Interferon therapy may speed recovery from COVID-19

NEW YORK (Reuters Health) - Treatment with the antiviral interferon alfa-2b (IFN-a2b) appears to speed up virus clearance and lower levels of key inflammatory markers in patients with COVID-19, according to an exploratory study conducted in Wuhan, China.

This study provides “the first compelling evidence of a potential treatment that is approved and we have decades of experience with,” Dr. Eleanor Fish of the Toronto General Hospital Research Institute and the University of Toronto Department of Immunology, in Canada, told Reuters Health by phone.

In a paper in Frontiers of Immunology, Dr. Fish and colleagues report the clinical course of 77 adults with confirmed COVID-19 who were treated with inhaled IFN-a2b (5 mU b.i.d), arbidol (200 mg t.i.d) or the combination of both broad-spectrum antivirals. All patients had only moderate illness; none required intensive care or oxygen supplementation or intubation.

Compared with arbidol alone (27.9 days), IFN-a2b treatment, with (20.3 days) or without arbidol (21.1 days), was associated with significantly accelerated viral clearance from the respiratory tract and reduced duration of elevated blood levels of the inflammatory markers interleukin-6 and C-reactive protein, the researchers report.

With IFN-a2b, “we achieved accelerated viral clearance by about seven days, which is faster than with remdesivir, and we showed a reduction in circulating levels of inflammatory markers, which really exacerbate disease,” Dr. Fish told Reuters Health.

Age, co-morbidities and sex did not negate the effects of IFN treatment on viral clearance times or on the reduction in the inflammatory markers.

“This was an exploratory study, but I see absolutely no reason why these exploratory studies should not have relevancy. Very often they are dismissed because they are not the gold-standard randomized controlled trial, which are very difficult to do during an outbreak,” Dr. Fish commented.

She and her colleagues previously demonstrated the therapeutic benefit of interferon during the Toronto SARS outbreak of 2002 and 2003. In that study, IFN treatment seemed to speed up the resolution of lung abnormalities in SARS-infected patients.

“Interferons are broad-spectrum antivirals that should be considered as ‘first responders’ for all acute virus infections that are severe,” Dr. Fish said. “The beauty is you don’t have to know the virus. Because they are polytrophic, they target many different facets and stages of a virus’ lifecycle and in addition they muster and activate immune cells to help clear the virus.”

“In response to any and all viruses, the very first we do is make interferons. That, if nothing else, should tell you they are important. In addition, viruses have evolved to very specifically block interferon production. So coming in with interferon has the potential to override or swing the balance in favor of the host,” she explained.

Dr. Fish noted that the biggest fear with interferon is the potential to generate a “cytokine storm,” but there is “absolutely no evidence of that” from the SARS outbreak in Toronto or in COVID-19 patients. “If anything, the evidence was in the other direction, that we reduce the inflammatory response. Fear of cytokine storm I really think needs to be put to bed once and for all,” Dr. Fish said.

Why inhaled interferon in this study? “We went with what we could mobilize quickly and in Wuhan that was nebulized interferon,” Dr. Fish said. It’s unclear now which route of administration is going to be most efficient. “We are doing trials now to answer that.”

Dr. Fish also sees a potential prophylactic role for interferon for healthcare workers, others severely at risk, the elderly, the immunocompromised, and post-exposure individuals.

She and her coauthors report no conflicts of interest.

SOURCE: Frontiers in Immunology, published online May 15, 2020.