Some remain at risk for serious COVID-19 complications, even after vaccinations

People with weakened immune systems wary of mask-free living

Holding all her masks, Anna Legassie is among the millions of Americans with a compromised immune system who may still be at risk for serious complications from COVID, despite her being vaccinated.David L. Ryan/Globe Staff

Anna Legassie is an avid runner who works out six days a week and has dearly missed going to the gym. The Dorchester resident is now fully vaccinated against COVID-19, but she’s not celebrating that vaccinated people in Massachusetts will no longer be required to wear a mask or socially distance in most places come May 29.

Legassie is among the millions of Americans with a compromised immune system who may still be at risk for serious complications from COVID, despite being vaccinated.

While many fully vaccinated Massachusetts residents will soon be ditching pandemic precautions, Legassie, 37, will be keeping her guard up. And like many other people whose immune systems have been weakened from certain powerful medications, she will be constantly wondering if the maskless people around her are vaccinated.

“There will be a lot of sticky situations to navigate, personally and professionally,” said Legassie, a longtime patient advocate and a member of the board of directors of the American Autoimmune Related Diseases Association. “It feels like this is a burden that isn’t going away anytime soon.”

Legassie has rheumatoid arthritis, a disease that causes her body’s immune system to attack her own tissue and ravage her joints. She takes medications to suppress that onslaught. So, too, do legions of people with other immune system diseases, such as lupus; those treated for many cancers; and transplant recipients.

But the medications can significantly dampen a vaccine’s effectiveness. COVID-19 vaccines, like other vaccines, teach the body’s immune system to mount an aggressive antibody response to repel a virus. People with weakened immune systems tend to produce fewer of these antibodies.

How much protection people with compromised immune systems receive from COVID-19 vaccines remains unknown, partly because they were not included in vaccine makers’ large-scale trials.

Today, scientists still are uncertain how many antibodies are needed to confer protection against COVID-19 and whether the various groups of immunocompromised people generate enough, said Dr. Eric Rubin, a microbiologist at the Harvard T.H. Chan School of Public Health and editor in chief of the New England Journal of Medicine.

“We don’t know what those antibody levels mean,” Rubin said. “Is there a magic level for which people are protected?”

Though the COVID-19 vaccines have been highly effective at preventing illness, they’re not perfect. Witness the recent cluster of cases among eight fully vaccinated members of the New York Yankees, in which the third base coach tested positive for COVID-19. Testing turned up seven more asymptomatic cases.

Doctors say the incident illustrates that the shots worked, because there were no serious illnesses. Such “breakthrough” cases are rare, according to the Centers for Disease Control and Prevention.

But breakthrough cases may be much more critical for those with compromised immune systems, and the severity will vary greatly from patient to patient.

“It’s very specific for what their [underlying] disease is, and what their treatments are,” Rubin said.

Now, studies from far-flung researchers are gradually filling in the considerable blanks in researchers’ knowledge about COVID-19 risks for immunocompromised people after they’re vaccinated.

A recent Johns Hopkins study of organ transplant patients who take drugs to suppress their immune system found that after two doses of the Moderna or Pfizer vaccines, 46 percent of study participants produced no detectable antibodies against the coronavirus. And those who did respond produced fewer antibodies than people with strong immune systems.

That means nearly half of the transplant patients had no measurable antibody response to being vaccinated, suggesting they may have received insufficient protection.

Even before the pandemic, many people with weakened immune systems were living life cautiously. Doctors are advising these patients, now that they’ve been vaccinated, to continue that approach. But that suddenly seems harder as many other Americans are starting to move past the pandemic.

Legassie is just itching to go back to the gym and to travel.

“I have always worn a mask to travel on airplanes,” said Legassie, who has undergone six hip replacement and three knee surgeries because of joint damage from rheumatoid arthritis. When she gets an infection, it can be dire. She was infected with E. coli a few years ago from a hamburger. A healthier person might have been OK, but Legassie ended up hospitalized for a week with internal bleeding and permanent damage to her small intestine.

“I am trying to strike this balance of rejoining the world and keeping myself safe,” she said. “I have made it through 15 months and it would be so horrid to get COVID now after everything.”

Doctors are recommending that patients taking medications to suppress their immune system get the vaccine, because any level of protection is better than none.

“For people who either choose not to be vaccinated or for whom it’s not as effective, it means they depend on others for protection,” said Dr. William F. Harvey, clinical director of rheumatology and chief medical informatics officer at Tufts Medical Center. “So we encourage patients to encourage their household to get vaccinated.”

Harvey said many of his patients are taking medications that have a mild-to-moderate impact on their immune system, but some are on drugs that are as powerful as strong cancer medications and that severely dampen their ability to fight off infections.

Evolving science has shown that the timing of COVID-19 vaccines for patients on some immunosuppressants may make the shots more effective. Recent guidance for autoimmune conditions such as rheumatoid arthritis suggests pausing regular treatment for up to a month before the first COVID-19 shot to give a patient’s immune system a chance to be as close to normal before vaccination.

For many cancer patients, however, such a drug “holiday” before or after a COVID-19 vaccine is not recommended, said Dr. Meghan Baker, who works with immunocompromised patients at Dana-Farber Cancer Institute and Brigham and Women’s Hospital.

“The risks of delaying treatment often do not outweigh the benefits,” she said.

Legassie jumped at the chance to be vaccinated early on. But that was before the recently updated guidance suggested delaying her type of monthly infusion for four weeks before the first shot. So she worries her body may not produce a robust response.

“I think the best any of us can do is take it day by day and make a decision based on the most up-to-date information we have available to us,” she said.

She tracks the state’s COVID-19 positivity rate to navigate where she feels most safe going and which activities she feels most safe doing. She confesses she sometimes felt safer when more people were testing positive because just about everyone was wearing a mask.

But now that mask rules are being dropped in most places for those fully vaccinated, she worries about the honor system, of trusting maskless people who say they’ve gotten their shots.

“This is the complex balancing act that immunocompromised folks will have to manage even more closely,” she said.