MedPage Today March 31, 2021

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.