What to Know About Monoclonal Antibodies as COVID-19 Treatments

COVID-19 is once again surging throughout the U.S., but deaths from the disease don’t seem to be following suit. That’s partly because many people have some level of immunity from vaccination or previous infection, but also because we now have an arsenal of tools to treat the disease.

Monoclonal antibodies were the first to arrive, and earlier on, they were considered the first line of defense against the disease. Over the course of the pandemic, the U.S. Food and Drug Administration (FDA) authorized four monoclonal antibodies to treat COVID-19 and one to help prevent the disease in people who can’t get or benefit from vaccines. But the new variants have rendered all but one of the antibody treatments ineffective; the antiviral drug Paxlovid is now the first choice for most patients at risk of severe disease, according to the National Institutes of Health (NIH) COVID-19 Treatment Guidelines. Still “monoclonal antibodies are going to continue to play a role and are probably going to continue to be updated for the new variants,” says Dr. James Cutrell, an infectious disease specialist at UT Southwestern Medical Center.

Here’s what we know about how well the monoclonal antibodies are working, and who might benefit from them.

What are monoclonal antibodies?

When the SARS-CoV-2 virus enters the body, it breaks into the cells and uses them to replicate itself. The spike proteins protruding from the virus’ surface act as a type of key to unlock those cells.

When the immune system identifies a pathogen like SARS-CoV-2, it begins to churn out antibodies: proteins that recognize and bind to specific proteins found on the virus. Antibodies that bind to the spike protein are called neutralizing antibodies, because they’re able to prevent SARS-CoV-2 from entering cells and replicating, thus neutralizing the infection.

Monoclonal antibodies are just like the antibodies the body makes when it sees SARS-CoV-2, except they’re designed in a laboratory to bind to specific parts of the spike protein.

“Monoclonal antibodies mimic your immune system and block the virus that causes COVID-19 from entering your body’s cells,” explains Dr. David T. Huang, a professor of clinical care medicine and emergency medicine at the University of Pittsburgh School of Medicine.

When you get sick, the virus has a head start on your immune system. Having monoclonal antibodies infused into your blood instead of having to wait for your body to make its own can help your immune system catch up and thwart the virus before it takes hold. “Monoclonal antibodies have been, really, a core strategy that we’ve been using throughout the pandemic,” says Cutrell.

Most monoclonal antibodies don’t last very long in the bloodstream. That’s why they’re only used after a person has been infected. But one type of monoclonal antibody, called Evusheld (tixagevimab and cilgavimab) can stay in the blood and provide protection for about six months before exposure to SARS-CoV-2. The FDA recommends this option for patients who can’t get vaccinated because they’re allergic to the shot’s ingredients or are immunocompromised severely enough that they won’t mount a sufficient response to the vaccine.

Do monoclonal antibodies still work?

Early in the pandemic, three monoclonal antibody treatments—bamlanivimab, casirivimab and imdevimab (which are administered together), and sotrovimab—were shown to reduce the risk of hospitalization and death from COVID-19. But the Omicron variant had mutations in its spike protein that made it unrecognizable to two of these three antibodies, rendering them ineffective in January 2022. Only sotrovimab retained the ability to fight the variant.

But by March 2022, new subvariants of Omicron had taken over, and on April 5, the FDA announced that even sotrovimab was no longer effective.

There is still one option, though. In February 2022, the FDA authorized a new monoclonal antibody, bebtelovimab, that was found to be effective against Omicron in small clinical trials. So far, a study in petri dishes that has not yet been peer reviewed suggests that bebtelovimab is also effective against the newer Omicron subvariants, BA.2.12.1, BA.4, and BA.5, but it’s unclear how it will perform against future variants and subvariants.

Evusheld, the antibody combination used to prevent rather than treat infection, still seems to be protective, but people may need additional doses.

“The Achilles heel of the monoclonal antibodies is that most of them target the same part of the virus—the spike protein—to help block entry into the cell,” says Cutrell. That part of the virus has been mutating with each variant.

Should I take Paxlovid or monoclonal antibodies?

The NIH Treatment Guidelines recommend Paxlovid as the first option for non-hospitalized patients at high risk of severe COVID-19 outcomes. If the drug is unavailable or the person can’t take it for some reason, they should be treated with another antiviral, remdesivir. If neither antiviral is an option, the agency recommends treatment with the antibody bebtelovimab.

The antiviral drug Paxlovid, which prevents disease progression by blocking an enzyme the virus needs in order to replicate in your body, was authorized in December 2021. When high-risk patients took the drug within three days of first experiencing symptoms, the treatment reduced the likelihood of hospitalization and death by 89%.

Since it comes as a set of pills you can pick up from your local pharmacy, Paxlovid is easier to take than monoclonal antibodies, which are infusions administered by a healthcare provider. But the antiviral drug has some downsides. It’s known to interact with many medications, including certain anti-hypertensives, cardiovascular drugs, and psychiatric drugs. If you’ve been prescribed a drug that interacts with Paxlovid, your doctor may recommend another antiviral drug or a monoclonal antibody instead.

It’s also possible that the advice could change, as reports emerge of “rebound infections”—completing a course of the drug, testing negative, and then testing positive shortly after—in patients who take Paxlovid. “We’re still trying to sort out how common that is,” says Cutrell, “and the full significance of it.” So far, the U.S. Centers for Disease Control and Prevention (CDC) says that rebound infections haven’t caused severe disease.

Clinical trials have not yet tested the option of taking both Paxlovid and monoclonal antibodies simultaneously.

Will COVID-19 evolve so that bebtelovimab is no longer effective?

“If there’s one thing COVID-19 has done, it’s been to teach humility,” says Huang. It’s important for researchers to continue regularly testing the efficacy of monoclonal antibodies against new variants, he says. Scientists will also need to continue to develop new versions of the treatment to keep up with the virus’s evolution. Still, he emphasizes, “The most important thing is vaccination and boosters, and taking reasonable precautions,” he says. “Paxlovid and monoclonal antibodies are important, but secondary.”