Interferon: The Latest Advancement in Covid-19 Treatment
A frontline doc unpacks results of a new clinical trial that shows interferon may reduce the odds of severe illness or death from Covid-19
As someone who provides care for those with Covid-19 in a hospital approaching its capacity, I’m constantly on the lookout for safe and effective treatment strategies — anything to help my patients recover faster and get home sooner. With so many therapies being studied, it can be difficult to determine which new piece of data is truly valuable. My attention was caught by a well-constructed clinical trial published November 12 in The Lancet by Phillip Monk, et al. Here’s why I believe it’s so important.
Recent studies have shown a significant portion of individuals who become severely ill from Covid-19 possess antibodies that disable naturally occurring immune proteins called interferons. Instead of targeting invading pathogens, these antibodies, called autoantibodies, act against the body’s own immune system.
Interferons are cell-signaling molecules that function to alert the immune system of a developing infection. When interferons are deactivated by autoantibodies, viruses like the novel coronavirus are able to evade the body’s early warning alarms.
The importance of interferons is also highlighted by studies observing individuals with mutations in genes that code for interferon production. When interferons are diminished because of a mutated gene, patients tend to suffer from more severe symptoms of Covid-19. The lead author of one such study, Qian Zhang, explains, “If you don’t get the alarm out, you could have viruses everywhere in large numbers.”
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It would stand to reason that providing the body with an added supply of interferon could potentially improve its response to the virus, SARS-CoV-2. This theory is supported by studies on animals infected with other coronaviruses, SARS and MERS. Unfortunately, the concept did not translate well to humans with Covid-19 as evidenced by the Solidarity trial conducted by the WHO earlier this year. Patients in this study failed to benefit from interferon injected under the skin, but what might happen if the medication was administered by a different route?
That’s the question Monk and colleagues sought to answer by treating patients with an inhaled formulation of interferon beta-1a. By targeting the organ most strongly affected by SARS-CoV-2 — the lungs — researchers hoped to deliver interferon directly to its area of greatest need.
What separates this study from many other pharmaceutical trials is its thoughtful design. Despite having a small sample size, being a randomized, double-blind, placebo-controlled trial allows this investigation to bypass many confounding elements that plague retrospective and observational studies. Moreover, publication in a peer-reviewed journal elevates its findings above data found on preprint servers which have become so prevalent lately.
The 97 hospitalized patients in the United Kingdom received either interferon beta-1a (code-named SNG001) or placebo for up to two weeks. At the end of four weeks, 58% of patients receiving interferon recovered compared to 35% of the placebo group as measured by the WHO Ordinal Scale for Clinical Improvement (figure below).
Of the 49 patients in the placebo group, three died, whereas all of the 48 patients receiving interferon survived. In her report on the study, Mary Van Beusekom, a writer for the Center for Infectious Disease Research and Policy notes, “A secondary analysis showed that SNG001 patients were more than three times more likely to recover, defined by resumption of ability to resume normal activities, than those receiving a placebo at 28 days.”
Lead investigator, Tom Wilkinson, PhD, recognizes that interferon has the ability to boost the lung’s defense against pathogens in a nonspecific manner which could prove especially beneficial this time of year when co-infections are more likely to occur. “This [interferon beta-1a] might carry additional advantages of treating Covid-19 infection when it occurs alongside infection by another respiratory virus, such as influenza or respiratory syncytial virus (RSV) that may well be encountered in the winter months.”
One drawback is that, despite showing a trend toward improving mortality, the study did not involve enough patients for this trend to be considered statistically significant. Authors of an associated commentary in The Lancet call for expanded research on the safety and efficacy of interferon. “Larger randomised clinical trials are therefore needed to further investigate the effectiveness of nebulised interferon beta-1a therapy in this setting.”
Because interferon plays a role in the initial response to a pathogen, the group is now studying the effects of the drug when administered prior to hospitalization. They also hope to examine the response to interferon in “ventilated, critically ill patients with Covid-19 who have evidence of active viral infection in the lungs.”
Randomization of a small sample of patients can also lead to an unintentional imbalance in the group characteristics. The authors note that “SNG001 and placebo groups were well matched for age, sex, and overall comorbidities, but were less well matched for disease severity at recruitment and for specific comorbid conditions — particularly diabetes, cardiovascular disease, and hypertension.”
Of the serious adverse events that occurred during the study, none were attributed directly to interferon beta-1a and all were thought likely to have been caused by Covid-19 itself. The most frequently reported adverse event was the development of headache which occurred in 15% of the interferon group and 10% of those receiving placebo.
Because inhaled interferon is not currently marketed to treat other diseases, information regarding its cost is lacking, but, undoubtedly, price will factor into its chance of widespread success. Despite some clear obstacles, I believe this novel therapeutic has as good a chance as any to become a game-changer in the pandemic. Here’s to inhaling a deep breath and waiting patiently for what happens next.