COVID-19 is once again on the rise across the United States, but deaths from the disease don’t seem to be keeping up. That’s partly because many people have some degree of immunity from previous vaccinations or infections, but also because we now have an arsenal of tools to treat the disease.
Monoclonal antibodies were the first to emerge, and before that, they were considered the first line of defense against the disease. During the pandemic, the U.S. Food and Drug Administration (FDA) has authorized four monoclonal antibodies to treat COVID-19 and one to help prevent the disease in people who cannot or benefit from vaccines. But new variants have made all but one of the antibody treatments ineffective; Antiviral drug Paxlovid is now first choice for most patients at risk of severe illness, according to the National Institutes of Health (NIH) COVID-19 Treatment Guidelines. “Monoclonal antibodies will continue to play some role and will likely continue to be updated for new variants,” said Dr. James Cutrell, infectious disease specialist at UT Southwestern Medical Center. .
Here’s what we know about how monoclonal antibodies work and who might benefit from them.
What is a monoclonal antibody?
When the SARS-CoV-2 virus enters the body, it enters the cells and uses them to replicate itself. The spike proteins protruding from the surface of the virus act as a sort of key to unlocking those cells.
When the immune system identifies a pathogen like SARS-CoV-2, it begins to make antibodies: proteins that recognize and bind to specific proteins found on the virus. Antibodies that bind to the mutant protein are called neutralizing antibodies, because they can prevent SARS-CoV-2 from entering cells and replicating, thereby neutralizing the infection.
Monoclonal antibodies are like the antibodies the body makes when it sees SARS-CoV-2, except they are designed in the lab to bind to specific parts of the mutant protein.
“Monoclonal antibodies mimic your immune system and prevent the virus that causes COVID-19 from entering your body’s cells,” said Dr. David T. Huang, professor of clinical care medicine. clinical and emergency medicine at the University of Pittsburgh School of Medicine explains.
When you get sick, the virus starts working on your immune system. Infusing monoclonal antibodies into your bloodstream instead of waiting for your body to make its own can help your immune system catch up and stop the virus before it survives. “Monoclonal antibodies are really a core strategy that we have been using throughout the pandemic,” says Cutrell.
Most monoclonal antibodies do not last long in the blood. That is why they are used only after a person has been infected. But a monoclonal antibody, called Evusheld (tixagevimab and cilgavimab) can stay in the blood and protect about six months prior to exposure to SARS-CoV-2. The FDA recommends this option for patients who cannot be vaccinated because they are allergic to the components of the shot or are so immunocompromised that they will not respond adequately to the vaccine.
Do monoclonal antibodies still work?
Early in the pandemic, three monoclonal antibody treatments—bamlaniximab, casirivimab and imdevimab (administered together), and sotrovimab—Proven to reduce the risk of hospitalization and death from COVID-19. But the Omicron variant has mutations in its mutant protein that make it unable to recognize two of these three types of antibodies, making them inefficient in January 2022. Only sotrovimab retains the ability to fight the variant.
But by March 2022, the new Omicron subvariables took over, and on April 5, FDA announced that even sotrovimab was no longer effective.
However, there is still an option. In February 2022, the FDA approved a new monoclonal antibody, bebtelovimab, which is found it effective against Omicron in small clinical trials. So far, one research in non-peer-reviewed petri dishes show that bebtelovimab is also effective against the newer Omicron sub-variants, BA.2.12.1, BA.4 and BA.5but it’s not clear how it will work for future variants and sub-variants.
Evusheld, the antibody combination used to prevent rather than treat infection, still seems to be protectedbut people may need additional doses.
“The Achilles’ heel of monoclonal antibodies is that most of them target the same part of the virus – the mutant protein – to help block entry into the cell,” says Cutrell. That part of the virus has mutated with each variant.
Should I take Paxlovid or monoclonal antibodies?
Principles of Treatment of NIH introduce Paxlovid is the first choice for non-hospitalized patients at high risk for a serious COVID-19 outcome. If medication is not available or the person cannot take it for some reason, they should be treated with another antiviral drug, remdesivir. If no antiviral medication is an option, the agency recommends treatment with the bebtelovimab antibody.
The antiviral drug Paxlovid, which stops the progression of the disease by blocking an enzyme the virus needs to replicate in your body, has Authorised in December 2021. When high-risk patients take the drug within three days of first symptoms, treatment reduced ability Hospitalization and mortality were 89%.
Because it’s a kit you can buy from your local pharmacy, Paxlovid is easier to take than monoclonal antibodies, which are given by a healthcare provider. But antivirals have some downsides. It is known to interact with many medications, including some antihypertensive drugs, cardiovascular drugs and psychiatric drugs. If you have been prescribed a drug that interacts with Paxlovid, your doctor may recommend another antiviral drug or a monoclonal antibody instead.
It is also possible that advice may change, as reports emerge about “recurrent infections”—completed a course of drug therapy, tested negative, and then tested positive shortly thereafter—in patients taking Paxlovid. “We’re still trying to figure out how popular it is, and what it means,” says Cutrell. So far, the U.S. Centers for Disease Control and Prevention (CDC) says the infection has flared up again not cause serious illness.
Clinical trials have not yet tested the option to administer both Paxlovid and monoclonal antibodies.
Will COVID-19 evolve so that bebtelovimab is no longer effective?
“If there’s one thing COVID-19 has done, it’s taught humility,” Huang said. It is important for researchers to continue to regularly test the effectiveness of monoclonal antibodies against new variants, he said. Scientists will also need to continue to develop new versions of treatments to keep up with the evolution of the virus. However, he stressed, “The most important thing is vaccinations and boosters, and taking reasonable precautions,” he said. “Monoclonal antibodies and paxlovid are important, but secondary.”
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