If I’ve Had COVID, Should I Get a Vaccine? And Other Questions About the New Vaccines

Um, I will go through. We do have plenty of time for some questions. So, I'm gonna go through a few for you, Shane, and I will feed out some of the ones that you've already answered. So, first, um, many of us and out patients are asking about getting an MMR booster to help protect against COVID. Any truth or benefit to this?

Dr. Shane Crotty:

No. That's not a thing.

Dr. Andrea Klemes:

(laughs) I love that answer. I'm gonna keep going. No, go ahead. All right. Um, so, uh, actually, this is the same question as I have. Although the studies show that the two mRNA vaccines prevented recipients from becoming very ill, do we know for sure that the recipients could not transmit the virus to others?

Dr. Shane Crotty:

Right. Perfect question. Um, definitely, definitely the number one thing that I, that I didn't, uh, talk about. So, no, that is not known and that's a, that, that is a, that's an important question about immunity to viruses, in general, and it's an important question about the design of the vaccine, uh, trials. So, so there was a specific decision made, okay, that for these, um, uh, RNA vaccine trials and, and the other vaccine trials in the US that the read out would be, uh, uh, symptomatic cases. Okay?

Um, not, not infection. So, infections being, um, uh, PCR positivity. And the reason is if you're gonna check for infections, you would basically have to have everybody in the clinical trial get tested for virus every week, so you could catch, uh, asymptomatic infections or, or symptomatic infections.

And to do that in, you know, 40,000 people spread around the country is just, uh, a huge logistical challenge, uh, and they said no. The, the primary goal here, right, is to prevent symptomatic disease, right, and prevent fatalities or hospitalizations. So, let's focus on, on that.

Um, and so, um, as a result, there isn't data to show whether, uh, whether some number of people were getting infected, right, you know, the vaccinated people, did they still get infected and could they still have enough virus that grew so that they could spread it to other people, but they themselves didn't, didn't get sick? Um, that is, that is still an open question, and that will remain an open question for, for a substantial period of time.

Uh, the available data on the topic really come from, uh, the monkey vaccine studies, where, where monkeys were given these RNA vaccines and then challenged the virus, um, and then measured for both symptoms and, and, and viral loads. And the monkey model has looked quite good, and in fact, it's looked to have been quite predictive so far of, of the vaccine clinical trial, uh, results.

And in those cases, the vaccines were able to, both of the RNA vaccines were able to, uh, substantially lower the amount of virus in the upper respiratory tract and a duration of virus in the upper respiratory tract. And so, um, it, it's plausible that vaccinated people, um, uh, most of the time probably don't, uh, uh, spread the virus, that they probably are restricting the viral replication to, to a very low level that even if they got an asymptomatic infection it, it would be, um, far less likely to spread at least in the current window of time, right?

And one of the, the other thing that I said, we don't know how durable these vaccines will be. So, there is no licensed RNA vaccine to look at to say, "Oh, yeah. These tend to generate immune memory for a decade." We just don't know. Um, it's possible that they will only generate, uh, protective immunity for, for less than a year in which case you'd have to get immunized, um, every year and which might mean, you know, at, at some window, there's, there'd be, uh, some, uh, some spread available, but those are, those are important unknowns at this point.

Dr. Andrea Klemes:

Actually, I wanted to add to your, um, muscle aches for everybody I think you've all head that I was part, I'm part of the AstraZeneca Oxford trial. And so got my shot and within 12 hours, I knew I had the good stuff because I had like a fever, chills, throbbing headache, muscle aches. I mean, I was hours in bed shaking, but, you know, within five, six hours, it went away. The headache was still there for a little while, but I felt better. And the only thing I could come in to work the next day and say to my colleagues who were also in the trial, "Well, I know I've got the good stuff."

Now, I don't know is how efficacious the AstraZeneca one versus the Moderna and Pfizer, but that's the one they were doing a trial locally, so that's the one some of us are involved in. But it really does worry me that people are gonna go back for the second shot because as being a physician I know, well, that was good news I had those symptoms to your point in your tweets. Um, hopefully, people will go back for their second shot just like the [crosstalk 00:45:07] God, I don't wanna go through that again. I, I will be able to tell everybody next year 'cause my second shot is the 17th how that goes and am I gonna be worse or better. So, we'll see.

Dr. Shane Crotty:

And I, I think, I think the available safety data they provided from the phase one, two trials was that it was pretty similar between the first and second shot for the vector. Um, uh-

Dr. Andrea Klemes:

Yeah. That's what the staff told me, too, that they've seen 'cause they, when they put the trial on hold, they had had a bunch of people who had the second shot before some of us got our first shot. So, all right. More questions I have since I have time.

Dr. Shane Crotty:

Just related to the viral vector, so there, there is, um, well, for one, there is hope for the AstraZeneca vaccine because they did have, you know, uh, some more positive signature. Um, honestly, the big trouble with them right now is they, they really didn't release enough information for, for scientists and public health officials to actually evaluate their numbers. Their numbers don't make a whole lot of sense. So, it's, it's more of an absence of information at this point and a suspicion that they might have to go through another clinical trial if they really, if the, if that other signal holds up.

There is, just to complete the story, right? There is a second major viral vector phase three clinical trial going on in the US and that's the Janssen, uh, J&J one. Um, that is a different vaccine than the AstraZeneca one. It is designed differently, um, in, in multiple ways, and in fact, in animal models, it did, um, it did appear to perform significantly better than the AstraZeneca one. So, so just keep an eye on that phase three trial as it, as it comes along. Sorry. Go ahead.

Dr. Andrea Klemes:

Well, no, it's okay. And I'll get whatever vaccine. By the time it comes, I'll get another one if I have to, right? If this one doesn't come out, I'll be doub- doubly protected. All right. Um, I think you sort of answered this, but I'm gonna ask it anyway. "Some COVID patients don't generate detectable antibodies, especially patients with no symptoms. Do they develop a T cell response? Do they generate memory cells?" I think that was your CD5 and all that, but go ahead.

Dr. Shane Crotty:

Yeah. So it, uh, so that's a, so that's a good question and actually, um, I should say in our study for as large as it was, um, i- it wa- We only had a handful of asymptomatic patients and, and that's in part because of the recruitment process, by the way. We're basically recruiting people who knew they'd been infected and so those were predominantly people who had had symptomatic disease.

And so, we do actually need more information on immune memory in asymptomatic cases. Um, uh, from other studies that have studied pieces of, of the immune response, um, in, in asymptomatic individuals, uh, I actually, I think it's pr- I think there's a reasonable chance it's gonna break into two categories. You're going to have a- people who are asymptomatic, who just had a really small infection, right? Just had a little bit of virus and it was gone, and it just didn't trigger much of an immune response, right, 'cause it was a, it was a fairly trivial event for lack of a better, uh, phrase. And so those people may have very little immune memory.

Um, and I think the second category is people who had, uh, as much of an infection or initial inoculum as, as some other people, but their immune system responded really quick. They had a really good T cell response, um, and/or antibody response, and they, they controlled the virus fast enough so they weren't symptomatic. And, and those people I would expect to have substantial immune memory. Um, but we don't have a way right now to categorize those individuals, um, uh, or even know what fraction, you know, is in each category.

Dr. Andrea Klemes:

Uh, multiple people asked, "If you've had a, if you have COVID-19, should you still get vaccinated?

Dr. Shane Crotty:

Yeah. Great question. I'm, I'm waiting to hear the recommendations about that, uh, as well. I'm, I'm presuming the recommendation, um, uh, COVID-19, uh, uh, people who previously had COVID-19 should still get vaccinated, um, if they're, uh, if they're in groups that are, right, that, that have, uh, accessibility to the vaccine. Um, and that's, uh, uh, for one because it's, it's very unlikely that there's any downside, um, to that and for two, um, uh, we don't know how long protective immunity, right, lasts to, to, to natural infection and it is, there are a number of vaccines that give longer lasting protective immunity than, than natural infection.

Um, and so, in, in the absence of, of being sure about what those time windows are, I, I expect the recommendations are going to be, going to be yes. If it had turned out from our data and data from other people that if you'd been infected and then a simple antibody test could tell you, "Oh, yeah. You're a person in this category who has tons of immune memory, right, and you're gonna be protected longterm," then I think it would be different.

Um, but since for us it takes a huge battery of tests (laughs) to tell how much immune memory somebody has, uh, uh, I, I think the recommendation will be for people to get immunized.

Dr. Andrea Klemes:

Right. Um, and it's funny the same question came in from two different people, uh, one in Texas and one in Georgia right after each other, but they asked, "Is there anybody who should not get vaccinated? Any contraindications we know of yet?"

Dr. Shane Crotty:

Yeah. That's a really good question. Um, and I had some dialogue with, uh, with a number of physicians in a, in an NIH workshop last week about this who, um, pointed out, and actually, I didn't have a chance to double check this, but, um, uh, uh, I believe people with active autoimmune diseases weren't, were excluded from the vaccine trials.

Dr. Andrea Klemes:

They were from the AstraZeneca. I know that 'cause that was one of the questions that we got. So-

Dr. Shane Crotty:

Um, and that, that's a pretty common thing for all kinds of phase three clinical trials, right? Just as a, just as a limita- just as a minimization of variables, uh, phenomenon. Um, and so, uh, so that's an unknown. So, I, I think that's one category, uh, uh, of people, um, for which they, they may specifically stay a contraindic- contraindication for until it can be specifically tested, but outside of that, um, no. I mean, uh, because these aren't ... For certain live viral vaccines, right, uh, uh, i- uh, if you're immunocompromised, i- it's contraindicated, but these aren't, um, uh, the RNA ones aren't live and the viral vector ones aren't, aren't replicating. And so, i- immunodeficiency is not a, uh, immunocompromised, uh, uh, won't be a contraindication.

Dr. Andrea Klemes:

Um, interestingly, several people wanna know if you know anything about what the Russia vaccine, the Russian vaccine or the Chinese vaccine. There were, there were multiple Russias, Russians only one Chinese, but I don't know if you wanna make any comments about those that were already approved in other places in the world and nowhere else but those countries or not. I can keep going if you want me to.

Dr. Shane Crotty:

Yeah. No, it's, uh, so I've said ... I'm not gonna comment on the Russian ones and it's because the, we have no idea if any other data is real. There's basically just no transparency about it. Um, for the Chinese, uh, for the inactivated vaccine, they did, they actually published, uh, data on that one and they also published data on their adeno one, but, uh, but not enough to tell if they, if they're, if they're working in humans. Um, definitely the data for the, the phase three clinical trials that, that, that you're aware of, the, the Moderna, the Pfizer, and AstraZeneca are, are world-removed in terms of, uh, quality and safety compared to, uh, compared to these other ones. Yeah.

Dr. Andrea Klemes:

Great. Um, a couple of questions on pregnancy, nursing moms. Do we worry about any of that? And then I, actually, there were a couple also about kids. So, if you could pontificate on when we think. I have a, a 13-year-old who's in the next room and so she's waiting to be in a trial or be part of something.

Dr. Shane Crotty:

Yeah. In the kids one i- uh, so pregnancy I don't, I don't have, uh, uh, uh, I don't have an answer. Um, I think there's not, there's not a general, uh, there's, there's not a general reason for, for concern there, but I, uh, uh, almost certainly they were excluded from the phase three clinical trials. And so, um, yeah, I mean, you, you know, u- usually it's not recommended until you actually have a study in a population, but it, I wouldn't, um, uh, I would certainly expect it to be fine just like, um, uh, essentially any other vaccine that's not, that's not a replicating, uh, virus.

Kids is, uh, is, uh, both a fascinating and frustrating topic. Uh, I have, yeah, I have, uh, children like you and it's just, uh, uh, i- it's just brutal, right, on, on the, uh, the, the societal effects. Um, the challenge with children in a COVID-19 vaccine is they almost never get sick, okay? So, well, there are two challenges. One is that they basically almost never get sick and, and two, for any vaccine, you basically, the, the rules are you basically have to have tested it in adults before you can start testing it in, in children, and you have to stage the trials in children by several age groups.

So, it can take, uh, several clinical trials before you can get down to like, uh, you know, six-year-olds. Um, uh, but there are, yeah, the, uh, thankfully, there's at least one clinical trial that's now, uh, planned and I think there are multiple now planned to, to get to those age groups.

I mean, the expectations, uh, are that if it's, if it's working in adults it's gonna work great in, in kids. Um, they'll have to do some, uh, they may have to figure out if they need to titrate the dose, you know, uh, o- or not, but, uh, the expectation would be that it would work great in kids and that, what I'm guessing they will do is decide to take a path of saying, "Okay. The world is in a tough spot."

Uh, you'd normally love to see proof of efficacy in children, but if instead if you an show immunogenicity in children that's not inferior to adults, that, that may be sufficient for, for an EUA to say, "Yes, if you can get antibody titers, um, in, in kids and maybe even do a small study that you can get T cells responses, if you can show that the kids are making a response equivalent to adults and you pass the safety threshold, uh, go for it. We all would really appreciate. (laughs)