A new drug requiring only a single injection could be a game changer in keeping people with COVID-19 infections out of the hospital, research by Stanford Medicine has found.

A single, under-the-skin shot of a biologically based antiviral medication given to patients within seven days of the onset of COVID-19 cut the likelihood of hospitalization in half. Patients who were treated within three days of showing symptoms fared even better. Side effects were no greater than those reported by placebo recipients and tended to be far less than those of other types of interferon medications, the researchers said. The drug was given to more than 3,000 people in other trials and was well-tolerated even when given weekly for a year.

What's more, the drug, pegylated lambda-interferon, or PEG-lambda, proved effective against all tested COVID-19 viral variants, including omicron, during the international trial.

PEG-lambda is a synthetic version of lambda-interferon, a naturally occurring protein secreted by infected cells as a first line of defense against viral infection. Interferons are secreted by cells that sense invasion by a virus. Different interferon types use different receptors — molecules inside or on the surface of a cell that bind to a specific substance and have a specific effect in the cell — and their distribution in the body varies widely from one interferon type to another. Interferon molecules can also make their way into the bloodstream and contact more distant cells, having identical antiviral effects on the cells they latch onto — but only those cells that have receptors for them.

Receptors for lambda-interferon are largely limited to the linings of the lungs, airways and intestines — the main places where SARS-CoV-2 strikes — and the liver.

Viruses, including SARS-CoV-2, the virus that causes COVID-19, have evolved and found ways to shut down interferon production in the cells they infect, but they can't impact cells' interferon receptors. Therefore, injected interferons are able to trigger potent antiviral activity, the researchers said.

"This drug would have saved millions of lives if we'd had it at the beginning of the pandemic, and it could still save millions of other lives," said Dr. Jeffrey Glenn, a co-principal investigator and director of [email protected], a Stanford Medicine program devoted to discovering and developing novel antiviral agents to prepare for pandemics.

"There's been a lot of talk to the effect that COVID's over. I don't think the virus got that memo. Meanwhile, lots of people are still unvaccinated, and this drug showed profound benefits for vaccinated and unvaccinated people alike," he stated in the press release.

Glenn founded Eiger BioPharmaceuticals Inc., a biotechnology company that acquired the rights to lambda-interferon to develop it as a drug for hepatitis D some years ago. When the COVID-19 pandemic struck, the company turned its attention to the new pathogen. Researchers from the company along with others from Cardresearch, Platform Life Sciences, RainCity Analytics and the Together Network joined Stanford Medicine in the study. The research was funded by FastGrants, the Rainwater Charitable Foundation, the Latona Foundation, the Bill and Melinda Gates Foundation, and Eiger BioPharmaceuticals Inc.

The Phase 3 drug trials (the last step before submission to the Food and Drug Administration for approval) used more than 2,000 patients in Brazil and Canada with an average age of 43. Slightly more than half were women. About 95% were mixed race and only 3% were white. About 85% had been vaccinated for COVID-19, the researchers said.

Overall, of the roughly 930 patients who received the single subcutaneous dose of PEG-lambda, only 25 (2.7%) were hospitalized or were placed under observation in an emergency clinic within four weeks of testing positive for COVID-19 compared to 57 patients (5.6%) who received the placebo.

Among vaccinated patients treated with PEG-lambda within seven days of the onset of symptoms, 51% fewer were hospitalized compared to those who received the placebo, the researchers said.

Administering the drug earlier had even more significant results.

Among unvaccinated patients treated within the first three days of symptom onset, 89% fewer were hospitalized compared with placebo group — the same 89% reduction observed with Pfizer's Paxlovid, another antiviral drug that is administered in the early stages of COVID-19 infection, the researchers said.

Only 11 (1.9%) of those 567 patients treated with PEG-lambda within the first three days after symptoms wound up in the hospital within four weeks of getting the shot, versus 28 (3.1%) of the 590 who received a placebo injection within three days of symptom onset.

There were no deaths among patients treated with PEG-lambda within three days of symptoms' onset compared to four COVID-19-related deaths in the placebo group.

Glenn said the need for effective COVID-19 therapies is paramount, given vaccine-induced immunity wearing off more rapidly than has been hoped, new SARS-CoV-2 variants constantly striving to outwit the immune system and people declining repeated rounds of vaccination due to fear of side effects both real and imagined or due to vaccine fatigue.

The study was published online Feb. 9 in the New England Journal of Medicine.