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

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.

Durability of Original Monovalent mRNA Vaccine Effectiveness Against COVID-19 Omicron-Associated Hospitalization in Children and Adolescents - United States, 2021-2023.

Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite the high frequency of reported underlying conditions associated with severe COVID-19. VE of the original monovalent vaccine against COVID-19-related hospitalizations was 52% (95% CI = 33%-66%) when the most recent dose was administered <120 days before hospitalization and 19% (95% CI = 2%-32%) if the interval was 120-364 days. VE of the original monovalent vaccine against COVID-19-related hospitalization was 31% (95% CI = 18%-43%) if the last dose was received any time within the previous year. VE against critical COVID-19-related illness, defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death, was 57% (95% CI = 21%-76%) when the most recent dose was received <120 days before hospitalization, 25% (95% CI = -9% to 49%) if it was received 120-364 days before hospitalization, and 38% (95% CI = 15%-55%) if the last dose was received any time within the previous year. VE was similar after excluding children and adolescents with documented immunocompromising conditions. Because of the low frequency of children who received updated COVID-19 vaccines and waning effectiveness of original monovalent doses, these data support CDC recommendations that all children and adolescents receive updated COVID-19 vaccines to protect against severe COVID-19.

SARS-CoV-2 Viral Shedding and Rapid Antigen Test Performance - Respiratory Virus Transmission Network, November 2022-May 2023.

As population immunity to SARS-CoV-2 evolves and new variants emerge, the role and accuracy of antigen tests remain active questions. To describe recent test performance, the detection of SARS-CoV-2 by antigen testing was compared with that by reverse transcription-polymerase chain reaction (RT-PCR) and viral culture testing during November 2022-May 2023. Participants who were enrolled in a household transmission study completed daily symptom diaries and collected two nasal swabs (tested for SARS-CoV-2 via RT-PCR, culture, and antigen tests) each day for 10 days after enrollment. Among participants with SARS-CoV-2 infection, the percentages of positive antigen, RT-PCR, and culture results were calculated each day from the onset of symptoms or, in asymptomatic persons, from the date of the first positive test result. Antigen test sensitivity was calculated using RT-PCR and viral culture as references. The peak percentage of positive antigen (59.0%) and RT-PCR (83.0%) results occurred 3 days after onset, and the peak percentage of positive culture results (52%) occurred 2 days after onset. The sensitivity of antigen tests was 47% (95% CI = 44%-50%) and 80% (95% CI = 76%-85%) using RT-PCR and culture, respectively, as references. Clinicians should be aware of the lower sensitivity of antigen testing compared with RT-PCR, which might lead to false-negative results. This finding has implications for timely initiation of SARS-CoV-2 antiviral treatment, when early diagnosis is essential; clinicians should consider RT-PCR for persons for whom antiviral treatment is recommended. Persons in the community who are at high risk for severe COVID-19 illness and eligible for antiviral treatment should seek testing from health care providers with the goal of obtaining a more sensitive diagnostic test than antigen tests (i.e., an RT-PCR test).

Postacute Sequelae of SARS-CoV-2 in Children.

The coronavirus disease 2019 (COVID-19) pandemic has caused significant medical, social, and economic impacts globally, both in the short and long term. Although most individuals recover within a few days or weeks from an acute infection, some experience longer lasting effects. Data regarding the postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) in children, or long COVID, are only just emerging in the literature. These symptoms and conditions may reflect persistent symptoms from acute infection (eg, cough, headaches, fatigue, and loss of taste and smell), new symptoms like dizziness, or exacerbation of underlying conditions. Children may develop conditions de novo, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, autoimmune conditions and multisystem inflammatory syndrome in children. This state-of-the-art narrative review provides a summary of our current knowledge about PASC in children, including prevalence, epidemiology, risk factors, clinical characteristics, underlying mechanisms, and functional outcomes, as well as a conceptual framework for PASC based on the current National Institutes of Health definition. We highlight the pediatric components of the National Institutes of Health-funded Researching COVID to Enhance Recovery Initiative, which seeks to characterize the natural history, mechanisms, and long-term health effects of PASC in children and young adults to inform future treatment and prevention efforts. These initiatives include electronic health record cohorts, which offer rapid assessments at scale with geographical and demographic diversity, as well as longitudinal prospective observational cohorts, to estimate disease burden, illness trajectory, pathobiology, and clinical manifestations and outcomes.

Outcome of BMI2+: Motivational Interviewing to Reduce BMI Through Primary Care AAP PROS Practices.

BACKGROUND: Pediatric obesity rates in the United States remain at an all-time high. Pediatric primary care clinicians and registered dietitians can help treat childhood obesity, and motivational interviewing (MI) has shown promising effects in prior trials. METHODS: We randomized 18 pediatric primary care practices to receive the Brief Motivational Interviewing to Reduce BMI or BMI2+ intervention or continue with usual care (UC). Practices were recruited through the American Academy of Pediatrics Pediatric Research in Office Settings network. The intervention comprised 4 components1: in-person and telehealth MI counseling by pediatric clinicians; 4 recommended sessions,2 6 telephone MI counseling sessions from a registered dietitian,3 text message reminders and tailored motivational messages, and4 parent educational materials. The main outcome was the change in the percentage of the 95th percentile of BMI. The study was conducted 2017 through 2021. RESULTS: There was a significant treatment x time interaction (b = 0.017, 95% confidence interval: [0.0066-0.027]) for the main outcome, favoring the UC group, with youth in the intervention arm showing a greater relative increase in their percent of the 95th percentile. CONCLUSIONS: There was no overall benefit of the intervention and, contrary to expectations, youth in the intervention arm gained more weight, based on percent of the distance from the 95th percentile than matched youth from UC practices. The absolute excess weight gain among intervention relative to UC youth was small, approximately 0.5 BMI units and 1 kg over 2 years. We offer several potential explanations for these unexpected findings.

Addressing adverse social determinants of health in pediatric primary care: Study protocol for a hybrid type 2 effectiveness-implementation randomized controlled trial in two national pediatric practice-based research networks.

BACKGROUND: Growing evidence linking social determinants of health (SDOH) to child health outcomes has prompted widespread recommendations for pediatricians to screen and refer for adverse SDOH at primary care visits. Yet there is little evidence to date demonstrating the effectiveness of practice-based SDOH screening and referral interventions on increasing family engagement with resources. This hybrid type 2 effectiveness-implementation trial aims to demonstrate the non-inferiority of a low-touch implementation strategy in order to facilitate dissemination of an existing SDOH screening and referral system (WE CARE) and demonstrate its effectiveness and sustainability in various pediatric practices. METHODS: We recruited eighteen pediatric practices in fourteen US states through two pediatric practice-based research networks. For this stepped wedge cluster RCT, practices serve as their own controls during the Usual Care phase and implement WE CARE during the intervention phase via one of two randomized implementation strategies: self-directed, pre-recorded webinar vs. study team-facilitated, live webinar. We collect data at practice, clinician/staff, and parent levels to assess outcomes grounded in the Proctor Conceptual Model of Implementation Research. We use generalized mixed effects models and differences in proportions to compare rates of resource referrals by implementation strategy, and intention-to-treat analysis to compare odds of engagement with new resources among families enrolled in the Usual Care vs. WE CARE phases. DISCUSSION: Findings from this trial may inform decisions about broader dissemination of SDOH screening systems into a diverse spectrum of pediatric practices across the US and potentially minimize the impact of adverse SDOH on children and families.

Pediatric Practices' Perceptions of Text Message Communication with Families: An American Academy of Pediatrics (AAP), Pediatric Research in Office Settings (PROS) Study.

Background: Text messages can be an effective and low-cost mechanism for patient reminders; however, they are yet to be consistently integrated into pediatric primary care. Objective: The aim of this study was to explore pediatric primary care clinician and staff perceptions of pediatric office text message communication with families. Methods: As part of the National Institutes of Health-funded Flu2Text randomized controlled trial of second-dose influenza vaccine text message reminders, we conducted 7 focus groups and 4 individual interviews in July-August 2019 with primary care pediatric clinicians and staff (n = 39). Overall, 10 Pediatric Research in Office Settings (PROS) pediatric practices in 10 states were selected using stratified sampling. Semi-structured discussion guides included perspectives on possible uses, perceived usefulness, and ease of use of text messages; practices' current text messaging infrastructure; and perceived barriers/facilitators to future use of texting. Two investigators independently coded and analyzed transcripts based on the technology acceptance model using NVIVO 12 Plus (intercoder reliability, K = 0.86). Results: Overall, participants were supportive of text reminders for the second-dose influenza vaccine, other vaccines, and appointments and perceived texting as a preferred method of communication for caregivers. Health information privacy and patient confidentiality were the main concerns cited. Only respondents from practices with no internal appointment text message reminder system prior to the study expressed concerns about technology implementation logistics, time, and cost. Conclusion: Text message reminders, for various uses, appear to be well accepted among a group of geographically widespread pediatric practices after participation in a trial of influenza vaccine text message reminders. Privacy, confidentiality, and resource barriers need to be addressed to facilitate successful implementation.