Do Antibody Levels Predict SARS-CoV-2 Infection? A Pan-Sarbecovirus Vax
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 rates of type 1 and type 2 diabetes in U.S. youths, new USPSTF recommendations on screening for prediabetes and type 2 diabetes, antibody levels and COVID infection, and a universal vaccine for sarbecoviruses.
0:41 Antibodies and COVID immunity
1:44 Inverse relationship between antibodies and infection
2:45 Antibodies to wild type
3:45 Not only antibody levels important
4:10 Screening for prediabetes and type 2 diabetes
5:10 Moved to begin screening at 35
6:10 Less than 25% properly controlled
6:45 A pan-sarbecovirus vaccine
7:47 Develop a vaccine against parent level virus
8:47 Like a universal influenza vaccine
9:15 Increased type 1 and type 2 diabetes in young people
10:22 Type 2 increased 100%
Elizabeth Tracey: New recommendations for screening for pre-diabetes and type 2 diabetes.
Rick Lange, MD: Can antibodies tell you whether the COVID vaccine is effective or not?
Elizabeth: Increasing incidence of both type 1 and type 2 diabetes among young people in the U.S.
Rick: The potential for developing vaccines against current and future coronavirus.
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 of 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 preprint server medRxiv? This is clearly a preprint, but it’s taking a look at this important issue of whether antibodies can predict whether someone is going to be able to overcome a SARS-CoV-2 infection.
Rick: All right. Elizabeth, these are an analysis [sic] of the individuals enrolled in one of the Moderna mRNA COVID vaccine trials where they looked to see how effective the vaccine was, but also had antibody levels, four different types of antibodies, a couple of what are called binding antibodies to different parts of the coronavirus, and then neutralizing antibodies. Here is what they determined.
Well, first of all, we know that it’s 95% effective in preventing COVID infection. The next question they ask is, “How does that correlate with antibody levels?” They drew antibody levels 29 and 57 days after the vaccine and they followed them for 3 to 4 months, but then they correlated antibody levels to risk of infection for those 5% that actually got infected. What they determined was there was an inverse relationship. That is, the higher the antibody level, the less likely the individuals were to actually develop COVID infection. That suggests that there is a direct relationship between antibody level and infection.
They were even able to narrow it down to give kind of cut-off values. What they determined is that if you look at the day 29 and 57 antibody levels, for the people that had either the lowest amount or undetectable binding or neutralizing antibody, their effectiveness of the vaccine was only 45% to 60%. For those that had the highest level, it was above 98%.
What the hope is, is that we’ll actually be able to use the antibody levels as kind of a surrogate marker. If you develop a certain level, that would predict vaccine effectiveness and we wouldn’t have to wait for months and months, but we could determine it as early as 29 days after the vaccine was given.
Elizabeth: This seems like a hopeful strategy. One of the questions clearly that I have is that as variants are developing, what are we going to do about this antibody level? These are antibodies to that wild type that we had lo these many months ago.
Rick: There are several considerations about this trial. You mentioned one: how does this predict effectiveness against variants? Secondly is they just follow these people for 3 to 4 months and we actually want to know if it predicts vaccine effectiveness over the course of a year or 2 years. The third thing is, this just correlated with the risk of infection; it didn’t correlate antibodies with the seriousness of the infection. Were these patients hospitalized or not? There are additional information that needs to be done, but this is at least a preliminary investigation showing that the antibody levels may be a surrogate marker.
Elizabeth: I think the other thing that would be interesting would be to see about these antibody levels and whether they could predict whether somebody would really need a booster because, as you know, we’re coming into a lot of international scrutiny about whether we ought to be offering people boosters. What about if you could draw an antibody level and say, “You know what, your antibodies are so high you really don’t need one?”
Rick: There are several things that go in that. Because what accounts for an immune response are not only antibody levels, but the ability of your B cells to make additional antibodies, and then a T cell response as well. It may be that antibody levels, as we know, they decline over time. But if these other mechanisms are truly active, maybe the antibody level doesn’t tell the whole story a year or two down the road. As we begin to give boosters and develop more information, I think we’ll be able to ascertain whether antibody levels are really the whole story or not.
Elizabeth: Let’s turn to JAMA. The USPSTF has stepped into this space of saying what’s the screening recommendation relative to pre-diabetes and type 2 diabetes. No surprise to anybody, of course, that diabetes is increasing in incidence and we know tons and tons of information about the negative sequelae of that.
They reviewed all the literature as is their wont. They had 89 publications and they looked at differences between screening and control groups for all-cause and cause-specific mortality at 10 years. They also looked at harms, of course, and they came up with basically — and I’m going to make this really short — lots of things about overweight people. Sure, intensive glucose control with Metformin improves their health outcomes. Lifestyle interventions are also important with improving intermediate outcomes such as reduced weight, body mass index, and systolic blood pressure. They didn’t really change these recommendations significantly at all from the previous set that they had had, except for that they moved slightly younger in terms of maybe you should be screening people at 35 rather than 40.
Rick: Yep. The recommendation is for individuals 35 to 70 that are overweight or obese is to do some screening looking for prediabetes or diabetes. It’s estimated that about 13% of all U.S. adults over the age of 18 have diabetes and about a third meet the criteria for pre-diabetes. Complications, leading cause of kidney failure, leading cause of blindness, cardiovascular disease, liver disease, yada, yada, yada.
So you’re right. After all this review, it just lowers the age a little bit, but actually you can make the case that this is the group that’s likely to benefit the most, because they are more likely to have it for a longer period of time and to suffer the consequences. What you want to do is you want to identify it earlier and begin to address it.
One of the unfortunate things was when you look over the last 10 years we really haven’t moved the needle on having individuals have properly controlled blood pressure and sugar. Less than 25% of all Americans that have pre-diabetes or diabetes have properly controlled sugar and blood pressure. When you look at the minorities, it’s under 10% to 15%.
Elizabeth: Right. They identify this as stagnation of the management of diabetes, which is kind of a daunting term. I guess I would ask you, if people aren’t going to do these things, then what’s the point of even identifying them earlier?
Rick: Yeah. The group that’s particularly recalcitrant are young adults. We need to have new science, new ideas, and new frameworks for addressing this particular group.
Elizabeth: Let’s turn now to the New England Journal of Medicine, something that might be a bit more uplifting. Gosh, can we develop something that would actually intervene in all of the coronaviruses that are out there rather than just SARS-CoV-2?
Rick: I’m going to frame this up. We are going to talk about something called sarbecovirus. I’m going to help people think about it as a family tree. You have grandparents, you have parents, and then a group of kids. These are the ways that viruses are organized as well. If we think of the grandparent as being the beta coronavirus, we think about their kids as being sarbecovirus, and the grandkids as being the coronaviruses. They all share some genetic information, but they are not all identical.
In the coronavirus, we’ve talked before about the fact that the COVID infection isn’t the first coronavirus infection. We had SARS in early 2000, we had MERS in the mid-2010s, and then we have COVID.
They share about 80% of the genetic material. What that means is if you have a SARS or MERS infection, you’re not protected against COVID. If you had a COVID infection, you’re not protected against SARS or MERS.
But let’s take it a step further. Instead of developing vaccines against all of the children, what if we develop vaccines that were a step above that, the parent level, that’s called sarbecovirus? That’s what this paper addressed.
They took a group of individuals that had had MERS and SARS and they gave them the COVID vaccine. What they determined is by vaccinating against both of those they had developed antibodies not only against those viruses, but another eight or 10 that are variants. What the authors are saying is if we address one level up, develop antibodies to the sarbecovirus, it may take care of all the coronaviruses that we see now and in the future as well.
Elizabeth: All right, so talk to me about the model that they used for this.
Rick: What they talked about is a future vaccine that targets the earlier coronavirus — that is the SARS and the MERS — and a second vaccine, a booster, that targets the other family members. It will protect against a much wider variety of coronaviruses in the future.
Elizabeth: This is reminding me of this notion that one of these days, and in the foreseeable future, we’re going to have a universal influenza vaccine.
Rick: Bingo, that’s a great term. I wish I had used that. We’re talking about a pan-sarbecovirus, but what you’re talking about is a better term. It’s a universal vaccine. You just give it once. You may need a booster. It protects not only against what’s going on now, but the variants that come in the future and that’s a problem we’re addressing right now.
Elizabeth: I like this hopeful study, and I wish we could stop here, but we can’t. We’ve got to turn back to JAMA, something I’m going to make very short work of, basically this survey of what’s going on with type 1 and type 2 diabetes among individuals younger than 20 years of age in the United States.
To assess this, they looked at 6 areas in the U.S.: four geographic areas, and one health plan, and select American Indian reservations. The bad news is that there have been increases in both of these things, both type 1 and type 2 diabetes, and a greater percentage increase in the type 2 diabetes. Type 1 largely impacting non-Hispanic White youth as well as non-Hispanic Blacks and type 2 impacting much more often the Black individuals as well as Hispanic youth.
It’s unclear to me. We have, of course, lots of strategies for intervening in type 2 diabetes. I do not know why the incidents of type 1 is increasing — I’m not sure anybody else knows either — so trying to target that. We don’t have an intervention.
Rick: It’s unfortunate that over the 16-year period, type 1 diabetes in kids and adolescents has increased 50% and type 2 has increased 100%.
You’re right. Type 1 diabetes is a combination of environmental factors and genetic factors that predispose to people having an immune response to their pancreas. It’s not clear exactly what those environmental factors are. The genetic factors don’t change. Type 2 diabetes, though, that’s preventable. I mean, that’s due to primarily childhood obesity and inactivity as well. The fact that both have increased substantially over the last 16 years is disappointing.
Elizabeth: Very disappointing. Also, as you pointed out, relative to the USPSTF recommendations, the longer you got it, the more likely you’re going to develop the dire outcomes.
Rick: Yep. It’s important that, again, we get our hands right and address this early on, not only to kids, but to parents as well, because parents control a lot of the eating habits that obviously kids exhibit. And then it needs to happen at the school level as well.
Elizabeth: 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.
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