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

tetano

Editor, Senior Moderator
Clin Infect Dis


. 2025 Aug 28:ciaf409.
doi: 10.1093/cid/ciaf409. Online ahead of print. Interferon-α Nasal Spray Prophylaxis Reduces COVID-19 in Cancer Patients: A Randomized, Double-Blinded, Placebo-Controlled Trial

Michelle K Yong[SUP] 1 2 3 4 [/SUP], Karin Thursky[SUP] 1 2 4 5 [/SUP], Megan Crane[SUP] 1 4 [/SUP], Tim Spelman[SUP] 2 4 5 [/SUP], Robert K Mahar[SUP] 6 7 8 [/SUP], Julie A Simpson[SUP] 6 7 [/SUP], Andrew M Scott[SUP] 9 10 11 12 [/SUP], Simon J Harrison[SUP] 2 4 13 [/SUP], Jeff Szer[SUP] 11 13 [/SUP], Marc Pellegrini[SUP] 14 15 16 17 [/SUP], Senthil Lingaratnam[SUP] 2 18 [/SUP], Ken C Pang[SUP] 19 20 21 [/SUP], Surekha Tennakoon[SUP] 1 4 [/SUP], Beatrice Z Sim[SUP] 2 4 [/SUP], Emily Blyth[SUP] 22 23 [/SUP], Hui K Gan[SUP] 24 [/SUP], Hang Quach[SUP] 11 25 [/SUP], Michelle P McIntosh[SUP] 26 [/SUP], Hayley Page[SUP] 1 3 4 [/SUP], Rachel Woolstencroft[SUP] 1 3 4 [/SUP], Monica Slavin[SUP] 1 2 3 4 [/SUP]



Affiliations
Abstract

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).

Keywords: COVID-19; immunocompromised; interferon; prophylaxis; respiratory viral infection.

 
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