Interferons occur naturally in the body; when a cell is infected by a virus, these signaling proteins are released to bolster other cells’ defenses. Once expensive to make, they can now be mass produced using genetically-modified bacteria. While appearing in the headlines less than other drugs, interferon may have an important role in fighting COVID-19. On July 10, Science asked, “Can interferons stop COVID-19 before it takes hold?” Reporting a “huge void” in COVID-19 treatments, it is argued that “Doctors have no drugs that, given early, have been proven to prevent infection or help beat back the virus before it takes hold.” So far, only remdesivir and dexamethasone have been validated, but they only seem to work on hospitalized patients. New research suggests SARS-CoV-2 disables interferons. “If so, synthetic interferons given before or soon after infection may tame the virus before it causes serious disease—a welcome possibility that additional recent studies support.” Several interferons have been FDA approved for decades, and their use includes cancer and hepatitis. Notably, a preventative trial in Hubei, China resulted in zero infections among 2,415 medical workers who used “daily interferon nose drops,” according to “a medRxiv preprint.”
Researchers at Sandford and the University of Southampton are asking the prevention question, and results from the later site are due in August. “Every study in every species has shown that if you induce interferons before [a] virus comes in, the virus loses,” according to Andreas Wack, immunologist at the Francis Crick Institute. “The earlier you can give it, the better, and the best thing you can do is to give it before the virus is there.” Miriam Merad is an immunologist at the Icahn School of Medicine at Mount Sinai. She notes, “It’s going to be important to know when to give these drugs.” Given late, they could exacerbate the out-of-control inflammation that marks that stage of the disease. COVID-19’s virus disables key defenses by “blocking the powerful interferons that lead to it,” says Mount Sinai virologist Benjamin tenOever. He and his team have looked at SARS-CoV-2 in human lung and bronchial cells, ferrets, and lung materials from dead patients. tenOever says that “interferon is badly suppressed” across these systems.
Another team led by immunologist Benjamin Terrier at Paris’ Cochin Hospital has also published as a medRxiv preprint. They looked at blood from 50 patients and found “strikingly depressed interferon activity and elevated chemokines in those whose disease became severe and critical—but not in those who ended up with mild or moderate disease.” They posit that once interferons are reduced, the virus “gins up tissue-damaging inflammation.” This, along with more inflammation from the immune systems, can result in death. But Rockefeller University infectious disease geneticist Jean-Laurent Casanova asks whether low interferons are “the cause or consequence of severe disease?” Since 2015, Casanova “has found three inherited mutations that profoundly inhibit the interferon response, raising the possibility that genetic predisposition plays a role in some cases of severe COVID-19.” Nature also notes that other studies have found evidence that suggest interferons are not suppressed during COVID-19.
Since April, “at least five studies” have shown that “interferon treatment or pretreatment has a protective effect in cells and in mice infected with SARS-CoV-2.” Earlier studies showed similar results for SARS and MERS, two cousins of the virus underlying our pandemic. “The data support giving interferons as a treatment for COVID-19, especially early in infection, advocates say.” Interferons are known for horrible side effects, but that is in the context of long-term usage, e.g. for cancer. And “one trial in chronic hepatitis showed that a synthetic type III interferon had fewer side effects than a type I interferon.” Two articles last month in Science “suggested type III interferons might be harmful if given late in infection.” One of these found that natural type III interferon, “disrupted the lung repair crucial to recovery from influenza,” while the other had similar findings in mice. The “take home message” for clinicians is, “If you want to give type III interferons as antivirals, give them early.”
Another researcher, University of Toronto immunologist Eleanor Fish, is starting two preventative interferon trials. She says that date points to the safety of interferons. Her research team did an uncontrolled study of “77 hospitalized patients in Wuhan, China.” They found that the patients given a type I interferon, “had lower levels of a key inflammatory biomarker than other patients—and also cleared the virus 7 days sooner.” Years ago, Fish published work looking at interferons for SARS and Ebola. She says that, “This notion of [interferons being] harmful later, I just want to throw it out the window.”