Fredrick Wilson, a spine doctor at the Cleveland Clinic, was asleep at home in June 2020 when he had a massive heart attack that destroyed more than three-quarters of his heart tissue. He was lucky to survive the ambulance ride to the hospital.
Until then, Wilson, now 66, had been a healthy cyclist who took no prescription drugs. But after the attack, he needed a heart transplant, and with it, 33 pills to swallow a day, including powerful immunosuppressants to prevent his immune system from attacking his transplanted heart. These drugs help keep his new heart pumping, but they also make it harder for his body to fight off infections. They put him at high risk for both catching Covid-19 and having severe outcomes from the infection.
As Covid-19 stutters into endemicity, the more than 7 million Americans with weakened immune systems, including Wilson, are left making hard choices that others don’t face. He feels conflicted: He misses taking care of his longtime patients and teaching junior colleagues his craft. But he’s also afraid to die from Covid-19 after such a miraculous survival.
“Every time I go to the office, I’m going to feel some risk involved, and I’m not really that comfortable with it,” he said. But, he added, “I’m just not ready to stop seeing patients just yet.”
Even for a doctor, making decisions as an immunocompromised person is difficult — especially now. There’s no obvious guidebook for this group, in part because immunocompromised states are almost as diverse as the individuals who cope with them. While the risks associated with these conditions are not uniform, many immunocompromised people are now making decisions under a blanket of fear.
Helping people with weakened immune systems navigate this stage of the pandemic means recognizing that the group contains a large spectrum of risk — but even those at more risk now have tools that allow them to be proactive about their safety, and both individual and collective actions can help protect them.
There’s a wide spectrum of risk among immunocompromised people
It’s really hard to assess the exact risk an immunocompromised person faces. That’s partly because “immunocompromised” is a catch-all term for a complex group of conditions. The immune system consists of many interrelated parts, and weaknesses in different components of it can lead to different levels of risk.
“It’s not like there is a clear category of ‘you’re immune compromised’ and ‘you’re not at all’ — there’s a gradient,” said Dimitri Drekonja, an infectious disease doctor at the University of Minnesota.
Immune systems can be weakened in different ways — via disease, such as advanced or untreated HIV; by treatments for certain medical conditions, such as medications used to treat rheumatoid arthritis, multiple sclerosis, and some cancers; or by medications that target normal immune systems in transplant patients, to prevent them from attacking new organs, or immune system components, such as in stem cell transplants.
When it comes to Covid-19, the important question for immunocompromised people is whether their immune system’s specific vulnerability places them at higher risk for either infection with or severe disease due to the coronavirus.
Immunocompromised people, overall, are thought to be at particular risk for Covid-19 because the SARS-CoV-2 virus is so new, said Christine Koval, who leads the transplant infectious disease team at the Cleveland Clinic. They’re also at relatively higher risk for severe outcomes from common cold and flu viruses, but their immune systems have encountered these viruses before. SARS-CoV-2 is too new for their immune systems to offer much protection against it.
The data is mixed on which immunocompromised people face the greatest danger when it comes to Covid-19, in large part because many in this group are older or have other medical conditions that raise the risk of severe disease.
Experts generally agree Covid-19 risk is elevated for people with cancers of the blood or immune systems (like leukemia, lymphoma, and multiple myeloma), lung cancer, advanced or progressive cancer, recent stem cell transplants, and advanced or untreated HIV. Those actively receiving chemotherapy that reduces bone marrow activity and people with some primary immunodeficiencies are also in the highest-risk category.
The CDC’s “moderately to severely immunocompromised” designation, created largely for the purposes of allocating Covid-19 vaccines, includes these high-risk categories. But it also includes more ambiguous ones, including people taking other immunosuppressive medicines and those who have received organ transplants, conditions whose risk scientists don’t understand as well.
Researchers have not yet developed a unifying theory to explain why certain immunocompromised states raise the risk from Covid-19, but many have proposed an important role for B cells. These immune cells are responsible for producing the antibodies key to the immune system’s sentinel function, which identifies invading germs and signals the need for a counterattack. That makes them critical to the body’s defenses against new pathogens; because people taking medicines that dampen these cells’ activity have a less robust vaccine response and higher risk for severe infection or death when it comes to Covid-19, scientists think there is a relationship between B cell function and risk.
When a medical condition or treatment weakens the entire immune system, it also weakens B cells; that could explain why people with blood cancers, stem cell transplants, and advanced HIV are at higher risk.
However, B cell dysfunction doesn’t explain all of the risk immunocompromised people face, said David Hafler, a neurologist and immunobiologist at the Yale School of Medicine. In some people with weakened B cells (for example, those who take the prescription medication rituximab) other parts of the immune system seem able to pick up the slack — but not in everyone.
Ultimately, that makes it hard to sort individuals definitively into risk categories.
Hafler attributes some of this variability to the “immune lottery” — that is, the role of genetics in determining individual strengths and vulnerabilities in each person’s defenses. “Everyone has a different immune system,” he said, which makes it hard to ascertain why some people have severe Covid-19 infections while others do not, without understanding underlying genetic differences. (It is possible to test for the presence and level of SARS-CoV-2 antibodies in the blood, which are products of the immune system’s defense against the virus. But these tests don’t tell you how protected you are — or are not — from an infection.)
Megan Ryan, an advocate for people with primary immunodeficiencies, who herself has common variable immunodeficiency, said the individually variable nature of immunocompromised states makes it particularly important that higher-risk people get their information from health care providers who know them — not from the public square. “It is a confusing time,” she said, “because there’s a lot of people who are either experts or self-proclaimed experts — there’s just a lot of voices in the system.” She recommended seeking medical advice from the health care team that knows you best “rather than crowdsourcing an answer,” she said.
That’s also the best advice for people concerned they have an undiagnosed immune system problem: Get evaluated by a health care provider — ideally, one who knows you well.
What immunocompromised people and their communities can do
While immunocompromised people should address questions about individual risk and recommendations with their health care providers, they should also be aware of the tools available to protect them from Covid-19’s worst outcomes.
1) Vaccines and masks: Vaccination remains a key component of prevention. For people who initially received mRNA vaccines, the CDC now recommends a total of four doses for immunocompromised people, with the option of a fifth dose. For those who initially received Johnson and Johnson vaccines, the recommendation is for a total of three doses (preferably including mRNA doses), with the option of a fourth. Immunocompromised people are somewhat less protected by vaccines than people with normal immune systems, but the protection isn’t zero.
“Except in the most extreme circumstances, they do have some protection if they’ve followed the recommendations for the vaccinations,” Koval said.
Wearing a properly fitted N95 mask also provides excellent protection during casual contact with others, even when they are unmasked. Koval said household members of immunocompromised people should also mask up in public places to avoid transmitting the virus when back at home.
2) Antibody treatments: A long-acting preventive antibody formulation called Evusheld should offer some hope to immunocompromised people hoping for a higher degree of protection. Early data showed this therapy reduced the risk of symptomatic infection in unvaccinated high-risk adults (including but not limited to immunocompromised people) by 77 percent, and that the protective effect may last long enough to allow recipients six months between doses.
But due to a short supply and confusion among health care providers about who should receive the drug, many immunocompromised people who want the drug have been unable to get it. Currently, the cost of this therapy itself is covered by the federal government, although the cost of infusing it varies by insurance plan. If Congress does not pass the latest, condensed version of a Covid-19 relief bill, Evusheld may become harder to access in the future.
3) Oral antivirals: If they do get infected, immunocompromised people may also benefit from treatment with Paxlovid, an oral antiviral medication people take early on during Covid-19 infections to prevent more severe illness. However, this medication cannot be taken with some other medicines commonly prescribed to treat high blood pressure and high cholesterol, so it will be off-limits to some immunocompromised people.
4) Services to connect patients with medications: A new Covid-19 therapeutics locator created by the federal government aims to help health care providers more effectively link treatments with patients who stand to benefit most from their protective effects.
Immunocompromised people can also use another new federal website geared toward patients to identify the nearest “test-to-treat” location, where people can be tested for Covid-19 and, if positive, get treated with either Paxlovid or molnupiravir, another antiviral medication that’s less effective than Paxlovid but doesn’t interact with other medications.
5) Non-immunocompromised people can be thoughtful, and policies can be proactive: Although mask mandates are no longer in effect in most of the US, an accommodating attitude from the general public — and policies that encourage a culture of consideration in places where there’s no way to remain masked around others — can help maximize safety for immunocompromised people.
Workplace lunchtimes are challenging for both adults and kids, said Drekonja: “I have a private office where I can go eat lunch, but many people don’t — they have a break room,” he said, or in the case of school children, a cafeteria. “They don’t get a magic forcefield for the 20 minutes that they’re eating — what do they do?” he said.
There are no easy answers on how to minimize exposure for immunocompromised people in these situations, especially in places where it’s too cold to be outside for half the year. However, improving ventilation and air filtration and maximizing vaccination rates and masking among those sharing air space with high-risk people in these scenarios would help.
Of course, the best way to reduce the risk Covid-19 poses to immunocompromised people is to reduce transmission of the SARS-CoV-2 virus altogether. The more we collectively take steps to avoid large waves of transmission going forward, the faster we lower the risk for everyone.
Assessing your risk tolerance and personal priorities might ease decision-making
At this stage of the pandemic, immunocompromised people have several tools to protect themselves from Covid-19. Still, some decisions remain difficult to think through. There is no way to know the absolute risk of any situation, and there is no way to do away with risk entirely. The uncertainty can feel unsettling and exhausting.
People who are able to balance caution and uncertainty with joy and meaningful activity are having an easier time right now. Personal preferences and priorities help determine how much these two years have felt like a loss, said Drekonja: If you’re someone who was looking forward to a retirement full of nights at the opera and dinners out, it has been brutal — but if you’re a homebody who just wants to read and go for walks outside, “It’s not a big deal,” he said. “Part of it is, what’s your baseline?”
Many people “get this message that they’re at such high risk for death that they can’t really function normally in the world,” said Koval. But she doesn’t believe that’s realistic.
“It is uncomfortable to live in these muddy situations, particularly when we’re two years in and the type of data that we have is just not that helpful for patients, and for us to help them make informed decisions,” Koval said. “I’m hoping it gets better.”
Fredrick Wilson, the doctor who suffered the heart attack, also hopes it gets better — ideally, in time to let him do just a little more of his life’s work before retiring. He would be reassured by proof that a combination of vaccines and antivirals would be 100 percent effective at preventing coronavirus deaths, but that proof does not yet exist, and it’s unclear if it ever will. Meanwhile, he has stayed up to date on his booster shots, and recently received a dose of Evusheld. He expects to start seeing patients again in early May.
Wilson recalls his earliest days of practice, when gaps in knowledge about the cause of AIDS made many clinicians afraid to care for patients. That uncertainty wasn’t all that different from the way the Covid-19 landscape feels right now, he said: “We don’t know all the answers yet — and it’s just going to take some time.”
Clarification, 11:30 am ET, April 6, 2022: This story was updated to clarify additional dose recommendations for immunocompromised people.