UVM Researcher: Antibody Response To COVID-19 'Bodes Well' For Eventual Vaccine

This week, the University of Vermont released new researchregarding the relationship between COVID-19 antibody levels and disease severity. To listen to this interview, head here.

Vermont Edition spoke with Sean Diehl, an associate professor of microbiology and molecular genetics at the University of Vermont's Larner College of Medicine. He led a study with several other UVM colleagues looking at COVID-19 antibody production and discovered that patients with more intense and serious symptoms produced more antibodies than people with milder cases, contrary to what some had assumed might be the case. 

Our guests are:

• Sean Diehl, associate professor of microbiology and molecular genetics at the University of Vermont’s Larner College of Medicine
• Tracy Dolan, deputy commissioner for the Vermont Department of Health

Broadcast on Oct. 20, 2020 at 1 p.m.; rebroadcast at 7 p.m.

The following interview has been edited and condensed for clarity. You can listen to the full episode and find Deputy Health Commissioner Tracy Dolan's remarks, here.

Jane Lindholm: So what was it that you were actually trying to figure out with this study? What was the problem you were trying to sell for? 

Sean Diehl: We were originally puzzled by the higher level of disease in men and in aged individuals. We focused on a kind of antibody that is like a little heat seeking missile that binds to the virus and prevents it from getting into other cells. These are protective antibodies. So we thought, well, could it be that men make less of these, or that older people make less of these antibodies, and maybe that's why they're at increased risk of disease? 

But we actually found that men make just as high levels of these antibodies as females and also that our oldest patients, even out to 93 years of age, made very robust antibody responses that were on par with those from people five decades younger than them. 

As I understand it, one of the questions about this antibody production was: for people who were getting very sick, are their bodies producing high levels of antibodies? Maybe they're getting sicker because they don't have a lot of antibodies. And that's not what you found. In fact, you didn't find a difference between men and women or older people and younger people. What does that actually tell you? 

We think that what that's telling us is that in those individuals with the highest antibody levels - that's probably reflective of how much virus was being produced in their bodies. 

The focus in this part of the study was on people who were hospitalized for COVID-19, so that was one arm of our study. And we found that the sicker patients were, the higher antibody count they had. 

This is likely reflective of an arms race between the virus and the immune system during this early period, but the antibodies, after that point, will probably lead to longer term protection.

So there is a sense that if you had a more challenging case — if you had more symptoms, if you were sicker — you might also have more protection if you've survived it?

Based on what we know about other viruses, we do think that's the case — that if you resolve your infection with a very high level of antibody, even when there's a little bit of attrition of that antibody response as it slightly goes down over time, that will still leave you with a high level of protection. And we know that now from the original SARS virus. 

Back in 2003, you may recall, there was a virus called SARS coronavirus that affected a few places in the world. Scientists in Singapore have gone back to patients who had the original SARS [CoV] virus 17 years ago and then measured their antibodies this year. And they still have very high levels of blocking antibodies, 17 years later. 

Do you expect that to be the case for COVID-19? Because I thought I had been hearing that there was a sense that many people might not have antibodies show up now, even six or seven months after they got the case. Do you think that might apply to people who had milder cases, but not necessarily those with more severe cases? 

I don't think that will be broadly the case. These individual patients may have slight differences in how they make antibodies and the level of virus to which they were exposed at a given time. So it's hard to say on a per person basis whether or not someone will make a really high level of antibodies. We don't have that level of prediction yet. But on the whole, this virus is very much related to the original SARS virus, and that one induced long-term antibody responses. And so I expect that this one will do that as well.

The interesting part about looking at antibodies is that right after an immune response, right after the virus infection, you get a really big boost in antibodies for these kinds of viruses. And then they wane a little bit after a few months. But then when you start looking out from many months to years later, generally these antibodies are kept at a high level, but not as high as they were at the peak of the infection. 

So where we are in this pandemic… eight months later, we're right in this phase where it looks like antibodies are waning. But we haven't had enough time to really show that long term stabilization of the antibody levels yet.

So, Sean, you mentioned that there doesn't appear to be a difference, in terms of people who have antibodies after a case of COVID-19, among men or women, old or young; it's not determined by those demographic prescriptions. 

But what about by race or ethnicity? Have you checked to see if people of different races and ethnicities have different antibody levels?

We have not had enough of a sample size in our study to be able to accurately look at that. We were able to look at those main demographic features of biological sex and age. And we were able to compare those hospitalized patients against those who acquired the virus that causes COVID-19 and had recovered without requiring any hospitalization. And that was really the extent to which I've been able to look at demographic background.

More from VPR: Race, COVID-19 And Health Disparities In Vermont

This is super interesting. But you also believe that this research may have applications for how all kinds of people do when there is a vaccine available. Can you connect the research to what that might mean for vaccine uptake? 

The vaccines are predominantly focused on eliciting exactly the kind of antibodies that we looked at. Based on the fact that such a broad swath of the patients that we studied were able to mount antibody responses, we think that bodes well for vaccines against COVID-19, which are based on the so-called spike protein, which is the target of the kind of antibodies that we looked at. 

There has been talk sometimes in the literature about personalized vaccines; we see them for the flu vaccine. We see certain vaccines for older individuals versus younger individuals. And at least at first, we think that a broad vaccine could be available for a lot of people based on our antibody results. 

Sean, you said you tested people who were hospitalized and had severe cases. You also tested asymptomatic people for their level of antibodies. We did a show recently on what looks like up to 30% of people who have had COVID-19 who experience long term health effects after the infectious portion of the virus has gone from their bodies. Do you have any sense of what your research might mean for what are being called the ‘long-haulers’? 

Yeah, this is an interesting phenomenon that's beginning to be understood. My understanding is that these long-haulers have had long term effects that are somewhat neurocognitive. They report having very foggy thoughts still, they have some some gastrointestinal symptoms and some residual muscle ache and fatigue. 

More from VPR: Some In It For The Long Haul After Contracting COVID-19

One of the things that the SARS-CoV-2 virus does is that it engages a very strong immune response - not just antibodies, but other cells that can make chemicals that affect other tissues within the body. And so this population is really interesting, to understand how their immune system may need a little bit more time to go back to its pre-infection set point and sort of calm down. So this population, I think, is something that will teach us a lot about what immune response looks like — it has to strike that balance of protecting you, but not causing too much damage.

Vermont Edition spoke with Vermont's deputy commissioner of health, Tracy Dolan, regarding the state's plan for distribution, public outreach and more once a vaccine for COVID-19 becomes available.

Larry, Vermont Edition caller: So I have a question about vaccine hesitancy. There's been a history in Vermont of skepticism about the value of vaccines. And I think right now we're in the midst of a world which is going to have lots of questions about vaccines. 

So as we move into the push to get more people accepting the flu vaccine and then hopefully, ultimately a COVID vaccine, we've got to look at how we get people to take it. 

I guess what I'm asking is: I think there needs to be more innovative approaches to having people accept the value of vaccines. And by innovative, I mean, it can't be simply providing facts. We're inundated with facts, everyday: facts, so-called facts. So, somehow we've got to create a system where people are motivated to get the vaccine that incorporates facts plus something else. So I wondered whether Vermont has a plan for that.

Tracy Dolan: We do. We have a COVID vaccine planning group with a variety of subcommittees. And one subcommittee is looking just at what he mentioned, which is we know that we've got vaccine hesitancy. We know people are particularly concerned about this vaccine because the politicization of some of it at the federal level. But we also feel very confident in our FDA partners and our CDC partners. We’re on the phone with them regularly. We know that the trials are rigorous. We have no concerns that there will be an unsafe vaccine. We feel very sure it will be safe. 

I know that Dr. Levine will be one of the first people to publicly have the vaccine administered to him, I'm sure probably on a live feed. And so we'll do everything that we can. But we are looking at that. We're looking at different kinds of people in Vermont to really promote it, you know, health professionals who are well known, but also other people and other roles in Vermont. And so we are aware of it. And really, though, taking this vaccine will be the key in addition to everything we're doing now to slowing this down and getting us back to regular life. And we'll do everything we can. But we understand that needs to be more than just facts. I did want to follow up with that phone number for contact tracing. 

Jane Lindholm: Yeah. And before you do, just also keeping in mind that the vaccine will not be available to everyone right away, in that the rollout is going to take some time. We don't know how long, but some time.

More from VPR: When It’s Ready, Who Gets The COVID-19 Vaccine First?

It will. It will. That's true. It will be healthcare providers first. But we do have plans in place. And I think he asked a great question. And we have people working on that very strategy. 

So, Tracy Dolan, you wanted to give us the contact tracing number, right? 

I did, yes. This is the number that will come up on your phone if somebody is calling you around contact tracing from the Department of Health: 802-863-7240. 

They may leave a message. Most cases they do. They'll just say Department of Health. Occasionally they may not. But that's the number. And if you're uncertain, I'd ask you to pick up, particularly if you're waiting for results, or are expecting a call. 

You should not call into that number, though, I assume.

You should not call into that number. Calling into that number will not help you. That's the number that will come up on your phone. And that will tell you that it's coming from the Department of Health.

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