Interferon therapy shows amazing results against COVID-19 | Science

From the earliest days of the pandemic, scientists have hoped that interferons, a family of potent proteins that are the body’s first line of defense against viruses, could become weapons against SARS-CoV-2. Because the virus effectively eliminates the interferon response, the researchers thought that providing additional interferons could counteract this. But for 2 years, interferons have been disappointing in trials in hospitalized patients.

Now, a surprisingly positive result from a large trial of non-hospitalized and high-risk people in Brazil has revived hopes. In a study of more than 1,900 people, those who received a single injection of a drug called peginterferon lambda within 7 days of developing COVID-19 symptoms were half as likely to be hospitalized or to have long visits. in the emergency room than those who received placebo. . The effect, which the trial sponsor, Eiger BioPharmaceuticals, reported in a press release., was seen in many variants of SARS-CoV-2, including Omicron.

Eiger said today that he plans to apply for an emergency use authorization for the vaccine with the U.S. Food and Drug Administration before June 30. The full test data is expected to be available at that time.

“If what they said in the press release is true, it’s a very good result,” said Ivan Zanoni, an immunologist at Harvard Medical School and Boston Children’s Hospital. But the trial is reserved until an article details the results, in part because a much smaller trial in younger outpatients with early and uncomplicated SARS-CoV-2 infection found that Eiger injection did not reduce duration of symptoms or how long it took people to clear it. virus. The scientists who led this trial agree. “Until we see a peer – reviewed post, I’m cautious[garding] Press release[s] “Upinder Singh, an infectious disease physician at Stanford University School of Medicine, said in an email.

Caution may also reflect discouraging results from trials of other types of interferons. Major trials sponsored by the National Institutes of Health, the World Health Organization, and the company Synairgen treated hospitalized patients and all failed.

The current trial was created to capture patients soon. This is because interferons act in the first hours and days after the viral infection, initiating a cascade of other proteins that attack the virus at each stage of its life cycle. Located in 12 places in Brazil, the trial was aimed at outpatients who were over 50 years of age and / or had a higher risk of severe COVID-19 because they had conditions such as diabetes, obesity, high blood pressure, and lung disease. . Eighty-four percent of participants were vaccinated. They received a single injection under the skin of placebo or pegda interferon lambda, a drug that Eiger was already developing to fight hepatitis D.

The company says 25 of the 916 patients (2.7%) in the treatment arm were hospitalized or spent more than 6 hours in an emergency room, compared with 57 of 1,020 patients (5.6%) who went receive a placebo. Eiger also reported that only one person in the treatment group died, compared with four in the placebo group, although the death toll was too small to be statistically significant.

“We believe we have a study that is highly generalizable to the current COVID environment in the U.S. and globally,” says Eiger CEO David Cory. He says that while the current leading antiviral, Pfizer’s Paxlovid, is given as a series of pills for 5 days, a single shallow injection of interferon, similar to people with type 1 diabetes who usually self-administer. “It has the potential to be a unique and tailor-made therapy, especially for high-risk patients.”

According to the press release, the results are “quite impressive,” says Andreas Wack, an immunologist at the Francis Crick Institute who has studied the role of lambda interferons in COVID-19. “I really hope this can get somewhere.”

“From a basic scientific perspective, that’s what was expected to happen,” Zanoni says.

Lambda interferons are type 3 interferons, which have receptors mainly on the epithelial surfaces, such as those lining the airways. The best known type 1 interferons act on all cells in the body, increasing the likelihood of off-target effects. They also promote inflammation more than type 3 interferons, a decided risk in a disease that, later in its course, can cause patients to reach hyperinflammatory states.

In mice inoculated with SARS-CoV-2, inhaled lambda interferon limited viral infection to the entire respiratory tract without causing excessive inflammation, a team from the University of Washington School of Medicine in St. Louis reported. Cell reports on April 15th. And when the same team designed mice not to have a specific receptor for interferon lambda-1 (IFNL-1), the protein in the Eiger product, their viral loads skyrocketed compared to mice with intact receptors.

Last year, Zanoni and colleagues analyzed lung and throat and nose fluid samples from patients with COVID-19. IFNL1 appeared to be associated with the most protective responses, keeping the virus closed in the upper respiratory tract. “I am just happy to be here [Eiger’s apparently successful interferon] it was lambda 1 because that would have been our prediction, “says Zanoni.

Other scientists also point out that the response to interferon is not vulnerable to the evolution of new resistant variants of SARS-CoV-2, unlike monoclonal antibodies, vaccine-induced immunity, or perhaps antiviral pills such as Paxlovid. . “This is a host-directed drug versus a virus-targeted drug … so resistance is really a minor issue,” says Jordan Feld, a hepatologist at the University of Toronto. He did a smaller trial of the drug Eiger in outpatients in the early stages and found that a single injection accelerated the elimination of the virus. (Feld has received consulting fees from Eiger.)

Eleanor Fish, an immunologist at the University of Toronto who is the researcher of two non-interferon-type 1 trials, wonders if a small business can make enough product to make a difference. “It simply came to our notice then. My question is, do they really have the capacity to make it available? ”(The company says it expects to have 300,000 doses ready by the end of this year).

Feld, who treats patients at Toronto General Hospital, says that if the data is maintained, the universal antiviral qualities of the drug Eiger could make it useful for future pandemics of respiratory diseases. “While you are waiting for the very specific targeted therapy … this is one that needs to be thought about soon because it is very likely to have activity against most viruses.”

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