Omicron subvariants present resistance and put some folks in danger

Emerging omicron subvariants are resistant to key antibody treatments for HIV patients, kidney transplant recipients and other immunocompromised people, making them particularly vulnerable to Covid this winter, the White House warned this week.

“With some of the new subvariants appearing, some of the key tools we had to protect immunocompromised like Evusheld may no longer work. And that’s a big challenge,” said Dr. Ashish Jha, head of the White House Covid Task Force, told reporters Tuesday.

President Joe Biden on Tuesday warned the estimated 7 million US adults who have compromised immune systems that they are particularly at risk, but he could offer little reassurance other than telling them to ask their doctor what precautions to take are to be met.

“New variants may render some existing protections for immunocompromised people ineffective,” the president said before receiving his refresher on Tuesday. “Unfortunately, that means you may be at particular risk this winter. I urge you to consult with your doctors on the right steps to protect yourself and take extra precautions.”

The message clashes with repeated assurances from the White House that the US has all the vaccines and treatments it needs to fight Covid this winter, as public health officials expect a further surge.

While this may be true for the general population, it is not true for people with compromised immune systems. This includes people with cancer, people after organ transplants, people with HIV, and people taking drugs for autoimmune diseases.

Evusheld is a Food and Drug Administration-approved antibody cocktail for the prevention of Covid in people 12 years and older with moderately or severely compromised immune systems. The drug is given as two injections every six months before infection.

Evusheld, manufactured by AstraZeneca, has helped close a protection gap for people with weakened immune systems who are unable to mount a strong response to the vaccines. The drug and multiple rounds of vaccinations have led to a significant drop in hospitalizations in this cohort in recent months, according to Camille Kotton, an infectious disease expert who specializes in treating people with compromised immune systems.

“We’ve been in a sweet spot for maybe a few months in terms of immunocompromised patients who have good protection and then good treatment options,” said Kotton, a physician at Massachusetts General Hospital and a member of the independent Centers for Disease Control and Prevention Vaccine Advisory Board.

But more immune-preventable Omicron subvariants such as BA.4.6, BA.2.75.2, BF.7, BQ.1, and BQ.1.1 are resistant to Evusheld, according to the National Institutes of Health. For example, scientists at Columbia University found that Evusheld had completely lost its effectiveness against BA.4.6.

And BQ.1 and BQ.1.1 are likely resistant to bebtelovimab, the monoclonal antibody developed by Eli Lili to prevent people with compromised immune systems who contract Covid from developing serious illness, according to the NIH.

This makes people with compromised immune systems increasingly susceptible as these subvariants become circulated in the United States. As omicron BA.5 declines, this swarm of newer subvariants together accounts for about 38% of infections in the US, according to CDC data.

Although Pfizer’s antiviral Paxlovid remains effective against the omicron subvariants, people who have had an organ transplant often can’t take the pill because it interacts with other drugs they need, Kotton said.

“I am concerned that the near future will be a challenging time for immunocompromised patients,” Kotton said. “The monoclonal antibodies in Evusheld will offer less protection and bebtelovimab will provide an ineffective treatment for several of the emerging variants.”

And help is not on the way at the moment. Kotton said she’s not aware of any monoclonal antibodies ready to replace those the subvariants are picking on. Jha acknowledged in the White House on Tuesday that as Covid develops, the US has dwindling treatment and prevention options for people with compromised immune systems. He accused Congress of failing to hand over $22.5 billion in funding for the nation’s Covid response due to Republican opposition.

“We had hoped that over time as the pandemic progressed and as we progressed in our fight against this virus, we would expand our medicine cabinet,” Jha told reporters. “Due to a lack of congressional funding, this medicine cabinet has actually shrunk and that is putting vulnerable people at risk.”

Andrew Pekosz, a virologist at Johns Hopkins University, said finding ways to protect people with compromised immune systems is the most critical issue of the pandemic right now and needs to be addressed quickly.

“What we really need to work on is getting new antibody treatments out of the lab and into the clinics,” Pekosz said. “In the lab, scientists know what next-generation monoclonal antibodies look like.”

Kotton said people with compromised immune systems should stay up to date on their vaccines, which means they get the new booster that targets Omicron BA.5. Those who have stayed connected during the pandemic have now received six shots.

Those starting from scratch would get a three-dose primary series of Moderna or Pfizer with the older-gen shots, and then a new booster targeting Omicron, per CDC guidelines.

People with compromised immune systems should continue to exercise caution this winter, as the immune-resistant omicron subvariants could be circulating when people gather for the holidays, Kotton said. However, she found that the group was more diligent than the rest of the population in wearing masks and practicing mitigation measures to avoid the virus.

The bigger problem is that the general population has largely moved on, no longer taking basic precautions that could reduce transmission and protect the vulnerable — like wearing masks, Kotton said.

“If we all masked more in public places, it would increase safety for them and allow them a higher likelihood of returning to many activities more safely,” she said.

Jha was asked by NBC News on Tuesday if Biden urging people with compromised immune systems to consult their doctors about precautions is an indication that the burden of responsibility has been shifted to individuals rather than the broader community.

“As a society — as a caring society, we care about all Americans, especially the most vulnerable Americans,” Jha said. “So I think it remains a collective responsibility for all of us to look after our fellow immune-compromised Americans.”

The CDC recommends people in communities where Covid risk levels are moderate to test themselves and wear a quality mask before meeting indoors with someone who is at high risk of getting sick. People who are particularly at risk should wear a high-quality mask in public.

In general, when Covid levels are high, people should consider wearing quality masks, and those vulnerable should consider avoiding non-essential indoor public activities, according to the CDC. You can check your county’s Covid level on the CDC’s website.