{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:29:59Z","timestamp":1788931799977,"version":"build-2803163510"},"reference-count":18,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["OT2HL156812"],"award-info":[{"award-number":["OT2HL156812"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clinical Trials"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Long COVID, the chronic sequela of SARS-CoV-2 infection, has affected millions of people worldwide. However, its pathogenesis and treatment remain unknown. To address this critical gap, the National Institutes of Health (NIH) developed the Researching COVID to Enhance Recovery (RECOVER) Initiative that included the Viral Persistence and Reactivation, and Immune Dysregulation (RECOVER-VITAL) study as one of the first of five NIH-sponsored, integrated platform protocols to support the rigorous and rapid investigation of potential interventions for Long COVID.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Experts across academia, the NIH, and the community of patients and caregivers were brought together to design the RECOVER-VITAL protocol. We present the challenges and rationale underpinning critical components of this protocol and provide evidence for use of the platform for efficient execution of current and future Long COVID clinical trials. Facets of the RECOVER-VITAL protocol, including inclusion criteria, intervention groups, study procedures, investigation of biomarkers, and endpoints, were carefully crafted to advance the current and future science and operations of Long COVID clinical trials, particularly in the absence of existing data. The initial trial within the RECOVER-VITAL platform evaluated two durations of an antiviral drug, nirmatrelvir\/ritonavir, to test the proposed etiology of viral persistence on the Long COVID symptom clusters of autonomic dysfunction, cognitive dysfunction, and exercise intolerance. The primary outcome measures were patient-reported, and secondary outcomes included performance-based measures for each of the symptom clusters of interest.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The RECOVER-VITAL platform protocol has substantial implications for the design and conduct of future Long COVID clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17407745261422437","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T18:49:23Z","timestamp":1773254963000},"page":"413-420","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Developing a platform protocol for clinical trials evaluating interventions that target proposed mechanisms of Long COVID: RECOVER-VITAL"],"prefix":"10.1177","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3748-6932","authenticated-orcid":false,"given":"Kanecia O","family":"Zimmerman","sequence":"first","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Whitley","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Microbiology, Medicine, and Neurosurgery, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Walt","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"},{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9784-7061","authenticated-orcid":false,"given":"Christine","family":"Maughan","sequence":"additional","affiliation":[{"name":"RECOVER Patient, Caregiver, or Community Representative, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Cerda","sequence":"additional","affiliation":[{"name":"RECOVER Patient, Caregiver, or Community Representative, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Olson","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucinda","family":"Bateman","sequence":"additional","affiliation":[{"name":"Bateman Horne Center, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyndya A","family":"Shibao","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Make","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Knopman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Redline","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Neurology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard A","family":"Jason","sequence":"additional","affiliation":[{"name":"Department of Psychology, DePaul University, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehul S","family":"Suthar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Low","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy L","family":"Nolen","sequence":"additional","affiliation":[{"name":"Social, Statistical, and Environmental Sciences, RTI International, Research Triangle Park, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Reist","sequence":"additional","affiliation":[{"name":"Social, Statistical, and Environmental Sciences, RTI International, Research Triangle Park, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5820-5019","authenticated-orcid":false,"given":"Lisa","family":"Berdan","sequence":"additional","affiliation":[{"name":"National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey R","family":"Baden","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"e_1_3_3_2_2","volume-title":"A Long COVID definition: a chronic, systemic disease state with profound consequences","author":"National Academies of Sciences, Engineering, and Medicine","year":"2024","unstructured":"National Academies of Sciences, Engineering, and Medicine. A Long COVID definition: a chronic, systemic disease state with profound consequences. Washington, DC: The National Academies Press, 2024."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00846-2"},{"key":"e_1_3_3_4_2","unstructured":"World Health Organization. A clinical case definition of post COVID-19 condition by a Delphi consensus 6 October 2021. https:\/\/iris.who.int\/handle\/10665\/345824"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lana.2024.100984"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00941-2"},{"key":"e_1_3_3_7_2","unstructured":"Pfizer. Paxlovid 2025. https:\/\/paxlovid.pfizerpro.com\/ (accessed 30 April 2025)."},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(20)30542-8"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14314"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaf383"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2020.104786"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12985-020-01457-0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics8030066"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-011-0146-2"},{"key":"e_1_3_3_15_2","unstructured":"Food and Drug Administration. Northera\u00ae prescribing information https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/203202s007lbl.pdf (accessed 30 April 2025)."},{"key":"e_1_3_3_16_2","unstructured":"HealthMeasures. PROMIS short form v2.0\u2014cognitive function 8a 2020 https:\/\/www.healthmeasures.net\/index.php?option=com_instruments&view=measure&id=758&Itemid=992 (Accessed 5 June 2025)."},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11136-021-02925-y"},{"key":"e_1_3_3_18_2","unstructured":"HealthMeasures. PROMIS adult profile instruments measure differences 2024. https:\/\/www.healthmeasures.net\/images\/PROMIS\/Differences_Between_PROMIS_Measures\/PROMIS_Adult_Profile_Measure_Differences_16Sept2024.pdf (accessed 4 June 2025)."},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0000000000000450"}],"container-title":["Clinical Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17407745261422437","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/17407745261422437","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17407745261422437","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T23:16:41Z","timestamp":1786231001000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/17407745261422437"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,6]]},"references-count":18,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1177\/17407745261422437"],"URL":"https:\/\/doi.org\/10.1177\/17407745261422437","relation":{},"ISSN":["1740-7745","1740-7753"],"issn-type":[{"value":"1740-7745","type":"print"},{"value":"1740-7753","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,6]]}}}