Though COVID-19 vaccines didn’t end the pandemic, they’ve helped beat back the virus; through March 2022, immunization prevented an estimated 17 million hospitalizations and two million deaths in the United States alone, according to the Commonwealth Fund.

But the vaccines don’t provide equal protection for all. If you’re one of the estimated 3 percent of the population who are moderately or severely immunocompromised, your body may not produce high levels of protective antibodies in response to immunization, leaving you vulnerable to severe disease, hospitalization, and even death.

Plus, some COVID-19 medications that helped fight earlier forms of omicron offer little defense against the now-predominant subvariants BQ.1 and BQ.1.1.

What do experts who work with immunocompromised people currently recommend when it comes to battling COVID-19 infection, hospitalization, and severe disease? Keep reading to get the latest guidance.

Who Is Immunocompromised?

“When we say someone is immunocompromised, generally what it means is the person isn’t able to mount a good immune response to the [COVID-19] vaccine for whatever reason,” says Shireesha Dhanireddy, MD, a professor of medicine in the division of allergy and infectious diseases and an infectious-disease specialist with UW Medicine in Seattle.

“That could be due to an underlying medical problem that makes the immune system weaker, or a medication that weakens or suppresses the immune system,” she adds.

There’s a broad range of people who are considered immunocompromised, Dr. Dhanireddy says. “Usually, these individuals would be under the care of a provider who would be managing their chronic condition.”

According to the University of Pittsburgh Medical Center, you may be considered immunocompromised if you:

Had a heart, lung, liver, kidney, or other solid organ transplant and are on antirejection medicine; or had a bone marrow transplant and are taking drugs to suppress your immune system
Have decreased immunity because of an autoimmune or chronic inflammatory disease such as rheumatoid arthritis, lupus, or multiple sclerosis, and you are taking medication (such as daily high-dose steroids) to tamp down your body’s immune response
Have cancer; either a solid tumor for which you are receiving chemotherapy, or a blood-related cancer like leukemia, lymphoma, or multiple myeloma
Have a chronic illness such as sickle cell anemia, untreated or advanced HIV, or stage 4 or 5 kidney disease. If you are receiving dialysis you qualify as immunocompromised.
Are 65 or older and can’t perform two or more tasks of daily living (such as bathing and dressing) without help; or are 65 or older and don’t develop antibodies against COVID-19 after three vaccine doses as measured by a blood test

This is not a comprehensive list of immune-system issues that might dramatically increase your COVID-19 risk. Talk to your doctor if you are unsure of your status.

Immunocompromised People Have Unique COVID-19 Vaccine and Booster Needs

Vaccine recommendations for the immunocompromised are special because both laboratory studies and real-world data have shown these individuals are less likely to respond well to immunization, says Dhanireddy.

A meta-analysis published in December 2021 in the Journal of Infection found that although COVID-19 vaccines were effective against symptomatic COVID-19 in immunocompromised people, the antibodies they generated were much lower than in people with normally functioning immune systems.

While most people get two doses of the Pfizer-BioNTech or Moderna vaccine for their so-called primary series, immunocompromised individuals should get three, according to current public-health guidelines. “Studies have noted that there was very low response in terms of antibodies after two doses for immunocompromised individuals, particularly in solid organ transplant patients, but a third primary dose led to a much more significant response,” Dhanireddy says.

Boosters are also an important weapon in the fight against COVID-19, and researchers strongly recommend them for people who are immunocompromised. The new bivalent boosters offer dual protection against both omicron and the original coronavirus strain.

Even though someone who is immunocompromised may not have the same robust antibody response to the bivalent booster as a person with a well-functioning immune system, they should still get the shot, says Rachel Bender Ignacio, MD, MPH, an infectious-disease doctor at UW Medicine in Seattle.

Timing is a factor to consider. People should wait at least two months between a prior booster and the bivalent booster, says Dr. Bender Ignacio. “And if a person has had a recent COVID infection, they should wait two to three months and then get the bivalent booster,” she adds.

Some individuals who may have been on heavy immunosuppressants around a transplant period, or were vaccinated pre-transplant and then had to take immunosuppressive medications that wiped out their immune system, may actually have to restart their vaccinations and get another primary series, says Dhanireddy.

“It can get a little complicated for these individuals regarding timing of these medications and whether to restart that series or not; that’s something they should discuss with their doctor,” she says.

What’s Happening With the Preventive Drug Evusheld?

Evusheld (tixagevimab and cilgavimab) is a monoclonal antibody (lab-produced antibody) treatment aimed at preventing COVID-19 infection in vulnerable and immunocompromised people. The U.S. Food and Drug Administration (FDA) granted it emergency use authorization (EUA) in December of 2021.

Evusheld, an injectable medication, is highly effective in staving off infection with the BA.5 subvariant, which is still circulating at significant levels in some parts of the country and the world. Unfortunately, it appears to offer little protection against BQ.1 and BQ.1.1, says Bender Ignacio.

Providers base their decision on whether or not to prescribe Evusheld using up-to-date data on which omicron subvariants are dominant in their area, she explains.

“Even if you are taking Evusheld, if you’re immunocompromised, you need to take additional precautions to avoid getting infected with COVID,” Bender Ignacio says.

COVID-19 Treatments Can Reduce the Risk of Severe Illness and Hospitalization

Immunocompromised people should be aware of three medications that work to prevent mild or moderate COVID-19 from becoming severe: Paxlovid, Lagevrio (molnupiravir), and Veklury (remdesivir).

These treatments all appear to work against BQ.1 and BQ.1.1 as well as BA.5, says Bender Ignacio. But a fourth medication, the monoclonal antibody treatment bebtelovimab, is not effective against the BQs (as they are sometimes known), prompting the FDA to remove its authorization for the drug.

Paxlovid This oral medication combines two generic drugs, nirmatrelvir and ritonavir. The FDA granted it emergency use authorization in December 2021, and the NIH has prioritized it over all other available treatments for people with a current COVID-19 infection.

“The drug was 89 percent effective against hospitalization and death in the clinical trial that led to its approval — and that study included both vaccinated and unvaccinated individuals. It’s a five-day course of medication that has to be given within five days of when symptoms develop,” says Dhanireddy.

Paxlovid can interact with other medications, including blood thinners and cholesterol medicines, so it may not be a good choice for everyone. “This drug can be especially problematic for solid organ transplant patients — Paxlovid is not a great option for them,” says Dhanireddy.

Veklury This medication is the first (and so far only) COVID-19 therapy to have full FDA approval for the treatment of critically ill COVID-19 patients who are hospitalized.

More recently the FDA also authorized this infusion drug (administered via IV) for treating high-risk patients with mild to moderate COVID-19 who are recovering at home.

This medication provides an 87 percent reduction in risk of hospitalization in nonhospitalized people who received the three-day dose, according to a study published in January 2022 in the New England Journal of Medicine.

“Logistics for this are a little bit difficult, because it’s three days in a row of IV medication that has to be delivered in a healthcare setting,” Dhanireddy says.

Patients must begin treatment within seven days of the onset of symptoms.

Lagevrio This oral medication is 30 percent effective at preventing hospitalization and death in people with COVID-19. Doctors should prescribe it only when Paxlovid and Veklury are not available, feasible, or clinically appropriate, per the NIH.

The CDC did not authorize the medication for people who are pregnant, and anyone of childbearing age needs to use it with caution, Dhanireddy says. It is not known if the drug may impact sperm.

Treatment must begin within five days of symptom onset.

In addition to these medications, moderately to severely immunocompromised people may also be eligible for treatment with convalescent plasma, donated by individuals who have recovered from COVID-19 and thus may have antibodies in their blood, according to NIH.

If You Get COVID-19, Don’t Delay Treatment

If you’re immunocompromised or have a number of risk factors for severe COVID-19 and begin to develop symptoms of infection or test positive, call your healthcare provider right away to see if you should begin a course of Paxlovid or another drug.

“Some people mistakenly believe that they should wait and see if they get sicker before they take these medications, but we know that they work best when taken earlier in the infection — the sooner, the better,” says Bender Ignacio.

Face Masks Remain Important

This stage of the pandemic presents special challenges for cancer patients, transplant recipients, and other immunocompromised people, says Steven Pergam, MD, MPH, a physician, researcher, and the associate director of infection control at Fred Hutchinson Cancer Center at UW Medicine in Seattle.

Earlier in the pandemic, measures like mask mandates and social distancing helped protect people who were most vulnerable to infection, says Dr. Pergam. “But now society has really opened up, and it’s up to the individual to protect themselves,” he says.

For anyone who is immunocompromised, Pergam recommends wearing a well-fitting N95 or KN95 mask when in public spaces, especially indoors. Although two-way masking is best, a modeling study published in December 2021 in the journal PNAS found that a high quality mask offers substantial protection even if others aren’t wearing face coverings.

If you know you’re dealing with a high-risk situation, prepare yourself, Pergam says. “Either avoid the situation — don’t go — or wear a mask as much as possible in that scenario,” he advises.

When you’re immunocompromised, you want to try to reduce your risk as much as you can, says Dhanireddy. She calls using multiple approaches — such as vaccines, boosters, medications, and masking — “creating a cocoon of protection around yourself.”

The “cocoon” should also include those in your household or close circle, who should all be mitigating their risk to keep you safe by protecting themselves with masking and other measures, Dhanireddy says.

The CDC has created a COVID-19 tool kit designed to help people understand the risk COVID-19 poses in their community, and it includes information on where to find free masks and “Test-to-Treat” programs where you can get tested and obtain treatment if you are diagnosed with COVID-19.