{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T09:05:50Z","timestamp":1740128750641,"version":"3.37.3"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"Supplement_2","license":[{"start":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T00:00:00Z","timestamp":1693440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI068636","UM1AI068634","UM1AI106701"],"award-info":[{"award-number":["UM1AI068636","UM1AI068634","UM1AI106701"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Time to symptom resolution measures were used in outpatient coronavirus disease 2019 (COVID-19) treatment trials without prior validation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>ACTIV-2\/A5401 trial participants completed a COVID-19 diary assessing 13 targeted symptoms and global experience (overall COVID-19 symptoms, return to pre\u2013COVID-19 health) daily for 29 days. We evaluated concordance of time to sustained (2 days) resolution of all targeted symptoms (TSR) with resolution of overall symptoms and return to health in participants receiving placebo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The analysis included 77 high-risk and 81 standard-risk participants with overall median 6 days of symptoms at entry and median age 47 years, 50% female, 82% white, and 31% Hispanic\/Latino. Correlation between TSR and resolution of overall symptoms was 0.80 and 0.68, and TSR and return to health, 0.66 and 0.57 for high- and standard-risk groups, respectively. Of the high- and standard-risk participants, 61% and 79%, respectively, achieved targeted symptom resolution, of which 47% and 43%, respectively, reported symptom recurrence. Requiring &amp;gt;2 days to define sustained resolution reduced the frequency of recurrences.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>There was good internal consistency between TSR and COVID-19\u2013specific global outcomes, supporting TSR as a trial end point. Requiring &amp;gt;2 days of symptom resolution better addresses natural symptom fluctuations but must be balanced against the potential influence of non-COVID-19 symptoms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT04518410.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiad300","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T07:34:18Z","timestamp":1693467258000},"page":"S83-S91","source":"Crossref","is-referenced-by-count":2,"title":["Validity and Characterization of Time to Symptom Resolution Outcome Measures in the ACTIV-2\/A5401 Outpatient COVID-19 Treatment Trial"],"prefix":"10.1093","volume":"228","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4865-4348","authenticated-orcid":false,"given":"Kara W","family":"Chew","sequence":"first","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles , Los Angeles, California , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5601-9112","authenticated-orcid":false,"given":"Carlee","family":"Moser","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eunice","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A","family":"Wohl","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric S","family":"Daar","sequence":"additional","affiliation":[{"name":"Division of HIV Medicine, The Lundquist Institute, Harbor-University of California, Los Angeles Medical Center , Torrance, California , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Ritz","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arzhang Cyrus","family":"Javan","sequence":"additional","affiliation":[{"name":"Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Rockville, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph J","family":"Eron","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith S","family":"Currier","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles , Los Angeles, California , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davey M","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego , La Jolla, California , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the ACTIV-2\/A5401 Study Team","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,8,31]]},"reference":[{"key":"2023090114564927800_jiad300-B1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1056\/NEJMoa2029849","article-title":"SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with COVID-19","volume":"384","author":"Chen","year":"2021","journal-title":"N Engl J Med"},{"key":"2023090114564927800_jiad300-B2","doi-asserted-by":"crossref","first-page":"e81","DOI":"10.1056\/NEJMoa2108163","article-title":"REGEN-COV antibody combination and outcomes in outpatients with COVID-19","volume":"385","author":"Weinreich","year":"2021","journal-title":"N Engl J Med"},{"key":"2023090114564927800_jiad300-B3","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1056\/NEJMoa2116846","article-title":"Early remdesivir to prevent progression to severe COVID-19 in outpatients","volume":"386","author":"Gottlieb","year":"2022","journal-title":"N Engl J Med"},{"key":"2023090114564927800_jiad300-B4","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1056\/NEJMoa2102685","article-title":"Bamlanivimab plus etesevimab in mild or moderate COVID-19","volume":"385","author":"Dougan","year":"2021","journal-title":"N Engl J Med"},{"key":"2023090114564927800_jiad300-B5","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1001\/jama.2021.0202","article-title":"Effect of Bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: a randomized clinical trial","volume":"325","author":"Gottlieb","year":"2021","journal-title":"JAMA"},{"key":"2023090114564927800_jiad300-B6","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1056\/NEJMoa2118542","article-title":"Oral nirmatrelvir for high-risk, nonhospitalized adults with COVID-19","volume":"386","author":"Hammond","year":"2022","journal-title":"N Engl J Med"},{"key":"2023090114564927800_jiad300-B7","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1056\/NEJMoa2116044","article-title":"Molnupiravir for oral treatment of COVID-19 in nonhospitalized patients","volume":"386","author":"Bernal A","year":"2022","journal-title":"N Engl J Med"},{"key":"2023090114564927800_jiad300-B8","doi-asserted-by":"crossref","first-page":"466","DOI":"10.15585\/mmwr.mm7112e2","article-title":"COVID-19-associated hospitalizations among adults during SARS-CoV-2 Delta and Omicron variant predominance, by race\/ethnicity and vaccination status\u2014COVID-NET; 14 states, July 2021-January 2022","volume":"71","author":"Taylor","year":"2022","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2023090114564927800_jiad300-B9","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1001\/jama.283.8.1016","article-title":"Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. 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