Journal article
Effect of inhaled interferon-β1a on SARS-CoV-2 diversity and evolution
Microbiology spectrum, Vol.14(7), pp.CP1-CP1
07/07/2026
DOI: 10.1128/spectrum.00541-26
PMCID: PMC13339817
PMID: 42148571
Abstract
Interferon resistance has been implicated in SARS-CoV-2 escape from innate immunity, but exogenous interferon’s impact on viral evolution and diversity is unknown. SNG001, an inhaled interferon-β1a treatment, was evaluated in the ACTIV-2/A5401 randomized controlled trial of therapeutics for COVID-19. We measured viral kinetics and performed whole-genome sequencing on longitudinal nasal swabs collected from ACTIV-2 participants who received either SNG001 or placebo to assess viral sequence diversity. No difference in nasal viral load decay was detected between study arms when stratifying by SARS-CoV-2 variant or by viral culture conversion. Compared to placebo participants, the SNG001-treated participants displayed significantly lower nonsynonymous amino acid average pairwise distance, indicating lower sequence diversity. Similarly, SNG001-treated individuals also developed numerically fewer nonsynonymous mutations during their infection in ORF1a, ORF1b, Spike, and Nucleocapsid. No specific emerging SARS-CoV-2 nonsynonymous amino acid changes indicating signatures of viral escape were enriched in those receiving SNG001. These in vivo data provide an intriguing signal that exogenous interferon-β1a may restrict SARS-CoV-2 viral diversity and add to growing evidence that interferon levels play a critical role in antiviral responses during COVID-19.IMPORTANCESARS-CoV-2 encodes several genes which can antagonize the interferon signaling cascade, preventing it from activating antiviral responses and thereby facilitating viral establishment and dissemination. It is unknown how the administration of exogenous interferon might affect viral evolution and immune escape. ACTIV-2/A5401 represents a unique opportunity to study the virologic effects of interferon treatment in a rigorous randomized, placebo-controlled clinical trial setting. Our characterization of longitudinal nasal samples shows that interferon-treated individuals had lower viral diversity and no evidence of viral escape mutations.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04518410.
Details
- Title: Subtitle
- Effect of inhaled interferon-β1a on SARS-CoV-2 diversity and evolution
- Creators
- Gregory E. Edelstein - Brigham and Women's HospitalTatum N. Sass - Brigham and Women's HospitalRinki Deo - Brigham and Women's HospitalOwen T. Glover - Ragon Institute of MGH, MIT and HarvardJulie Boucau - Ragon Institute of MGH, MIT and HarvardPrasanna Jaganathan - ,Kara W. Chew - University of California, Los AngelesMark J. Giganti - Harvard UniversityMichael D. Hughes - Harvard UniversityCarlee Moser - Harvard UniversityArzhang Cyrus Javan - National Institutes of HealthCourtney V. Fletcher - University of Nebraska Medical CenterCaitlyn McCarthy - Harvard UniversityDavid A. Wohl - University of North Carolina at Chapel HillEric S. Daar - Harbor–UCLA Medical CenterJoseph J. Eron - University of North Carolina at Chapel HillJudith S. Currier - University of California, Los AngelesUpinder Singh - Stanford MedicineDavey M. Smith - ,William Fischer - University of North Carolina at Chapel HillAmy K. Barczak - Ragon Institute of MGH, MIT and HarvardManish C. Choudhary - Brigham and Women's HospitalJonathan Z. Li - Brigham and Women's HospitalACTIV 2 A5401 Study Team
- Contributors
- J. J. Miranda (Editor)
- Resource Type
- Journal article
- Publication Details
- Microbiology spectrum, Vol.14(7), pp.CP1-CP1
- DOI
- 10.1128/spectrum.00541-26
- PMID
- 42148571
- PMCID
- PMC13339817
- NLM abbreviation
- Microbiol Spectr
- ISSN
- 2165-0497
- eISSN
- 2165-0497
- Publisher
- American Society for Microbiology
- Number of pages
- 15
- Language
- English
- Date published
- 07/07/2026
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985244540402771
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