Clinical Features of Critical Coronavirus Disease 2019 in Children

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Objectives: We sought to describe the presentation, course, and outcomes of hospitalized pediatric coronavirus disease 2019 patients, with detailed description of those requiring mechanical ventilation, and comparisons between critically ill and noncritical hospitalized pediatric patients. Design: Observational cohort study. Setting: Riley Hospital for Children at Indiana University Health in Indianapolis in the early weeks of the coronavirus disease 2019 pandemic. Patients: All hospitalized pediatric patients with confirmed coronavirus disease 2019 as of May 4, 2020, were included. Interventions: Patients received therapies including hydroxychloroquine, remdesivir, tocilizumab, and convalescent serum and were managed according to an institutional algorithm based on evidence available at the time of presentation. Measurements and Main Results: Of 407 children tested for severe acute respiratory syndrome-coronavirus 2 at our hospital, 24 were positive, and 19 required hospitalization. Seven (36.8%) were critically ill in ICU, and four (21%) required mechanical ventilation. Hospitalized children were predominantly male (14, 74%) and African-American or Hispanic (14, 74%), with a bimodal distribution of ages among young children less than or equal to 2 years old (8, 42%) and older adolescents ages 15–18 (6, 32%). Five of seven (71.4%) of critically ill patients were African-American (n = 3) or Hispanic (n = 2). Critical illness was associated with older age (p = 0.017), longer duration of symptoms (p = 0.036), and lower oxygen saturation on presentation (p = 0.016); with more thrombocytopenia (p = 0.015); higher C-reactive protein (p = 0.031); and lower WBC count (p = 0.039). Duration of mechanical ventilation averaged 14.1 days. One patient died. Conclusions: Severe, protracted coronavirus disease 2019 is seen in pediatric patients, including those without significant comorbidities. We observed a greater proportion of hospitalized children requiring mechanical ventilation than has been reported to date. Older children, African-American or Hispanic children, and males may be at risk for severe coronavirus disease 2019 requiring hospitalization. Hypoxia, thrombocytopenia, and elevated C-reactive protein may be useful markers of critical illness. Data regarding optimal management and therapies for pediatric coronavirus disease 2019 are urgently needed.This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health (grant numbers K23 HD095778, T32 HD069047); and by the National Institute of Allergy and Infectious at the National Institutes of Health Diseases (grant number T32 AI07637). Drs. Bhumbra, Malin, Khaitan, John, Rowan, and Enane disclosed off-label use of remdesivir, convalescent plasma, hydroxychloroquine, and tocilizumab. Drs. Kirkpatrick and Enane are supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health (grant numbers K23 HD095778, T32 HD069047). Dr. Bhumbra is supported by the National Institute of Allergy and Infectious at the National Institutes of Health Diseases (grant number T32 AI07637)

Effectiveness of Maternal mRNA COVID-19 Vaccination During Pregnancy Against COVID-19–Associated Hospitalizations in Infants Aged <6 Months During SARS-CoV-2 Omicron Predominance — 20 States, March 9, 2022–May 31, 2023

Infants aged <6 months are not eligible for COVID-19 vaccination. Vaccination during pregnancy has been associated with protection against infant COVID-19–related hospitalization. The Overcoming COVID-19 Network conducted a case-control study during March 9, 2022–May 31, 2023, to evaluate the effectiveness of maternal receipt of a COVID-19 vaccine dose (vaccine effectiveness [VE]) during pregnancy against COVID-19–related hospitalization in infants aged <6 months and a subset of infants aged <3 months. VE was calculated as (1 – adjusted odds ratio) x 100% among all infants aged <6 months and <3 months. Case-patients (infants hospitalized for COVID-19 outside of birth hospitalization and who had a positive SARS-CoV-2 test result) and control patients (infants hospitalized for COVID-19–like illness with a negative SARS-CoV-2 test result) were compared. Odds ratios were determined using multivariable logistic regression, comparing the odds of receipt of a maternal COVID-19 vaccine dose (completion of a 2-dose vaccination series or a third or higher dose) during pregnancy with maternal nonvaccination between case- and control patients. VE of maternal vaccination during pregnancy against COVID-19–related hospitalization was 35% (95% CI = 15%–51%) among infants aged <6 months and 54% (95% CI = 32%–68%) among infants aged <3 months. Intensive care unit admissions occurred in 23% of all case-patients, and invasive mechanical ventilation was more common among infants of unvaccinated (9%) compared with vaccinated mothers (1%) (p = 0.02). Maternal vaccination during pregnancy provides some protection against COVID-19–related hospitalizations among infants, particularly those aged <3 months. Expectant mothers should remain current with COVID-19 vaccination to protect themselves and their infants from hospitalization and severe outcomes associated with COVID-19

Staphylococcus lugdunensis: novel organism causing cochlear implant infection

A majority of cochlear implant infections are caused by <em>Staphylococcus aureus</em> or <em>Pseudomonas aeruginosa</em>. Reported here is a pediatric patient with a cochlear implant infection caused by methicillin-resistant <em>Staphylococcus lugdunensis</em>, a coagulase-negative <em>Staphylococcus</em> that has only recently been determined to be clinically relevant (1988). Unlike other coagulase-negative Staphylococcus, it is more aggressive, carrying a greater potential for tissue destruction. In pediatrics, the organism is uncommon, poorly described, and generally pan-susceptible. Described herein is the presentation and management of this unusual organism in a pediatric setting

Management of Acute Osteomyelitis: A Ten-Year Experience

Osteomyelitis is an infection of the bone; proper management requires prolonged antibiotic treatment. Controversy exists as to when a patient should transition from intravenous to oral antibiotics. However, due to the high bioavailability of some oral antibiotics, optimal time to transition from high to low bioavailability antibiotics is a more valid consideration. Additionally, there are questions surrounding the efficacy of certain antibiotics, specifically trimethoprim-sulfamethoxazole (TMP-SMX), in treating osteomyelitis. After obtaining Institutional Review Board approval from both universities, a retrospective chart review was conducted, utilizing an author-created severity scale, on all patients seen by Pediatric Infectious Diseases at the Universities of Michigan and Toledo with an acute osteomyelitis diagnosis from 2002-2012. There were 133 patients, 106 treated successfully. Success was defined in this study specifically as treatment of &lt;14 weeks without recurrence within 30 days of stopping antibiotics or permanent site disability. Seventeen patients were treated with TMP-SMX at comparable cure rates. Patients with pre-existing bone defects (noted in radiological reports), initial erythrocyte sedimentation rate (ESR) ≥70, hematogenous osteomyelitis with soft tissue extension, and skull osteomyelitis were associated with increased failure rate. Switch to low bioavailability antibiotics occurred, on average, at 3.5 weeks; however, switching before then was not associated with decreased cure rate. As prevalence of methicillin-resistant Staphylococcus aureus (MRSA), especially clindamycin- resistant MRSA, increases, TMP-SMX appears to be an acceptable antibiotic. There does not appear to be a minimum length of high bioavailability treatment required for cure. Prior bone defect, extensive infection, ESR≥70, or skull osteomyelitis may be indications for more aggressive management

Identifying and Validating Pediatric Hospitalizations for MIS-C Through Administrative Data

BACKGROUND: Individual children\u27s hospitals care for a small number of patients with multisystem inflammatory syndrome in children (MIS-C). Administrative databases offer an opportunity to conduct generalizable research; however, identifying patients with MIS-C is challenging. METHODS: We developed and validated algorithms to identify MIS-C hospitalizations in administrative databases. We developed 10 approaches using diagnostic codes and medication billing data and applied them to the Pediatric Health Information System from January 2020 to August 2021. We reviewed medical records at 7 geographically diverse hospitals to compare potential cases of MIS-C identified by algorithms to each participating hospital\u27s list of patients with MIS-C (used for public health reporting). RESULTS: The sites had 245 hospitalizations for MIS-C in 2020 and 358 additional MIS-C hospitalizations through August 2021. One algorithm for the identification of cases in 2020 had a sensitivity of 82%, a low false positive rate of 22%, and a positive predictive value (PPV) of 78%. For hospitalizations in 2021, the sensitivity of the MIS-C diagnosis code was 98% with 84% PPV. CONCLUSION: We developed high-sensitivity algorithms to use for epidemiologic research and high-PPV algorithms for comparative effectiveness research. Accurate algorithms to identify MIS-C hospitalizations can facilitate important research for understanding this novel entity as it evolves during new waves

Effectiveness of BNT162b2 (Pfizer-BioNTech) mRNA Vaccination Against Multisystem Inflammatory Syndrome in Children Among Persons Aged 12-18 Years - United States, July-December 2021.

Multisystem inflammatory syndrome in children (MIS-C) is a severe postinfectious hyperinflammatory condition, which generally occurs 2-6 weeks after a typically mild or asymptomatic infection with SARS-CoV-2, the virus that causes COVID-19 (1-3). In the United States, the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine is currently authorized for use in children and adolescents aged 5-15 years under an Emergency Use Authorization and is fully licensed by the Food and Drug Administration for persons aged ≥16 years (4). Prelicensure randomized trials in persons aged ≥5 years documented high vaccine efficacy and immunogenicity (5),§ and real-world studies in persons aged 12-18 years demonstrated high vaccine effectiveness (VE) against severe COVID-19 (6). Recent evidence suggests that COVID-19 vaccination is associated with lower MIS-C incidence among adolescents (7); however, VE of the 2-dose Pfizer-BioNTech regimen against MIS-C has not been evaluated. The effectiveness of 2 doses of Pfizer-BioNTech vaccine received ≥28 days before hospital admission in preventing MIS-C was assessed using a test-negative case-control design¶ among hospitalized patients aged 12-18 years at 24 pediatric hospitals in 20 states** during July 1-December 9, 2021, the period when most MIS-C patients could be temporally linked to SARS-CoV-2 B.1.617.2 (Delta) variant predominance. Patients with MIS-C (case-patients) and two groups of hospitalized controls matched to case-patients were evaluated: test-negative controls had at least one COVID-19-like symptom and negative SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) or antigen-based assay results, and syndrome-negative controls were hospitalized patients without COVID-19-like illness. Among 102 MIS-C case-patients and 181 hospitalized controls, estimated effectiveness of 2 doses of Pfizer-BioNTech vaccine against MIS-C was 91% (95% CI&nbsp;=&nbsp;78%-97%). All 38 MIS-C patients requiring life support were unvaccinated. Receipt of 2 doses of the Pfizer-BioNTech vaccine is associated with a high level of protection against MIS-C in persons aged 12-18 years, highlighting the importance of vaccination among all eligible children

Effectiveness of Maternal mRNA COVID-19 Vaccination During Pregnancy Against COVID-19-Associated Hospitalizations in Infants Aged &lt;6 Months During SARS-CoV-2 Omicron Predominance - 20 States, March 9, 2022-May 31, 2023.

Infants aged &lt;6 months are not eligible for COVID-19 vaccination. Vaccination during pregnancy has been associated with protection against infant COVID-19-related hospitalization. The Overcoming COVID-19 Network conducted a case-control study during March 9, 2022-May 31, 2023, to evaluate the effectiveness of maternal receipt of a COVID-19 vaccine dose (vaccine effectiveness [VE]) during pregnancy against COVID-19-related hospitalization in infants aged &lt;6 months and a subset of infants aged &lt;3 months. VE was calculated as (1 - adjusted odds ratio) x 100% among all infants aged &lt;6 months and &lt;3 months. Case-patients (infants hospitalized for COVID-19 outside of birth hospitalization and who had a positive SARS-CoV-2 test result) and control patients (infants hospitalized for COVID-19-like illness with a negative SARS-CoV-2 test result) were compared. Odds ratios were determined using multivariable logistic regression, comparing the odds of receipt of a maternal COVID-19 vaccine dose (completion of a 2-dose vaccination series or a third or higher dose) during pregnancy with maternal nonvaccination between case- and control patients. VE of maternal vaccination during pregnancy against COVID-19-related hospitalization was 35% (95% CI&nbsp;=&nbsp;15%-51%) among infants aged &lt;6 months and 54% (95% CI&nbsp;=&nbsp;32%-68%) among infants aged &lt;3 months. Intensive care unit admissions occurred in 23% of all case-patients, and invasive mechanical ventilation was more common among infants of unvaccinated (9%) compared with vaccinated mothers (1%) (p = 0.02). Maternal vaccination during pregnancy provides some protection against COVID-19-related hospitalizations among infants, particularly those aged &lt;3 months. Expectant mothers should remain current with COVID-19 vaccination to protect themselves and their infants from hospitalization and severe outcomes associated with COVID-19