1. Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design.
- Author
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Horwitz LI, Thaweethai T, Brosnahan SB, Cicek MS, Fitzgerald ML, Goldman JD, Hess R, Hodder SL, Jacoby VL, Jordan MR, Krishnan JA, Laiyemo AO, Metz TD, Nichols L, Patzer RE, Sekar A, Singer NG, Stiles LE, Taylor BS, Ahmed S, Algren HA, Anglin K, Aponte-Soto L, Ashktorab H, Bassett IV, Bedi B, Bhadelia N, Bime C, Bind MC, Black LJ, Blomkalns AL, Brim H, Castro M, Chan J, Charney AW, Chen BK, Chen LQ, Chen P, Chestek D, Chibnik LB, Chow DC, Chu HY, Clifton RG, Collins S, Costantine MM, Cribbs SK, Deeks SG, Dickinson JD, Donohue SE, Durstenfeld MS, Emery IF, Erlandson KM, Facelli JC, Farah-Abraham R, Finn AV, Fischer MS, Flaherman VJ, Fleurimont J, Fonseca V, Gallagher EJ, Gander JC, Gennaro ML, Gibson KS, Go M, Goodman SN, Granger JP, Greenway FL, Hafner JW, Han JE, Harkins MS, Hauser KSP, Heath JR, Hernandez CR, Ho O, Hoffman MK, Hoover SE, Horowitz CR, Hsu H, Hsue PY, Hughes BL, Jagannathan P, James JA, John J, Jolley S, Judd SE, Juskowich JJ, Kanjilal DG, Karlson EW, Katz SD, Kelly JD, Kelly SW, Kim AY, Kirwan JP, Knox KS, Kumar A, Lamendola-Essel MF, Lanca M, Lee-Lannotti JK, Lefebvre RC, Levy BD, Lin JY, Logarbo BP Jr, Logue JK, Longo MT, Luciano CA, Lutrick K, Malakooti SK, Mallett G, Maranga G, Marathe JG, Marconi VC, Marshall GD, Martin CF, Martin JN, May HT, McComsey GA, McDonald D, Mendez-Figueroa H, Miele L, Mittleman MA, Mohandas S, Mouchati C, Mullington JM, Nadkarni GN, Nahin ER, Neuman RB, Newman LT, Nguyen A, Nikolich JZ, Ofotokun I, Ogbogu PU, Palatnik A, Palomares KTS, Parimon T, Parry S, Parthasarathy S, Patterson TF, Pearman A, Peluso MJ, Pemu P, Pettker CM, Plunkett BA, Pogreba-Brown K, Poppas A, Porterfield JZ, Quigley JG, Quinn DK, Raissy H, Rebello CJ, Reddy UM, Reece R, Reeder HT, Rischard FP, Rosas JM, Rosen CJ, Rouphael NG, Rouse DJ, Ruff AM, Saint Jean C, Sandoval GJ, Santana JL, Schlater SM, Sciurba FC, Selvaggi C, Seshadri S, Sesso HD, Shah DP, Shemesh E, Sherif ZA, Shinnick DJ, Simhan HN, Singh U, Sowles A, Subbian V, Sun J, Suthar MS, Teunis LJ, Thorp JM Jr, Ticotsky A, Tita ATN, Tragus R, Tuttle KR, Urdaneta AE, Utz PJ, VanWagoner TM, Vasey A, Vernon SD, Vidal C, Walker T, Ward HD, Warren DE, Weeks RM, Weiner SJ, Weyer JC, Wheeler JL, Whiteheart SW, Wiley Z, Williams NJ, Wisnivesky JP, Wood JC, Yee LM, Young NM, Zisis SN, and Foulkes AS
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- Humans, Observational Studies as Topic, Post-Acute COVID-19 Syndrome, Prospective Studies, Retrospective Studies, SARS-CoV-2, Adolescent, Adult, Multicenter Studies as Topic, COVID-19 epidemiology
- Abstract
Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis., Methods: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms., Discussion: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options., Registration: NCT05172024., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Helen Chu reported consulting for Merck, GSK, Pfizer, Ellume, Janssen, Vindico CME, and the Bill and Melinda Gates Foundation, and receiving research support from Gates Ventures, Ellume, and Sanofi Pasteur. She also serves as a co-investigator on studies funded by Pfizer, Novavax, and GSK. Maged Costantine reported receiving grant support for work not related to RECOVER work/publications from Baxter International and Siemens Healthcare and personal consulting fees not related to this paper from Progenity, Quidel Ortho, and Siemens Healthcare. Kristine Erlandson reported research funding from Gilead Sciences and consulting payments from Gilead Sciences, Merck, and ViiV Pharmaceuticals, all paid to the University of Colorado. Emily Gallagher reported consulting for Novartis, Flare Therapeutics and Seagen. Edward Gardner reported research support (clinical trials) from Gilead Sciences, ViiV Healthcare, and Cepheid. Jason Goldman reported research support from Gilead, Eli Lilly and Regeneron; grants from Gilead, Merck (BARDA); personal fees for consulting from Gilead, Eli Lilly; and non-financial support from Adaptive Biotechnologies and Labcorp/Monogram Biosciences outside the submitted work. Timothy Heinrich reported grant support from Merck Inc. and consulting fees from Roche. Rachel Hess reported serving as Data Safety Monitoring Board member for Astellas Pharmaceuticals unrelated to the current work. Leora Horwitz reported being a member of the National Academy of Medicine Committee on the Long-Term Health Effects Stemming from COVID-19 and Implications for the Social Security Administration. Priscilla Hsue reported receiving honoraria from Gilead and Merck unrelated to study topic, receiving study drug from Regeneron unrelated to study topic, and receiving a research grant from Novartis. Judith James reported OMRF has licensed her IP to Progentec Biosciences, has received grant support from Progentec Biosciences, and serves on Advisory Committees to Glaxo Smith Klein, Merck and Novartis. Arthur Kim reports providing educational materials to Clinical Care Options and UpToDate and serving on a Data Safety Monitoring board for Kintor Pharmaceuticals, Ltd. Bruce Levy reported serving as a consultant for AstraZeneca, Entrinsic Biosciences, Gossamer Bio and Nocion Therapeutics and receiving research support from Amgen, Genentech, GlaxoSmithKline, Pieris Pharmaceuticals, SRA and Sanofi unrelated to the current work. Vincent Marconi reported receiving grants from NIH during the conduct of the study and grants from NIH, Veteran Affairs, and Centers for Disease Control and Prevention; grants, personal fees, nonfinancial support, and other from Lilly and Gilead; grants and personal fees from ViiV; and nonfinancial support from Bayer outside the submitted work. Grace McComsey reported serving as consultant for Merck, Gilead, ViiV, Janssen and have received research support from Pfizer, Vanda, Genentech, Roche, Redhill and Cognivue. Torri Metz reported being a site PI and a participant in the medical advisory board for the planning of a Pfizer clinical trial of SARS-CoV-2 vaccination in pregnancy. She also reported being a site PI for a Pfizer study evaluating the pharmacokinetics of Paxlovid in pregnant people with COVID-19. Janet Mullington reported support for investigator-initiated research by "Open Medicine Foundation and the Patient-Led Research Collaborative" Princess Ogbogu reported research support from Astrazeneca, GSK, Blueprint medical; advisory board for Astrazeneca, GSK, Sanofi, Kalvista; and consulting for Astrazeneca, GSK Sairam Parthasarathy reported research funding to Institution from Sergey Brin foundation of COVID and Long-COVID research. Michael Peluso reported consulting fees from Gilead Sciences and AstraZeneca, and service on data safety monitoring board for American Gene Technologies. Sean Quigley reported service on speaker Board for Servier, Alnylam, Agios; service on advisory board for Recordati, Alexion. Franz Rischard reported research support from NIH/NHLBI, United Therapeutics, Acceleron/Merck, Janssen, Insmed, Aerovate, and Bayer; and consulting/advisory compensation from Acceleron and Bayer. Nadine Rouphael reported being a consultant for ICON and EMMES as a safety consultant for clinical trials; service on the advisory boards for Moderna; funds to institution from Sanofi, Lilly, Merck, Quidel and Pfizer. PJ Utz reported stock ownership of Gilead and PI of biomarker studies for Pfizer STOP-PASC paxlovid trial Juan Wisnivesky received receiving consulting honorarium from Sanofi, Banook, Prospero, PPD and Atea and research grants from Sanofi, Regeneron, Axella, and Arnold Consultants., (Copyright: © 2023 Horwitz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
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