Residents of nursing homes like Louisa Perreault in Marlborough, Massachusetts, suffered more from COVID-19 than any other population – and a new study suggests that they may benefit more from monoclonal antibodies used as preventives.
Craig F. Walker /The Boston Globe via Getty Images
By Jon Cohen
Science‘s COVID-19 reports are supported by the Pulitzer Center and the Heising-Simons Foundation.
A study in US nursing homes showed for the first time that monoclonal antibodies, mass produced in a laboratory, can protect people from the development of symptomatic COVID-19. Its manufacturer, Eli Lilly, hopes that these antibodies will provide an additional way to protect people at risk of serious illnesses caused by the pandemic coronavirus. But given the success of COVID-19 vaccines and their increasing availability, it is unclear whether the expensive and somewhat complicated intervention will be widely used.
Both the Eli Lilly monoclonal antibody and a similar cocktail of two antibodies from Regeneron Pharmaceuticals – famous for treating former US President Donald Trump in October 2020 – have already received emergency use authorization (USA) as therapy for those who have been infected and are at high risk of developing severe COVID-19. So far, they are not widely used because they must be administered at the beginning of the infection and infused in a hospital or clinic. But now that they appear effective in preventing even minor illnesses, Eli Lilly plans to ask the U.S. Food and Drug Administration to expand the U.S. to include use as a preventative.
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In the new study, nearly 1,000 people who lived or worked in American nursing homes received a single infusion of Eli Lilly’s antibody – containing four times the dose used for therapeutic purposes – or a placebo. In a press release yesterday, the company announced that the antibody reduced the risk of falling ill with COVID-19 over the next 8 weeks by 57%. Among nursing home residents, who represented about a third of study participants, the risk of COVID-19 disease fell by 80%. Only four COVID-19–related deaths occurred in the study, and all were resident in nursing homes in the placebo group.
“I am very happy with these results,” said Davey Smith, an infectious disease clinician at the University of California, San Diego, who was not involved in the study. He says that antibodies can be “really useful” in long-term care facilities, which account for nearly 40% of COVID-19 deaths in the United States. “If this is confirmed, and I think there is every reason to think it will be, then it is another tool,” says Rajesh Gandhi, an infectious disease clinician at Massachusetts General Hospital. But he wants to see more specific data than that provided by the press release.
The finding that the antibody worked better in nursing home residents than in the team may seem intriguing – and, in fact, the press release omits details that statisticians contacted by Science they said they needed to make sense of it. But Janelle Sabo, from Eli Lilly, explains that the study measured reductions in risk, and residents are at a higher risk of developing symptomatic COVID-19: they are older and generally have weaker immune systems and more underlying diseases, and never will though. Employees spend less time on the premises and can stay home if there is an outbreak, she says. “What we found then, of course, is that there is more opportunity to reduce the risk of infection [among residents] than in the general population, ”says Sabo, a pharmacologist.
How the Eli Lilly antibody would be used is not entirely clear. Sabo suggests that if an outbreak occurs at a nursing clinic, it can be administered to residents who have not been vaccinated or who have received only one of the two vaccines. “This is likely to be the niche population,” she says.
Myron Cohen of the University of North Carolina School of Medicine, one of the study’s principal investigators, says he hopes that preventive doses can be administered as easy-to-administer subcutaneous injections rather than infusions. Studies to test this strategy have already started. Ideally, people infected with the virus should receive a SARS-CoV-2 antibody test first, he adds: “People who are already making antibodies probably don’t need this.”
Cohen adds that prevention and treatment tests also had a basic scientific reward: clarifying how antibodies prevent SARS-CoV-2 from causing serious illness. “For the first time, I have a real sense of how the infection progresses,” says Cohen.
The infection, he notes, begins in the nose, and serious illness occurs when the virus reaches the lungs. Three days after an infected person received monoclonal antibodies, Cohen said, nose smears showed a “huge” drop in virus levels in the nose, not seen in people who received a placebo. This, in turn, has led to better clinical results. Therefore, antibodies, whether administered as a preventive or as a treatment, appear to largely confine infection to the nose.
A potential disadvantage is that these monoclonal antibodies can impair the effectiveness of vaccines. The two vaccines authorized in the United States contain messenger RNA (mRNA) that directs cells in the body to produce the SARS-CoV-2 surface protein, spike, which then activates the immune system to produce antibodies against spike. Monoclonal antibodies Eli Lilly and Regeneron also target the peak, and the concern is that they could bind to the protein produced by the mRNA, stopping the killed vaccine in its path. Eli Lilly plans to launch studies to test this in vaccinated people, Sabo said.
Monoclonal antibodies can also lose their potency because of viral mutations. A study of a SARS-CoV-2 mutant circulating widely in South Africa, published on January 19 on the prepress server bioRxiv, has already demonstrated this in test tube experiments.
But now that vaccines, which are cheaper and easier to administer, are being distributed by the millions – with priority for the most vulnerable populations – the question is which role remains for monoclonals in the first place. Cohen says they may be important for the elderly and other people with compromised immune systems who have no vigorous responses to vaccines. “We just created a fail-safe system,” he says. “If we never have to use it in the nursing home again, I will be thrilled.”