COVID-19 Update 11/10: Immunity, Boosters, and More

In this week's COVID-19 update, Dr. Bishop discusses a couple of studies related to natural immunity and boosters, a few potential treatments for COVID, and more. Watch the full update below and read on for the recap. 

Natural Immunity: A Study from Israel

The first thing I want to talk about is a study that is going around and making the rounds sort of on the internet and social media and such. And that's this study out of Israel related to natural immunity. Here is a link to the study.

• Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections

Remember, anything that is listed there on medRx may mean that it hasn't gone through a full peer-review process just yet. So take that caveat in mind. I'm not saying that the study is bad or that there are any problems with it.

It's just good to know that not everything has been completely vetted just yet, but this one, in particular, is coming from some fairly reputable researchers and such, so I think it's fine to use.

They followed a very large portion of the Israeli population for a number of months after they started giving vaccines. And essentially, they compared those people to people who were not vaccinated, but who had had COVID.

What are they trying to find out? Is re-infection, recurrent infection, or breakthrough infection more common in people who are vaccinated or more common in people who already had COVID natural infection one time?

What the data that they showed is that patients who had the vaccine but were never infected previously had a much higher risk of having a subsequent breakthrough infection than people who had natural infection and then subsequently had a lower risk of having a repeat infection.

And this is a big study. They looked at a lot of people and there have been some other smaller studies that have come out from Qatar and a few other places perhaps showing maybe that's not quite as robust of a data point there. They're claiming a 13-fold higher rate of breakthrough infection in vaccine recipients versus people who had natural infection.

Some other studies have come out showing not quite that same strong relationship. I think really what I'm trying to show you guys with this study, and then I'll link to another one, is that the bottom line is that there's still a lot about this virus that we don't fully understand.

And like we've talked about, we don't always know everything that we would like to know, even at this point. It will take years before we find out the full extent of: How long does immunity last? Do we need to be repeating boosters? And if so, how frequently does that need to be done?

It really is just too early to tell. We have to try to make the best decisions we can with the limited data that we do have available to us.

Booster Doses Effectiveness

And to that point, moving away a little bit from the natural immunity question, is this question of booster doses, and these things are related. Here is a second article to review. 

• Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: an observational study

There's a study out of Israel again. Israel is getting used a lot because they've vaccinated so much of their population. What this study is showing is how effective a booster dose, the third dose of Pfizer, was.

Essentially, because what they were finding was that the hospitalization rates were starting to tick up five and six months out from the second dose of the vaccine, what this study shows is getting that third dose boosts that protection back up to the 93, 92, or 80% protection for death from after getting a third dose.

For those who were vaccinated, the immunity does wane down over that six-month period in a lot of folks. That is why the CDC and ACIP and all, they're recommending if you're at higher risk for getting bad disease — meaning you're older, 65 and up, or have a medical problem like diabetes, hypertension, obesity, etc. — you really should think about getting a booster dose about six months out.

I think that makes a lot of good sense for people who are high risk or for older folks because the data is fairly clear that, in those who were vaccinated, the immunity does wane after about the six-month mark in terms of the vaccine effectiveness. 

The jury is still a little out on whether people who have had natural immunity and have had vaccination need boosters. And if so, when? We just don't know. And there's not a lot of great data on that yet. And so I think a lot of people are trying to figure this out at this point.

The recommendations continue to be — get the vaccination even if you've had COVID. I think for many people, given the overall safety profile of the vaccines for high-risk people — meaning you've got a medical issue or you're say, 50 and older — I think waiting a few months after you get COVID and have recovered and then getting vaccinated is totally a reasonable and probably a good thing to do because the immunity probably doesn't last forever.

It doesn't last forever with the vaccine either. And that's okay. We have to do boosters of all kinds of vaccines all the time. Just like the flu shot, right? Got to get a new flu shot every year.

I think we may see something similar arise over the long-term with COVID where it may be something like a seasonal yearly vaccine, like the flu shot, because the immunity probably is not going to last forever with vaccination and probably it's not going to last forever with natural infection either.

Again, that's fairly consistent with the way respiratory viruses in general act. We don't tend to retain lifelong immunity to respiratory infections. And so it doesn't overly surprise me, right? We can get the flu every year. You can get a cold multiple times, The immunity doesn't last forever.

Potential Treatments

So let's circle around just a slightly different topic here on a potential treatment that was tried, and it didn't work out. But it's interesting just to talk about in general.

There's a drug called ciclesonide. It's an asthma drug. It's an inhaled steroid that was in trials to try to reduce the risk of infection, and as a treatment for COVID-19 in outpatient adults as a phase two trial.

It didn't end up showing any positive result in terms of it didn't really seem to help anything. But I think it's interesting and brings up this idea again of targeting the nasal pharynx and nasal passages for both treatment and prevention of COVID. I think that ultimately what we may find over time is that getting some sort of nasal vaccine might be better than these injectable vaccines for reasons we've talked about in the past.

Sometimes the intranasal vaccines can do a better job creating that mucosal surface immunity with the IgA antibodies that might be better at actually blocking the transmission of the virus and not just reducing severe disease, but reducing the ability of the virus to infect the nasal pharynx in general. So I think it's interesting that people are still working on this.

I know there are some mouse models working on intra-nasal vaccines and things like that, so I'm hoping we're going to see some of those come to clinical trials here in the next six months or so to a year. And we'll see how that goes as well.

Immunity from Regeneron 

Another piece of interesting data that did come out this past week was that Regeneron does seem to provide strong immunity for a number of months, up to six or eight months after the Regeneron is given — 80% or so protection from COVID infection. I think that's really promising news as well.

And so if you've got someone who either can't get vaccinated for some reason or they just haven't gotten vaccinated, giving them the post-exposure prophylaxis treatment is probably a good idea with Regeneron because it lasts for a good while — 6, 8, 9 months.

The protection is almost on par with the vaccine, which makes sense because you're giving the antibodies to them directly versus the body creating the antibodies via the vaccine. At the end of the day, it's kind of the same thing.

You're just giving the antibodies directly versus stimulating the body to make those antibodies itself. It's good to see that. It does make a lot of scientific and mechanistic sense. The problem, of course, is that antibodies don't last forever.

They will eventually be degraded and removed from the immune system, but it might be a good way to bridge people, either to a vaccine or bridge them if they've gotten sick to natural immunity plus or minus a vaccine down the line. So lots of interesting stuff has come out in the news.

Pfizer's COVID Pill

"Any thoughts on the Pfizer COVID pill?"

Yeah, I'm waiting to see all the data come out about that. Haven't seen as much information about that as the other drug from Merck, Molnupiravir. They keep naming these stuff weird names.

The Pfizer drug, it's like a combo drug, but one of the things is an older drug, a protease inhibitor that we've been using for a long time to treat HIV. This has that in it as well. Again, it seems fairly promising.

I'd like to see a bigger trial of it, but it does seem to work. It's not going to be as long-acting as that Regeneron is because the pill is just not going to stay in the system as long. But I think that that will also be another promising area of interest in the coming weeks and months. I'm hoping to see a more robust dataset come out of that.

Long COVID + Booster?

"Should someone who had COVID with mild symptoms, but had severe after-effects of COVID get a booster?"

If they would otherwise be eligible or be strongly considering getting a booster dose, then yes, I would say to go ahead and do that. If they got long COVID, they certainly don't want to get COVID again.

Even though the risk of reinfection is low, they certainly don't want it again. So I think it's very reasonable to get a booster dose to prevent a re-infection or reduce the risk of reinfection. So I think that does make sense for that person, especially.

Pfizer Pill vs. Monoclonal Antibodies

"If the Pfizer pill goes well, would that probably replace monoclonal antibodies as the best or most convenient treatment early on or prophylactically?"

It may end up being complementary. The problem with a lot of these antiviral pills and things like that is they work on the virus's ability to replicate. They don't necessarily prevent transmission really great. They tend to shorten the course of the illness to a small degree, but not to a huge degree.

I think you'll certainly see some, that's why I want to see the bigger trials come out, and I mean, it has a 90% reduction in hospitalization, which is really good. I would want to see sort of the breakdown of what we're looking at and see, okay, how many people of those people were vaccinated? how many were not vaccinated? I just haven't seen all that data yet.

I tend to be a little circumspect just because of my experience with things like Tamiflu, where Tamiflu is, "oh, we'll just take Tamiflu and it's going to help your flu." And it really only shortens the course by a day or two, and most people don't need Tamiflu because they were going to do fine anyway.

I just don't know how it's going to stack up with things like Regeneron and the Regeneron is going to last longer than the pills. I think that you'll certainly see some replacement of using these pills instead of the Regeneron because it's easier to deal with and take.

But I think for the higher-risk people who either need post-exposure prophylaxis or treatment, the Regeneron is still going to, from my perspective, be more of a mainstay than these pills until we get more data coming out. but great question.

Antibody Level Testing

"Thoughts on having antibody levels tested to see if a booster is needed or warranted?"

Yeah, so that's a really good reasonable question. I think that that is a reasonable thing to do.

It's not what's recommended by CDC or anybody else in terms of getting a booster or not getting a booster.

But I think if you're on the fence about whether you want to get a booster or not, and getting an antibody level is going to help you make that decision — meaning, I'm really not sure if I need one, I want one at this point, but I might be at higher risk — if you were to get your antibody levels checked and they were on the low side, then that might help you make a decision to go ahead and get boosted.

But if your antibody levels were still high and you're on the fence, then it might give you some reassurance that maybe it's okay to wait a little while on that. I think it's reasonable to do.

Certainly, it is not officially recommended, certainly is not required, but if you're on the fence and can't really decide about whether you're getting a booster or not, then an antibody level can be helpful to you in making that decision I think.

Booster Side Effects

"I've heard of several people that already were vaccinated then recently got the booster and had pretty bad reactions, much worse than the first time. Why would that be? What is the dosage of the booster shot?"

Immune reactions can escalate over time. As your body gets re-exposed to things, it reactivates the memory of the prior exposure. And usually, that can be kind of a more intense reaction each time because the body remembers it from before.

I've heard that too. I've seen that some people who are getting the boosters are feeling a little worse than after the second shot. And that's probably because of this priming effect of the first two doses.

The dosage of the boosters is different for the different ones. For J&J, it's the same dose as before. For Pfizer, it's the same dose as before. For Moderna, it's actually a half dose, so it's a half a dose compared to the other two.

That being said, I've heard some of the same anecdote stories. However, when we looked at the data that came out from Pfizer, they didn't really report any huge increase in symptomatology after the third dose compared to after the second.

So you're going to hear those stories here and there, and it's going to be true for some people. They're going to feel worse than after dose two, but the data doesn't really seem to indicate that there's some dramatic escalation of side effects after the third dose. I think we can feel confident about that while also saying, yeah, some people might feel a little worse than the first two and that is going to happen.

Mix-and-Match J&J + Pfizer

"I got the J&J shot in March and got Pfizer yesterday at the doctor's office. What do you think?"

Yeah, totally a reasonable thing to do. Okay to mix and match per the CDC and the FDA. So totally fine to do that. And it should provide you with good protection. No problems there.

Antibody Tests: Where to go? What level? How much? 

"Where can you go to get the antibody test? What should the level be and is there a cost?"

Your doctor can order it. If your doctor uses standard labs like LarbCorp, which is a common one around here, they can order an antibody test. It's called a semi-quantitative COVID antibody test. It tests only for the antibodies to the spike protein, which is the attachment protein, which is the protein that you make from the vaccination. You make it from natural infection too.

We don't really know what the level should be for sure. What I can tell you from what I have seen from testing myself and from testing patients who have both recovered and who've been vaccinated is that probably your level should be around 1000 units per milliliter.

And that's consistent with people who've recovered from disease or who've been vaccinated. If your level is lower than that, then that's indicative that you probably don't have as robust immunity as you might want.

That being said, there are no official reference ranges or known quantities that are specified as enough or sufficient. This is purely my best guess based on what I have seen clinically. So just a full disclaimer on that. It hasn't been tested in big studies. So just take that for what it's worth.

The cost is variable. It's around 50 bucks to get the antibodies checked through LabCorp. That's the cost. Usually, insurance is not going to cover it, but it's around $50. 

When is the next update?