Antiviral and clinical activity of bamlanivimab in a randomized trial of non-hospitalized adults with COVID-19

{ 'indexed': {'date-parts': [[2022, 8, 23]], 'date-time': '2022-08-23T04:10:44Z', 'timestamp': 1661227844659}, 'reference-count': 28, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2022, 8, 22]], 'date-time': '2022-08-22T00:00:00Z', 'timestamp': 1661126400000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2022, 8, 22]], 'date-time': '2022-08-22T00:00:00Z', 'timestamp': 1661126400000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'funder': [ { 'DOI': '10.13039/100000060', 'name': 'U.S. Department of Health & Human Services | NIH | National Institute of Allergy ' 'and Infectious Diseases', 'doi-asserted-by': 'publisher', 'award': ['UM1AI068636', 'UM1AI068634', 'UM1AI106701', 'R01AI028433']}, { 'name': 'U.S. Department of Health & Human Services | NIH | National Institute of Allergy ' 'and Infectious Diseases'}, { 'name': 'U.S. Department of Health & Human Services | NIH | National Institute of Allergy ' 'and Infectious Diseases'}, { 'name': 'U.S. Department of Health & Human Services | NIH | National Institute of Allergy ' 'and Infectious Diseases'}, { 'DOI': '10.13039/100000052', 'name': 'U.S. Department of Health & Human Services | NIH | NIH Office of the Director', 'doi-asserted-by': 'publisher', 'award': ['R01OD011095']}, { 'DOI': '10.13039/100008902', 'name': 'DOE | LDRD | Los Alamos National Laboratory', 'doi-asserted-by': 'publisher', 'award': ['LDRD 20200743ER, 20200695ER, and 20210730ER']}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'abstract': '<jats:title>Abstract</jats:title><jats:p>Anti-SARS-CoV-2 monoclonal antibodies are mainstay ' 'COVID-19 therapeutics. Safety, antiviral, and clinical efficacy of bamlanivimab were ' 'evaluated in the randomized controlled trial ACTIV-2/A5401. Non-hospitalized adults were ' 'randomized 1:1 within 10 days of COVID-19 symptoms to bamlanivimab or blinded-placebo in two ' 'dose-cohorts (7000\u2009mg, <jats:italic>n</jats:italic>\u2009=\u200994; 700\u2009mg, ' '<jats:italic>n</jats:italic>\u2009=\u2009223). No differences in bamlanivimab vs placebo were ' 'observed in the primary outcomes: proportion with undetectable nasopharyngeal SARS-CoV-2 RNA ' 'at days 3, 7, 14, 21, and 28 (risk ratio\u2009=\u20090.82–1.05 for 7000\u2009mg ' '[<jats:italic>p</jats:italic>(overall)\u2009=\u20090.88] and 0.81–1.21 for 700\u2009mg ' '[<jats:italic>p</jats:italic>(overall)\u2009=\u20090.49]), time to symptom improvement ' '(median 21 vs 18.5 days [<jats:italic>p</jats:italic>\u2009=\u20090.97], 7000\u2009mg; 24 vs ' '20.5 days [<jats:italic>p</jats:italic>\u2009=\u20090.08], 700\u2009mg), or grade 3+ adverse ' 'events. However, bamlanivimab was associated with lower day 3 nasopharyngeal viral levels and ' 'faster reductions in inflammatory markers and viral decay by modeling. This study provides ' 'evidence of faster reductions in nasopharyngeal SARS-CoV-2 RNA levels but not shorter symptom ' 'durations in non-hospitalized adults with early variants of SARS-CoV-2.</jats:p>', 'DOI': '10.1038/s41467-022-32551-2', 'type': 'journal-article', 'created': {'date-parts': [[2022, 8, 22]], 'date-time': '2022-08-22T15:05:35Z', 'timestamp': 1661180735000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Antiviral and clinical activity of bamlanivimab in a randomized trial of non-hospitalized adults ' 'with COVID-19', 'prefix': '10.1038', 'volume': '13', 'author': [ { 'ORCID': 'http://orcid.org/0000-0003-4865-4348', 'authenticated-orcid': False, 'given': 'Kara W.', 'family': 'Chew', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-5601-9112', 'authenticated-orcid': False, 'given': 'Carlee', 'family': 'Moser', 'sequence': 'additional', 'affiliation': []}, {'given': 'Eric S.', 'family': 'Daar', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-7764-0212', 'authenticated-orcid': False, 'given': 'David A.', 'family': 'Wohl', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-9914-9662', 'authenticated-orcid': False, 'given': 'Jonathan Z.', 'family': 'Li', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-2709-0512', 'authenticated-orcid': False, 'given': 'Robert W.', 'family': 'Coombs', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-6307-4849', 'authenticated-orcid': False, 'given': 'Justin', 'family': 'Ritz', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mark', 'family': 'Giganti', 'sequence': 'additional', 'affiliation': []}, {'given': 'Arzhang Cyrus', 'family': 'Javan', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yijia', 'family': 'Li', 'sequence': 'additional', 'affiliation': []}, {'given': 'Manish C.', 'family': 'Choudhary', 'sequence': 'additional', 'affiliation': []}, {'given': 'Rinki', 'family': 'Deo', 'sequence': 'additional', 'affiliation': []}, {'given': 'Carlos', 'family': 'Malvestutto', 'sequence': 'additional', 'affiliation': []}, {'given': 'Paul', 'family': 'Klekotka', 'sequence': 'additional', 'affiliation': []}, {'given': 'Karen', 'family': 'Price', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ajay', 'family': 'Nirula', 'sequence': 'additional', 'affiliation': []}, {'given': 'William', 'family': 'Fischer', 'sequence': 'additional', 'affiliation': []}, {'given': 'Veenu', 'family': 'Bala', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-3988-8241', 'authenticated-orcid': False, 'given': 'Ruy M.', 'family': 'Ribeiro', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-2455-0002', 'authenticated-orcid': False, 'given': 'Alan S.', 'family': 'Perelson', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-3703-7849', 'authenticated-orcid': False, 'given': 'Courtney V.', 'family': 'Fletcher', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-4938-0644', 'authenticated-orcid': False, 'given': 'Joseph J.', 'family': 'Eron', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-4279-4737', 'authenticated-orcid': False, 'given': 'Judith S.', 'family': 'Currier', 'sequence': 'additional', 'affiliation': []}, {'given': 'Michael D.', 'family': 'Hughes', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-3603-1733', 'authenticated-orcid': False, 'given': 'Davey M.', 'family': 'Smith', 'sequence': 'additional', 'affiliation': []}, {'name': 'ACTIV-2/A5401 Study Team', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2022, 8, 22]]}, 'reference': [ { 'key': '32551_CR1', 'doi-asserted-by': 'crossref', 'unstructured': 'Taubenberger, J. 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' 'Open Source Softw. 6, 3773 (2021).', 'DOI': '10.21105/joss.03773'}], 'container-title': 'Nature Communications', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.nature.com/articles/s41467-022-32551-2.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41467-022-32551-2', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41467-022-32551-2.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 8, 22]], 'date-time': '2022-08-22T15:05:51Z', 'timestamp': 1661180751000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.nature.com/articles/s41467-022-32551-2'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 8, 22]]}, 'references-count': 28, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2022, 12]]}}, 'alternative-id': ['32551'], 'URL': 'http://dx.doi.org/10.1038/s41467-022-32551-2', 'relation': {}, 'ISSN': ['2041-1723'], 'subject': [ 'General Physics and Astronomy', 'General Biochemistry, Genetics and Molecular Biology', 'General Chemistry', 'Multidisciplinary'], 'container-title-short': 'Nat Commun', 'published': {'date-parts': [[2022, 8, 22]]}, 'assertion': [ { 'value': '4 May 2022', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '4 August 2022', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '22 August 2022', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': 'K.W.C. has received research funding to the institution from Merck Sharp & ' 'Dohme and is a consultant for Pardes Biosciences. E.S.D. receives consulting ' 'fees from Gilead Sciences, Merck, and GSK/ViiV and research support through the ' 'institution from Gilead Sciences and GSK/ViiV. D.A.W. has received funding to ' 'the institution to support research and honoraria for advisory boards and ' 'consulting from Gilead Sciences. J.Z.L. has consulted for Abbvie. C.M. has ' 'received research funding to the institution from E.L. P.K., K.P., and A.N. are ' 'employees and shareholders of E.L. W.F. has received research funding to the ' 'institution from Ridgeback Biopharmaceuticals, served on adjudication ' 'committees for Janssen, Syneos, and consulted for Roche and Merck. J.J.E. is an ' 'ad hoc consultant to GSK/VIR, data monitoring committee (DMC) chair for Adagio ' 'Phase III studies. J.S.C. has consulted for Merck and Company. D.M.S. has ' 'consulted for the following companies Fluxergy, Kiadis, Linear Therapies, ' 'Matrix BioMed, Arena Pharmaceuticals, VxBiosciences, Model Medicines, Bayer ' 'Pharmaceuticals, Signant Health and Brio Clinical. All other authors (R.C., ' 'C.M., J.R., M.G., A.C.J., Y.L., M.C.C., R.D., V.B., R.M.R., A.S.P., C.V.F., and ' 'M.D.H.) report no competing interests.', 'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '4931'}