New Jersey Congresswoman Bonnie Watson Coleman announced on January 11th that she had caught the coronavirus and was experiencing mild symptoms, days after being potentially exposed during the Capitol insurrection. Hours later, she headed to a local hospital, on the advice of her doctor, for a monoclonal antibody therapy.

Monoclonal antibodies have proven one of the few treatments that may help slow or prevent the course of COVID-19. These proteins are made in a lab but mirror the protective armory made by your body’s immune system to fight off an infection. When given within the first ten days of symptoms, the drugs can reduce hospitalizations by up to 70 percent and diminish other severe symptoms in high-risk patients—or at least, that was the case before coronavirus variants emerged in the United Kingdom and South Africa.

The two drugmakers behind these therapies—Regeneron and Eli Lilly—said these mutated viruses may partially bypass or weaken the protections afforded by their life-saving therapeutics. In particular, both companies said the variant identified in South Africa, named B.1.351 or 501Y.V2, is most likely to impact their drugs’ effectiveness.

This disclosure arrived after the federal government spent mightily to stockpile these drugs, including a newly announced $2.6 billion deal for Regeneron, which is based in Tarrytown, New York. President Donald Trump received Regeneron’s cocktail when he was ill with COVID-19 and has ties to the company’s billionaire CEO Dr. Leonard Schleifer.

Here’s why the variants pose challenges for monoclonal antibody therapies: Each coronavirus is a sphere, covered in proteins called spikes. When the virus invades, our immune system tries to learn the curves and contours of these spikes, so it can build antibodies that recognize them. Over the past years, scientists found 20 such curves, known as epitopes, that serve as places where the antibodies target.

Eli Lilly’s antibody, called bamlanivimab, focuses on one epitope to block the coronavirus’s ability to enter human cells. Regeneron uses a cocktail of two separate antibodies, casirivimab and imdevimab, to two different individual epitopes. Although clinical trials remain ongoing, in November, the Food and Drug Administration granted emergency authorization to both treatments.

Now, however, the spike protein that these drugs target is changing. Every new case of the coronavirus gives the germ a chance to mutate and evade the defenses of its human hosts—and create new potent variants.

“We’ve been letting it run rampant, and giving it plenty of opportunities to make copies of itself,” said Stephanie Spielman, assistant professor of biological sciences at Rowan University in Glassboro, New Jersey.

Not all of these changes will make the virus more deadly or infectious, but inevitably, some will. In December, U.K. officials raised the alarm over another variant called B.1.1.7, which has now overwhelmed British hospitals and spilled into 52 countries including the United States. It appears to be 50% more contagious, on average. It is unclear if the same boost applies to the germ from South Africa, or other newly identified variants confirmed in Brazil.

All of the germs above have a common mutation in their spike proteins called N501Y, which allows the variants to bind more tightly to our cells—essentially making it easier to invade. Each variant, however, carries a plethora of other physical alterations—one has up to 17 such changes—that may be working in combination to increase transmission.

That’s troubling because Eli Lilly said in a written statement to Gothamist/WNYC that based on results from company lab tests, their drug bamlanivimab may prove less effective against the South African variant, which is likely already in the U.S. The company is currently running further tests to confirm this prediction. On the bright side, they expect their drug will continue to neutralize the variant from the UK.

These results are complemented by independent research conducted by Ivet Bahar, a distinguished professor of computational and systems biology at the University of Pittsburgh. Bahar ran a computer model on the South African variant, finding that in the 11 monoclonal antibodies they investigated, four may no longer be as effective. That wasn’t due to the N501Y mutation, but because of genetic changes to other parts of the virus.

Bamlanivimab was not one of the antibodies Bahar examined, but she said her findings are consistent with Eli Lilly’s statement. (She cautions the results will need to be confirmed with further experiments.) The federal government has spent $375 million on 300,000 doses of Eli Lilly’s antibody treatment.

Regeneron expects the variant from South Africa to escape one of the two antibodies in its drug cocktail, although it said the second should still effectively neutralize the virus. Christos Kyratsous, the vice-president of infectious disease research at Regeneron, said that designing a cocktail is harder and takes longer, but the effort could pay off in situations where the virus changes.

“We specifically selected two epitopes in two different regions to avoid escape,” he said, adding that both antibodies appear to still protect against the variant discovered in Britain.

Unlike Europe, the United States hasn’t been widely conducting genomic sequencing to spot these cases, so “we don’t have much surveillance,” said Daniel Griffin, an infectious disease specialist at Columbia University. Globally, "There needs to be a system in place to understand what each of these mutations mean, what these variants mean, and how it impacts the behavior of the virus,” said Maria Van Kerkhove, the World Health Organization’s COVID-19 technical lead in a press conference on January 16th.

Sequencing Congresswoman Watson’s infection, for example, could have revealed which antibody treatment might be most effective. (Watson did not respond to an interview request, and it is unclear which antibody she was treated with.) Widespread genetic sequencing would also allow pharmaceutical companies to redesign their antibodies based on how the virus is changing, something Kyratsous said would take at least a few months.

If antibodies can continue to be well-matched to viral mutations, it’s possible that these treatments could be regularly administered to protect people who can’t be vaccinated like those who are immunocompromised. Antibody treatments also provide some temporary protection from reinfection.

But Griffin added that antibody therapies, like vaccines, only succeed when they actually get into patients. He said that the therapies are free to patients, but so far, demand for the drug has vastly exceeded supply.

Northwell Health, New York’s largest healthcare provider, has set up a hotline physicians can call to schedule a treatment for eligible patients at select infusion sites. But the distribution is patchy. Griffin had a patient in Manhattan this week who had to take the subway and ferry to a hospital on Staten Island to get antibody therapy. The only other option was Catholic Health Services of Long Island, which provides the treatments right in their ER.

“When you get on the subway, you should realize a percentage of your fellow riders are positive,” Griffin said.

United Healthcare has announced a nationwide research collaboration with Eli Lilly to deliver infusions of bamlanivimab to up to 500,000 eligible patients’ homes. Yet currently, patients in many parts of the U.S. who need treatment face a long and frustrating wait. The federal government has launched a website with a list of locations that are distributing antibodies, but as of December 14th, only 22 states were listed. “California is drowning in COVID-19 patients,” Griffin said. "they should also be drowning in antibody therapy.”

“We desperately need a better system.”

Lois Parshley is a freelance journalist covering COVID-19. Follow her on Twitter @loisparshley.