How COVID-19 threatens people with weakened immune systems

Host Amber Smith: Upstate Medical University in Syracuse, New York invites you to be The Informed Patient with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith. People with compromised immune systems are more vulnerable to viruses, including COVID-19. In this interview, we'll focus on issues that matter to the immunocompromised with Dr. Elizabeth Asiago-Reddy. She's the chief of infectious disease at Upstate and an expert in how the immune system functions. Welcome back to The Informed Patient, Dr. Asiago-Reddy.

Elizabeth Asiago-Reddy, MD: Thank you very much for having me.

Host Amber Smith: I've seen estimates that 3% of people in the U.S. are immune compromised. What are some of the reasons a person's immune system may not be functioning properly?

Elizabeth Asiago-Reddy, MD: Actually, especially in the United States, the major reason why people have immunocompromise is due to treatments that we are actually giving them for another health condition. So examples of that include chemotherapy for cancer, medications that are given to people with, for example, an organ transplant. So if you have an organ transplant, you need to take medication to suppress the immune system so your body doesn't reject that organ. And also people who have autoimmune or inflammatory conditions such as Crohn's disease, for example, lupus, those individuals need to take medications to calm down the immune system and prevent the types of responses that are making them sick.

So those reasons are actually the most common reasons why people are immune compromised. Additional other causes include the HIV virus, which is known to cause immune compromise. Although how immune compromised people are when they're living with HIV really depends on their treatment status. And then also certain people are born with immune system problems. So there are rare conditions, but certainly they do exist, where someone might be born with a defect in the immune system that places them at increased risk of infection.

Host Amber Smith: Is there a difference between those with compromised immune systems and those during the pandemic that we've seen described as "high risk." People with diabetes or heart disease, they were categorized as being at high risk, but are they high risk because their underlying disease impacts their immune system, too?

Elizabeth Asiago-Reddy, MD: Yes. I like to look at this in two separate ways. One is, what is the risk of somebody becoming very severely ill or even dying if they acquire COVID? So that's the first question. And the second question is, how likely is it that someone will respond adequately to a COVID vaccine? And those two questions are interrelated, but they're, slightly different. So, when we're thinking about how sick someone is likely to become when they encounter COVID, there are a whole host of conditions that raise the risk of severe COVID. And, when you're looking at the whole population, that includes things that are very common, such as obesity, diabetes. Those ones have really actually been involved in some of the lion's share of the severe complications that we've seen with COVID because those are very common conditions. Another one that we really can't forget about is age. So, if you look at it as a condition, age is probably what is most significantly associated with elevated risk when it comes to COVID. So we know that compared to, for example, an 18 year old, an 85 year old is 10 to 15 times more likely to die of COVID. So it's very significant as we age. And then numbers of conditions, people who have multiple different conditions at the same time. As you add on conditions, you get higher and higher risk of severe disease.

Now, the ones that I was mentioning earlier, the severe immune compromised. People who have severe immune compromise, who include those individuals who are actively taking chemotherapy or taking medications to suppress their immune system, who have organ transplants, an innate immune disorder or an uncontrolled HIV infection. Those individuals have two significant problems. One is that they are at significantly increased risk of very severe COVID, if they do catch COVID. And number two is that they also do not mount as good of a response to the vaccines as others. And what I mean by that is something called immunogenicity. So immunogenicity is how well our body makes antibodies after we're given a vaccine. The better job our body does of making antibodies, the more likely it is that we will be protected when we encounter a particular condition, the condition that we are vaccinated against. So, the severely immune compromised individuals are less likely to mount an immune response. So their immunogenicity to the vaccines is weaker and, that's an additional risk factor for those individuals, because it could be that even though they go through the full vaccine series, they might not be as well protected as others.

Host Amber Smith: You mentioned about the immune system in older people not working as well. It made me wonder, are babies born with a fully functioning, powerful immune system, or does it take time to sort of develop after they're born?

Elizabeth Asiago-Reddy, MD: Babies are, generally speaking, also immune compromised individuals. Uh, they're unique because they are developing their immune system very rapidly. And so they're sort of in their own special category in terms of how immune compromised they are. But neonates, which is during the first month of life, are particularly at risk for severe illness and infections. And up to the first six months of life, babies are higher risk for a lot of different infections compared to, as they get older. Maternal antibodies are one of the prime ways that babies are protected against infectious diseases. And those maternal antibodies are transmitted through the placenta prior to birth, and then they're also transmitted during breastfeeding.

So, this is one of the reasons why maternal vaccination during pregnancy is so important when it comes to COVID. Because that's actually been demonstrated that infants born to parents who are vaccinated have actually detectable levels of antibodies against COVID when they're born. And those antibodies appear to, by and large, persist all the way through six months of life.

Host Amber Smith: Regarding immunogenicity, is there an affordable way for someone to be able to tell whether their vaccination is working?

Elizabeth Asiago-Reddy, MD: Unfortunately, there is not a very clear cut way. So you can go and ask your primary care provider or even your specialty provider to do a COVID antibody test on you. And there are two major COVID antibody tests that are commercially available. One looks at the spike protein, and the other looks at the nucleocapsid protein. All the vaccines that we have available are against the spike protein. So anybody who has either been sick with COVID or who has had a vaccine, ideally should have a positive test for the spike protein. The nucleocapsid protein is not part of the vaccines. So if that one tests positive, that indicates that the individual has had a natural infection. So you can get some sort of a sense if you have a positive antibody for either of those. The problem is that, that is not a perfect assessment of what will happen when you encounter the virus, because the commercial assays only go up to a certain level. They only have a certain amount of antibody that they're assessing. And then also, they're only looking at that one particular antibody, whereas the antibodies generated during vaccination or infection and are much broader than the one antibody that's being examined. So. I will say that with the currently available, so for example, the spike protein assay that we're using here at Upstate, the cutoff for that is 250 international units per mil, (milliliter.) And if you have something that's 250 international units per mil or higher, you don't know how much higher after that. And the available data suggests that as the virus mutates, we probably need higher and higher levels of antibodies to be fully protected.

So it leaves the gray zone where we just don't have a good sense for how well protected somebody might be after doing that test. On the other hand, I can say that if somebody does not have a positive spike protein antibody test, and they have been vaccinated, that is very concerning, that they will not be adequately protected. Or, even if they have a low titer. So let's say, I just mentioned that 250 international units per mil. Let's say they get a result of 50. That would also be very concerning to me that that individual would not be well protected if they encountered the virus.

Host Amber Smith: So given that the vaccine maybe isn't working as well in people who are immune compromised, what are the recommendations for vaccination?

Elizabeth Asiago-Reddy, MD: So for those individuals who fit into the moderately or severely immunocompromised category, and those are the individuals that I mentioned previously, they would be recommended to get three doses of an mRNA vaccine upfront. So the mRNA vaccines include the Pfizer vaccine or the Moderna vaccine. The typical primary series for that is two shots separated by either three or four weeks, in some cases now eight weeks. Then after receiving their second dose, you would wait 28 days and give them a third dose. After that, they are still in the pool of people who would be recommended for a booster after five months. So they end up, with the current situation that we have, with a total of four vaccines, if they've received an mRNA and a vaccine series -- three as part of the primary series, and then their five month booster.

The Johnson and Johnson vaccine is a bit different. There's no specific recommendation for immunocompromised people that's different from others. So that now is recommended as a two dose series with a primary vaccine followed by another vaccine after two months.

Host Amber Smith: Where does this new medication I've heard of Evusheld, where does that come into play?

Elizabeth Asiago-Reddy, MD: So Evusheld -- or it's tixagevimab cilgavimab -- is a monoclonal antibody cocktail. So there are two different antibodies in it, both against the spike protein. And, initially this product was tested as something that could be used to immunize people who basically hadn't gotten a vaccine, so it was actually studied around the same time that vaccines were being developed. And initially it was studied in all comers. So, it was an adult study, but there was no specific inclusion criteria that related to severe immune compromise. It was just looked at it as, is this a product that can help prevent COVID? So, what this product is, is it's an intramuscular injection that's given. So it's two different antibodies. It's given in the gluteals. And it's one dose on either side, and that's every six months. So it actually is a very long-acting preparation that lasts in the body for six months. The initial data -- again, this is with all comers, so people who had potentially healthier immune systems than the folks who are using this now -- they showed a 78% reduction in risk of acquiring COVID after having received this product, compared to individuals who received the placebo. So it is highly effective. And it appears to function, at this point, as far as we can tell, against all the circulating variants of the coronavirus.

Host Amber Smith: This is Upstate's The Informed Patient podcast. I'm your host, Amber Smith talking with Dr. Elizabeth Asiago-Reddy. She's the chief of infectious disease at Upstate. And we're talking about the impact of COVID-19 on people with compromised immunity.

Host Amber Smith: If people with compromised immune systems have had to be cautious during the pandemic and sort of behave like they're unvaxxed, just to be safe, what about the people who live with them or have close contact with them? Do they all want also need to be as vigilant?

Elizabeth Asiago-Reddy, MD: Ideally. Covid, by and large, is an infection that spreads within families and close contacts. So we know over and over again from experience that times when people are gathering together with others, not necessarily in giant crowds, but in groups for special events, holidays, et cetera, we see significant spikes in the community. So yes, absolutely. If you are living with somebody who is severely immune compromised and your immune system is okay, it's still important for you to keep in mind that you could be a vector to that person whose immune system is not as healthy

Host Amber Smith: The mask mandates have pretty much ended, even as another variant is becoming a concern. What do reasonable precautions look like now for someone with compromised immunity? Should they still be masking?

Elizabeth Asiago-Reddy, MD: I would argue, yes, and particularly in the environments that we know are the highest risk. So those include enclosed, poorly ventilated environments where you're around other people who are unmasked. Those are your highest risk locations. And ideally if possible, you want to use a mask with a higher level of protection, such as a well-fitting KN95 mask or N95 mask in those types of situations.

Host Amber Smith: I'd like to ask about what happens if someone with compromised immunity becomes infected with COVID-19. Are they automatically more likely to need hospitalization?

Elizabeth Asiago-Reddy, MD: Yes, on average. But we do have, now, several treatments available to those individuals to help prevent them from becoming severely ill. So, first of all, even though we discussed that moderately to severely immune compromised individuals might not mount as good of an immune response to vaccines. They still can definitely mount a vaccine response.

So number one is that we don't look at someone with severe immune compromise and say, "oh, it's not even worth doing the vaccine because it's not going to work." We should definitely still, absolutely 100%, pursue vaccination. And many such individuals will mount an immune response, especially if they follow the full series, like I reviewed. Then again, those individuals, we would hope would be people who are eligible for the monoclonal antibody product, Evusheld, that you had mentioned. So hopefully that would help them, even if they were to get sick, that they would already have some antibodies on board to help alleviate the severity of the illness. But regardless, at the point when somebody actually tests positive, who falls into one of these categories, we have a couple of different options for treatments at this point. So this is something that I bring up with all my patients, but I really emphasize with my patients who have a compromised immune system: please call me, if you're sick. Number one, get tested ASAP. And number two, call me and let me know if you test positive, because I want to make sure you access treatment.

So the options right now, actually the first preferred option is a pill that is nirmatrelvir ritonavir, and the brand name for that one is Paxlovid. And that has been shown to reduce the risk of severe COVID by 88% in unvaccinated adults. So these are people who have significant risk. And in fact, those individuals included in the trial had other medical conditions as well, that would place them at higher risk for severe disease. So this product performed very, very well. It's. A five-day course of medication, and it's all pills. It does have some interactions with other medications. So it's very important to review with your healthcare provider, whether or not you can take this medication depending on what other medications you are taking.

If there are significant drug interactions that exist, the next option that we are going to is now monoclonal antibody infusions, and those monoclonal antibodies have had to be changed a couple of times throughout the course of the pandemic in order to respond to the variants that have occurred. We're constantly monitoring which variants are circulating and what monoclonal antibody treatments we're offering to people who are sick so that we target, ideally, the best treatment for them. So those are really the two primary options. And then there are a couple others to include -- IV (intravenous) therapies, additional IV therapies or additional oral therapies. But the, the top two are really the ones that I had mentioned.

Host Amber Smith: If someone is taking a medication -- chemotherapy or something that suppresses the immune system -- do they generally discontinue that while they're infected and being treated for COVID?

Elizabeth Asiago-Reddy, MD: Not usually. And most of the time that's because they really need it, right? So occasionally you'll come into a situation where somebody maybe is taking, let's say steroids for a condition where it might be okay to stop the steroids for a period of time, to allow them to respond better. That's a possibility. But honestly, in most cases, we're in a situation where the patients really need those medications that they're taking, and it's not realistic to stop them. Or even if we did stop them, it wouldn't result in a quick enough immune rebound to make a big difference. So it's really the supplementary treatments that are going to be especially important for those patients.

Host Amber Smith: We've heard more and more about people who are infected with COVID, they survive, but they develop these symptoms that linger, the long-haul COVID patients. Is there any reason to suspect that someone who's immune compromised is at greater risk for having the lingering symptoms of COVID?

Elizabeth Asiago-Reddy, MD: That is actually not very clear, that this group of individuals, severely immune compromised people, are at higher risk for long COVID. It looks like, actually, people across the spectrum of immune health are at risk for a long COVID, and we're still accumulating data on who is at highest risk. Certainly individuals who have very severe illness are at high risk for having long COVID. That having been said, we've seen long COVID develop in quite a high proportion of people who even had mild illness. So, some of this comes to the case definition for long COVID, which is -- I find it to be a bit flexible -- it's any symptom that is not attributable to another cause that is present three months after a documented COVID infection. And that's pretty broad. So, you know, you could have a range of somebody who is experiencing more fatigue than they did prior to their COVID infection, or you could have someone who is really debilitated with multiple different symptoms requiring specialty care. So that I feel like the spectrum is actually, at this point, a little bit too broad. So I will say that if you have severe illness, yes, you are more likely to be continuing to experience symptoms three months after the original infection. And from that perspective, knowing that severely immune compromised people are more likely to have severe illness, then it is a risk for them. But long COVID, I would say is still tricky, and we're still learning a lot about it.

Host Amber Smith: How optimistic or pessimistic right now is the infectious disease expert community -- yourself included -- about where the pandemic is, where it's going and how long it will be around?

Elizabeth Asiago-Reddy, MD: So how long it'll be around is probably the easiest one. I would say for the long, foreseeable future, this is with us to stay. So that's number one. Where we're at right now, I mean, we have to admit that we are in a much better place in terms of the likelihood that any given person who acquires COVID is going to end up in the hospital or dead. I mean, a much better place. So that, I think, is obviously a huge relief.

Host Amber Smith: But what do I think is going to happen? I mean, the virus is tricky. So there's a whole bunch of things that have happened. It's invaded animal populations. It's living within animal populations. It's living within populations of every human throughout the world. So, do we have the potential for some random strain to come and be significantly more severe than what we would have anticipated? Yes, it exists. But I think it's becoming less likely just because of the background immunity that exists the world over. Well, thank you so much for making time for this interview, Dr. Asiago-Reddy.

Elizabeth Asiago-Reddy, MD: Absolutely. It's my pleasure. Thank you for having me.

Host Amber Smith: My guest has been Upstate's chief of infectious disease, Dr. Elizabeth Asiago-Reddy. The Informed Patient is a podcast covering health, science and medicine brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe. Find our archive of previous episodes at upstate.edu/informed. I'm your host, Amber Smith, thanking you for listening.