Community-Onset Bacterial Coinfection in Children Critically Ill With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Background: Community-onset bacterial coinfection in adults hospitalized with coronavirus disease 2019 (COVID-19) is reportedly uncommon, though empiric antibiotic use has been high. However, data regarding empiric antibiotic use and bacterial coinfection in children with critical illness from COVID-19 are scarce. Methods: We evaluated children and adolescents aged <19 years admitted to a pediatric intensive care or high-acuity unit for COVID-19 between March and December 2020. Based on qualifying microbiology results from the first 3 days of admission, we adjudicated whether patients had community-onset bacterial coinfection. We compared demographic and clinical characteristics of those who did and did not (1) receive antibiotics and (2) have bacterial coinfection early in admission. Using Poisson regression models, we assessed factors associated with these outcomes. Results: Of the 532 patients, 63.3% received empiric antibiotics, but only 7.1% had bacterial coinfection, and only 3.0% had respiratory bacterial coinfection. In multivariable analyses, empiric antibiotics were more likely to be prescribed for immunocompromised patients (adjusted relative risk [aRR], 1.34 [95% confidence interval {CI}, 1.01-1.79]), those requiring any respiratory support except mechanical ventilation (aRR, 1.41 [95% CI, 1.05-1.90]), or those requiring invasive mechanical ventilation (aRR, 1.83 [95% CI, 1.36-2.47]) (compared with no respiratory support). The presence of a pulmonary comorbidity other than asthma (aRR, 2.31 [95% CI, 1.15-4.62]) was associated with bacterial coinfection. Conclusions: Community-onset bacterial coinfection in children with critical COVID-19 is infrequent, but empiric antibiotics are commonly prescribed. These findings inform antimicrobial use and support rapid de-escalation when evaluation shows coinfection is unlikely.

Life-Threatening Complications of Influenza versus COVID-19 in U.S. Children.

BACKGROUND: Clinical differences between critical illness from influenza infection versus coronavirus disease 2019 (COVID-19) have not been well characterized in pediatric patients. METHODS: We compared U.S. children (8 months to 17 years) admitted to the intensive care or high acuity unit with influenza (17 hospitals, 12/19/2019-3/9/2020) or COVID-19 (52 hospitals, 3/15/2020-12/31/2020). We compared demographics, underlying conditions, clinical presentation, severity, and outcomes. Using mixed-effects models, we assessed the odds of death or requiring life-support for influenza versus COVID-19 after adjustment for age, sex, race and Hispanic origin, and underlying conditions including obesity. RESULTS: Children with influenza (n = 179) were younger than those with COVID-19 (n = 381; median 5.2 vs. 13.8 years), less likely to be non-Hispanic black (14.5% vs. 27.6%) or Hispanic (24.0% vs. 36.2%), and less likely to have ≥1 underlying condition (66.4% vs. 78.5%) or be obese (21.4% vs. 42.2%). They were similarly likely to require invasive mechanical ventilation (both 30.2%), vasopressor support (19.6% and 19.9%), or extracorporeal membrane oxygenation (2.2% and 2.9%). Four children with influenza (2.2%) and 11 children with COVID-19 (2.9%) died. The odds of death or requiring life-support in children with influenza vs. COVID-19 were similar (adjusted odds ratio, 1.30 [95% CI: 0.78-2.15; P = 0.32]). Median duration of hospital stay was shorter for influenza than COVID-19 (5 versus 7 days). CONCLUSIONS: Despite differences in demographics and clinical characteristics of children with influenza or COVID-19, the frequency of life-threatening complications was similar. Our findings highlight the importance of implementing prevention measures to reduce transmission and disease severity of influenza and COVID-19.

Impact of the COVID-19 Pandemic on Diagnostic Frequency of Febrile Seizures: An Electronic Health Record Database Observational Study.

Background and Purpose: Febrile seizures are common in children and are associated with viral infection. Mitigation strategies implemented during the coronavirus disease 2019 (COVID-19) pandemic have slowed the spread of all viral illnesses potentially impacting febrile seizure frequency. The objective of this study is to assess the impact of COVID-19 mitigation strategies on the diagnostic frequency of febrile seizures. Methods: This was a retrospective observational cohort study utilizing TriNetX ® electronic health record (EHR) data. We included subjects aged 0 to 5 years of age reported to have a febrile seizure diagnosis. After the query, the study population was divided into 2 groups [pre-COVID-19 (April 1st, 2019 until March 31st, 2020) and COVID-19 (April 1st, 2020 until March 31st, 2021). We analyzed the following data: age, sex, race, diagnostic, medication, and procedural codes. Results: During the pre-COVID time frame, emergency or inpatient encounters made up 688,704 subjects aged 0 to 5 years in the TriNetx database, while in the COVID-19 pandemic time frame, it made up of 368 627 subjects. Febrile seizure diagnosis frequency decreased by 36.1% [2696 during COVID-19 vs 7462 during the pre-COVID-19] and a higher proportion of status epilepticus was coded [72 (2.7%) vs 120 (1.6%)] (P < .001) during the COVID-19 pandemic. Hospitalization, lumbar puncture, critical care services, mechanical ventilation procedural codes were similar between the 2 cohorts. Antimicrobial use was higher in the pre-COVID-19 pandemic group [424 (15.7%) vs 1603 (21.5%)] (P < .001). Conclusions: Less children were diagnosed with febrile seizures during the COVID-19 pandemic, but a higher proportion were coded to have the complex subtype. The medical interventions required with the exception of antimicrobial use was similar. Further study is needed regarding mitigation strategies and its impact on pediatric diseases associated with viruses.

Pediatric Acute Lung Injury and Sepsis Investigators (PALISI): Evolution of an Investigator-Initiated Research Network.

The Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network originated over 20 years ago to foster research to optimize the care of critically ill infants and children. Over this period, PALISI has seen two major evolutions: formalization of our network infrastructure and a broadening of our clinical research focus. First, the network is unique in that its activities and meetings are funded by subscriptions from members who now comprise a multidisciplinary group of investigators from over 90 PICUs all over the United States (US) and Canada, with collaborations across the globe. In 2020, the network converted into a standalone, nonprofit organizational structure (501c3), making the PALISI Network formally independent of academic and clinical institutions or professional societies. Such an approach allows us to invest in infrastructure and future initiatives with broader opportunities for fund raising. Second, our research investigations have expanded beyond the original focus on sepsis and acute lung injury, to incorporate the whole field of pediatric critical care, for example, efficient liberation from mechanical ventilator support, prudent use of blood products, improved safety of intubation practices, optimal sedation practices and glucose control, and pandemic research on influenza and COVID-19. Our network approach in each field follows, where necessary, the full spectrum of clinical and translational research, including: immunobiology studies for understanding basic pathologic mechanisms; surveys to explore contemporary clinical practice; consensus conferences to establish agreement about literature evidence; observational prevalence and incidence studies to measure scale of a clinical issue or question; case control studies as preliminary best evidence for design of definitive prospective studies; and, randomized controlled trials for informing clinical care. As a research network, PALISI and its related subgroups have published over 350 peer-reviewed publications from 2002 through September 2022.

Impact of the COVID-19 Pandemic on Diagnostic Frequency of Febrile Seizures: An Electronic Health Record Database Observational Study

Background and Purpose Febrile seizures are common in children and are associated with viral infection. Mitigation strategies implemented during the coronavirus disease 2019 (COVID-19) pandemic have slowed the spread of all viral illnesses potentially impacting febrile seizure frequency. The objective of this study is to assess the impact of COVID-19 mitigation strategies on the diagnostic frequency of febrile seizures. Methods This was a retrospective observational cohort study utilizing TriNetX ® electronic health record (EHR) data. We included subjects aged 0 to 5 years of age reported to have a febrile seizure diagnosis. After the query, the study population was divided into 2 groups [pre-COVID-19 (April 1st, 2019 until March 31st, 2020) and COVID-19 (April 1st, 2020 until March 31st, 2021). We analyzed the following data: age, sex, race, diagnostic, medication, and procedural codes. Results During the pre-COVID time frame, emergency or inpatient encounters made up 688,704 subjects aged 0 to 5 years in the TriNetx database, while in the COVID-19 pandemic time frame, it made up of 368 627 subjects. Febrile seizure diagnosis frequency decreased by 36.1% [2696 during COVID-19 vs 7462 during the pre-COVID-19] and a higher proportion of status epilepticus was coded [72 (2.7%) vs 120 (1.6%)] (P < .001) during the COVID-19 pandemic. Hospitalization, lumbar puncture, critical care services, mechanical ventilation procedural codes were similar between the 2 cohorts. Antimicrobial use was higher in the pre-COVID-19 pandemic group [424 (15.7%) vs 1603 (21.5%)] (P < .001). Conclusions Less children were diagnosed with febrile seizures during the COVID-19 pandemic, but a higher proportion were coded to have the complex subtype. The medical interventions required with the exception of antimicrobial use was similar. Further study is needed regarding mitigation strategies and its impact on pediatric diseases associated with viruses.

Effect of Coronavirus Disease 2019 (Covid-19), a Nationwide Mass Casualty Disaster on Intensive Care Units: Clinical Outcomes and Associated Cost-of-Care.

OBJECTIVE: The COVID-19 pandemic resulted in millions of deaths worldwide and is considered a significant mass-casualty disaster (MCD). The surge of patients and scarcity of resources negatively impacted hospitals, patients and medical practice. We hypothesized ICUs during this MCD had a higher acuity of illness, and subsequently had increased lengths of stay (LOS), complication rates, death rates and costs of care. The purpose of this study was to investigate those outcomes. METHODS: This was a multicenter, retrospective study that compared intensive care admissions in 2020 to those in 2019 to evaluate patient outcomes and cost of care. Data were obtained from the Vizient Clinical Data Base/Resource Manager (Vizient Inc., Irvine, Texas, USA). RESULTS: Data included the number of ICU admissions, patient outcomes, case mix index and summary of cost reports. Quality outcomes were also collected, and a total of 1304981 patients from 333 hospitals were included. For all medical centers, there was a significant increase in LOS index, ICU LOS, complication rate, case mix index, total cost, and direct cost index. CONCLUSION: The MCD caused by COVID-19 was associated with increased adverse outcomes and cost-of-care for ICU patients.

Evaluation of reported medical services provided to pediatric viral bronchiolitis diagnoses during the COVID-19 pandemic.

BACKGROUND: Mitigation strategies were implemented during the coronavirus disease 2019 (COVID-19) pandemic that slowed the spread of this virus and other respiratory viruses. The objective of this study is to assess the impact of COVID-19 mitigation strategies on the medical services that children less than 1 year of age with acute bronchiolitis required (emergency department services, hospitalization, critical care services, and mechanical ventilation). METHODS: This was a retrospective observational cohort study utilizing TriNetX ® electronic health record (EHR) data. We included subjects less than 1 year of age with a diagnosis of acute bronchiolitis. After the query, the study population was divided into two groups [pre-COVID-19 (March 1st, 2019 until February 29th, 2020) and COVID-19 (March 1st, 2020 until February 1th, 2021)]. We analyzed the following data: age, sex, race, diagnostic codes, common terminology procedures (CPT), and antimicrobials administered. RESULTS: A total of 5063 subjects (n,%) were included [4378 (86.5%) pre-COVID-19 and 685 (13.5%) during the COVID-19 pandemic]. More subjects were diagnosed with acute bronchiolitis in the pre-COVID time frame (4378, 1.8% of all hospitalizations) when compared to the COVID-19 pandemic time frame (685, 0.5%). When diagnosed with acute bronchiolitis, the frequency of emergency department services, critical care services, hospitalization, and mechanical ventilationwere similar between the two cohorts. CONCLUSIONS: During the COVID-19 pandemic, less infants were diagnosed with acute bronchiolitis but the frequency of emergency department services, hospitalization, and mechanical ventilation, reportedly required was similar. Longer-term studies are needed to evaluate the benefits of COVID-19 mitigation strategies on common viruses that require critical care.

Evaluation of Febrile Seizure Diagnoses Associated With COVID-19.

BACKGROUND/OBJECTIVES: Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be associated with febrile seizures, but the overall frequency and outcomes are unknown. The objectives of this study are to (1) determine the frequency of pediatric subjects diagnosed with febrile seizures and COVID-19, (2) evaluate patient characteristics, and (3) describe the treatments (medications and need for invasive mechanical ventilation) applied. METHODS: This was a retrospective study utilizing TriNetX electronic health record data. We included subjects ranging from 0 to 5 years of age with a diagnosis of febrile seizures (R56.00, R56.01) and COVID-19 (U07.1). We extracted the following data: age, race, ethnicity, diagnostic codes, medications, laboratory results, and procedures. RESULTS: During this study period, 8854 pediatric subjects aged 0-5 years were diagnosed with COVID-19 among 34 health care organizations and 44 (0.5%) were also diagnosed with febrile seizures (simple, 30 [68.2%]; complex, 14 [31.8%]). The median age was 1.5 years (1, 2), there were no reported epilepsy diagnoses, and a proportion required hospitalization (11; 25.0%) and critical care services (4; 9.1%). CONCLUSIONS: COVID-19 infections in children can be associated with febrile seizures. In our study, 0.5% of COVID-19 subjects were diagnosed with febrile seizures and approximately 9% of subjects were reported to require critical care services. Febrile seizures, although serious, are not a commonly diagnosed neurologic manifestation of COVID-19.

A Description of COVID-19-Directed Therapy in Children Admitted to US Intensive Care Units 2020.

BACKGROUND: It is unclear how acute coronavirus disease 2019 (COVID-19)-directed therapies are used in children with life-threatening COVID-19 in US hospitals. We described characteristics of children hospitalized in the intensive care unit or step-down unit (ICU/SDU) who received COVID-19-directed therapies and the specific therapies administered. METHODS: Between March 15, 2020 and December 27, 2020, children <18 years of age in the ICU/SDU with acute COVID-19 at 48 pediatric hospitals in the United States were identified. Demographics, laboratory values, and clinical course were compared in children who did and did not receive COVID-19-directed therapies. Trends in COVID-19-directed therapies over time were evaluated. RESULTS: Of 424 children in the ICU/SDU, 235 (55%) received COVID-19-directed therapies. Children who received COVID-19-directed therapies were older than those who did not receive COVID-19-directed therapies (13.3 [5.6-16.2] vs 9.8 [0.65-15.9] years), more had underlying medical conditions (188 [80%] vs 104 [55%]; difference = 25% [95% CI: 16% to 34%]), more received respiratory support (206 [88%] vs 71 [38%]; difference = 50% [95% CI: 34% to 56%]), and more died (8 [3.4%] vs 0). Of the 235 children receiving COVID-19-directed therapies, 172 (73%) received systemic steroids and 150 (64%) received remdesivir, with rising remdesivir use over the study period (14% in March/April to 57% November/December). CONCLUSION: Despite the lack of pediatric data evaluating treatments for COVID-19 in critically ill children, more than half of children requiring intensive or high acuity care received COVID-19-directed therapies.

COVID-19-Associated Pulmonary Embolism in Pediatric Patients.

BACKGROUND AND OBJECTIVES: Coronavirus disease 2019 (COVID-19) is associated with pulmonary embolism in adults, but the clinical circumstances surrounding its presence are unknown in children. The objectives of this study are to determine the prevalence of pulmonary embolism in pediatric subjects with COVID-19, evaluate patient characteristics, and describe treatments applied. METHODS: We performed a retrospective cohort study using TriNetX electronic health record data of subjects aged <18 years who were diagnosed with COVID-19 infection (International Classification of Diseases, 10th Revision, code U07.1). Pulmonary embolism was identified by using International Classification of Diseases, 10th Revision, code I26. We additionally collected data on age, sex, race, ethnicity, all diagnostic codes, medications, procedures, laboratory results, comorbidities, and outcomes. RESULTS: During the study period, 24 723 pediatric subjects were reported to have a COVID-19 infection diagnosis among 41 health care organizations, of which 693 (2.8%) were hospitalized. Eight subjects (0.03% overall and 1.2% of hospitalized patients) were diagnosed with pulmonary embolism. The median age (25th to 75th percentile) of patients diagnosed with pulmonary embolism was 16.5 years, and median (25th to 75th percentile) BMI was 22.1 (19.6-47.9). Three (37.5%) received critical care services, and 1 (12.5%) underwent mechanical ventilation. Five (62.5%) subjects had potentially significant risk factors (obesity, malignancy, recent surgery, and oral contraceptive use). All patients received anticoagulation, but none underwent thrombolysis. There were no reported deaths. CONCLUSIONS: Although pulmonary embolism is diagnosed less commonly in children than in adults, its occurrence appears to be more frequent in children hospitalized with COVID-19, as compared with previous reports in hospitalized children in general. All patients survived, with only 1 requiring mechanical ventilation.

Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome.

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.