COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19 that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of granulocytic-MDSC (G-MDSC) may in part explain the severity COVID-19, in particular the association with pulmonary complications. Large infiltrates by Arginase 1+ G-MDSC (Arg+G-MDSC), expressing NOX-1 and NOX-2 (important for production of reactive oxygen species) were found in the lungs of patients who died from COVID-19 complications. Increased circulating Arg+G-MDSC depleted arginine, which impaired T cell receptor and endothelial cell function. Transcriptomic signatures of G-MDSC from patients with different stages of COVID-19, revealed that asymptomatic patients had increased expression of pathways and genes associated with type I interferon (IFN), while patients with severe COVID-19 had increased expression of genes associated with arginase production, and granulocyte degranulation and function. These results suggest that asymptomatic patients develop a protective type I IFN response, while patients with severe COVID-19 have an increased inflammatory response that depletes arginine, impairs T cell and endothelial cell function, and causes extensive pulmonary damage. Therefore, inhibition of arginase-1 and/or replenishment of arginine may be important in preventing/treating severe COVID-19.

OBJECTIVES: Targeted parental education reduces acute visits for pediatric asthma. Whether the use of education sources readily available to parents relates to nonadherence to asthma treatments is uncertain. This study describes asthma education sources and assesses for a relationship to risks for nonadherence. METHODS: Caregivers of children with asthma completed a cross-sectional survey at 2 sites: a pediatric emergency department (ED) and an asthma clinic (AC). Measured items included the use of 7 education sources (primary care, ED, AC, friends/family, TV, internet, and printed materials), scores of child asthma morbidity, parental asthma knowledge, and risks for nonadherence, the primary outcome. Recruitment site, preferred language (English/Spanish), and demographics were recorded. Descriptive statistics, bivariate analyses, and multivariate regressions were performed. RESULTS: A total of 260 participants, 158 from ED and 102 from AC, used a variety of education sources. They reported 4.1 (2.0) of 13 risk factors for nonadherence, with more risks in ED parents than AC parents (4.8 vs 3.9, P < 0.001). The ED parents worried more about medications and had worse access to primary care. The regression did not show a significant relationship between education sources and risks for nonadherence, but ED recruitment, Spanish language, and worse morbidity contributed to higher risks. CONCLUSIONS: The use of more asthma education sources was not associated with reduced risks for nonadherence. Of the education sources, a primary care provider may benefit ED parents, who also need refills and education about medications. Spanish-speaking parents report more risks for nonadherence, warranting further study of Spanish-language asthma education.

BACKGROUND: COVID-19 testing policies for symptomatic children attending U.S. schools or daycare vary, and whether isolated symptoms should prompt testing is unclear. We evaluated children presenting for SARS-CoV-2 testing to determine if the likelihood of having a positive SARS-CoV-2 test differed between participants with one versus ≥2 symptoms, and to examine the predictive capability of isolated symptoms. METHODS: Participants ≤ 18 years presenting for clinical SARS-CoV-2 molecular testing in six sites in urban/suburban/rural Georgia (July-October, 2021; delta variant predominant) were queried about individual symptoms. Participants were classified into three groups: asymptomatic, one symptom only, or ≥2 symptoms. SARS-CoV-2 test results and clinical characteristics of the three groups were compared. Sensitivity, specificity, and positive/negative predictive values (PPV/NPV) for isolated symptoms were calculated by fitting a saturated Poisson model. RESULTS: Of 602 participants, 21.8% tested positive and 48.7% had a known or suspected close contact. Children reporting one symptom (n=82; OR=6.00, 95% CI: 2.70-13.33) and children reporting ≥2 symptoms (n=365; OR=5.25: 2.66-10.38) were significantly more likely to have a positive COVID-19 test than asymptomatic children (n=155), but they were not significantly different from each other (OR=0.88: 0.52-1.49). Sensitivity/PPV were highest for isolated fever (33%/57%), cough (25%/32%), and sore throat (21%/45%); headache had low sensitivity (8%) but higher PPV (33%). Sensitivity/PPV of isolated congestion/rhinorrhea were 8%/9%. CONCLUSIONS: With high delta variant prevalence, children with isolated symptoms were as likely as those with multiple symptoms to test positive for COVID-19. Isolated fever, cough, sore throat, or headache, but not congestion/rhinorrhea, offered highest predictive value.

Importance: Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized. Objective: To estimate the proportion of children with severe outcomes within 14 days of testing positive for SARS-CoV-2 in an emergency department (ED). Design, Setting, and Participants: This prospective cohort study with 14-day follow-up enrolled participants between March 2020 and June 2021. Participants were youths aged younger than 18 years who were tested for SARS-CoV-2 infection at one of 41 EDs across 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States. Statistical analysis was performed from September to October 2021. Exposures: Acute SARS-CoV-2 infection was determined by nucleic acid (eg, polymerase chain reaction) testing. Main Outcomes and Measures: Severe outcomes, a composite measure defined as intensive interventions during hospitalization (eg, inotropic support, positive pressure ventilation), diagnoses indicating severe organ impairment, or death. Results: Among 3222 enrolled youths who tested positive for SARS-CoV-2 infection, 3221 (>99.9%) had index visit outcome data available, 2007 (62.3%) were from the United States, 1694 (52.6%) were male, and 484 (15.0%) had a self-reported chronic illness; the median (IQR) age was 3 (0-10) years. After 14 days of follow-up, 735 children (22.8% [95% CI, 21.4%-24.3%]) were hospitalized, 107 (3.3% [95% CI, 2.7%-4.0%]) had severe outcomes, and 4 children (0.12% [95% CI, 0.03%-0.32%]) died. Characteristics associated with severe outcomes included being aged 5 to 18 years (age 5 to <10 years vs <1 year: odds ratio [OR], 1.60 [95% CI, 1.09-2.34]; age 10 to <18 years vs <1 year: OR, 2.39 [95% CI 1.38-4.14]), having a self-reported chronic illness (OR, 2.34 [95% CI, 1.59-3.44]), prior episode of pneumonia (OR, 3.15 [95% CI, 1.83-5.42]), symptoms starting 4 to 7 days prior to seeking ED care (vs starting 0-3 days before seeking care: OR, 2.22 [95% CI, 1.29-3.82]), and country (eg, Canada vs US: OR, 0.11 [95% CI, 0.05-0.23]; Costa Rica vs US: OR, 1.76 [95% CI, 1.05-2.96]; Spain vs US: OR, 0.51 [95% CI, 0.27-0.98]). Among a subgroup of 2510 participants discharged home from the ED after initial testing and who had complete follow-up, 50 (2.0%; 95% CI, 1.5%-2.6%) were eventually hospitalized and 12 (0.5%; 95% CI, 0.3%-0.8%) had severe outcomes. Compared with hospitalized SARS-CoV-2-negative youths, the risk of severe outcomes was higher among hospitalized SARS-CoV-2-positive youths (risk difference, 3.9%; 95% CI, 1.1%-6.9%). Conclusions and Relevance: In this study, approximately 3% of SARS-CoV-2-positive youths tested in EDs experienced severe outcomes within 2 weeks of their ED visit. Among children discharged home from the ED, the risk was much lower. Risk factors such as age, underlying chronic illness, and symptom duration may be useful to consider when making clinical care decisions.

Background: Sickle cell disease (SCD) is an inherited, autosomal recessive blood disorder, among the most prevalent genetic diseases, globally. While the genetic and hemolytic dynamics of SCD have been well-characterized, the etiology of SCD-related pathophysiological processes is unclear. Although limited, observational evidence suggests that environmental factors, including urban air pollution, may play a role. Objectives: We assessed whether daily ambient air pollution concentrations are associated with corresponding emergency department (ED) visit counts for acute SCD exacerbations in Atlanta, Georgia, during a 9-year (2005–2013) period. We also examined heterogeneity in response by age and sex. Methods: ED visit data were from 41 hospitals in the 20-county Atlanta, GA area. Associations between daily air pollution levels for 8 urban air pollutants and counts of SCD related ED visits were estimated using Poisson generalized linear models. Results: We observed positive associations between pollutants generally indicative of traffic emissions and corresponding SCD ED visits [e.g., rate ratio of 1.022 (95% CI: 1.002, 1.043) per interquartile range increase in carbon monoxide]. Age stratified analyses indicated stronger associations with traffic pollutants among children (0–18 years), as compared to older age strata. Associations involving other pollutants, including ozone and particulate matter and for models of individuals >18 years old, were consistent a null hypothesis of no association. Discussion: This analysis represents the first North American study to examine acute risk among individuals with SCD to urban air pollution and provide evidence of urban air pollution, especially from traffic sources, as a trigger for acute exacerbations. These findings are consistent with a hypothesis that biological pathways, including several centrally associated with oxidative stress, may contribute towards enhanced susceptibility in individuals with SCD.

BACKGROUND: Fever is a common symptom in children presenting to the Emergency Department (ED). We aimed to describe the epidemiology of systemic viral infections and their predictive values for excluding serious bacterial infections (SBIs), including bacteremia, meningitis and urinary tract infections (UTIs) in children presenting to the ED with suspected systemic infections. METHODS: We enrolled children who presented to the ED with suspected systemic infections who had blood cultures obtained at seven healthcare facilities. Whole blood specimens were analyzed by an experimental multiplexed PCR test for 7 viruses. Demographic and laboratory results were abstracted. RESULTS: Of the 1114 subjects enrolled, 245 viruses were detected in 224 (20.1%) subjects. Bacteremia, meningitis and UTI frequency in viral bloodstream-positive patients was 1.3, 0 and 10.1% compared to 2.9, 1.3 and 9.7% in viral bloodstream-negative patients respectively. Although viral bloodstream detections had a high negative predictive value for bacteremia or meningitis (NPV = 98.7%), the frequency of UTIs among these subjects remained appreciable (9/89, 10.1%) (NPV = 89.9%). Screening urinalyses were positive for leukocyte esterase in 8/9 (88.9%) of these subjects, improving the ability to distinguish UTI. CONCLUSIONS: Viral bloodstream detections were common in children presenting to the ED with suspected systemic infections. Although overall frequencies of SBIs among subjects with and without viral bloodstream detections did not differ significantly, combining whole blood viral testing with urinalysis provided high NPV for excluding SBI.

We thank authors Greenky et al. for their thoughtful comments regarding our article “Prevalence of SARS-CoV-2 antibodies in pediatric healthcare workers (pHCWs)” (Morris et al., 2021). Our study suggested that pHCWs, especially those in the pediatric emergency department, were at risk of contracting COVID-19 early in the pandemic.

Objectives: To determine SARS-CoV-2-antibody prevalence in pediatric healthcare workers (pHCWs). Design: Baseline prevalence of anti-SARS-CoV-2-IgG was assessed in a prospective cohort study from a large pediatric healthcare facility. Prior SARS-CoV-2 testing history, potential risk factors and anxiety level about COVID-19 were determined. Prevalence difference between emergency department (ED)-based and non-ED-pHCWs was modeled controlling for those covariates. Chi-square test-for-trend was used to examine prevalence by month of enrollment. Results: Most of 642 pHCWs enrolled were 31-40years, female and had no comorbidities. Half had children in their home, 49% had traveled, 42% reported an illness since January, 31% had a known COVID-19 exposure, and 8% had SARS-CoV-2 PCR testing. High COVID-19 pandemic anxiety was reported by 71%. Anti-SARS-CoV-2-IgG prevalence was 4.1%; 8.4% among ED versus 2.0% among non-ED pHCWs (p < 0.001). ED-work location and known COVID-19 exposure were independent risk factors. 31% of antibody-positive pHCWs reported no symptoms. Prevalence significantly (p < 0.001) increased from 3.0% in April–June to 12.7% in July–August. Conclusions: Anti-SARS-CoV-2-IgG prevalence was low in pHCWs but increased rapidly over time. Both working in the ED and exposure to a COVID-19-positive contact were associated with antibody-seropositivity. Ongoing universal PPE utilization is essential. These data may guide vaccination policies to protect front-line workers.

Background: Nitrous oxide (N O) is an inhalational medication that has anxiolytic, amnestic, potent venodilatory and mild-to-moderate analgesic properties commonly used in the emergency department (ED) setting. N2O has a rapid onset of action (<5 minutes) and recovery (<5 minutes) and can be quickly titrated to effect without the need for IV access. It has few side effects, does not require renal or hepatic metabolism for excretion and has no reports of allergic reaction. Priapism is a serious complication of sickle cell disease (SCD) affecting approximately 35% of males, with an adverse impact on quality of life. Treatment options are limited and not evidence based, including hydration, alkalization, analgesia, oxygenation to prevent further sickling, and exchange transfusion. Patients who do not respond within 4 hours often require a painful invasive procedure that includes aspiration of blood from the corpus cavernosum and phenylephrine injections. Case reports have described a therapeutic benefit from oral pseudoephedrine, sildenafil, and intravenous (IV) arginine, however controlled clinical trials are lacking. Although a 50:50 nitrous oxide/oxygen mix is commonly used in France to enhance analgesia in patients with SCD and vasoocclusive pain events (VOE) not sufficiently responding to IV morphine, there are no reports of its use to treat priapism. We describe the effects of N2O for the treatment of acute priapism associated with SCD in a pediatric ED. Methods: This is a case series of two adolescent boys with Hb-SS who on 3 separate occasions presented to the ED with acute priapism that failed oral therapy (pseudoephedrine and opioids). N2O gas was utilized to help facilitate IV catheter placement. Results: In each presentation (at ages 8 and 10 years for patient 1; age 15 years for patient 2), the patient experienced complete resolution of the priapism within 4-15 min of receiving N2O (max 60%). The patients were discharged from the ED following each presentation and had no recurrence during the subsequent week. Conclusions: Priapism is a challenging complication of SCD associated with long-term morbidity and a paucity of treatment options. Opioids are commonly used. Given the risks and inconsistent results of current recommended therapy, N2O may represent a potential opioid-sparing treatment option for priapism presenting to the ED that warrants further investigation. Although anecdotal, N2O inhalation is an intervention to consider during a time when a treating ED physician may have few alternatives.