesn’t attach to the receptor. It attaches to a site of the virus that really doesn’t mutate. So it’s kind of a pan-coronavirus antibody.
It was administered 500 mg in a single intravenous dose to about 300 individuals and a 300-comparator group that didn’t get it. What they were able to show was it decreased hospitalization and death rate by 85%. Seven percent of individuals that didn’t receive the antibody experienced hospitalization or death, and only 1% of individuals who received the antibody. It seems to be incredibly effective. By the way, those that were hospitalized, none of the individuals that got the antibody actually were in the ICU. This is great evidence that this new monoclonal antibody may be effective.
Now, a couple of other things. One is, this may be able to be injected intramuscular, which would be nice — we don’t have to give an IV. Secondly, in the future, we may be able to combine it with other antibodies, some that would attach to the receptor and some that would attached to this other epitope that I have mentioned.
Elizabeth: I find that this notion of a pan-sarbecovirus monoclonal antibody is really attractive. I guess my question is if this is a part of the virus that doesn’t mutate, why aren’t we generating vaccines against this?
Rick: That’s a great question, Elizabeth. I am not sure that we’re not doing that. I just don’t know the answer.
Elizabeth: Hmm. I guess the other thing I would say about these antibodies is this adverse events, which I thought it was really curious they occurred more often in the placebo group than they did in the treatment arm.
Rick: Yeah. It appears to be a pretty effective and safe antibody for use in COVID-infected patients.
Elizabeth: Now, all we have to do is worry about the cost and the means of administration.
Now, we’re going to have a complete change of topic. We’re going to turn to JAMA. One of these questions — and I can’t even tell you how many times we’ve addressed, but once again, we’re addressing it — what is the association of maternal antidepressant prescription use during pregnancy, and this with the outcome of standardized test scores of Danish school-aged children? Of course, we love those things from Denmark and all those areas of the world because they just have such amazing databases and data collection.
They were looking at a retrospective cohort of children between January 1, 1997 and December 31st, 2009, who were attending public, primary and lower secondary schools in Denmark. Their age range was 7 to 17 years. The association was maternal prescription fill for antidepressants during pregnancy and, again, from their amazing register of the Danish prescriptions that they keep among everybody.
They had in this cohort 575,000+ children who were born during this period. Of that number, 10,000+ were born to mothers who did fill an anti-depressant prescription during their pregnancy.
The outcome was, this prescription fill was significantly associated with a poorer performance in mathematics assessments — a modest, I would say, poorer performance — but not in language assessments. About a two-point lower standardized test score in mathematics and really no impact on language. It adds to the evidence that if a woman needs an antidepressant during pregnancy that she ought to take it, because the potential deleterious impact of untreated depression during pregnancy seems worse than this outcome to me.
Rick: It’s statistically significant. This is on a scale of 0 to 100, there was a two-point difference. But clinically, it’s really irrelevant.
This is an important issue because about 9% of women who are pregnant actually develop depression. We know that this depression leads to or is associated with elevated risk of postpartum depression, preterm birth, and other perinatal complications. They can include child development, social, and behavioral problems.
Previous studies have suggested that the use of antidepressants during pregnancy doesn’t affect the outcome in the perinatal period — that is, in young children. This is the first study that I’m aware of that looks at it in a large population of older children as well to show that, in fact, it can be safe and therefore should not be avoided by mothers that have moderate or severe depression that doesn’t respond to psychotherapy or cognitive behavioral therapy.
Elizabeth: Right. As we know, pregnant women, and I think justifiably, are famously averse to interventions during pregnancy because of their concerns about what might happen to the fetus. We are seeing that right now, of course, with vaccination for COVID during pregnancy. My hope, at least for this, is that if you have moderate or severe depression and you’re pregnant, please get it treated.
Rick: That’s basically an analysis of the risk-benefit ratio. The risk of depression and the consequences are high, but the benefits of treating it effectively outweigh those small risks. So I’m glad you brought that up.
Elizabeth: Okay. 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.