Nucleic acid biomarkers of immune response and cell and tissue damage in children with COVID-19 and MIS-C

Differential host responses in coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) remain poorly characterized. Here we use next-generation sequencing to longitudinally analyze blood samples from pediatric patients with acute COVID-19 (n=70) or MIS-C (n=141) across three hospitals. Profiling of plasma cell-free nucleic acids uncovers distinct signatures of cell injury and death between COVID-19 and MIS-C, with increased multi-organ involvement in MIS-C encompassing diverse cell types including endothelial and neuronal cells, and an enrichment of pyroptosis related genes. Whole blood RNA profiling reveals upregulation of similar pro-inflammatory pathways in COVID-19 and MIS-C, but also MIS-C specific downregulation of T cell-associated pathways. Profiling of plasma cell-free RNA and whole blood RNA in paired samples yields different yet complementary signatures for each disease state. Our work provides a systems-level view of immune responses and tissue damage in COVID-19 and MIS-C and informs the future development of new disease biomarkers. Graphical Loy et al. use cell-free RNA, whole blood RNA, and cell-free DNA sequencing to characterize distinct host response and cellular injury profiles in pediatric patients with MIS-C and/or COVID-19. This study highlights the complementary information from cell-free and whole blood RNA analyses, with broad implications for future liquid biopsy applications.

Positive and negative effects of the COVID-19 pandemic on families of young children in rural Colombia and implications for child outcome research.

BACKGROUND: The COVID-19 pandemic has impacted the lives of children and families worldwide. The objective of this study is to examine exposures and impact of the COVID-19 pandemic on preschool-aged children and caregivers in the Atlántico region of Colombia. METHODS: The COVID-19 Exposure and Family Impact Scales (CEFIS) questionnaire was administered in Fall 2021 to 63 caregivers of children in Sabanalarga, Colombia enrolled in a neurodevelopment study as healthy controls. The CEFIS assesses pandemic-related exposures/events and impact; higher scores indicate greater exposure and negative impact. Descriptive and correlation analyses among exposure and impact scores were conducted. RESULTS: Caregivers reported a mean (standard deviation[SD]) of 11.1 (3.2) among 25 COVID-19-related exposures/events; most common types included stay-at-home orders, school closures, disruptions to living conditions and income loss. Total number of events was correlated with higher caregiver (P < .001) and child distress (P = .002). However, the mean (SD) impact score of 2.0 (0.6) suggests a trend toward more positive impact than negative. Caregivers reported improvements to sleep, exercise and family interactions. Some caregivers (n = 21) qualitatively reported negative effects including unemployment, fear/anxiety and inability to visit family, and positive effects such as unification, family closeness and spending more time with children. CONCLUSIONS: This study highlights the importance of comprehensively exploring positive and negative impacts of COVID-19 and families' subsequent resilience and transformation. Using tools like the CEFIS, those seeking to mitigate negative impacts can contextualize data to better understand study outcomes and tailor services, resources and policy to families' unique needs. CEFIS data likely depend on timing, economic/public health resources and cultural values; future work should prioritize understanding the generalizability of CEFIS findings across samples.

Neurodevelopment in infants with antenatal or early neonatal exposure to SARS-CoV-2.

BACKGROUND: Antenatal and neonatal viral exposure may put the developing brain at risk for abnormal neurodevelopment. A clinical program at Children's National Hospital provides detailed follow-up of infants with in utero or neonatal SARS-CoV-2 exposure. AIMS: To determine impact of early SARS-CoV-2 exposure on neurodevelopment. STUDY DESIGN: We performed a prospective observational study of infant evaluations between 3/2020 and 11/2021. Demographics, pregnancy and birth details, SARS-CoV-2 data, specialty consultations, and NICU records were extracted from infants' medical records. Infants had neurologic exams and developmental screening with Ages and Stages Questionnaire (ASQ). Correlations between SARS-CoV-2 exposure type and neurodevelopmental outcomes were analyzed. SUBJECTS: Thirty-four infants evaluated in the SARS-CoV-2 follow-up program. OUTCOME MEASURES: Abnormal neurologic exams or ASQ scores near or below suggested cut-offs. RESULTS: Infants received up to three evaluations. Most (28/34; 82 %) were exposed in utero - 16 to symptomatic mothers (IU-S) and 12 to asymptomatic mothers (IU-A). Six were exposed only as a neonate. IU-S had abnormal neurologic exams at mean (SD) age 112 (24) days and ASQ scores near or below cut-offs for all domains more frequently than IU-A or neonatally exposed infants. IU-S were more likely to score below any ASQ cutoff compared to IU-A (P = .04); differences were significant for Fine Motor (P = .01) and Personal-Social (P = .02) domains. CONCLUSIONS: Early SARS-CoV-2 exposure may impact neurodevelopment, especially among infants exposed in utero to symptomatic gestational parents. Vaccination and other precautions to reduce early-in-life infection may protect against neurodevelopmental delays. Children with early SARS-CoV-2 exposure should have additional longitudinal screening for neurodevelopmental delays.