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Astra Vax and South African Variant; Post-COVID Depression: 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 the AstraZeneca vaccine and the South African variant, spread of the U.K. variant in long-term care facilities, depression after COVID, and vaccine efficacy in solid organ transplant recipients.

Program notes:

0:44 Immunogenicity of vaccines in solid organ transplant recipients

1:44 Positive antibody test in 17%

2:44 Intensive immunosuppressive therapy

3:42 Pool small compared to general population

4:46 Vaccine efficacy against South Africa variant

5:46 Antibodies but not protective

6:48 Depression after COVID

7:48 Mean age 38 years

8:35 Variant spread in long term care facilities

9:35 Short time period

11:00 U.K. variant found domestically

12:03 End

Transcript:

Elizabeth Tracey: Do vaccines work in people who’ve had an organ transplant?

Rick Lange, MD: Is the AstraZeneca vaccine effective against the South African variant?

Elizabeth: What is the rate of depression in people who’ve had COVID-19?

Rick: And spread of the UK COVID variant in long term care facilities.

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, where I’m also dean of the Paul L. Foster School of Medicine.

Elizabeth: Rick, in spite of our best efforts we’re back to all COVID again this week. Why don’t we turn to JAMA? This is one that’s homegrown. It’s from Johns Hopkins, and it’s taking a look at the immunogenicity of a single dose of a messenger RNA vaccine in folks who’ve had a solid organ transplant, in this case, largely kidney transplantation.

As we know, these people are immunosuppressed because in order to keep their bodies from rejecting the organ they often are on multiple different meds in order to keep their immune systems damped down so that the organ survives.

In this case, they took a look at 436 transplant recipients. None of them had had a prior PCR test confirming a diagnosis of COVID-19. Their median age was just about 56 years. About half of the group received the Pfizer vaccine and the other half received the Moderna vaccine. They looked for their immune response based on two different types of antibody tests.

It was pretty scary. It turned out that the rate of conversion to a positive antibody test was only 17% among this group. Older transplant recipients were among those who were less likely to develop an antibody response.

The scary part about this, of course, is the idea that not only are these folks more susceptible to infection with SARS-CoV-2, they could also be those people in whom — when they become infected they turn out to be the perfect place for the development of variants.

Rick: It’s not terribly surprising, I think, to either one of us, or probably to our listeners, that people that are on immunosuppressive therapy are less likely to mount a robust immune response.

Now, a couple of things about this particular study. One is it only looked at the mRNA vaccine, and this was antibodies tested after only the first dose. Secondly, the antibody test was a semi-quantitative test — just says, “Is the antibody there or not?” And the last thing is it doesn’t measure T-cell response.

Having said all that, neither one of us is surprised that people that are on intense immunosuppressive therapy will have a less antibody response. I don’t think either one of us would recommend that these individuals not get immunized, because they’re the ones that are most likely, as you said, to get infection and to have a more severe infection as well.

Elizabeth: I’d like you to comment on this idea, though, that these folks who are immunosuppressed could be people in whom the virus really gains a lot of traction. We’ve seen case reports of this, where somebody has still been shedding infectious virus literally months after their initial infection.

Rick: I’m going to push back a little bit. You said that they’re still shedding infectious virus. There were clearly viral particles detected, but it looks like for the vast majority of individuals, the infectious time period is relatively short. Now, we don’t have a lot of data. Do I think that they’re more likely to develop variants than other individuals? Probably not. However, they are more likely to develop an infection.

Fortunately, the pool of these individuals is relatively small compared to the general population. If you have 100 million people infected, they’re more likely to have variants because of the vast number than there are 10,000 individuals that are immunosuppressed. Would you agree with that?

Elizabeth: I am going to respectfully disagree with you here, and I’m going to put a little notation out there that I suspect we’re going to talk about this again, because there was the case report of the immunocompromised person who shed infectious particles for months. And my belief is that we’ve got a lot more immunosuppressed people out there than we’ve ever had in history, and I’m just guessing that we’re going to find out some pretty important stuff relative to following them.

Rick: Well, again, one of the important messages, that regardless of whether people get vaccinated or not, we still need to do the other measures that we know prevent spread, because even in those people that are immunocompetent, at least 5% of those may still get infected, even with the most robust vaccines.

Elizabeth: So speaking of vaccines, why don’t we turn to an abstract that we saw this weekend in the New England Journal of Medicine? This is taking a look at, “Wow, hmm. Do we have vaccine efficacy against the variant from South Africa?”

Rick: Right, and so this is called the B.1.351 variant. There has been concern that the South African variant may not be as responsive to antibodies or to the vaccine because the vaccines we developed were done prior to the introduction of this into the population, so the AZ — or the AstraZeneca — vaccine, and this particular analysis looked at its administration in South Africa.

This is individuals that did not have HIV, so they weren’t immunocompromised. They were 18 to 65 years of age, and they either received placebo or they received two doses of the AstraZeneca vaccine 21 to 35 days apart. Did they in fact develop antibodies? And then they looked at the rate of mild to moderate disease.

What they discovered, of over 2,000 HIV negative individuals, half of whom received the vaccine and half of whom received placebo, when they looked at antibodies they could clearly find antibodies in those that received the vaccine. But then when they looked at whether they developed infection or not, that’s what was concerning: 3.2% of the placebo patients versus 2.5% of those that received the vaccine still developed mild to moderate disease. That puts the vaccine efficacy at only about 22%. Of the individuals that got infected, how many of those actually had the South African variant? It was about 93%. By the way, in those individuals, the vaccine was only about 10% effective.

Elizabeth: Yeah. This is very concerning, of course, and there’s lots and lots of discussion about modification of the mRNA vaccines so that they can accommodate the fact that these variants are popping up.

Rick: That’s currently under study. Both Moderna and Pfizer have developed new vaccines, a single dose targeted specifically toward this variant. Hopefully soon we’ll be reporting on that. Those studies are going on right now.

Elizabeth: On that hopeful note, let’s turn to JAMA Network Open. We’re, of course, hearing lots and lots about long-term sequelae or so-called “long-hauler” COVID-19 disease, and one of the things that we’ve also been hearing a lot about is all the mental health issues that have been surrounding the pandemic. This is a research letter taking a look at symptoms of depression and that association with acute symptoms of COVID-19.

They have been looking at a number of surveys that they have been conducting monthly between June 2020 and January 2021, a lot of surveys, 82,000-plus. Of that number they identified 3,904 who had prior COVID-19 illness and completed the survey questions that were used in this particular analysis.

The analysis is looking at symptoms of major depressive disorder, and they have 9 items that they scored and a score of 10 or greater is considered to be moderate depression. The mean age of these respondents is only 38.1 years, about half of whom were women, slightly more men, and a range of ethnicities also. A total of 52.4% met the criteria for symptoms of major depressive disorder. I thought that that was a rather astonishing number.

Interestingly, to me, women were less likely to have these symptoms than the men were in the study, and also, the likelihood of symptoms decreased with increasing age. So once again, this is underscoring that symptoms of major depressive disorder may very well follow COVID-19 disease and maybe need to be considered as part of the constellation of things that attend long-term sequelae or long-hauler.

Rick: Elizabeth, this study clearly establishes that one needs to look at the neurocognitive or neurobehavioral consequences, and we don’t know what percentage of these individuals had depression beforehand. Is this a recrudescence, or did they have active depression and were less likely to recover from it, or did the disease somehow make them more likely to develop it acutely and newly diagnosis?

I did find it interesting, as you did, that the older you are the less likely you are to get depression. It also seemed to correlate with severity of illness, by the way — that is, the more severe the COVID symptoms, the more likely someone was to have depressive symptoms as well, and of all the symptoms that people developed with COVID, the one that seemed to correlate most with depression was headache. We clearly need to pay attention to this.

Elizabeth: Yeah. Among the whole constellation of things that are developing regarding mental health and the pandemic, this is one more concern and one more pressure on that group of practitioners.

Rick: Yeah, and so we need to begin to use this information so we can examine how to mitigate this elevated risk of depressive symptoms following acute COVID infections.

Elizabeth: Finally, let’s turn to our last one. That’s also in the New England Journal, and this is taking a look at long-term care facilities and what’s going on there.

Rick: Specifically, the spread of this U.K., United Kingdom, variant. I thought this was really very interesting. We hear reports of the spread in Europe, and specifically in the United Kingdom, of this particular variant because it’s more infective. It’s thought to be 40% to 70% more transmissible. It’s also associated with increased mortality that’s been recently shown.

This particular study looked at, “How rapidly did it spread, specifically in long term care facilities?” These are individuals that are obviously relatively isolated and their only exposure primarily is to staff. What they did was they looked at over 140, almost 144,000 samples of blood that had been obtained from staff and residents of long term care facilities throughout England.

They determined that over 4,400 — that is about 3% of them — were positive for COVID. Then when they looked at the variants, what they discovered is that in a relatively short period of time, from mid-November to mid-December, that the percentage of variants increase from about 12% to 60%. That’s in one month, Elizabeth.

Then they even examined it by various regions. They could kind of follow it from where it went from the southeast region to the east region and then went up to London, and in all of these particular regions it started in the low double digits, — 10% or 15%, again — to as high as 50% to 70% in a very short period of time.

Elizabeth: Yikes, and of course, we’ve identified that variant right here in the US.

Rick: It is. In fact, that’s the most prominent variant here in the US. We have a relatively small number of the South African variants, primarily in the Mid-Atlantic States, a very small number of the Brazilian, but over 1,000 cases of the UK variant here in the United States. Antibody data would suggest that the current vaccines do provide protection against it, but it’s only effective in individuals who’ve gotten the vaccine.

Elizabeth: Once again, that same old, same old. Distance, wear your mask, wash your hands, and try to avoid getting infected.

Rick: And do everything we can to provide vaccine to these, our most vulnerable population.

Elizabeth: Okay. On that note, 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.