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Introduction: Inequities in COVID-19 infection and vaccine uptake among historically marginalised racial and ethnic groups in the USA persist. Individuals with rheumatic conditions, especially those who are immunocompromised, are especially vulnerable to severe infection, with significant racialised inequities in infection outcomes and in vaccine uptake. Structural racism, historical injustices and misinformation engender racial and ethnic inequities in vaccine uptake. The Popular Opinion Lleader (POL) model, a community-based intervention that trains trusted community leaders to disseminate health information to their social network members (eg, friends, family and neighbours), has been shown to reduce stigma and improve care-seeking behaviours., Methods and Analysis: This is a community-based cluster randomised controlled trial led by a team of community and academic partners to compare the efficacy of training POLs with rheumatic or musculoskeletal conditions using a curriculum embedded with a racial justice vs a biomedical framework to increase COVID-19 vaccine uptake and reduce vaccine hesitancy. This trial began recruitment in February 2024 in Boston, Massachusetts and Chicago, Illinois, USA. Eligible POLs are English-speaking adults who identify as Black and/or of African descent, have a diagnosis of a rheumatic or musculoskeletal condition and have received >=1 COVID-19 vaccine after 31 August 2022. POLs will be randomised to a 6-module virtual educational training; the COVID-19 and vaccine-related content will be the same for both groups however the framing for arm 1 will be with a racial justice lens and for arm 2, a biomedical preventative care-focused lens. Following the training, POLs will disseminate the information they learned to 12-16 social network members who have not received the most recent COVID-19 vaccine, over 4 weeks. The trial's primary outcome is social network member COVID-19 vaccine uptake, which will be compared between intervention arms., Ethics and Dissemination: This trial has ethical approval in the USA. This has been approved by the Mass General Brigham Institutional Review Board (IRB, 2023P000686), the Northwestern University IRB (STU00219053), the Boston University/Boston Medical Center IRB (H-43857) and the Boston Children's Hospital IRB (P00045404). Results will be published in a publicly accessible peer-reviewed journal., Trial Registration Number: NCT05822219., Competing Interests: Competing interests: RG-R receives research support from her institution (Northwestern), from the NIH, the Lupus Foundation of America, the American College of Rheumatology, The Medical University of South Carolina, the University of Alabama and the Lupus Research Alliance (LuCIN). She receives consulting fees from the State University of New York, Syracuse, Merck, Biogen, Exagen Diagnostics, Duke University, Ampel Solutions, Clarivate, Bristol Myers Squibb and Cabaletta. She received honoraria from AstraZeneca and Georgetown University, and she previously served as the Chair of the COIN Committee for the American College of Rheumatology. CF receives research support to her institution from the NIH/NIAMS, the Arthritis Foundation and the BMS Foundation. She has served as a consultant on grants to the American College of Rheumatology, Lupus Foundation of America and the University of Alabama and has consulted for Bain Capital, LP, Harvard Pilgrim and OM1. CF received honoraria for presentations at Northwestern University and the University of Alabama, Birmingham. She is the Lupus Science & Medicine Associate Editor and is a former Associate Editor for ACR Open Rheumatology. CF serves on the AC&R Editorial Board, the AF DEI Task Force, the ACR DEI Committee, and LFA Medical and Scientific Advisory Board. MC receives research support from the NIH, Childhood Arthritis and Rheumatology Research Alliance, Honoria at the Roxbury YMCA and meeting/travel support from the Lupus Research Alliance. JW receives support from Bristol Myers Squibb Foundation, and Lupus Research Alliance. She receives consulting fees from CVS Pharmacy, honoraria from the Lupus Foundation of America and meeting/travel support from RILITE Foundation. JW serves on the Lupus Foundation of America–Medical Scientific Advisory Council, NIH-NIAMS P30 VERITY Research Community External Advisory Board, Project CHANGE by Lupus Therapeutics steering committee, American College of Rheumatology Systemic Lupus Erythematosus and Lupus Nephritis Guideline Development Group and American College of Rheumatology Research and Publications Subcommittee (October 2020-October 2023). AD, BO, DE, EL, GS, LNM, MSon, MC-B, MJ-J, MY, NP, TR and HM receive support from the NIH (NIAMS R01 AR 080089). All other authors have no relevant financial disclosures or conflict of interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)