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Observational Study
. 2024 May 7;19(5):e0285635.
doi: 10.1371/journal.pone.0285635. eCollection 2024.

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

Rachel S Gross  1 , Tanayott Thaweethai  2 , Erika B Rosenzweig  3 , James Chan  2 , Lori B Chibnik  2 , Mine S Cicek  4 , Amy J Elliott  5 , Valerie J Flaherman  6 , Andrea S Foulkes  2 , Margot Gage Witvliet  7 , Richard Gallagher  8 , Maria Laura Gennaro  9 , Terry L Jernigan  10   11 , Elizabeth W Karlson  12 , Stuart D Katz  13 , Patricia A Kinser  14 , Lawrence C Kleinman  15 , Michelle F Lamendola-Essel  13 , Joshua D Milner  16 , Sindhu Mohandas  17 , Praveen C Mudumbi  18 , Jane W Newburger  19 , Kyung E Rhee  20 , Amy L Salisbury  14 , Jessica N Snowden  21 , Cheryl R Stein  8 , Melissa S Stockwell  22   23 , Kelan G Tantisira  24 , Moriah E Thomason  8 , Dongngan T Truong  25 , David Warburton  26 , John C Wood  27 , Shifa Ahmed  2 , Almary Akerlundh  28 , Akram N Alshawabkeh  29 , Brett R Anderson  3 , Judy L Aschner  30 , Andrew M Atz  31 , Robin L Aupperle  32 , Fiona C Baker  33 , Venkataraman Balaraman  34 , Dithi Banerjee  35 , Deanna M Barch  36 , Arielle Baskin-Sommers  37 , Sultana Bhuiyan  13 , Marie-Abele C Bind  2 , Amanda L Bogie  38 , Tamara Bradford  39 , Natalie C Buchbinder  40 , Elliott Bueler  13 , Hülya Bükülmez  41 , B J Casey  42 , Linda Chang  43 , Maryanne Chrisant  44 , Duncan B Clark  45 , Rebecca G Clifton  46 , Katharine N Clouser  30 , Lesley Cottrell  47 , Kelly Cowan  48 , Viren D'Sa  49 , Mirella Dapretto  50 , Soham Dasgupta  51 , Walter Dehority  52 , Audrey Dionne  19 , Kirsten B Dummer  53 , Matthew D Elias  54 , Shari Esquenazi-Karonika  13 , Danielle N Evans  55 , E Vincent S Faustino  56 , Alexander G Fiks  57 , Daniel Forsha  58 , John J Foxe  59 , Naomi P Friedman  60 , Greta Fry  61 , Sunanda Gaur  15 , Dylan G Gee  37 , Kevin M Gray  62 , Stephanie Handler  63 , Ashraf S Harahsheh  64 , Keren Hasbani  65 , Andrew C Heath  66 , Camden Hebson  67 , Mary M Heitzeg  68 , Christina M Hester  69 , Sophia Hill  13 , Laura Hobart-Porter  70 , Travis K F Hong  34 , Carol R Horowitz  71 , Daniel S Hsia  72 , Matthew Huentelman  73 , Kathy D Hummel  74 , Katherine Irby  74 , Joanna Jacobus  75 , Vanessa L Jacoby  76 , Pei-Ni Jone  77 , David C Kaelber  78   79 , Tyler J Kasmarcak  80 , Matthew J Kluko  56 , Jessica S Kosut  34 , Angela R Laird  81 , Jeremy Landeo-Gutierrez  82 , Sean M Lang  83 , Christine L Larson  84 , Peter Paul C Lim  85 , Krista M Lisdahl  84 , Brian W McCrindle  86 , Russell J McCulloh  87 , Kimberly McHugh  80 , Alan L Mendelsohn  88 , Torri D Metz  89 , Julie Miller  90 , Elizabeth C Mitchell  91 , Lerraughn M Morgan  92 , Eva M Müller-Oehring  33 , Erica R Nahin  13 , Michael C Neale  93 , Manette Ness-Cochinwala  15 , Sheila M Nolan  94 , Carlos R Oliveira  56 , Onyekachukwu Osakwe  95 , Matthew E Oster  96 , R Mark Payne  97 , Michael A Portman  98 , Hengameh Raissy  99 , Isabelle G Randall  13 , Suchitra Rao  100 , Harrison T Reeder  2 , Johana M Rosas  13 , Mark W Russell  101 , Arash A Sabati  102 , Yamuna Sanil  103 , Alice I Sato  104 , Michael S Schechter  105 , Rangaraj Selvarangan  35 , S Kristen Sexson Tejtel  106 , Divya Shakti  95 , Kavita Sharma  107 , Lindsay M Squeglia  62 , Shubika Srivastava  108 , Michelle D Stevenson  109 , Jacqueline Szmuszkovicz  110 , Maria M Talavera-Barber  111 , Ronald J Teufel 2nd  31 , Deepika Thacker  108 , Felicia Trachtenberg  90 , Mmekom M Udosen  18 , Megan R Warner  28 , Sara E Watson  109 , Alan Werzberger  112 , Jordan C Weyer  113 , Marion J Wood  18 , H Shonna Yin  114 , William T Zempsky  115 , Emily Zimmerman  116 , Benard P Dreyer  1 ; RECOVER-Pediatric Consortium
Affiliations
Observational Study

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

Rachel S Gross et al. PLoS One. .

Abstract

Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science.

Conclusions and relevance: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions.

Clinical trials.gov identifier: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

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Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: Brett Anderson reported receiving direct support for work not related to RECOVER work/publications from Genentech and the National Institute of Allergy and Immunology. Walter Dehority reported receiving grant support from Merck and participating in research for the Moderna COVID-19 pediatric vaccine trial and the Pfizer Paxlovid trial. Alex Fiks reported receiving support from NJM insurance and personal consulting fees not related to this paper from Rutgers University and the American Academy of Pediatrics. Ashraf Harahsheh reported serving as a scientific advisory board member unrelated to this paper for OP2 DRUGS. Lawrence Kleinman reported serving as an unpaid member of the Board of Directors for the DARTNet Institute, as a principle investigator at Quality Matters, Inc., and as the Vice Chair for the Borough of Metuchen Board of Health. Dr. Kleinman also reported grant support for work not related to RECOVER work/publications from NIH, HRSA, and the Robert Wood Johnson Foundation. Dr. Kleinman also reported minority individual stock ownership in Apple Computer, Sanofi SA, Experion, GlaxoSmithKline, Magyar Bank, Regeneron Pharmaceuticals, JP Morgan Chase, and Amgen Inc. Torri Metz reported participating as a Principle Investigator in the medical advisory board for the planning of a Pfizer clinical trial of SARS-CoV-2 vaccination in pregnancy. She is also a principle investigator for a Pfizer study evaluating the pharmacokinetics of Paxlovid in pregnant people with COVID-19. Joshua Milner reported serving as a member of the Scientific Advisory Board for Blueprint Medicines, in a capacity unrelated to RECOVER work/publications. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Overview of RECOVER-Pediatrics (de novo and ABCD cohorts).
See this image and copyright information in PMC

References

    1. Centers for Disease Control and Prevention (CDC). Long COVID or Post-COVID Conditions 2023 [cited 2023 September 28, 2023]. https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html.
    1. Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2022;22(4):e102–e7. Epub 20211221. doi: 10.1016/S1473-3099(21)00703-9 . - DOI - PMC - PubMed
    1. Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023;21(3):133–46. Epub 20230113. doi: 10.1038/s41579-022-00846-2 . - DOI - PMC - PubMed
    1. World Health Organization. WHO Coronavirus (COVID-19) dashboard 2023 2023. https://covid19.who.int/.
    1. Zimmermann P, Pittet LF, Curtis N. How common is Long COVID in children and adolescents? Pediatr Infect Dis J. 2021;40(12):e482–e7. doi: 10.1097/INF.0000000000003328 . - DOI - PMC - PubMed

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