{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:15:56Z","timestamp":1788225356969,"version":"build-2803163510"},"reference-count":69,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,7,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Interferon resistance has been implicated in SARS-CoV-2 escape from innate immunity, but exogenous interferon\u2019s impact on viral evolution and diversity is unknown. SNG001, an inhaled interferon-\u03b21a 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\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      data provide an intriguing signal that exogenous interferon-\u03b21a 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.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>SARS-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.<\/jats:p>\n                    <\/jats:sec>\n                    <jats:sec>\n                      <jats:title>CLINICAL TRIALS<\/jats:title>\n                      <jats:p>\n                        This study is registered with ClinicalTrials.gov as\n                        <jats:related-object xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" document-id=\"NCT04518410\" document-id-type=\"clinical-trial-number\" source-id=\"ClinicalTrials.gov\" source-id-type=\"registry-name\" source-type=\"clinical-trials-registry\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04518410\">NCT04518410<\/jats:related-object>\n                        .\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00541-26","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T12:00:47Z","timestamp":1779105647000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Effect of inhaled interferon-\u03b21a on SARS-CoV-2 diversity and evolution"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3415-3167","authenticated-orcid":true,"given":"Gregory E.","family":"Edelstein","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00raa0r66","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Brigham and Women's Hospital","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatum N.","family":"Sass","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00raa0r66","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Brigham and Women's Hospital","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinki","family":"Deo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00raa0r66","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Brigham and Women's Hospital","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen T.","family":"Glover","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham","place":["Cambridge, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Boucau","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham","place":["Cambridge, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6305-758X","authenticated-orcid":true,"given":"Prasanna","family":"Jaganathan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00f54p054","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Stanford University School of Medicine","place":["Stanford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara W.","family":"Chew","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/046rm7j60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Giganti","sequence":"additional","affiliation":[{"name":"Harvard T.H. 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