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.
The monoclonal antibodies arrived first, but they weren’t considered to be the best line of defense. 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. The new versions have made all of the existing antibody treatments useless. According to National Institutes of Health’s COVID-19 Treatment Guidelines, Paxlovid now is the preferred choice of patients most at high risk of serious disease. 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 is monoclonal antibody?
SARS CoV-2 enters your body by infecting cells. It then uses those cells to create new ones. The spike proteins protruding from the virus’ surface act as a type of key to unlock those cells.
The immune system recognizes pathogens like SARS and produces antibodies. These proteins are proteins that recognize the virus’ proteins. 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.
The virus can get a leg up on your immune system if you are sick. Monoclonal antibody injections into the blood can boost immune function and prevent it from becoming a problem. “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. Evusheld, a monoclonal antibody called tixagevimab or cilgavimab can remain in the blood for up to six months and protect against 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.
Does monoclonal anti-bodies 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. The Omicron variant was unable to recognize two of the three monoclonal antibodies due to mutations in its spike proteins. They were rendered ineffective by January 2022. Sotrovimab was able to defeat the variant.
However, Omicron’s subvariants had already taken control by March 2022 and the FDA declared that sotrovimab is no longer efficacious on April 5.
However, there is one more option. FDA granted approval in February 2022 for a new monoclonal anti-Omicron antibody, bebtelovimab. This was confirmed to work against Omicron by 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 (an antibody combination that is used to prevent and not treat infections) still appears to be effective, although people might require additional dosages.
“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. This part of the virus is mutating in each variation.
What should I do?
According to the NIH Treatment Guidelines, Paxlovid is recommended as the first choice for patients who are not hospitalized and at risk of serious COVID-19 complications. If the drug is unavailable or the person can’t take it for some reason, they should be treated with another antiviral, remdesivir. The agency will recommend treatment with bebtelovimab if no antiviral options are available.
Paxlovid was approved by the FDA in December 2021. This drug prevents disease progression and blocks an enzyme that viruses need to reproduce in your body. The treatment decreased the risk of death and hospitalization by 89% for high-risk patients who took it within 3 days after they first experienced symptoms.
Paxlovid comes in a convenient set of pills that you can get from your local pharmacy. This makes it easier than monoclonal antibody, which require an injection administered by healthcare professionals. The antiviral drug does have some drawbacks. 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.
Trials haven’t yet shown that it is possible to take both monoclonal and Paxlovid simultaneously in clinical trials.
What will happen to COVID-19 if bebtelovimab becomes less 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.”
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