Postacute Sequelae of SARS-CoV-2 in Children

Abstract

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.

FIGURE 1

Conceptual model of the PASC. Legend: The NIH defines the PASC as symptoms or conditions which may reflect exacerbation of underlying conditions, persistent symptoms of acute infection, or may be new symptoms or conditions arising de novo, distinct from the acute SARS-CoV-2 infection period.

FIGURE 2

Organ system involvement of PASC in children. Legend: The figure outlines symptoms and conditions, grouped by body system, which have been associated with the PASC. Some symptoms may be transient and rare in children, and a description of more common manifestations is provided in the main text.

FIGURE 3

Outline of the pediatric-specific components of the RECOVER Initiative. Legend: The RECOVER Initiative includes 4 cores: (1) clinical science core, which leads study implementation and provides scientific leadership in collaboration with hub and site principal investigators; (2) data resource core, which conducts statistical leadership and data management; (3) biorepository core, which manages biospecimens; and (4) administrative coordinating center, which provides administrative support. The enrolling cohorts form the basis of the observational studies. Up to 19 500 participants will be enrolled in these studies in a combined retrospective and prospective, longitudinal observational meta-cohort. The RECOVER enrolling cohorts include the de novo cohort (prospective cohort including children and young adults ages birth through 25 years, with or without a known history of infection, and their caregivers), Adolescent Brain Cognitive Development Cohort, COVID MUSIC study, evaluating the long-term outcomes of MIS-C in children, and in utero exposure cohort (including children <3 years old born to individuals with and without a SAR-CoV-2 infection during pregnancy). The EHR/Health Systems Studies utilizes 8.9 million inpatient and outpatient records from PEDSnet and PCORnet sites (for more information about these cohorts, go to https://pedsnet.org/ and https://pcornet.org/data/). From these elements, RECOVER will encompass diverse data types, including clinical, imaging, mobile and digital health, and EHR data.