New COVID Antiviral Cuts Hospitalizations in Half

An injection of a type of interferon drastically reduced the risk of severe COVID in a late-stage trial

The pandemic is not over, despite some proclamations to the contrary. The good news is that we now have some effective therapeutics that are helping drive fatality rates down. Chief among these is Paxlovid, which significantly reduces the risk of hospitalization and death and was first granted an emergency use authorization by the Food and Drug Administration in December 2021. Paxlovid is not an option for everyone, though. And SARS-CoV-2, the virus that causes COVID, has the potential to evolve resistance to it. The world desperately needs more options to ensure we stay ahead of the virus.

Now a new antiviral treatment is showing promise. Clinical trial results show that a single injection of a substance called pegylated interferon lambda (PEG-lambda) is highly effective at preventing severe COVID. In a cohort of mostly vaccinated patients, participants given the drug within seven days of showing symptoms were 51 percent less likely to be hospitalized or to go to an emergency room, compared with those given a placebo. People given PEG-lambda within three days saw that risk reduced by 58 percent. The treatment may also lower the risk of death, but the numbers were too small to be significant. The findings were published on Wednesday in the New England Journal of Medicine.

The drug was even more effective in unvaccinated patients. Side effects were minimal, and PEG-lambda has other advantages. It is a “broad spectrum” antiviral that could be useful against numerous diseases. The researchers hope the new data will lead to FDA authorization that will enable doctors to give PEG-lambda to patients. “The tragedy is, had we been able to use this at the beginning of the pandemic, we could have saved millions of lives,” says Jeffrey S. Glenn of Stanford University, who is senior author of the study. “We still can.”


“This was a well-designed, well-controlled trial. Confounding factors, such as age, race, comorbidities, etcetera have all been taken into account,” says immunologist Evangelos Andreakos of the Academy of Athens, who was not involved in the work. “The findings are convincing.” One caveat is the large number of people who had to be treated for just a few to benefit, but this is not specific to PEG-lambda. “Antivirals need to be administered early, before anyone knows if these individuals will develop severe disease,” Andreakos says. “This will be solved with better identification of high-risk patients and targeted treatment.”
PEG-lambda is a synthetic version of a naturally produced protein called an interferon that is attached to a molecule that slows its clearance from the blood. It is administered with a single subcutaneous injection. Paxlovid, by comparison, involves taking three pills twice a day for five days.

Interferons are signaling molecules that are part of the innate immune response, the body’s first line of defense against invaders. Type I interferons (such as alpha and beta) have been explored as antivirals for decades, but they can have significant side effects, including fever, nausea, vomiting and muscle aches. This happens because the receptor they bind to is found in numerous tissues, as well as on immune cells, so boosting type I interferons can put the immune response into overdrive. But interferon lambda (a type III interferon) only binds to receptors on epithelial cells, such as those located in the lungs, airways and gut—where SARS-CoV-2 primarily acts—and the liver. Researchers think this is why lambda has minimal side effects. This was not a big surprise because it has been safely given to more than 3,000 patients in clinical trials as a treatment for hepatitis

https://www.scientificamerican.com/article/new-covid-antiviral-cuts-hospitalizations-in-half/


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