Interferon emerges as potential treatment for COVID-19

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In the race to find an effective therapy for COVID-19, a class of drugs called interferons may be stepping into the spotlight thanks to encouraging results from two clinical trials and a call from a key Canadian expert to test the treatment on a larger scale.

Both of the newly reported trials involved small numbers of patients, and scientists stress that more work is needed to determine whether the effects they see are real. Other trials are now under way and, as a further layer of complexity, the studies make use of different types of interferon.

But Eleanor Fish, a researcher with Toronto’s University Health Network and the senior author on one of the studies, said that awareness of interferon as a potential COVID-19 treatment has been slow to build and should be prioritized for larger-scale clinical trials.

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“We should be aggressively pursuing the front-runners who look as if they’re going to make a difference during this outbreak, right now,” said Dr. Fish, who is also a professor at the University of Toronto.

The word interferon describes an entire family of proteins that are generated naturally by the body’s immune system. Interferons are also produced as medications and were widely used for treating hepatitis C before other options emerged.

Unlike remdesivir – an Ebola drug that was recently approved by the U.S. Food and Drug Administration for emergency use as a treatment for COVID-19 – interferon marshals the body’s own defences against a broad spectrum of infections. It also acts against viruses in a variety of ways, for example by altering cell membranes to deny their entry or exit.

Some forms of interferon are associated with significant side effects, including depression, nausea and muscle pain. Dr. Fish, who conducted clinical research with interferon during the SARS outbreak in 2003, said that is why interferons are better suited for treating acute rather than chronic infections and should be considered an appropriate first line of defence against COVID-19.

Evidence supporting this view has been emerging gradually as researchers publish their results from studies conducted earlier in the pandemic. In one of those studies, Dr. Fish and colleagues in China investigated the use of interferon alpha-2b on 77 patients in a Wuhan hospital with moderate cases of COVID-19. The study found that the drug significantly accelerated clearance of the virus from the airways of patients. Details of the study are scheduled for publication this Friday in the journal Frontiers of Immunology.

A second study, published last week in The Lancet, tested another type of interferon, called beta-1b, in a trial with 127 patients in a Hong Kong hospital. In that case, only some patients received interferon as part of a triple-drug-combined therapy with two anti-virals, lopinavir and ritonavir. The study offered the therapy as soon as possible to those in early stages of infection – an approach that was possible in Hong Kong because everyone who tested positive for the virus there was admitted to hospital regardless of case severity.

The results showed that the patients who received the therapy that included interferon cleared the virus and were able to leave hospital, on average, four to five days sooner than those who received the other two drugs alone.

“Even though we were just able to treat patients with mild or moderate disease, we believe we are able to prevent a lot of patients from developing complications in the second week, perhaps that would have required intensive care,” said Ivan Hung, a physician and professor at the University of Hong Kong who led the study.

Neither studies reported significant side effects but both had other limitations. All patients knew the treatment they were getting and neither study involved the use of a placebo as a control. Since none of the participants developed serious cases it’s also not clear what effect, if any, interferon may have on mortality owing to COVID-19.

Sarah Shalhoub, an infectious-disease researcher at the University of Western Ontario who has conducted trials involving the use of interferon with MERS, in which the drug did not appear to have much effect, said that the interpretation of the new studies “should be made with caution." But she added that there was good reason to continue clinical studies with interferon as a therapy for COVID-19 as hopes for repurposing other drugs begin to fade.

“I think it is something definitely worth looking at," she said. “The options are becoming limited.”

Howard Young, a senior investigator with the U.S. National Cancer Institute in Bethesda, Md., who has studied the anti-viral properties of interferon, echoed the need for more study. He said an important question to be explored is whether mild versus more-severe cases of COVID-19 produce different responses to the drug.

“If mild cases have a stronger response … then this might warrant the increased testing and use of interferons in future therapy," he said.

Upinder Singh, a professor of medicine at Stanford University in California, said evidence that interferon clears the virus sooner than would otherwise occur is an important data point because it means the treatment may not only improve outcomes for patients but reduce transmission in the community.

This week, Dr. Singh and colleagues launched a trial in which interferon lambda, another form of the drug, will be given to COVID-19 patients with mild infections who ride out the virus at home. The randomized study will include the use of a placebo to measure against the effect of the interferon.

Dr. Fish said she is collaborating on another trial, planned in Australia, to evaluate whether interferon can prevent COVID-19 infection in uninfected individuals.

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