Immunosuppressed patients face a potential triple threat from COVID-19: higher risk of serious illness from infection, lack of immune response to that illness, and reduced vaccine effectiveness.
In the second part of this exclusive MedPage Today video (watch part one here), Editor-in-Chief Marty Makary, MD, MPH, of Johns Hopkins University in Baltimore, speaks to Dorry Segev, MD, PhD, associate vice chair of surgery at Johns Hopkins University School of Medicine and professor of epidemiology at Bloomberg School of Public Health, who authored a study on immunosuppressed patients' response to the COVID-19 vaccine. They discussed ongoing research into transplant patients and COVID-19, how to treat the disease in this population and how to handle post-vaccination risk when they're already starting "three steps behind" their immunocompetent counterparts.
Following is a transcript of their remarks; note that errors are possible.
Makary: Hi, I'm Marty Makary with MedPage Today. I'm here with Dr. Dorry Segev, a professor and transplant surgeon at Johns Hopkins, a good friend and colleague. Dorry, I want to switch gears for a second. You've also done broader research on COVID risk among those who are immunosuppressed and those who have had organ transplant. Trying to get at the question, are those groups at higher risk of getting COVID infection and are they at higher risk of dying from COVID?
So can you talk a little bit about that body of research that you've been working on and how those come out over the last couple months?
Segev: Yeah, so, early on in the pandemic, transplant patients did not fare well whatsoever to COVID infection. There were more reported mortality rates in the 40-50% range from the U.S., from Europe -- this was really, really scary for transplant patients.
As we've learned how to take care of this disease of COVID-19 in general in everybody, we've learned also how to take care of it in transplant patients. It's interesting because, the immunoinflammatory stage 3 of COVID infection is quite similar biologically to the immunoinflammatory process of allograft rejection, right?
You have an immune system reaction that activates the inflammatory system that causes end organ damage. And we see that in transplant recipients. And we also see that in sort of that last stage of really bad COVID-19 infection. So it wasn't a huge surprise to us when administration of steroids, which is what we do for rejection, also worked for COVID-19 infection, right?
So we're learning a lot about sort of how best to treat this in both our transplant patients and non-transplant patients, to the point where even recently -- our report for example, at Hopkins showed that we were able to get the mortality of transplant patients to equal the mortality of non-transplant patients who get COVID-19.
Now some of this may have to do with the fact that transplant patients, if you think about who is most carefully following public health guidelines, it is the people who know that they are at higher risk. And one of the things we have hypothesized is that the level of inoculum of disease that you get kind of dictates how aggressive that disease is going to be.
And so if a transplant patient is sitting in the vicinity of somebody who is spreading the virus, but they're wearing a mask, their risk of getting a higher inoculum is lower.
And it's possible that they're actually coming in with less of an immune activation because they have less of sort of an immunoinflammatory activation, because they have seen a smaller inoculum of the virus.
So that's one of the things that might actually be helping transplant patients in all of this is because they know they're immunosuppressed. They know they need to be more careful.
Our transplant patients are always more careful in the community anyway around flu season and things like that. They're incredibly careful to keep themselves as healthy as possible. So it may be that we're seeing some of that from there.
Now, one question that comes to mind, of course, is, if somebody is a transplant patient, they've gotten a full vaccine series and they still have no detectable antibodies, what do we do for them?
And the emergence and success of monoclonal antibodies could potentially help patients. So my understanding right now is that at least, on the day that we're speaking today, post-exposure prophylaxis is available readily on a clinical level to people.
So I would say if you're a transplant patient, you have no antibodies, and there was any question of exposure to COVID-19, we should be treating those patients with post-exposure or monoclonal antibody prophylaxis.
What I'm hoping is that the pre-exposure trials prove efficacious, and we may even be able to give pre-exposure prophylaxis to transplant patients. But that's something for hopefully the near future.
Makary: So in terms of a summarizing or an estimate of the quantified risk to transplant recipients and the quantified risk to those on immunosuppression who are not transplant recipients, of getting the infection and dying of the infection, where would you put those numbers, roughly?
Segev: So pre-vaccine era, I would have said that immunosuppressed patients were in exactly the same scenario -- probably five to 10 times more likely of acquiring the disease compared to immunocompetent people. And that then their mortality could be the same or higher depending on the care that they give. So I think that would be quite variable.
Makary: Could it be better?
Segev: I don't think it could be better, but I think if with really good care and with the luck of detecting it early, et cetera, et cetera, it could be equivalent.
I think post-vaccine now this risk difference is even higher, right? Because immunocompetent people are going to get vaccinated. They're gonna be fine.
As we've discussed before, people who are immune, who are around other people who are immune, it's almost life as it was ever before. And even the CDC guidelines are kind of catching up with that.
But I would say that immunosuppressed people will not have as robust of an immune response. And now we'll be even more at risk than their sort of general population counterparts. Again, emphasizing that their bubbles, the people that they live with, the people that they see on a regular basis, need to be vaccinated and need to be prioritized for that vaccination.
Makary: And how much of that surprise in the data, that those immunocompromised who get COVID don't have a significantly worse mortality risk. How much of that do you think is the steroids that they may be on chronically?
Segev: It could be. A year ago I would have told you transplant patients are not going to do well with COVID-19 because this is a really bad disease. They're immunosuppressed, they're already three steps behind, and then they're going to get really, really hurt from this. And early on that indeed was the case. And it was very, very scary.
I think as we're learning the fact that they're already on a regimen to stop immunoinflammatory responses from harming their allograft -- they were three steps behind, now they're like back to being sort of on par with their immunocompetent counterparts. I would use a golf analogy, but I know nothing about golf. So I would totally get the golf analogy wrong, but you can insert one if you would like, Marty.
Makary: It's good for your mental health that you don't play golf. And now this is what I love about your work, Dorry. I think we were all really worried about organ transplant recipients and immunosuppressed patients. I was certainly warning the public and a lot of media channels back in the spring and pre-pandemic that when we realized this could be bad, that this might be an exceptionally vulnerable group.
So, thanks for all your research, great study in JAMA, congratulations. Any final thoughts here?
Segev: I guess my final thought is, there's a lot we have left to learn about the immune system in immunosuppressed patients and its response to vaccines, but we are working hard to learn as much as we possibly can.
And in the meantime, the thing I'm telling transplant patients is, do not assume you're immune just because you were vaccinated. For immunocompetent people, that is a totally reasonable assumption. For immunosuppressed people, we need more data.
Makary: And so just to follow up on that point, Dorry. In your own clinical practice, how are you using the results to change your practice? Are you testing patients after vaccination for antibodies?
Segev: So I would say that any transplant patient who wants to do anything other than what they were doing prior to vaccination, which is to socially distance, to wear masks, to minimize contact with anybody else, anyone who wants to relax their restrictions in any way should be antibody tested before allowing themselves to do that.
Even antibody testing is not a 100% guarantee. Remember nothing is 100% here, but if you're going to say to yourself, I really need to hug my grandkids in order to feel alive, I got the vaccine, I'm going to say to you, if we don't check your antibodies, you can't have any reassurance that you actually had a response to the vaccine.
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