Researching COVID to enhance recovery (RECOVER) adult study protocol: Rationale, objectives, and design

Author:

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

Abstract

AbstractImportanceSARS-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.MethodsRECOVER-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.DiscussionRECOVER-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.

Publisher

Cold Spring Harbor Laboratory

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