Latest / The SHEA Podcast / Booster Vaccinations for Immunocompromised Individuals

Transcript

Booster Vaccinations for Immunocompromised Individuals · The SHEA Podcast

• 0:07
  SPEAKER_00: Welcome to the Rapid Response Podcast brought to you by Society of Healthcare Epidemiology of America, Shea, promoting the prevention of healthcare-associated infections and antibiotic resistance in seeking to advance the field of healthcare epidemiology and antibiotic stewardship.
• 0:24
  SPEAKER_00: I'm Wali Javed, hospital epidemiologist at Mount Sinai Downtown, and I'll serve as your moderator.
• 0:32
  SPEAKER_00: Discussions on the podcast does not reflect Shay's perspective, but facilitates communication of multiple perspectives and experiences as we go through this challenging time together.
• 0:43
  SPEAKER_00: Shay is excited to launch this episode of podcast COVID-19 updates, What We Know Now.
• 0:49
  SPEAKER_00: Today's discussion focuses on COVID-19 booster vaccinations for immunocompromised individuals.
• 0:56
  SPEAKER_00: Our speaker today is Dr.
• 0:57
  SPEAKER_00: Dory Sajev, Professor of Surgery and Epidemiology and Associate Vice Chair of Surgery at John Hopkins University.
• 1:05
  SPEAKER_00: Dr.
• 1:05
  SPEAKER_00: Sajjeev, thank you so much for joining us.
• 1:08
  SPEAKER_00: Let's move right into our conversation.
• 1:10
  SPEAKER_01: Thanks for having me on the podcast.
• 1:12
  SPEAKER_01: Looking forward to talking about these things.
• 1:14
  SPEAKER_00: Thank you.
• 1:15
  SPEAKER_00: So our first question: what individuals should be getting their boosters doses?
• 1:20
  SPEAKER_00: And what is the evidence behind this recommendation?
• 1:23
  SPEAKER_01: Right.
• 1:23
  SPEAKER_01: So this is a big question.
• 1:25
  SPEAKER_01: It's one that, in a way, the FDA and CDC already answered recently, but in another way, kind of causes even more confusion across the field.
• 1:35
  SPEAKER_01: So the FDA's sort of overarching decision was that people who were transplant recipients or immunocompromised at the level of transplant recipients should be getting third doses.
• 1:50
  SPEAKER_01: I think we need to be careful also that when we talk about a booster dose for immunocompromised people, we are not talking about a booster to compensate for waning kinetics to deal with the durability of the vaccines, but we're talking about a booster to supplement what was an inadequate two-dose mRNA regimen for people who are immunocompromised.
• 2:16
  SPEAKER_01: Meaning this is a booster to get immunocompromised people up to the level of immunity, immune response that people with normal healthy immune systems reached with a two-dose series.
• 2:30
  SPEAKER_01: And that's why the recommendation is a third dose, which is not a huge surprise.
• 2:34
  SPEAKER_01: There's a long history of lower immune response and immunocompromised people to vaccinations, which will then require them to get an extra dose of a vaccine.
• 2:45
  SPEAKER_01: The evidence for this recommendation has been building since March when we first released in JAMA evidence that transplant patients who got one dose of the mRNA.
• 3:00
  SPEAKER_01: So this was very early.
• 3:01
  SPEAKER_01: Remember, the vaccine rollout in the US started in December.
• 3:03
  SPEAKER_01: So we followed several hundred transplant patients.
• 3:06
  SPEAKER_01: And after their first dose, already they showed a major problem.
• 3:11
  SPEAKER_01: And fewer than 20% of transplant patients who remember take quite a bit of immunosuppression, even demonstrated any antibody whatsoever to the first dose of the mRNA vaccine compared to 100% of immunocompetent people in the big randomized trials.
• 3:30
  SPEAKER_01: So we already knew in March that there was going to be a problem.
• 3:34
  SPEAKER_01: By May, we had two-dose data on transplant recipients.
• 3:38
  SPEAKER_01: And again, what was less than 20% became around 50%.
• 3:42
  SPEAKER_01: But still, even those who had antibodies had lower antibody levels than immunocompetent people.
• 3:48
  SPEAKER_01: And only half of them even had any evidence of antibody levels, which is again in stark contrast to the immunogenicity you see in immunocompetent people and, you know, sort of in the general population, which was, you know, we obviously want everybody in the population to reach the level of immunity that was observed in the randomized trial.
• 4:08
  SPEAKER_01: Add to this clinical evidence as well.
• 4:11
  SPEAKER_01: So again, I'm talking about transplant patients.
• 4:14
  SPEAKER_01: We'll generalize this to the to other immunocompromised people soon, but there's probably the most evidence is available in the transplant population.
• 4:22
  SPEAKER_01: So recently, 17 transplant centers got together, pooled 18,000 transplant recipients, and looked at the risk of a breakthrough infection in a fully vaccinated transplant patient versus the fully vaccinated general population using CDC numbers.
• 4:40
  SPEAKER_01: And the results from that were as shocking, if not maybe more shocking, than the results from the antibody studies.
• 4:48
  SPEAKER_01: If you are a transplant patient and you are fully vaccinated, you have 82-fold higher risk of getting a breakthrough infection and 485-fold higher risk of getting a breakthrough infection associated with hospitalization or death compared to fully vaccinated people in the general population.
• 5:09
  SPEAKER_01: And that's a big deal.
• 5:10
  SPEAKER_01: And that connects clinical findings and clinical lack of protection to the immunologic findings.
• 5:18
  SPEAKER_01: We can sew all of those things together with a recent paper that came out showing that antibody levels correlate to neutralization assays, which correlate to actual clinical protection.
• 5:30
  SPEAKER_01: Now, that's in transplant patients.
• 5:32
  SPEAKER_01: So then the question is who else looks like transplant patients?
• 5:36
  SPEAKER_01: Well, the CDC has a very nice list of all these things.
• 5:40
  SPEAKER_01: I don't need to read you the CDC guidelines on this, but basically it's the search for people who are immunocompromised to the level of transplant recipients.
• 5:50
  SPEAKER_01: So, for example, people with primary immunodeficiencies, people with hematologic malignancies, people taking immunosuppression for other things like rheumatic and musculoskeletal diseases, people taking high dose steroids for whatever reason they take high dose steroids, et cetera.
• 6:06
  SPEAKER_01: So people whose immune system is either reduced because they take medication to purposefully reduce their immune system, or people whose immune system is reduced because they have an inherent disease that is inhibiting their immune system from mounting a good immune response to the vaccines.
• 6:26
  SPEAKER_01: So all of that is motivation for okay, Houston, there is a problem in this population.
• 6:32
  SPEAKER_01: Why a third dose?
• 6:33
  SPEAKER_01: Are there data supporting a third dose?
• 6:35
  SPEAKER_01: And indeed there are.
• 6:36
  SPEAKER_01: In June, our data came out from the US, and shortly thereafter, there were data from several reports from France and even a placebo-controlled clinical trial from Toronto, all showing that if you give people who did not respond well to a second dose, a third dose of the mRNA vaccine, there is a good chance that their immunogenicity will improve.
• 7:02
  SPEAKER_01: Now, this is not 100%, not everybody will achieve off the charts antibody levels, and probably not everyone will achieve adequate protection with this booster dose.
• 7:13
  SPEAKER_01: But it seems like, given that the risk seem to be very, very small, it seems like there will probably be a benefit for everyone.
• 7:21
  SPEAKER_01: Remember, we haven't done a lot of testing in terms of T cell repertoire, T cell metabolomics, T cell activation, memory B cells, et cetera.
• 7:30
  SPEAKER_01: So you're probably, in addition to priming the antibody response, you're also priming other deeper aspects of the immune system.
• 7:37
  SPEAKER_00: Thank you very much for this detailed explanation.
• 7:40
  SPEAKER_00: I think I'll jump to the question: what is the difference between a booster and a third dose of the vaccine?
• 7:46
  SPEAKER_00: The reason I ask is that these terms are usually used interchangeably, but is there any difference?
• 7:52
  SPEAKER_00: And if there is, how should we be communicating this to our staff and patients?
• 7:58
  SPEAKER_01: Yeah, so a booster to me, again, these are terms we're defining now, basically.
• 8:03
  SPEAKER_01: We're we're building the plane as we fly it.
• 8:05
  SPEAKER_01: So we're going to do some weird things as we build the plane.
• 8:08
  SPEAKER_01: To me, a booster just means anything you give somebody to try to boost their immune response.
• 8:13
  SPEAKER_01: A third dose is a vaccine, is somebody who had two doses and gets a third dose.
• 8:17
  SPEAKER_01: I think the phrasing that I've been using is a supplement booster.
• 8:22
  SPEAKER_01: That is for somebody who did not have a good immune response up front and needs additional vaccine doses to supplement them to the level of somebody with a normal immune system.
• 8:36
  SPEAKER_01: That's what we're talking about, you know, the doses in transplant recipients and other immunocompromised people.
• 8:41
  SPEAKER_01: A durability booster would be to take people who we know have waning immune responses.
• 8:47
  SPEAKER_01: That's everybody.
• 8:48
  SPEAKER_01: You know, ultimately we will all need a durability booster.
• 8:51
  SPEAKER_01: And then I think probably in the next year or so, we'll start to see the emergence of variant boosters.
• 8:58
  SPEAKER_01: And these would be new vaccines designed specifically against some of the variants of concern that might, you know, activate a part of the immune system that would handle a variant of concern better than that would be handled by the vaccines designed initially for the wild type of the virus.
• 9:18
  SPEAKER_00: That's actually a very, very good way of looking at it.
• 9:21
  SPEAKER_00: So is there a minimum time to wait to get this booster?
• 9:25
  SPEAKER_00: And should these individuals have their antibody levels checks prior to this booster dose?
• 9:31
  SPEAKER_01: Yeah, again, very good questions.
• 9:33
  SPEAKER_01: I think the general consensus is that you should wait at least a month after your second dose before you get a third dose, so that you have time to respond to the second dose.
• 9:45
  SPEAKER_01: And, you know, it was pretty similar to the amount of time we wait between dose one and dose two.
• 9:50
  SPEAKER_01: Now, that duration can be much longer, obviously.
• 9:52
  SPEAKER_01: There are a lot of people who received their second dose in March and now will be seeking the third dose.
• 9:58
  SPEAKER_01: And that's totally fine as well.
• 10:00
  SPEAKER_01: It probably should be at least longer than a month, though.
• 10:04
  SPEAKER_01: Now, antibody testing has been a major issue of discussion and contention.
• 10:11
  SPEAKER_01: I will admit going into this that I have been studying vaccines in immunosuppressed people since December.
• 10:18
  SPEAKER_01: We have had about 8,000 people participate in our national observational study, which includes transplant patients, people with autoimmune diseases, people with HIV, other populations that are immunocompromised that were excluded from the initial randomized trials.
• 10:33
  SPEAKER_01: And we've been measuring antibody levels on everybody.
• 10:37
  SPEAKER_01: So admittedly, I feel weird not knowing somebody's antibody level when we're trying to make decisions about whether they need a third dose or not.
• 10:48
  SPEAKER_01: In addition, we just launched an NIH clinical trial of a third dose to better understand the deeper immunology, to explore things like homologous versus heterologous boosting, to explore things like immunosuppression reduction at the time of a booster.
• 11:04
  SPEAKER_01: And we do have an antibody cutoff below which you have to be in order to participate in the trial.
• 11:11
  SPEAKER_01: And as I told you before, there's mounting evidence that antibodies correlate with neutralization assays, which correlate with clinical protection.
• 11:18
  SPEAKER_01: So I think it makes sense that antibody levels give us something useful.
• 11:25
  SPEAKER_01: The real question is: if you are an immunosuppressed person and you had two doses of the vaccine and we do an antibody level and it's off the charts, should you get a booster dose?
• 11:36
  SPEAKER_01: The FDA and CDC and France and Israel all say that yes, no matter what your antibody level is, a booster dose is recommended.
• 11:45
  SPEAKER_01: And as a result, they don't recommend checking your antibody levels.
• 11:49
  SPEAKER_01: That's probably reasonable because remember, antibody levels only measure one part, one component of the immune system.
• 11:56
  SPEAKER_01: And there is an entire deeper aspect of T cell immunology and memory B cell immunology that is probably also being boosted, even if your antibody levels were off the charts.
• 12:08
  SPEAKER_01: But on the other hand, one might say if there were a risk to this, then antibody levels might actually give you some information.
• 12:17
  SPEAKER_01: Now, we published 30 transplant patients who got third doses, and one of them did demonstrate a slight self-limited rejection of their allograft.
• 12:28
  SPEAKER_01: Now, that may have had nothing to do with the third dose, but it may have had something to do with the third dose.
• 12:34
  SPEAKER_01: And if you tell me, well, there is a potential risk of rejection for an allograft, and maybe somebody is at higher risk for rejection because they have other drivers of heightened alloimmunity.
• 12:48
  SPEAKER_01: And maybe a rejection for them would be absolutely disastrous.
• 12:52
  SPEAKER_01: Well, it might be reasonable for their transplant center to say, okay, well, let's check your antibodies first.
• 12:57
  SPEAKER_01: If they're low, then it seems like the risk benefit is reasonable to get a booster.
• 13:02
  SPEAKER_01: But if they're very high, it might not be worth that risk benefit.
• 13:05
  SPEAKER_01: So I would say in general, for the overwhelming majority of people who are immunocompromised, there is no reason to check an antibody level.
• 13:12
  SPEAKER_01: Remember, there are a ton of antibody assays out there.
• 13:15
  SPEAKER_01: There's a lot of unreliability in these antibody assays.
• 13:18
  SPEAKER_01: Very few people know in any way whatsoever how to interpret these antibody assays.
• 13:22
  SPEAKER_01: The data correlating them to neutralization and clinical protection are very, very new.
• 13:27
  SPEAKER_01: So I would say, in general, if you are taking care of people who are immunocompromised, for the most part, they do not need antibodies.
• 13:34
  SPEAKER_01: And that is consistent with the FDA and CDC guidance that say don't check antibodies before giving booster doses.
• 13:40
  SPEAKER_01: Although I will say that, again, you know, I'm a doctor, I take care of patients, I take the data that are available to me, I, you know, connect them in a Bayesian framework based on what we know mechanistically and what evidence is emerging as we build the plane while we're flying it.
• 13:54
  SPEAKER_01: And if I had somebody who was at a higher risk of alloimmune activation, I would probably want to know their antibody levels before giving them the recommendation to go out and get a third dose.
• 14:07
  SPEAKER_00: I think that's a very, very comprehensive explanation.
• 14:10
  SPEAKER_00: I think, as you said, in general, the value of antibody levels as well as the variability kind of limit their usability for the vast majority of people in possible scientific studies, research in certain experts' hands, the antibody levels can be very useful, like yours.
• 14:27
  SPEAKER_00: And I think that's the message that we kind of need to follow is that in general, the antibody levels do not really help determining the need for a third dose or so on and so forth.
• 14:38
  SPEAKER_00: But thank you.
• 14:38
  SPEAKER_00: So, what is the evidence around getting a booster of the same mRNA product, the first two doses of Pfizer getting a Pfizer booster versus getting a booster dose of another mRNA vaccine product?
• 14:52
  SPEAKER_01: Right.
• 14:52
  SPEAKER_01: Another good question.
• 14:54
  SPEAKER_01: The CDC kind of addressed this by saying if you got two Pfizers, you should boost with the Pfizer.
• 14:59
  SPEAKER_01: If you got two Modernas, you should boost with the Moderna.
• 15:01
  SPEAKER_01: But if the only one available to you is the opposite mRNA product, then that is okay too.
• 15:07
  SPEAKER_01: And I think that the reason underlying that is there is no evidence that switching mRNA products would be more beneficial than sticking with the same product that you got.
• 15:19
  SPEAKER_01: And there are no data on people who got two doses of one mRNA platform and then got a third dose of a different mRNA, although there are, again, emerging data from the manufacturers themselves of people who got three doses of the product that they made.
• 15:36
  SPEAKER_01: So I think given that the safety data come from the same product and there are no compelling reasons to switch products, I think the reasonable approach is exactly as the CDC recommended to try to get the same product a third time.
• 15:52
  SPEAKER_01: But if you're in an area where that's not available to you, then it's probably okay to switch.
• 15:56
  SPEAKER_00: One thing to mention here is that CDC did not recommend a booster for Johnson Johnson vaccine, but only the mRNA vaccines for the immunocompromise.
• 16:07
  SPEAKER_00: So I think just using the same mRNA vaccine as you said is probably the best strategy.
• 16:12
  SPEAKER_00: And if not available, using a different mRNA vaccine might be an alternate if one is not available.
• 16:20
  SPEAKER_01: And I feel compelled to add before we go to the next question that I wish that the FDA and CDC would figure out this supplement booster for immunocompromised people who did get the J and J vaccine.
• 16:32
  SPEAKER_01: We published months ago that the transplant recipient response, immune response to the J and J vaccine is far inferior with one dose of J and J than two doses of the mRNA.
• 16:44
  SPEAKER_01: So if people who got two doses of the mRNA need a supplement booster, there is no doubt in my mind that people who got one dose of the J and J need a supplement booster as well.
• 16:53
  SPEAKER_01: I understand that they have data that they need to comb through and they need to figure out if two doses of the J and J are safe or if you need to switch platforms and all these other things, but I hope they do this quickly because until then, we have a lot of immunocompromised people who got the J who are kind of stuck right now.
• 17:09
  SPEAKER_00: Yeah, I think I'll quote you here as we are building this plane while we are flying it.
• 17:15
  SPEAKER_00: And and and I think that's really like as researchers like you are doing a lot of research.
• 17:20
  SPEAKER_00: I'm hoping, and you're totally right, like I'm hoping that DJ will also get a second booster based on the evidence that is coming out at this time.
• 17:29
  SPEAKER_00: So is there any evidence that the booster is or will be effective on the delta variant?
• 17:35
  SPEAKER_01: So if we're talking about a booster to supplement immunocompromised people to a higher level of immune response, I would say there isn't direct evidence, but there are certainly strong inferences that we can feel comfortable making.
• 17:51
  SPEAKER_01: Meaning, if you have no detectable antibodies, right now you're probably highly vulnerable to the delta variant.
• 17:58
  SPEAKER_01: If we're able to boost you to getting very high levels of detectable antibodies, which we know correlate with neutralization assays, in fact, our group just looked at neutralization assays correlating to antibody levels in transplant patients and including neutralization against the delta.
• 18:17
  SPEAKER_01: We know that higher antibody levels will likely mean more neutralization against the delta and more clinical protection.
• 18:23
  SPEAKER_01: So I think yes, absolutely, immunocompromised people need to get their immune system responses boosted, and that will benefit them for all of the at least currently known variants of concern.
• 18:35
  SPEAKER_00: Perfect.
• 18:36
  SPEAKER_00: Thank you.
• 18:36
  SPEAKER_00: This is extremely helpful and very, very precise.
• 18:39
  SPEAKER_00: I think another question that you might have already answered, well still asked, is that, and I get this question several times.
• 18:46
  SPEAKER_00: I've already, since last two weeks, I've been getting this question about from my immunocompromised patients about boosters.
• 18:54
  SPEAKER_00: And so some actually haven't even received the first dose.
• 18:57
  SPEAKER_00: So what do you recommend as healthcare professionals that we be telling immunocompromised patients asking about the booster?
• 19:05
  SPEAKER_01: So the journey to immunity is a journey.
• 19:09
  SPEAKER_01: And if you want to get some immunity and you haven't gotten a first dose, you need to get a first dose and then a second dose, and then probably a third dose as well.
• 19:17
  SPEAKER_01: And that's the journey to developing enough of an immune response to where you're going to get incremental protection.
• 19:24
  SPEAKER_01: I would say this number one, no question whatsoever unless you have one of the very, very rare indications to getting vaccinated.
• 19:32
  SPEAKER_01: Everybody should get vaccinated.
• 19:33
  SPEAKER_01: And that's people who are immunocompetent, people who are immunocompromised across the political aisles.
• 19:39
  SPEAKER_01: Everybody should get vaccinated because that is the only way we are going to deal with this.
• 19:45
  SPEAKER_01: Now, immunocompromised people who have had two doses and are considering a third dose, again, for the most part, it's reasonable to follow the FDA and CDC guidelines and just go to CDS and self-attest and get a booster dose.
• 19:59
  SPEAKER_01: However, there are nuances to this.
• 20:03
  SPEAKER_01: And for people who have the opportunity to do so, and I hope that's everybody, but I realize that given inequities in our healthcare system, that's not necessarily everybody.
• 20:14
  SPEAKER_01: But for people who have the opportunity to do so, at least talk to their doctor to make sure that their doctor thinks it is safe and reasonable for them to get a third dose.
• 20:26
  SPEAKER_01: I mentioned earlier in response to a different question, sort of that clinical dilemma of the transplant patient who you might be worried about further activating alloimmunity and things like that.
• 20:36
  SPEAKER_01: There are some instances in which a more nuanced thinking about this is important.
• 20:42
  SPEAKER_01: But I think for the most part, you know, the CDC and FDA have made it very clear these are recommended, the risk benefit for the overwhelming majority of immunocompromised people supports supplement boosters.
• 20:54
  SPEAKER_00: And this is also very helpful.
• 20:56
  SPEAKER_00: I think several of my patients have said that, which uh I think is incorrect, but they have said that their oncologists told them that they might not respond to the vaccine.
• 21:06
  SPEAKER_00: So it's not really very beneficial for them or something on those lines.
• 21:10
  SPEAKER_00: And I think the way to communicate to our colleagues and our patients is that vaccines, as you said, are 100% needed at this time for everyone and are protective, especially for immunocompromise.
• 21:22
  SPEAKER_00: They should embark on the journey with the first dose and the second dose, third dose as needed.
• 21:28
  SPEAKER_00: So, do you have any final thoughts for our listeners?
• 21:31
  SPEAKER_01: So, first I would say thank you again for the opportunity to participate in this podcast.
• 21:36
  SPEAKER_01: It's been a great conversation, and I hope it is helpful and useful for people listening to the podcast.
• 21:42
  SPEAKER_01: Obviously, I cannot end any discussion about the vaccines without saying, please do everything in your power to encourage everybody in this country to get vaccinated.
• 21:55
  SPEAKER_01: That's our way out of this.
• 21:57
  SPEAKER_01: Healthcare professionals and epidemiologists and other people who are well informed in vaccine science are the ones who can spread accurate information in a compassionate way to our friends and acquaintances and coworkers and loved ones who might be so confused about all the information that's out there that they're reluctant to get vaccinated, not because they're bad people, but just because it is incredibly hard for any of us to keep up with the literature, let alone for the general population to keep up with the literature.
• 22:33
  SPEAKER_01: So keep up the efforts to spread accurate information in a compassionate way.
• 22:39
  SPEAKER_01: And hopefully we'll all get through this soon.
• 22:41
  SPEAKER_00: Absolutely.
• 22:41
  SPEAKER_00: I think we are all in it together.
• 22:43
  SPEAKER_00: And people like you who are doing the research that supports the efforts are so critical.
• 22:48
  SPEAKER_00: And then people like us on the forefront who are trying to encourage others need to continue to do so, as this is literally the only way out of this pandemic.
• 22:59
  SPEAKER_00: So thank you so much to our speaker for sharing his perspectives and experiences.
• 23:04
  SPEAKER_00: This podcast can be accessed on Shay's online education center, learning CE, under the Rapid Response Program, where you will find also resources such as Shea COVID 19 town halls.
• 23:18
  SPEAKER_00: This concludes today's episode of Rapid Response Podcast.
• 23:22
  SPEAKER_00: Thank you for tuning in.