How the Pandemic Has Punished People With Weakened Immune Systems

Many mount a weak immune response, leaving them more vulnerable to breakthrough infections.

Colin Powell smiling at something off-camera

Updated on November 11, 2021.

Former secretary of state, Colin Powell, died on October 18 from complications of COVID-19. The 84-year-old retired four-star general was fully vaccinated against the disease, but he had undergone treatment for multiple myeloma—a type of cancer that affects certain white blood cells and significantly weakens the immune system.   

Powell’s tragic death serves as a reminder that there are millions of adults and children in the United States whose immune systems are severely weakened by disease or medications, making them more vulnerable to the coronavirus than other people.

David Lee (whose name has been changed to protect his privacy), a 43-year-old kidney transplant recipient living in the Midwest, is one of them. Although he’s fully vaccinated, he’s taking drugs that weaken his immune system to prevent his body from rejecting his transplanted organ. This leaves him more vulnerable to COVID-19.

Moderately to severely immunocompromised people, like Lee, make up about 3 percent of the U.S. population, according to the Centers for Disease Control and Prevention (CDC). Some live with cancer, HIV/AIDS, or a genetic disorder that impairs their immune system. Others need to take drugs that suppress their immune system. And some 15 million people in these groups won’t develop a strong immune response after being vaccinated against COVID-19, according to Johns Hopkins Medicine.

Previously, the hope had been that these people would be protected by herd immunity—when enough people were immune to a disease either through infection or immunization that it’s spread becomes unlikely. But as of October 19, about 25 percent of people who are eligible to be vaccinated still haven’t gotten even one shot, the CDC reports.

“Vaccination is not just an individual thing,” Lee says. “It’s a population thing.”

What the research shows

All three of the COVID-19 vaccines available in the U.S. are highly effective in preventing serious illness, hospitalization, and death in people with normally functioning immune systems.

But evidence is growing that immunocompromised people do not always build up enough immunity after being fully vaccinated against the coronavirus. Studies also suggest these people account for a large proportion of severe “breakthrough” cases among vaccinated people. And they face a higher risk of catching COVID-19 from the people around them.

A July 2021 study published in Transplantation has estimated that the risk of breakthrough infection is 82 times higher among organ transplant recipients than the general population. Their risk for hospitalization and death was also estimated to be 485 times higher.

Researchers at NYU-Langone documented a weak COVID vaccine response among 51 adults with rheumatoid arthritis (RA) and related conditions who were taking drugs to suppress their immune system. After being vaccinated, most patients did mount an immune response. The June 2021 study in Annals of the Rheumatic Diseases found however, that antibody levels were lower among those taking an immune-suppressing medicine called methotrexate than in healthy people, suggesting weaker protection.

“Does that mean that they’re not protected at all? No. Does it mean that they should probably be a little more cautious? Yes. I think so,” says Rebecca Blank, MD, PhD, the study’s co-author and a postdoctoral fellow in rheumatology at NYU.

A separate September 2021 Johns Hopkins study published in The Lancet found that of 809 immunocompromised patients, 7 percent had no antibody response at all three months after a second dose of the Pfizer–BioNTech or Moderna vaccine. Most commonly, those patients were taking one of five immune-suppressing drugs: rituximab, steroids, mycophenolate mofetil or mycophenolic acid, or methotrexate. Another 9.5 percent had a low antibody response at that time.  

In patients with a low or no antibody response, “we would be concerned that they will be at higher risk of infection,” says co-author Caoilfhionn Connolly, MD, a Johns Hopkins Medicine postdoctoral fellow in rheumatology.

The U.S. Food and Drug Administration (FDA) authorized the emergency use of a third "additional" dose for immunocompromised people at least 28 days after a second dose of either the Pfizer-BioNTech or the Moderna COVID vaccine. But for some, even three doses may not be enough.

A June 2021 study published in The New England Journal of Medicine followed 101 organ transplant recipients living in France. Researchers found that after three doses of Pfizer-BioNTech’s mRNA vaccine, only 68 percent had developed antibody responses four weeks after their third dose. 

In October, health officials recommended a fourth booster dose for this group. The CDC says moderately and severely immunocompromised adults who have received the three-dose mRNA vaccine regimen may receive a fourth shot from any of the three vaccine makers (Pfizer-BioNTech, Moderna, or J&J) at least six months later. Those initially vaccinated with J&J should receive a booster shot from any of the vaccine makers—but not more than two doses at this time, the agency further advises.

Living through the pandemic

To a certain extent, immunocompromised people rely on those around them—their neighbors, their community, strangers passing through town—to help protect them from COVID-19.

If most people had strong immunity to COVID-19, the 3 percent of people in the U.S. with weakened immune systems would be less likely to catch the coronavirus. Not because they’re inherently less vulnerable to it, but because the virus would have far fewer opportunities to mutate or spread.

Since 25 percent of those eligible for a COVID vaccine in the U.S. remain unvaccinated, many people with compromised immune systems have not yet been able to return to pre-pandemic habits, like gathering indoors or shopping unmasked.

“When people with normal immune systems are vaccinated and have had a normal response to the vaccine, they can kind of offer some protection to the immunosuppressed patients,” Dr. Connolly explains.

Before Lee leaves his house, he checks on local coronavirus activity in his metro area. He runs errands and schedules appointments in the early morning in hopes that the air inside stores is less likely to contain airborne viral particles at that time of day. In order to go grocery shopping, he drives an hour away to a city where more than 65 percent of the population is vaccinated, and where he says most people continue to mask in public. Still, Lee wears an N95 mask under a regular surgical mask in crowded places. And apart from one socially distanced encounter with a visitor on his driveway, he hasn’t gotten together with friends since the pandemic started nearly two years ago.

“Early on, I was pretty confident that the vaccine would be helpful in giving me a little bit more freedom to go around,” Lee says. But, he added, that as evidence mounts that immunocompromise can make vaccination less effective, and as the highly contagious delta variant spreads, “it feels like I’m almost back to the sensation of not even being vaccinated anymore.”

“The only way some people are going to be protected from diseases, especially immunocompromised people, is if people who are immunocompetent get vaccines,” Lee says. “That’s the best way to ensure that people who, for legit medical reasons, don’t have the same health or ability, do not end up needlessly suffering from a disease that can be avoided.”

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