Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design

Leora I. Horwitz, Tanayott Thaweethai, Shari B. Brosnahan, Mine S. Cicek, Megan L. Fitzgerald, Jason D. Goldman, Rachel Hess, S. L. Hodder, Vanessa L. Jacoby, Michael R. Jordan, Jerry A. Krishnan, Adeyinka O. Laiyemo, Torri D. Metz, Lauren Nichols, Rachel E. Patzer, Anisha Sekar, Nora G. Singer, Lauren E. Stiles, Barbara S. Taylor, Shifa AhmedHeather A. Algren, Khamal Anglin, Lisa Aponte-Soto, Hassan Ashktorab, Ingrid V. Bassett, Brahmchetna Bedi, Nahid Bhadelia, Christian Bime, Marie Abele C. Bind, Lora J. Black, Andra L. Blomkalns, Hassan Brim, Mario Castro, James Chan, Alexander W. Charney, Benjamin K. Chen, Li Qing Chen, Peter Chen, David Chestek, Lori B. Chibnik, Dominic C. Chow, Helen Y. Chu, Rebecca G. Clifton, Shelby Collins, Maged M. Costantine, Sushma K. Cribbs, Steven G. Deeks, John D. Dickinson, Sarah E. Donohue, Matthew S. Durstenfeld, Ivette F. Emery, Kristine M. Erlandson, Julio C. Facelli, Rachael Farah-Abraham, Aloke V. Finn, Melinda S. Fischer, Valerie J. Flaherman, Judes Fleurimont, Vivian Fonseca, Emily J. Gallagher, Jennifer C. Gander, Maria Laura Gennaro, Kelly S. Gibson, Minjoung Go, Steven N. Goodman, Joey P. Granger, Frank L. Greenway, John W. Hafner, Jenny E. Han, Michelle S. Harkins, Kristine S.P. Hauser, James R. Heath, Carla R. Hernandez, On Ho, Matthew K. Hoffman, Susan E. Hoover, Carol R. Horowitz, Harvey Hsu, Priscilla Y. Hsue, Brenna L. Hughes, Prasanna Jagannathan, Judith A. James, Janice John, Sarah Jolley, S. E. Judd, Joy J. Juskowich, Diane G. Kanjilal, Elizabeth W. Karlson, Stuart D. Katz, J. Daniel Kelly, Sara W. Kelly, Arthur Y. Kim, John P. Kirwan, Kenneth S. Knox, Andre Kumar, Michelle F. Lamendola-Essel, Margaret Lanca, Joyce K. Lee-Lannotti, R. Craig Lefebvre, Bruce D. Levy, Janet Y. Lin, Brian P. Logarbo, Jennifer K. Logue, Michele T. Longo, Carlos A. Luciano, Karen Lutrick, Shahdi K. Malakooti, Gail Mallett, Gabrielle Maranga, Jai G. Marathe, Vincent C. Marconi, Gailen D. Marshall, Christopher F. Martin, Jeffrey N. Martin, Heidi T. May, Grace A. McComsey, Dylan McDonald, Hector Mendez-Figueroa, Lucio Miele, Murray A. Mittleman, Sindhu Mohandas, Christian Mouchati, Janet M. Mullington, Girish N. Nadkarni, Erica R. Nahin, Robert B. Neuman, Lisa T. Newman, Amber Nguyen, Janko Z. Nikolich, Igho Ofotokun, Princess U. Ogbogu, Anna Palatnik, Kristy T.S. Palomares, Tanyalak Parimon, Samuel Parry, Sairam Parthasarathy, Thomas F. Patterson, Ann Pearman, Michael J. Peluso, Priscilla Pemu, Christian M. Pettker, Beth A. Plunkett, Kristen Pogreba-Brown, Athena Poppas, J. Zachary Porterfield, John G. Quigley, Davin K. Quinn, Hengameh Raissy, Candida J. Rebello, Uma M. Reddy, Rebecca Reece, Harrison T. Reeder, Franz P. Rischard, Johana M. Rosas, Clifford J. Rosen, Nadine G. Rouphael, Dwight J. Rouse, Adam M. Ruff, Christina Saint Jean, Grecio J. Sandoval, Jorge L. Santana, Shannon M. Schlater, Frank C. Sciurba, Caitlin Selvaggi, Sudha Seshadri, Howard D. Sesso, Dimpy P. Shah, Eyal Shemesh, Zaki A. Sherif, Daniel J. Shinnick, Hyagriv N. Simhan, Upinder Singh, Amber Sowles, Vignesh Subbian, Jun Sun, Mehul S. Suthar, Larissa J. Teunis, John M. Thorp, Amberly Ticotsky, Alan T.N. Tita, Robin Tragus, Katherine R. Tuttle, Alfredo E. Urdaneta, P. J. Utz, Timothy M. VanWagoner, Andrew Vasey, Suzanne D. Vernon, Crystal Vidal, Tiffany Walker, Honorine D. Ward, David E. Warren, Ryan M. Weeks, Steven J. Weiner, Jordan C. Weyer, Jennifer L. Wheeler, Sidney W. Whiteheart, Zanthia Wiley, Natasha J. Williams, Juan P. Wisnivesky, John C. Wood, Lynn M. Yee, Natalie M. Young, Sokratis N. Zisis, Andrea S. Foulkes

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


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.

Original languageEnglish
Article numbere0286297
JournalPLoS ONE
Issue number6 June
StatePublished - Jun 2023

Bibliographical note

Publisher Copyright:
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.

ASJC Scopus subject areas

  • General


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