Scientists study interferons as possible early treatment

Coronavirus appears to disarm body’s proteins that fight infections.

Researchers across the planet are racing to harness one of our immune system’s front-line defenders as an early treatment for COVID-19, the disease caused by coronavirus that has killed more than 800,000 people globally.

Until now, early-stage treatments have remained elusive. But an improved understanding how the virus disarms some of the body’s immune fighters, called interferons, is creating excitement among scientists who theorize they might be able to counter that process and prevent infections from developing into severe disease.

Interferons are immune proteins that normally interfere with a virus’ life cycle – hence the name, interferon. In addition to their antiviral properties, they summon natural killer cells, “the best soldiers, as it were, of the innate immune system,” Anthony S. Fauci, director of NIH’s National Institute of Allergy and Infectious Diseases, said in an interview.

That system is both the body’s whooping air-raid siren and its emergency responders rushing to the scene. The virus’s ability to hamstring this system may be one of the keys to its success.

Now, several trials are underway in the United States and elsewhere to see whether giving interferon to coronavirus patients early on might prevent severe disease, or hasten recovery, if administered later.

Driving the trials are a spate of recent studies showing that interferons are weakest in the worst coronavirus cases. Scientists in France came to this conclusion after examining cells in the blood of 50 COVID-19 patients who had spent 10 days in the hospital, as they wrote in a study published Aug. 7 in the journal Science.

“We found that the more severe the patients were, the less interferon type-1 they were producing,” said Benjamin Terrier, a professor of internal medicine at the National Reference Center for Rare Systemic Autoimmune Diseases in Paris’s Cochin Hospital, referring to a subset of the proteins normally deployed against viruses.

This spring, Benjamin tenOever, a microbiology professor at the Icahn School of Medicine at New York’s Mount Sinai Hospital, and his colleagues came to similar conclusions after studying the virus in samples taken from humans, ferrets and infected cells grown in a lab. Interferons, as they reported in the journal Cell, were lacking in all of those.

“The virus is very actively repressing both the production of and the sequencing of interferons,” meaning the process by which the body makes these proteins, tenOever said.

This weakening happens not only in patients’ lungs but in their blood, according to new research by Bali Pulendran, an immune system expert at Stanford University School of Medicine, and his colleagues.

The team isolated immune cells from the blood of patients with severe COVID-19, placed them in petri dishes and tried to provoke them with bacteria and viruses. Normally, such provocations would cause the immune cells to erupt in a shower of interferons and other defensive molecules.

But, as the scientists reported in a paper published Aug. 11 in Science, those cells in COVID19 patients were inert. It was as though the coronavirus, or a consequence of its infection, had snipped their fuses.

“After eight days or so, the type-1 interferon system is completely absent, and silenced, by the infection,” Pulendran said.

Researchers caution that many questions remain unanswered about interferon’s use in coronavirus patients. Past clinical studies that tested it to treat SARS and MERS showed little or no benefit.

A large, NIH-sponsored clinical trial launched this month will test interferon as a drug injected in patients hospitalized with COVID19. Those patients will receive interferon beta-1a, a synthetic molecule identical to the protein our bodies make, every other day for the first week of their hospital stay.

The patients in the study will also get remdesivir, an antiviral agent the FDA authorized in the spring. Researchers will compare their recovery against that of COVID-19 patients who received remdesivir alone. “The purpose of it is to determine whether you get added value,” Fauci said. The trial is slated to run through November 2023.

Should interferon beta-1a prove useful, Fauci doubted there would be shortages because it is already widely used, for instance, to treat multiple sclerosis. Interferon drugs were also previously used as a standard treatment for hepatitis C, though newer, more effective therapies have largely replaced them.

Despite their potential, interferons may not be a panacea, scientists cautioned.

“In principle, you could think, why don’t we just give it to everybody who has a viral infection ever,” said Tufts University microbiologist Marta Gaglia. “But in reality, it has proven less effective than we would like.”

A critical factor may be getting the timing right. The new studies suggest interferon would be most helpful in the earliest stages of the disease, but that window may close before most people are hospitalized and doctors can treat them.

“Interferon also has a lot of side effects,” Gaglia pointed out. These include muscle aches, fever and other ailments associated with flu infections. “So we wouldn’t want to use it unless we think it’s going to be beneficial.”

NEW YORK TIMES FILE With interferons, a critical factor may be getting the timing right. The new studies suggest interferon would be most helpful in the earliest stages of the disease, but that window may close before most people are hospitalized and doctors can treat them.