One-and-done injection halves risk of COVID hospitalization in large trial

photo shows a young woman with light brown skin lifting up the sleeve of her t shirt to show a bandage on her arm, implying she recently got an injection — An injectable medication reduced people's risk of being hospitalized with COVID-19 in a large trial.

(Image credit: Poike via Getty Images)

A one-time shot with an experimental drug halved COVID-19 patients' risk of being hospitalized with the illness compared with a placebo, a late-stage trial shows. However, the treatment may still be early in its journey to approval in the U.S., the drug's maker told Live Science.

The trial participants received an injection of the drug, called pegylated interferon lambda (PEG-lambda), within one week of developing COVID-19 symptoms. Those who received PEG-lambda early, within the first three days of developing symptoms, reaped the most benefit: Overall, these individuals were 65% less likely to be hospitalized in the following month. Among the subset of these individuals who were unvaccinated, the risk of hospitalization fell by about 89%, compared with a placebo.

Pfizer's antiviral pill Paxlovid (generic name nirmatrelvir) also lowers unvaccinated people's risk of hospitalization by about 89%, according to a late-stage trial that helped the drug earn emergency use authorization (EUA) from the Food and Drug Administration (FDA). However, one major difference between PEG-lambda and Paxlovid is that, while the former is a one-and-done injection, the latter requires users to take three tablets twice a day for five days, which totals 30 pills.

PEG-lambda contains a type of protein known as a type III interferon, which the body naturally produces in response to viral invasion. Once released, these proteins travel to cell surfaces, where they lock into receptors. Latching onto these receptors sets off a chain reaction inside the cell that ultimately raises its guard against viruses, making it more difficult for pathogens to infiltrate cells, replicate and spread.

The late-stage trial of PEG-lambda took place in Brazil and Canada and included more than 1,900 participants between ages 18 and 92. All the participants tested positive for SARS-CoV-2 on a rapid antigen test and were treated at outpatient clinics within seven days of developing COVID-19 symptoms. The majority had at least one characteristic that put them at high risk of severe infection, including a history of diabetes, smoking or lung disease. Around 83% of the participants had received at least one dose of a COVID-19 vaccine, and up to three doses.

The trial took place between June 2021 and February 2022, and genetic analyses suggested the participants were infected by a variety of SARS-CoV-2 variants, including alpha, delta, gamma, zeta and the BA.1 lineage of omicron. PEG-lambda fared equally well against all these variants. And again, because the treatment boosts human cells' defense systems, rather than targeting SARS-CoV-2 directly, future variants aren't likely to develop resistance to the drug, as they might against other antivirals, Glenn said.

Although this positive data has now been published in a peer-reviewed journal, PEG-lambda still faces barriers to approval in the U.S. In October 2022, Eiger announced that it had requested a pre-EUA meeting with the FDA and had been denied. At that time, the FDA cited concerns about the "conduct" of the clinical trial and noted that, "in the current context of the pandemic," it would be unlikely to issue an EUA based on that trial's data.

Typically, to earn FDA authorization, a company runs its own trial start to finish; collaborates with the FDA to set the protocols ahead of time; and periodically sends experts to each study site to ensure rigorous, industry standards are being followed. The FDA didn't have the same level of oversight over the TOGETHER Trial, and in addition, by the time Eiger was preparing to apply for an EUA, the urgency of the pandemic in the U.S. had somewhat "waned," Choong noted.

At this point, Eiger may seek the emergency use authorization for PEG-lambda in countries beyond the U.S., and the company is currently evaluating how it might pursue traditional approval in the U.S., as the FDA has suggested. To that end, rather than going after only COVID-19, the company may consider testing the interferon as a "panviral" treatment that can be used against many viruses, Apelian said.

"It's pretty likely that this could work in a similar fashion for flu and for RSV [respiratory syncytial virus], so I would see that as maybe a more prudent way of developing this through a traditional path," Apelian said. (Separately, Eiger will also continue testing the drug's effectiveness against hepatitis D, he noted; the liver disease was the first condition the company attempted to treat with PEG-lambda.)

Nicoletta Lanese is the health channel editor at Live Science and was previously a news editor and staff writer at the site. She is a recipient of the 2026 AHCJ International Health Study Fellowship, with a project focused on antibiotic stewardship practices in Japan and the U.S. They hold a graduate certificate in science communication from UC Santa Cruz and degrees in neuroscience and dance from the University of Florida. Beyond Live Science, Lanese's work has appeared in The Scientist, Science News, the Mercury News, Mongabay and Stanford Medicine Magazine, among other outlets. Based in NYC, she also remains involved in dance and performs in local choreographers' work.