Nursing home residents like Louisa Perreault in Marlborough, Massachusetts, have suffered more from COVID-19 than any other population – and a new study suggests they can benefit most from monoclonal antibodies used as a preventative.
Craig F. Walker /The Boston Globe via Getty Images
By Jon Cohen
Science‘COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.
A study in American nursing homes showed for the first time that monoclonal antibodies, which are manufactured in a laboratory, can protect people against the development of symptomatic COVID-19. Their manufacturer, Eli Lilly, hopes that these antibodies will provide an additional way to protect people at risk of serious diseases from the pandemic coronavirus. However, given the success of COVID-19 vaccines and their increasing availability, it is not clear that the costly and somewhat cumbersome intervention will be widely used.
Both Eli Lilly’s monoclonal antibody and a similar two-antibody cocktail from Regeneron Pharmaceuticals – known in October 2020 for treating former US President Donald Trump – have already received an emergency authorization (EUA) as a therapeutic remedy for those who have become infected and high risk of developing severe COVID-19. So far it is not used much because it has to be given early in infection and administered in a hospital or clinic. Now that it seems effective in preventing even mild illnesses, Eli Lilly plans to ask the U.S. Food and Drug Administration to expand the EUA to include use as a preventative measure.
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In the new study, nearly 1,000 people who lived or worked in American nursing homes received a single administration of Eli Lilly’s antibody – containing four times the dose used for therapeutic purposes – or a placebo. The company announced in a press release yesterday that the antibody had reduced the risk of becoming ill with COVID-19 in the next 8 weeks by 57%. Among residents of nursing homes, who made up about a third of the participants in the trial, the risk of COVID-19 disease decreased by 80%. Only four COVID-19–related deaths occurred in the study, and all were in nursing home residents in the placebo group.
“I am very pleased 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 the antibodies can be ‘very useful’ in long-term care facilities, which account for nearly 40% of US COVID-19 deaths. “If it’s exhausted, and I think there’s every reason to think it will be, then it’s a different tool,” said Rajesh Gandhi, a clinician on the disease at Massachusetts General Hospital. But he wants to see more specific information than the press release provides.
The finding that the antibody works better among nursing home residents than staff may seem puzzling – and the press release indeed leaves out details that statisticians contacted by Science said they should make sense of this. But Jani Sabo of Eli Lilly explains that the study has a reduced risk and that residents are at a higher risk of developing COVID-19 symptoms: they are older and often have weaker immune systems and more underlying diseases, and they never leave. Staff spend less time at the facilities and can stay home if there is an outbreak, she says. “What we then naturally find is that there is more chance of reducing the risk of infection. [among residents] than in the general population, ”says Sabo, a pharmacologist.
How Eli Lilly’s antibody would be used is not entirely clear. Sabo suggests that if an outbreak occurs in a nursing home, it can be given to residents who have not yet been vaccinated, or have received only one of the two shots. “It’s probably going to be the niche population,” she says.
Myron Cohen of the University of North Carolina School of Medicine, one of the lead investigators of the study, says he hopes preventative doses can be administered as subcutaneous shots, rather than infusions. Studies have been started to test the strategy. Ideally, those infected with the virus should first receive a SARS-CoV-2 antibody test. He adds: “People who already make antibodies probably don’t need them.”
Cohen adds that the prevention and treatment trials also had a basic scientific payoff: to explain how antibodies prevent SARS-CoV-2 from causing serious diseases. “For the first time, I have a good understanding of how the infection progresses,” Cohen says.
He notes that infection begins in the nose and serious diseases occur when the virus reaches the lungs. Three days after an infected person received the monoclonal antibodies, Cohen says, nasal swabs showed a “large” drop in virus levels in the nose, not seen in people who received a placebo. This in turn led to better clinical outcomes. It therefore appears that the antibodies restrict the infection to the nose, whether preventive or treated.
One possible disadvantage is that these monoclonal antibodies can undermine the effectiveness of vaccines. The two vaccines authorized in the United States contain messenger RNA (mRNA) that directs the body cells to make the surface protein, peak, of SARS-CoV-2, which then triggers the immune system to make antibodies against peak. The monoclonal antibodies of Eli Lilly and Regeneron are also targeted, and the concern is that it could bind to the protein produced by the mRNA, stopping the vaccine from dying in its tracks. Eli Lilly plans to launch studies to test it in vaccines, Sabo says.
Monoclonal antibodies can also lose their potency due to viral mutations. One study of a widely distributed SARS-CoV-2 mutant in South Africa, published on the preprint server bioRxiv on 19 January, has already shown this in test tube experiments.
But now that millions of vaccines, cheaper and easier to administer, are being used – with priority for the most vulnerable populations – the question is first and foremost the role that monoclonal people remain. Cohen says it could be important for the elderly and other people with an compromised immune system who do not have powerful responses to vaccines. “We just made a failure,” he says. “If we never have to use it in the nursing home again, I’ll be excited.”