In this study evaluating BNT162b2, vaccine effectiveness against hospitalization for Covid-19 in the delta-predominant period among adolescents 12 to 18 years of age was more than 90%; during the ...omicron period, vaccine effectiveness was 40% against hospitalization and 79% against critical illness. Vaccine effectiveness against hospitalization was 68% among children 5 to 11 years of age.
Abstract
Background
Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. Therefore, we aimed to develop a ...highly sensitive metagenomic next-generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children.
Methods
We collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children’s hospitals from 2014–2016. Samples underwent mechanical homogenization, parallel RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the National Center for Biotechnology Information nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort.
Results
We identified a rich cross-domain pulmonary microbiome that contained bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median, 0.61; interquartile range IQR, 0.33–0.72 vs median, 0.96; IQR, 0.94–0.96; P < .001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (P < .001).
Conclusions
An optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease.
Pulmonary infections in immunocompromised children frequently evade detection by current clinical diagnostics. We optimized metagenomic sequencing of pulmonary pathogens in immunocompromised children and show that metagenomic RNA sequencing identified pulmonary pathogens in approximately half of patients with negative clinical diagnostics.
Investigators used a case–control, test-negative design to assess the effectiveness of the BNT162b2 vaccine in adolescents for the prevention of Covid-19–related hospitalization, ICU admission, or ...receipt of life support. Among 445 case patients and 777 controls, of the 180 patients admitted to an ICU, only 2 had been fully vaccinated; all 7 deaths occurred in unvaccinated patients.
IMPORTANCE: Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. OBJECTIVE: To understand ...the range and severity of neurologic involvement among children and adolescents associated with COVID-19. SETTING, DESIGN, AND PARTICIPANTS: Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. EXPOSURES: Severe acute respiratory syndrome coronavirus 2. MAIN OUTCOMES AND MEASURES: Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. RESULTS: Of 1695 patients (909 54% male; median interquartile range age, 9.1 2.4-15.3 years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 22%) compared with those without (113 of 1330 8%), but a similar number were previously healthy (195 53% vs 723 54%) and met criteria for multisystem inflammatory syndrome in children (126 35% vs 490 37%). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 49% vs 72 22%). Of 43 patients who developed COVID-19–related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. CONCLUSIONS AND RELEVANCE: In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.
An analysis of surveillance data on inpatients younger than 21 years of age who had multisystem inflammatory syndrome in children and were hospitalized between March 15 and October 31, 2020, showed ...that initial treatment with IVIG plus glucocorticoids was associated with a lower risk of cardiovascular dysfunction and a lower incidence of adjunctive therapy use than IVIG alone.
In this study, maternal vaccination with an mRNA vaccine during pregnancy was less common among infants hospitalized for Covid-19 than among controls. The effectiveness of maternal vaccination ...against Covid-19 hospitalization of infants was 52% overall and was greater when delta, rather than omicron, was predominant.
Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complication that has disproportionately affected ...racial/ethnic minority children. We conducted a pilot study to investigate risk factors for MIS-C aiming to understand MIS-C disparities.
This case-control study included MIS-C cases and SARS-CoV-2-positive outpatient controls less than 18 years old frequency-matched 4:1 to cases by age group and site. Patients hospitalized with MIS-C were admitted between March 16 and October 2, 2020, across 17 pediatric hospitals. We evaluated race, ethnicity, social vulnerability index (SVI), insurance status, weight-for-age and underlying medical conditions as risk factors using mixed effects multivariable logistic regression.
We compared 241 MIS-C cases with 817 outpatient SARS-CoV-2-positive at-risk controls. Cases and controls had similar sex, age and U.S. census region distribution. MIS-C patients were more frequently previously healthy, non-Hispanic Black, residing in higher SVI areas, and in the 95th percentile or higher for weight-for-age. In the multivariable analysis, the likelihood of MIS-C was higher among non-Hispanic Black children adjusted odds ratio (aOR): 2.07; 95% CI: 1.23-3.48. Additionally, SVI in the 2nd and 3rd tertiles (aOR: 1.88; 95% CI: 1.18-2.97 and aOR: 2.03; 95% CI: 1.19-3.47, respectively) were independent factors along with being previously healthy (aOR: 1.64; 95% CI: 1.18-2.28).
In this study, non-Hispanic Black children were more likely to develop MIS-C after adjustment for sociodemographic factors, underlying medical conditions, and weight-for-age. Investigation of the potential contribution of immunologic, environmental, and other factors is warranted.
Pulmonary infections are common in hematopoietic cell transplant (HCT) patients of all ages and are associated with high levels of morbidity and mortality. Bacterial, viral, fungal, and parasitic ...pathogens are all represented as causes of infection. The lung mounts a complex immune response to infection and this response is significantly affected by the pre-HCT conditioning regimen, graft characteristics, and ongoing immunomodulatory therapy. We review the published literature, including animal models as well as human data, to describe what is known about the pulmonary immune response to infection in HCT recipients. Studies have focused on the pulmonary immune response to Aspergillus fumigatus, gram-positive and gram-negative bacteria, and viruses, and show a range of defects associated with both the innate and adaptive immune responses after HCT. There are still many open areas for research, to delineate novel therapeutic targets for pulmonary infections as well as to explore linkages to non-infectious inflammatory lung conditions.
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