Short-term IFN-α nasal spray may be a beneficial addition to vaccination and monoclonal antibodies for COVID-19 prevention.A study shows that daily nasal interferon-alpha (IFN-α) spray reduces the incidence of COVID-19 among adult patients with cancer.
The incidence of COVID-19 was lower in the IFN-α than in the placebo group (8.3 percent vs 14.4 percent), representing a 40-percent reduction in the risk of infection with IFN-α (relative risk [RR], 0.60) in the intention-to-treat (ITT) analysis. This was also observed in the per-protocol (PP) cohort (7.7 percent vs 16 percent; RR, 0.50).
The incidence of other respiratory viral infections was similar between the experimental and placebo groups in the ITT cohort (5.1 percent in both; RR, 1.12) and slightly lower in the former than in the latter in the PP cohort (4.6 percent vs 5.7 percent). [Clin Infect Dis 2026;82:e208-e216]
The cumulative incidence of COVID-19 was lower with IFN-α than with placebo in both ITT (hazard ratio [HR], 0.55; p=0.04) and PP populations (HR, 0.46; p=0.008).
Subgroup analysis showed lower COVID-19 incidence in the IFN-α group in individuals aged <65 years (ITT: RR, 0.48; PP: RR, 0.36), females (RRs, 0.44 and 0.36, respectively), and COVID-19–vaccinated individuals (RRs, 0.50 and 0.49). Of note, there was also a reduced infection risk among patients with solid tumours in the PP analysis (RR, 0.39).
The reduced COVID-19 incidence among patients aged <65 years and female patients suggests that being younger and female were markers of high risk, with associated working and caring responsibilities and, thus, higher community exposure to COVID-19, the researchers noted.
There were no significant differences between the IFN-α and placebo groups with regard to any adverse events (AEs; 10.1 percent vs 6 percent), any serious AEs (4.1 percent vs 2.8 percent), AEs of special interest (epistaxis grade ≥2; 0.5 percent for both), and all-cause mortality (0.5 percent for both).
Suboptimal vaccine responses
With compromised immune defences, many cancer patients experience breakthrough infections and have suboptimal vaccine responses. [Open Forum Infect Dis 2023;10:ofad550; Blood Adv 2022;6:2014-2034; Leuk Lymphoma 2023;64:1600-1604; N Engl J Med 2025; 392:306-308]
Evidence shows that nasal IFN-α is effective in preventing community-acquired respiratory viral infections, such as rhinovirus and influenza. [Science 2020;370:eabd4570; Lancet Rheumatol 2021;3:e246-e247; Antiviral Res 2020;178:104791]
A total of 433 participants (median age 62 years, 51 percent women; n=389 in the PP cohort) were randomized 1:1 to receive IFN-α 40,000 IU nasal spray or placebo daily. “We evaluated an IFN dose of 40,000 IU per day based on published literature and a desire to avoid systemic side effects that could interfere with cancer treatment,” the researchers noted.
The primary cancer diagnoses were solid tumour cancers (52 percent); the rest were haematologic malignancies.
A simple, acceptable intervention
The results remain clinically relevant and impactful in the post-pandemic era, the investigators said. “COVID-19 reinfection occurs frequently despite vaccination, haematologic cancer populations have suboptimal vaccine responses, and avoiding COVID-19 with subsequent delays in cancer treatment and surgery significantly reduces excess and earlier-than-expected deaths. The intervention may prevent COVID-19 reinfection.”
The findings may also be relevant to other immunocompromised or comorbid populations, such as individuals awaiting major surgery or solid-organ transplantation, or in residential care facilities.
“The cancer population represents a highly vulnerable group for developing severe COVID-19 and respiratory viral infections … IFN-α nasal spray as a daily prophylactic measure is a simple, acceptable intervention that was well tolerated and safe, and avoided complex drug interactions, particularly with cancer therapies,” the investigators said.
Short-term IFN-α nasal spray may be a beneficial addition to vaccination and monoclonal antibodies for COVID-19 prevention, they added. “It may allow safe and vital cancer care to continue without interruption during high-risk, crucial clinical [treatment] periods.”