Coronavirus cases are on the rise in the South. Much of the region has been designated as a “red zone.” That’s the bad news.
The good news? Globally, some vaccinations are starting to see encouraging results in human trials. But when will we see those publicly available?
This week, on the Reckon Interview, we’re speaking with Dr. Jeanne Marrazzo, the Director of the Division of Infectious Diseases at the University of Alabama at Birmingham School of Medicine.
She’s on the frontlines of the battle against the virus and walks us through what we know now that we didn’t know in March, what activities we should and should not feel comfortable doing right now, whether it’s possible to safely return to school or football stadiums, addresses some of the biggest myths about the virus and discusses the earliest possible hope for a vaccine.
The whole conversation may address many of your biggest questions about the virus, but here are a few excerpts to get you started.
On the increased strain on Alabama’s hospitals
I’m very worried right now. We’re not a huge state. We don’t have a huge number of hospitals, particularly in the most hard-hit Black Belt areas, in particular, of the state, right. That’s why Montgomery and Tuscaloosa are struggling particularly with hospital and ICU capacity. I’m really worried about it.
I think that right now hospitals are handling it. But, you know, earlier this week, I heard that Huntsville hospital had 111 patients with COVID. Well, UAB had 85. We’re a considerably bigger hospital than Huntsville, and you know, everybody’s managing. But I would say we are getting close to the razor’s edge of mostly capacity, not just beds. And I really wish people would remember it takes healthcare workers in force to take care of patients with COVID.
Remember, about 20 to 25% of people who are sick enough to come into the hospital with COVID infection, end up going into the intensive care unit and a fair proportion of those, maybe about half, end up requiring mechanical ventilation or being intubated on a ventilator. Those people, particularly if you want to give them the state-of-the-art care, which requires proning or moving them around pretty frequently, they require very high level of skilled nursing care, one on one.
And our healthcare workforce is not inexhaustible. It’s a really intensive physical ask. And it’s also a big emotional ask because you’re having people in the trenches being exposed every day. Remember, patients can’t see family, they can’t see friends, because of the rules of trying to keep everybody safe. So, the emotional burden on care providers in those settings is huge. So, we’re really worried about that. And we’re, you know, we’re hiring new nurses. I know at UAB we are. We are certainly hiring people who are coming in from other places.
When people talk about bed capacity, ventilator capacity, obviously that’s critical, but if you don’t have enough skilled people who are not exhausted and not completely demoralized to take care of patients, then you’re going to be in double jeopardy.
On the best-case scenario for a possible vaccine
The Phase One study that was reported in New England Journal – what a Phase One study is, for people who don’t know, is really a first in-humans safety study. And that’s why it includes such a small number of people, only 45 people. And you want to enroll very healthy people who are going to be very unlikely to experience any consequences of the vaccine. And that’s really super important because the first time you’re putting anything into anybody is a huge risk.
And I want to call out the people who participate in vaccine trials. To me, they are true public health heroes. I mean, these are people who, you know, you never know what’s going to happen and they went ahead and stepped forward and we have a lot of gratitude that’s owed to them.
So anyway, Phase One study, it’s called open label trial, meaning everybody knew that they were going to get a vaccine. It’s a dose escalation trial, meaning when you first start you really don’t have, other than what you know from data in animals, what the appropriate dosing is. They give a small group of 15 people each of three different gradually escalating doses. And that tries to give you a sense of how safe and well tolerated the vaccine is and what the immune response is to each of those doses. Incredibly well done. Safely done.
And what it looked like was that the people in the highest dose group actually, after a second vaccination, really produced good levels of what looked like the right kind of antibody.
And when I say the right kind of antibody…remember the visual of the coronavirus, right? It’s that ball with all those spikes coming out and you’ve seen toys of it and models of it. The antibodies, remember, are formed to every single part of that surface. So, it’s not just a single antibody that gets made to anything your immune system responds to. Everybody makes sometimes hundreds, sometimes thousands of antibodies, even to a single virus like that. Because they all have very small surface components that your body’s capable of reacting to.
So it’s not just a matter of making antibody to the virus, it’s a matter of making the right antibody. And that means the antibody, that’s going to be able to take the virus out before it infects you. So it has to be able to bind to the right part of the virus, it has to be able to bind very closely and it has to be able to have a sustained enough effect on that virus to really take it out. So what we think is the target that is the most appropriate for that job is the spike protein and that’s that spiky thing that comes out that you can see out of the virus. There’s a part of it that seems to be the most important. When they looked at the kinds of antibodies that would confer what we called neutralizing antibody, which means it neutralizes the virus, it takes it out, again in the lab.
So remember, people get the vaccine, we get their serum and their cells after they get it, and then we go back to the lab and test what they’ve made against the virus. That’s how we do it. We don’t expose people at this stage to the virus ever, you know, we really don’t do anything that is not super safe.
So bottom line, I think that this is very, very cautiously good information.
What’s really critical is your second question: what is the timeline? I emphasize Phase One. So one incredible thing I think people should realize is, you know, we’re sitting here six months after really finding out more about this virus than we knew and hearing about its genetic sequence, right, seven months after hearing about the outbreak in Wuhan and we have a Phase One Study in the New England Journal, which is truly unprecedented. There has never been any case like this in my experience in medicine for an infectious disease. So that’s pretty remarkable.
But the caveat is that you now have to escalate this to a Phase Two or a Phase Three study, that’s when you start to bring the vaccine into larger groups of people, include people ideally who are at significant risk from getting the infection. So for us, that means a lot of our vulnerable populations. And it means a lot of older people, since we know age is the principal determinant really of mortality from this virus.
Imagine now, going to a Phase three, we are actually skipping Phase Two for this vaccine. Phase Two, normally would be like a 500 to 800-person trial, where you start to expose people to the vaccine and the placebo, right? The placebo being a non-active comparator. And nobody knows what you get. The person who injects you doesn’t know. The participant doesn’t know. And then you follow people out and you see was it safe and what kind of immune markers that I talked about before did it generate, right? This is so urgent that we can’t even afford to plan a 500 to800-person trial. We are planning at the end of July. We are planning to enroll 30,000 people in a Phase Three study of the Moderna vaccine, probably starting next week. And that will happen globally…And then you follow them forward. And you see what happens.
Now, the question people have is, are you going to be able to see if it works in real world time, in terms of getting COVID? Or is it just going to be another immune marker study? With that many people, with this much transmission, we should be able to get a signal of whether or not it’s efficacious, and that is the goal.
So now you’re going to say, well, when is that? Well, you can imagine that enrolling 30,000 people in a study like this, and how long are you going to follow them? My sense is that you’re going to have to follow people for a year, at least.
Although, again, if people are getting exposed, things may happen faster. And you know, you’re going to be looking at the data periodically. So maybe they’ll stop the study early, if it looks good. But let’s say we start at the end of July and let’s say by some miracle we enroll at least half of the group by the end of the year, part of its going to depend on how enthusiastic people are going to be. I would be first in line. So best case scenario, maybe you get a bunch of people enrolled by the end of this year, you follow them into next year, and maybe, maybe you can get a signal/answer that is definitive, or at least strong enough that you can say, let’s move this out wider by the fall or winter of next year.
So, we’re easily looking at late ’21. Absolutely.
For Dr. Jeanne Marrazzo’s thoughts about the possibility of safely returning to schools, football games and more, listen to the full episode here.