[Preprint/Protocol] Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design, 2023, Gross et al.

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

Spoiler: Multiple Authors - RECOVER

Rachel Gross; Tanayott Thaweethai; Erika B. Rosenzweig; James Chan; Lori B. Chibnik; Mine S. Cicek; Amy J. Elliott; Valerie J. Flaherman; Andrea S. Foulkes; Margot Gage Witvliet; Richard Gallagher; Maria Laura Gennaro; Terry L. Jernigan; Elizabeth W. Karlson; Stuart D. Katz; Patricia A. Kinser; Lawrence C. Kleinman; Michelle F. Lamendola-Essel; Joshua D. Milner; Sindhu Mohandas; Praveen C. Mudumbi; Jane W. Newburger; Kyung E. Rhee; Amy L. Salisbury; Jessica N. Snowden; Cheryl R. Stein; Melissa S. Stockwell; Kelan G. Tantisira; Moriah E. Thomason; Dongngan T. Truong; David Warburton; John C. Wood; Shifa Ahmed; Almary Akerlundh; Akram N. Alshawabkeh; Brett R. Anderson; Judy L. Aschner; Andrew M. Atz; Robin L. Aupperle; Fiona C. Baker; Venkataraman Balaraman; Dithi Banerjee; Deanna M. Barch; Arielle Baskin-Sommers; Sultana Bhuiyan; Marie-Abele C. Bind; Amanda L. Bogie; Natalie C. Buchbinder; Elliott Bueler; Hülya Bükülmez; B.J. Casey; Linda Chang; Duncan B. Clark; Rebecca G. Clifton; Katharine N. Clouser; Lesley Cottrell; Kelly Cowan; Viren D'sa; Mirella Dapretto; Soham Dasgupta; Walter Dehority; Kirsten B. Dummer; Matthew D. Elias; Shari Esquenazi-Karonika; Danielle N. Evans; E. Vincent S. Faustino; Alexander G. Fiks; Daniel Forsha; John J. Foxe; Naomi P. Friedman; Greta Fry; Sunanda Gaur; Dylan G. Gee; Kevin M. Gray; Ashraf S. Harahsheh; Andrew C. Heath; Mary M. Heitzeg; Christina M. Hester; Sophia Hill; Laura Hobart-Porter; Travis K.F. Hong; Carol R. Horowitz; Daniel S. Hsia; Matthew Huentelman; Kathy D. Hummel; William G. Iacono; Katherine Irby; Joanna Jacobus; Vanessa L. Jacoby; Pei-Ni Jone; David C. Kaelber; Tyler J. Kasmarcak; Matthew J. Kluko; Jessica S. Kosut; Angela R. Laird; Jeremy Landeo-Gutierrez; Sean M. Lang; Christine L. Larson; Peter Paul C. Lim; Krista M. Lisdahl; Brian W. McCrindle; Russell J. McCulloh; Alan L. Mendelsohn; Torri D. Metz; Lerraughn M. Morgan; Eva M. Müller-Oehring; Erica R. Nahin; Michael C. Neale; Manette Ness-Cochinwala; Sheila M. Nolan; Carlos R. Oliveira; Matthew E. Oster; Ronald M. Payne; Hengameh Raissy; Isabelle G. Randall; Suchitra Rao; Harrison T. Reeder; Johana M. Rosas; Mark W. Russell; Arash A. Sabati; Yamuna Sanil; Alice I. Sato; Michael S. Schechter; Rangaraj Selvarangan; Divya Shakti; Kavita Sharma; Lindsay M. Squeglia; Michelle D. Stevenson; Jacqueline Szmuszkovicz; Maria M. Talavera-Barber; Ronald J. Teufel; Deepika Thacker; Mmekom M. Udosen; Megan R. Warner; Sara E. Watson; Alan Werzberger; Jordan C. Weyer; Marion J. Wood; H. Shonna Yin; William T. Zempsky; Emily Zimmerman; Benard P. Dreyer; RECOVER Initiative

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 five 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.

Link | PDF (Preprint: MedRxiv)

 

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Of the 112 listed affiliations 15 are departments of psychology or psychiatry with another 3 or 4 aligned but with a different name.

The pandemic began with a misconception that children were spared. We now recognize that children and families are greatly impacted during both acute and chronic phases.

Additional phenotypes of childhood PASC are being reported, including phenotypes similar to postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postintensive care unit syndrome, and potentially many others.

RECOVER-Pediatrics scientific aims are to:

1. Characterize the prevalence and incidence of new onset or worsening symptoms related to PASC
2. Characterize the spectrum of clinical symptoms of PASC, including distinct phenotypes, and describe the clinical course and recovery.
3. Identify risk and resiliency factors for developing PASC and recovering from PASC.
4. Define the pathophysiology of PASC, including subclinical organ dysfunction, and identify biological mechanisms underlying the pathogenesis of PASC.

Physical health domains include anthropometrics, vital signs, an active standing test measuring orthostatic blood pressures, joint flexibility tests, electrocardiograms, and spirometry.

Physical health domains of cardiopulmonary function are assessed by echocardiogram, cardiopulmonary exercise testing, cardiac MRI, pulmonary function tests, and sputum induction.

Gastrointestinal function is assessed using abdominal ultrasound, and neurological function is assessed using brain MRI, electroencephalogram, and measures of neurocognitive function and psychiatric symptoms.

I would comment that abdominal ultrasound gives very limited information about small and large bowel structure and even less about its function. It mainly looks at the anatomy of liver, biliary system and pancreas, eg lesions or duct dilation.

Tier 1 biospecimens consist of saliva and whole blood. [...] Whole blood is collected using a TASSO M20 device, which collects capillary blood using 4 volumetric sponges that each hold 17.5µL of blood (70 µL total). One sponge is used for SARSCoV-2 spike and nucleocapsid antibody testing and remaining sponges are banked for future use.

That's not a lot of blood, even assuming they fill the Tasso device.

 

[SNT Gatchaman]

Published as —

Researching COVID to enhance recovery RECOVER pediatric study protocol: Rationale, objectives and design
Rachel S. Gross et al.; on behalf of the RECOVER-Pediatric Consortium

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.

TRIAL REGISTRATION
http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Link | PDF (PLOS ONE) [Open Access]