Antibodies that attack a particle of coronavirus (illustration).Credit: Juan Gaertner / SPL / Alamy
Two clinical trials suggest that treatments with specific antibodies can prevent deaths and hospitalizations among people with mild or moderate COVID-19 – particularly those who are at high risk of developing serious illness.
One study found that an antibody to the coronavirus developed by Vir Biotechnology in San Francisco, California, and GSK, based in London, reduced the chances of hospitalization or death among participants by 85%. In another study, a cocktail of two antibodies – bamlanivimab and etesevimab, both made by Eli Lilly of Indianapolis, Indiana – reduced the risk of hospitalization and death by 87%.
The results of the study, both announced on March 10, come from randomized, double-blind, placebo-controlled clinical trials, but have not yet been published. They add to a growing body of evidence that treatments can help prevent serious illnesses when administered early, says Derek Angus, an intensive care physician at the University of Pittsburgh, Pennsylvania.
The antibodies “appear to be incredibly effective,” he says. “I am very excited about the results of these tests.”
The body’s natural response to viral infection is to generate a variety of antibodies, some of which are able to directly interfere with the virus’s ability to replicate. In the early days of the pandemic, researchers rushed to identify the most effective antibodies against the coronavirus and to mass produce them. The resulting ‘monoclonal antibodies’ have been tested in a variety of settings as treatments for COVID-19.
Vir and GSK’s antibody, called VIR-7831, was isolated for the first time in 2003 from someone recovering from a severe acute respiratory syndrome (SARS), which is caused by a similar coronavirus. Later, it was discovered that the antibody also bound to the SARS-CoV-2 spike protein.
The companies also announced that in laboratory studies1, VIR-7831 linked to SARS-CoV-2 variants – including the 501Y.V2 fast-spreading variant (also called B.1.351) first identified in South Africa. They attributed the antibody’s resilience to its target: a particular region of the spike protein that does not tend to accumulate mutations.
Low absorption
VIR-7831 joins a list of monoclonal antibodies that have been tested against COVID-19, some of which – including Lilly’s combination – have already been authorized for use in the United States and elsewhere. But there has been relatively little acceptance by American doctors and their patients, says Angus.
One problem, he says, is that while the results have been released to the press and submitted to the US Food and Drug Administration, companies have not yet published data from major clinical trials in specialized journals. Medicines are also expensive and must be administered by infusion at a specialized service, such as a hospital or outpatient treatment center – a difficult task when medical resources have already been overwhelmed by an increase in cases.
Another challenge has been sending mixed messages. At the beginning of the pandemic, some major clinical trials involving people who were hospitalized with COVID-19 found no benefit from monoclonal antibodies. Many researchers have predicted this result: monoclonal antibody therapy is expected to work better at the onset of the disease, and symptoms in advanced stages of severe COVID-19 are sometimes motivated more by the immune system itself than by the virus.
Still, the failures of clinical trials created a narrative that competed with positive results in studies of milder infections, says Angus, fueling skepticism. “People said, ‘But I thought it didn’t work,'” he says. “It’s totally in the way.”
And while studies on mild infections have shown promise, they are too small to allow researchers to draw definitive conclusions, says Saye Khoo, a pharmacologist at the University of Liverpool, UK, who leads the AGILE Coronavirus Drug Testing Initiative. from UK. Only a small fraction of people with mild COVID-19 will progress to serious illness, meaning that, although trials enrolled hundreds of participants, the number of those who were hospitalized or died was low.
But it will be a long wait until everyone is vaccinated, and monoclonal antibodies can provide an important bridge between vaccines and treatments that have been found for people who are hospitalized, said Jens Lundgren, an infectious disease doctor at the University of Copenhagen and Rigshospitalet. “It is not a substitute for vaccines, but it is a plan B,” he says, adding that the drugs may be particularly important for those who are unable to mount an immune response to vaccination.
The speed with which these monoclonal antibodies were developed is a lesson for future pandemics, says Khoo. “These compounds are certainly exciting,” he says. “We must not forget that, because there will be other pandemics coming to us. This was a real lesson in how to be prepared. “