COVID-19 Vaccines May Not Protect Immunocompromised People

IRA FLATOW: This is Science Friday. I’m Ira Flatow. Later in the hour, we kick off our summer of sci-fi with some book picks for your summertime reading. But first, across the country vaccination numbers are slowly ticking up. That’s the good news.

The bad news is that some people may not be well protected, even if they do get the vaccine. These are people with compromised immune systems. It could be due to another illness or due to immune-suppressing drugs taken for other medical conditions such as a transplant. The problem is immunocompromised people may not mount a strong antibody response to the vaccines, may not be able to fight off the disease.

Joining me now to talk about what options immunocompromised people may have to deal with are my guests, Dr. John Mellors, distinguished professor of medicine at the University of Pittsburgh and chief of the Division of Infectious Diseases at UPMC, and Dr. Lindsay Ryan, an internist at UC San Francisco. She is immunocompromised and wrote about this problem in a recent issue of the Journal of the American Medical Association. Thank you for joining us.

LINDSAY RYAN: Thanks so much for having me on the show.

JOHN MELLORS: Thanks, Ira.

IRA FLATOW: You’re Welcome. John, let’s begin with you. Let’s start with a definition. What does it actually mean to be immunocompromised?

JOHN MELLORS: It means very broadly that one’s immune system is not normal. That can have very different features depending on what component of the immune system is not normal. For example, and in the context that we’re talking about, which is vaccine response, lymphocytes are key, and there are two key types of lymphocytes– B cells that make antibodies and T cells that help B cells make anybodies. And if you’re deficient in either of those, you may not respond to a vaccine like somebody who has a normal immune system.

IRA FLATOW: Can you tell me or give me an idea of what kinds of illnesses or diseases this may be true?

JOHN MELLORS: So there are many types of medications that alter the lymphocyte function and numbers. For example, there are antibodies that basically wipe out B cells. Again, B cells are the precursors of the cells that make antibodies. And B cell depletion, or B cell therapy, is for diseases where antibodies are produced that are undesirable and actually cause disease.

So that’s one large category of physician-induced abnormalities of the immune system. There are a host of other treatments for cancer, for immunosuppression to prevent organ rejection. There are other disorders of the immune system that are a consequence of age. We could go on to a very long list of abnormalities of the immune system.

IRA FLATOW: Let me go to Lindsay. Lindsay Ryan, you are immunocompromised yourself due to a drug called rituximab. Is that correct?

LINDSAY RYAN: Yeah, it’s a drug called rituximab, and it’s just what John was talking about. It’s a drug that wipes out your B cells. And B cells are extremely adaptive cells and that they help us produce antibodies to fight disease, to fight foreign pathogens like the coronavirus. However, if the B cells mistake parts of your own body, proteins in your own body, cells in your own body, as foreign pathogens if they misidentify the self as something dangerous, they can produce antibodies that actually attack you.

And that’s the nature of autoimmune disease. So you end up wiping out the B cells, and you suppress it is used by doing that. But by suppressing the ability of B cells to produce antibodies against yourself, you also suppress the ability to produce antibodies against things like coronavirus.

IRA FLATOW: What I find amazing is that I know that you’re a doctor working in an emergency room setting in a large urban center. How do you do that, knowing your immune system isn’t firing on all cylinders?

LINDSAY RYAN: I think everyone who’s made– who’s immunocompromised and is making these decisions during the pandemic does it on an extremely personal level and weighing a lot of different factors. So early in the pandemic, I didn’t go to work. I was more immunosuppressed than I am now. The pandemic was worse. There was a lot less information about how transmission occurred, whether there was a lot of transmission from surfaces. There were personal protective equipment shortages.

And there have been shifts in that. Things have improved in that. I feel very confident in the personal protective equipment. I’m meticulous about using it. I’m blessed with lovely colleagues who will usually take the hacking patients with fevers of 102 off my hands, which is not to say that I never see coronavirus patients.

Coronavirus is a protean disease, and I’ve also seen coronavirus patients who are– people who are asymptomatic who come in with a broken leg. And you swab them prior to surgery, and their swab is positive. But I think some of this is a matter of practicing risk mitigation and learning to live with that.

IRA FLATOW: And John, how much do we know about how well vaccines work, if at all, in people like Dr. Ryan?

JOHN MELLORS: It’s a really important question, and there’s limited information. We need to do broader studies across different types of individuals with varying degrees of immunodeficiency. If one does not have B cells as a consequence of antibodies to CV20 like with rituximab, then it’s unlikely that a vaccine would produce an antibody response. And so with those individuals, we don’t expect a good antibody response.

And I would say there’s less than 50% chance of a response and probably much lower than that. But again, Ira, the data are limited, and we put out an editorial, suggesting we need to figure this out as soon as possible. And we have large studies going on to try to figure out what is the rate of vaccine response in individuals with different degrees of immunosuppression.

IRA FLATOW: And in fact, you are vaccinated yourself against COVID.

LINDSAY RYAN: I am vaccinated, yeah, but with fairly limited response to the vaccine, I think it would be fair to say.

IRA FLATOW: I’ve been seeing commercials on TV for monoclonal antibody treatments for COVID. Would it be possible is this the right kind of treatment, to give immunocompromised people artificial antibodies?

JOHN MELLORS: Absolutely. Monoclonal antibodies, when given early, before hospitalization, can be lifesaving and can prevent hospitalization. That’s very clear. Well-conducted, well-controlled clinical trials show that. In individuals who do not have antibodies, because they haven’t been vaccinated or have been vaccinated and haven’t responded, are very good candidates for getting monoclonal antibody to mitigate the disease.

And in cases like Lindsay’s, if I were the physician and there was an exposure and suspected COVID, I would rapidly get a test and administer the monoclonal antibodies if the test was positive. There are even some data, Ira, suggesting that, if one is exposed and immunocompromised or elderly, giving the antibody without documenting infection can prevent infection.

IRA FLATOW: So you’re talking about giving it prophylactically before–

JOHN MELLORS: Well, that’s another thing we need to discuss. I’m talking about giving it therapeutically in those who have infection, and I’m talking about post-exposure prophylaxis, meaning that there was exposure. There’s risk of having acquired infection and presumptively giving the antibiotic to prevent the infection from spreading within that individual.

There’s another form of prophylaxis, which we call primary prophylaxis, where we give a preventive even though there hasn’t been exposure because of the possibility that there will be exposure. So that’s primary prophylaxis versus post-exposure prophylaxis versus therapeutic use of antibodies.

IRA FLATOW: Do people who are immunocompromised realize the options that they have?

JOHN MELLORS: I think many do, but I don’t think at all do. Individuals who recognize that they have an immune deficiency are likely to [INAUDIBLE] counsel, not always, and to be made aware of the options for early diagnosis and treatment. And I’d love to hear Lindsay’s take on this, what she knows about others who are in similar situation, whether they’re aware. I think there are likely to be gaps. Lindsay?

LINDSAY RYAN: I think there are definitely gaps in awareness. For me, as you said, if I had COVID symptoms, I would go immediately and get a test and, if it was positive, get monoclonals as soon as possible. And I think that actually becomes a little bit more tricky and may become more tricky over time as different variants affect the efficacy of different monoclonals.

But that said, I would go get monoclonals immediately. I think there are gaps. I don’t think all immunocompromised people know that. I don’t even think all immunocompromised people realize that they may have reduced vaccine efficacy, which is a really dangerous thing not to know that.

So I think there’s huge gaps in knowledge. And part of that has been that public health messaging has had to be that these vaccines are almost 100% effective in preventing hospitalization and death. And they are. And having nationwide public health messaging about the cases that are exceptions to that rule is not the most effective thing to communicate to millions and millions and millions of people, but I think it’s important. But there are exceptions to the rules and that doctors, family members, other people communicate to immunocompromised folks and their families that, yeah, they might not be protected by these vaccines.

IRA FLATOW: I’m talking with Dr. John Mellors, distinguished professor of medicine at the University of Pittsburgh and chief of the Division of Infectious Diseases at UPMC, and Dr. Lindsey Ryan, an internist at UCSF in San Francisco. We’re going to take a short break and continue this conversation about the challenges of protecting immunocompromised people during the pandemic. Stay with us. We’ll be right back.

This is Science Friday. I’m Ira Flatow. We’re talking about protecting and treating people with compromised immune systems during the COVID-19 pandemic. My guests, Dr. John Mellors, distinguished professor of medicine at the University of Pittsburgh and chief of the Division of Infectious Diseases at UPMC, Dr. Lindsay Ryan, an internist at UCSF in San Francisco. She is immunocompromised and wrote about this problem in a recent issue of JAMA.

What advice have you been given for living with your medical condition during a pandemic? Is there anything else that you have figured out for yourself how to do or been told what kinds of precautions you should be taking?

LINDSAY RYAN: I’m fairly careful, but I also have to balance it with wanting to live my life. So I take things on a case-by-case basis. And we can talk more about what’s happening now that things are reopening. It becomes more complicated.

But I think the best advice I’ve heard is that, if your vaccine may not be completely effective, you need to build a wall, a circle of vaccinated people around you, your co-workers, your close contacts, your friends, your family members, ideally, concentric circles of vaccination. Ideally, their close contacts will also be vaccinated to the extent possible. And that’s probably your best bet.

IRA FLATOW: And you did just say about the situation is in flux now. It is changing. People are now getting out more. Does that change your situation?

LINDSAY RYAN: I think it does. Obviously, we know that masking is pretty effective in preventing transmission. And if one of those people is unmasked, if the other person in the grocery store is unmasked, obviously, that’s a higher risk to me. I’m fortunate to live somewhere without high prevalence. But I do think I’ll take into account in terms of my own practices the fact that other people might not be wearing masks, especially in places where there’s more likely to be sick people like a pharmacy line.

One concern for me is now that we’re seeing, for instance, the delta variant, the one that originated in India, starting to take hold in the US. And it seems like there’s growing evidence that that’s more transmissible, maybe on the order of 40%, 50%, possibly a more severe variant. And so if I’m dealing with both the mask mandate being dropped and potentially more transmissible variants taking hold, that’s definitely a concern.

IRA FLATOW: How do you react to people who decide not to get vaccinated?

LINDSAY RYAN: It’s tough. Ideally, you want to react with quiet curiosity about the reasons, humility, a chance to have a conversation with people. And often, the barriers are structural. People are afraid. If they register, it will endanger their immigration status, which it shouldn’t, but these sorts of things are certainly concerns. Or people don’t have a good relationship with health care providers or have had bad experiences with clinics.

There definitely people who don’t fall into that category, who just think, they get COVID, it’s not going to be severe. It’s a matter of personal liberty. And that I find really tough. That I find tough because one of the really gratifying things for me as a doctor during the pandemic has been a lot of support for frontline workers. And that’s been rewarding. But for me, the biggest action someone could take, the most respected that they could show for the fact that I have put my life at risk to some degree by working through the pandemic, is to get vaccinated, is to reduce the chance that they’re going to see me in the ER with a virus that could kill me.

JOHN MELLORS: Let just add one footnote. I encourage everybody to read Lindsay’s article about how the pandemic and the medications she has to take have impacted her life and that we all have a level of civic responsibility to protect our fellow citizens from a preventable disease.

IRA FLATOW: John, what would you really like to know as we speak about the immune system and COVID? Is there something that you would really like to know that you don’t know that would help you in your research and treatment?

JOHN MELLORS: Anything, every day, I’d like to know, but it takes months to years to figure out. I’d like to know who responds to a vaccine, who doesn’t, whether two doses of a vaccine or three doses or four doses are optimal for those who could respond. So one of the most pressing questions in my mind is who doesn’t respond to a standard vaccination regimen that’s designed for people who have a healthy immune system. Can we get more responders by vaccinating harder? And by harder, I mean more frequently. So that, to me, is a really, really important pressing question.

IRA FLATOW: Do you think we’re going to be seeing vaccine booster shots down the road as we get toward the fall and winter time?

JOHN MELLORS: I do think that responses to vaccines will not be forever. I do think there’s concerns about variance and transmission and potential for more severe disease from variants. And we may have to cover a broader range of variants than exists today in the future with boosters. So boosters could be used to boost the initial response in people who have kind of a borderline response, and a booster could be made up of a different sequence of the virus that covers the variants that are circulating and spreading around the globe.

IRA FLATOW: Well, we have run out of time, but I can’t end without thanking both of you for your service during this pandemic. Dr. John Mellors, distinguished professor of medicine at the University of Pittsburgh and chief of the Division of Infectious Diseases at UPMC, Dr. Lindsay Ryan, an internist at UCSF in San Francisco. She is immunocompromised and wrote about this problem in a recent issue of JAMA, up there on their website at sciencefriday.com/jama. Thank you both for taking time to be with us today.

LINDSAY RYAN: Thank you, Ira.

JOHN MELLORS: Thank you, Ira.

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