Pre-Pandemic Normalcy Far Off for the Immunocompromised

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Though the rollout of the COVID-19 vaccines has allowed many Americans to find some pre-pandemic normalcy, little has changed for Victoria Graham of Washington, DC, who is still exercising the same heightened caution she did in early 2020 because she is immunocompromised from a complicated medical history that includes Ehlers-Danlos syndrome.

“The pandemic isn’t over for everyone,” says Graham, 27. “Those of us who are immunocompromised are so vulnerable to COVID. I think it’s difficult for people to understand if they are lucky enough to have a healthy body and a strong immune system. I just wish more people realized how many are still deeply impacted by the threat of this virus. But unfortunately, it feels like so many people now are screaming with their actions and showing that they don’t care or aren’t thinking about what risks they’re imposing on those of us who are immunocompromised. It’s lonely, isolating, and a hard phase of the pandemic to be living through.”

Graham says she’s been met with everything from confusion to annoyance and downright outrage as she takes steps to protect herself. She did get vaccinated, but since she’s medically complex, immunocompromised, and has a history of not producing enough response to some vaccines, doctors can’t be certain her body is mounting the same response to the vaccine as a healthy person. People with weakened immune systems like Graham may also be at increased risk from breakthrough infections and the Delta variant. If she gets sick, her case could be more severe.

Graham’s doctors say she needs to be very cautious, using every protection, including the vaccine. That means limiting where she goes, who she’s around, always wearing a mask inside, and wearing one in crowded outdoor areas when she can’t physically distance from people.

Graham says she was recently verbally attacked while shopping at an outdoor market for taking these extra precautions.

“‘Why are you wearing that mask? You should take it off,’ the salesman said to me in a really accusatory tone,” Graham recalls. “I was startled, but my first inclination was to try and educate him, so I explained that I’ve been chronically ill for 27 years and my doctor says I need to keep it on to protect my health. He immediately started arguing with me, [saying], ‘Nah, we’re outside. You don’t need that. It doesn’t do anything anyway.'”

“He went on and on,” she says “He wouldn’t stop. He was just relentless and kept talking to me like he was accusing me of doing something wrong. It was awful and dehumanizing, and all I could do was just walk away.”

Immunocompromised During This Stage of the COVID-19 Pandemic

It’s not known exactly how many people have weakened immune systems in the U.S., but studies show that as many as 4% of Americans say they’ve have been told by a doctor that they fall into this category.

“Having a weakened immune system can make you more likely to get severely ill from COVID-19,” the CDC states online. The agency is recommending that immunocompromised people get the vaccine, if recommended by their doctor. But how well it works in this population is not fully known because people with compromised immune systems were not generally included in vaccine trials.

These factors, combined with the lifting of mask mandates across the country, make this a challenging time for those who are immunocompromised.

“I wish there was more awareness and understanding about that. This is a public health crisis, which by definition means we all should be acting in ways that are going to be best for everyone in our communities, including those who are immunocompromised, and it just doesn’t feel like that’s happening,” Graham says.

Several academic institutions are now working to investigate and better understand vaccine response for various groups with compromised immune systems. And there’s been promising news for some: Data out of Israel showed that HIV-positive patients produced high levels of antibodies after two doses of the Pfizer vaccine, while another study from the same country offered hopeful news for patients with rheumatoid arthritis after finding that 86% of nearly 700 patients studied developed an immune response after two doses of the vaccine. Early studies show patients with inflammatory bowel disease are mounting a good response, too.

But the results of vaccine response in many other immunocompromised groups have been very disappointing.

“For vaccinated people, the world is a celebration right now. And for unvaccinated people, the world has gotten a little bit scarier,” says Dorry Segev, MD, a transplant surgeon at Johns Hopkins University School of Medicine in Baltimore. “The problem is that many patients with weakened immune systems who have tried to be vaccinated are not immune. They don’t have the same level of protection that vaccinated people with normal immune systems have, and so despite their best efforts, the world has become a scarier place.”

“Those who are immunosuppressed, even if they survive the viral illness, they sometimes cannot clear it from their body because their immune system isn’t strong enough and then they can succumb to COVID later on. That happened to one of my patients who passed away, so this is very serious,” says Mounzer Agha, MD, a hematologist at the University of Pittsburgh Medical Center in Pennsylvania.

Vaccines and Transplant Patients

Segev is the lead author of several studies looking at responses to the COVID-19 vaccine in people who got organ transplants. He expected some impact from the medications that transplant recipients take to reduce their immune response so their bodies don’t reject their donated organs, but he admits he was surprised and devastated at just how little of a response they observed. His research shows just 17% developed antibodies after one dose, and only about half (54%) developed them after a second dose.

“Things got better after a second dose, but still half of transplant patients we studied had no detectable antibody, which obviously is terrible. And the half who had detectable antibodies had a much lower level than people with normal immune systems. So even those with antibodies were likely less protected than people with normal immune systems,” Segev explains. “Based on the COVID cases we’re seeing and hearing about, I estimate that the risk of a breakthrough infection is about 100 times higher in a transplant patient who’s fully vaccinated versus somebody with the normal immune system. That’s what we’re seeing in the real world with people who are getting sick, and that’s frightening.”

Segev and his research team studied the effects of a third booster in transplant patients, and while some still didn’t develop an immune response, “antibody titers [or levels] increased after the third dose in one-third of patients who had negative antibody titers and in all patients who had low-positive antibody titers,” they found

All patients who had a low response after the second dose boosted to a high positive, and six of 24 patients who had no response after the first two doses developed a high response after the third.

“This is really encouraging, and I think begins to offer some hope to our patients,” Segev says, adding that much more still needs to be known to fully protect this patient group.

Vaccines and Blood Cancer Patients

Similar challenges have been seen in vaccine response among some blood cancer recipients. Agha, the hematologist at the University of Pittsburgh Medical Center, was the lead author of a study that found 46% of patients were vaccine non-responders and did not produce antibodies to the COVID-19 vaccine. Those taking medications that affect their B-cell function were at especially high risk for lack of a response, with only 23% having detectable antibodies — even though most of them weren’t having cancer therapy at the time. Agha’s paper is currently under review for formal publication in a peer-reviewed journal.

“I tell my patients with antibodies-negative following the COVID vaccination that it is best to assume that they have no immunity against COVID, and they should insist everybody around them is vaccinated,” Agha says. “It’s important they understand they cannot go out and mix with the general population and assume they’re going to be safe, especially now that the CDC is loosening masking and public health guidelines and states are opening and people say you can go back to normal life. I think those who are immunocompromised need to be careful right now until we understand more about how to best protect them.”

Vaccines and Multiple Sclerosis Patients

Vaccine response has not been encouraging for multiple sclerosis patients who are on certain medications. A study out of Israel found those with MS who aren’t on treatment mount a normal response to the vaccine, while antibody levels were good in patients taking a medication called cladribine. But only 22.7% on a medication called ocrelizumab developed antibodies, while most patients taking fingolimod had very low antibody levels or none at all.

Joshua Katz, MD, the co-director of the Elliot Lewis Center, a private MS center just outside of Wellesley, MA., says his center has repeated a similar study, which is not yet published, and found nearly identical vaccine response levels.

“People who have MS who are not on treatment generally aren’t more susceptible to infections than anybody else. It’s really some of these medications that cause problems with the immune system. But these treatments are really important because when patients take them, they generally have very low levels of disability,” he explains. “So, this development with the COVID vaccine is certainly disappointing.”

Katz points out that the immune system is complex and other parts of it, such as T cells, may still protect against COVID in patients who don’t have an antibody response. He’s now testing that theory in some of his patients.

“What we have to tell people is there’s a lot that we really don’t know,” he says. “If you’re on a medicine that we know can interfere with the vaccine, we can check to see if you’ve made antibodies and if you’ve developed a T-cell response. So far, we’re finding that many of our patients at least have a T-cell response, and we hope that will protect them from getting a severe infection if they’re exposed, but it’s still early in this research.”

How to Navigate the Pandemic if You’re Immunocompromised

Since there are many reasons for a compromised immune system, health experts say people really need to talk with the doctor to learn the best advice for them when it comes to vaccines, masks, and their daily activities. Lots of research is underway to get more answers on how well third boosters work, the use of monoclonal antibodies to provide additional immune protection, assessments of vaccines on parts of the immune system like T cells, and studies looking to better understand the best timing of additional doses.

A third booster hasn’t yet been approved in the U.S., although Pfizer plans to ask for that soon. The CDC and the FDA released a joint statement in response to that news in early July, saying, in part, “Americans who have been fully vaccinated do not need a booster shot at this time.” But the statement made no mention of immunocompromised people.

“It feels like all decisions at every level are being made with only healthy people in mind. I think people who are immunocompromised are left out of consideration, we’re left out of the conversation and just generally overlooked and disregarded in this part of the pandemic,” Graham says. “It’s really disheartening.”

The best advice for those who are immunocompromised? Stick with the precautions that have been recommended since the beginning of the pandemic, experts say

“I’m telling patients that they shouldn’t have to wear a mask if they’re outside and not in big crowds, because the risk there is extremely low. But if you’re in a public place around people who may not be vaccinated and you’re going to be in close proximity to them, I recommend you continue to wear a mask until we know more about how to best protect you,” Katz says.

Agha agrees and says he hopes more attention will be paid to this issue to encourage higher vaccination rates among healthy people, too — to protect not only themselves, but also those in their communities who are immunocompromised.

“Certain members of the immunosuppressed population will never have a normal immune response, and I believe it is our duty to protect those patients and help them get back to a normal life. That happens when everyone around them is vaccinated,” Agha says. “I just want to say to people: Please don’t forget about this patient population. I’m happy for everyone who is getting their lives back right now. Please think of how you can help immunocompromised people do that, too, and get vaccinated.”

“As someone whose body doesn’t have the ability to fight infection overall, the risk of COVID exposure remains high for me and would result in serious hospitalization or illness at best, and death at worst. So, I’m still exercising incredible caution in what I do, where I go, and who I’m around,” Graham says. “I just wish people understood how complicated life is for immunocompromised people right now, were more understanding about it, and willing to help. And I wish we knew more about how to protect ourselves, too.”

Sources

Mounzer Agha, MD, University of Pittsburgh Medical Center, Pittsburgh.

Victoria Graham, Washington, DC.

Joshua Katz, MD, co-director, Elliot Lewis Center, Wellesley, MA.

Dorry Segev, MD, PhD, Johns Hopkins University School of Medicine, Baltimore.

Therapeutic Advances in Neurologic Disorders: “Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies.”

Annals of the Rheumatic Diseases: “Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study.”

JAMA Network: “Prevalence of Immunosuppression Among US Adults 2013.”

The Lancet: “Immunogenicity and Safety of the BNT162b2 mRNA COVID-19 Vaccine in People Living with HIV-1.”

NEJM Journal Watch, June 14, 2021.

CDC: “Joint CDC and FDA Statement on Vaccine Boosters,” “COVID-19, People with Certain Medical Conditions.”

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Annals of Internal Medicine: “Safety and Immunogenicity of a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series.”

JAMA: “Immunogenicity of a Single Dose of SARS-CoV-2 Messenger RNA Vaccine in Solid Organ Transplant Recipients,” “Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients.”

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