Interferon-α Nasal Spray Prophylaxis Reduces COVID-19 in Cancer Patients: A Randomized, Double-Blinded, Placebo-Controlled Trial.

BACKGROUND: We evaluated whether a daily nasal spray of interferon-alpha (IFN-α) would reduce the incidence of COVID-19 or community-acquired respiratory viral infections in adult cancer patients. METHODS: In this multicenter, randomized, double-blinded, placebo-controlled trial, participants were randomized 1:1 to receive daily 40 000†IU IFN-α nasal spray or normal saline placebo. Participants who developed influenza-like symptoms self-collected nasal swabs for PCR testing of SARS-CoV-2, influenza A/B, respiratory syncytial virus, parainfluenza, adenovirus, seasonal coronavirus, picornavirus, human metapneumovirus, and/or SARS-CoV-2 rapid antigen testing. Co-primary endpoints were incidence of COVID-19 and/or other respiratory viruses ≤90 days of randomization. RESULTS: Four hundred and thirty-three participants were randomized to IFN-α (n = 217) or placebo (n = 216). The incidence of COVID-19 was lower in the IFN-α group versus placebo (8.3% vs 14.4%), indicating a 40% reduced risk of infection (relative risk [RR]: .60; 95% credible interval [CrI]: .33-.97). Other respiratory viral infection incidence was 5.1% and 5.1% in both groups (RR: 1.12; .43-2.34). In the per-protocol cohort (n = 389), the incidence of COVID-19 in IFN-α and placebo groups was 7.7% and 16.0% (RR: .50; .26-.84) with other respiratory virus incidence of 4.6% and 5.7%, respectively. Subgroup analysis demonstrated lower COVID-19 in the IFN-α group for ages <65 years (RR: .48; .20-.92), female sex (RR: .44; .19-.85), and COVID-19 vaccinated (RR: .50; .26-.82), but no difference by underlying malignancy. No differences were observed in secondary endpoints of severity, hospitalization, and mortality. IFN-α was well tolerated and safe. CONCLUSIONS: IFN-α nasal spray prophylaxis reduced the incidence of COVID-19 among adult cancer patients. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT04534725 (ANZCTR: ACTRN12620000843954).