Racial/Ethnic Differences in Long-COVID-Associated Symptoms among Pediatrics Population: Findings from Difference-in-differences Analyses in RECOVER Program.

Racial/ethnic differences are associated with the potential symptoms and conditions of post-acute sequelae SARS-CoV-2 infection (PASC) in adults. These differences may exist among children and warrant further exploration. We conducted a retrospective cohort study for children and adolescents under the age of 21 from the thirteen institutions in the RECOVER Initiative. The cohort is 225,723 patients with SARS-CoV-2 infection or COVID-19 diagnosis and 677,448 patients without SARS-CoV-2 infection or COVID-19 diagnosis between March 2020 and October 2022. The study compared minor racial/ethnic groups to Non-Hispanic White (NHW) individuals, stratified by severity during the acute phase of COVID-19. Within the severe group, Asian American/Pacific Islanders (AAPI) had a higher prevalence of fever/chills and respiratory symptoms, Hispanic patients showed greater hair loss prevalence in severe COVID-19 cases, while Non-Hispanic Black (NHB) patients had fewer skin symptoms in comparison to NHW patients. Within the non-severe group, AAPI patients had increased POTS/dysautonomia and respiratory symptoms, and NHB patients showed more cognitive symptoms than NHW patients. In conclusion, racial/ethnic differences related to COVID-19 exist among specific PASC symptoms and conditions in pediatrics, and these differences are associated with the severity of illness during acute COVID-19.

"Where Did This Come From?": Antibiotic Prophylaxis in Biliary Atresia After Kasai Procedure.

For patients with Biliary atresia, antibiotic prophylaxis after Kasai portoenterostomy is a common practice. Societal guidelines often cite one reference as supportive evidence for this practice. In this paper, we go back to review the quality of this evidence and suggest more research is required to demonstrate the efficacy of antibiotic prophylaxis in this population.

Development and validation of a federated learning framework for detection of subphenotypes of multisystem inflammatory syndrome in children.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe post-acute sequela of SARS-CoV-2 infection. The highly diverse clinical features of MIS-C necessities characterizing its features by subphenotypes for improved recognition and treatment. However, jointly identifying subphenotypes in multi-site settings can be challenging. We propose a distributed multi-site latent class analysis (dMLCA) approach to jointly learn MIS-C subphenotypes using data across multiple institutions. Methods: We used data from the electronic health records (EHR) systems across nine U.S. children's hospitals. Among the 3,549,894 patients, we extracted 864 patients < 21 years of age who had received a diagnosis of MIS-C during an inpatient stay or up to one day before admission. Using MIS-C conditions, laboratory results, and procedure information as input features for the patients, we applied our dMLCA algorithm and identified three MIS-C subphenotypes. As validation, we characterized and compared more granular features across subphenotypes. To evaluate the specificity of the identified subphenotypes, we further compared them with the general subphenotypes identified in the COVID-19 infected patients. Findings: Subphenotype 1 (46.1%) represents patients with a mild manifestation of MIS-C not requiring intensive care, with minimal cardiac involvement. Subphenotype 2 (25.3%) is associated with a high risk of shock, cardiac and renal involvement, and an intermediate risk of respiratory symptoms. Subphenotype 3 (28.6%) represents patients requiring intensive care, with a high risk of shock and cardiac involvement, accompanied by a high risk of >4 organ system being impacted. Importantly, for hospital-specific clinical decision-making, our algorithm also revealed a substantial heterogeneity in relative proportions of these three subtypes across hospitals. Properly accounting for such heterogeneity can lead to accurate characterization of the subphenotypes at the patient-level. Interpretation: Our identified three MIS-C subphenotypes have profound implications for personalized treatment strategies, potentially influencing clinical outcomes. Further, the proposed algorithm facilitates federated subphenotyping while accounting for the heterogeneity across hospitals.

Postacute Sequelae of SARS-CoV-2 in Children.

The coronavirus disease 2019 (COVID-19) pandemic has caused significant medical, social, and economic impacts globally, both in the short and long term. Although most individuals recover within a few days or weeks from an acute infection, some experience longer lasting effects. Data regarding the postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) in children, or long COVID, are only just emerging in the literature. These symptoms and conditions may reflect persistent symptoms from acute infection (eg, cough, headaches, fatigue, and loss of taste and smell), new symptoms like dizziness, or exacerbation of underlying conditions. Children may develop conditions de novo, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, autoimmune conditions and multisystem inflammatory syndrome in children. This state-of-the-art narrative review provides a summary of our current knowledge about PASC in children, including prevalence, epidemiology, risk factors, clinical characteristics, underlying mechanisms, and functional outcomes, as well as a conceptual framework for PASC based on the current National Institutes of Health definition. We highlight the pediatric components of the National Institutes of Health-funded Researching COVID to Enhance Recovery Initiative, which seeks to characterize the natural history, mechanisms, and long-term health effects of PASC in children and young adults to inform future treatment and prevention efforts. These initiatives include electronic health record cohorts, which offer rapid assessments at scale with geographical and demographic diversity, as well as longitudinal prospective observational cohorts, to estimate disease burden, illness trajectory, pathobiology, and clinical manifestations and outcomes.

Funding and Resourcing Quality Improvement Effort in Infectious Diseases.

Infectious diseases physicians are frequently called upon to perform quality improvement and patient safety (QIPS) work. We describe a newly created faculty position at our institution that allows a faculty member with graduate training in quality and safety methodologies to address QIPS priorities at both the division and hospital level.

Real-World Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents.

BACKGROUND: The efficacy of the BNT162b2 vaccine in pediatrics was assessed by randomized trials before the Omicron variant's emergence. The long-term durability of vaccine protection in this population during the Omicron period remains limited. OBJECTIVE: To assess the effectiveness of BNT162b2 in preventing infection and severe diseases with various strains of the SARS-CoV-2 virus in previously uninfected children and adolescents. DESIGN: Comparative effectiveness research accounting for underreported vaccination in 3 study cohorts: adolescents (12 to 20 years) during the Delta phase and children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase. SETTING: A national collaboration of pediatric health systems (PEDSnet). PARTICIPANTS: 77 392 adolescents (45 007 vaccinated) during the Delta phase and 111 539 children (50 398 vaccinated) and 56 080 adolescents (21 180 vaccinated) during the Omicron phase. INTERVENTION: First dose of the BNT162b2 vaccine versus no receipt of COVID-19 vaccine. MEASUREMENTS: Outcomes of interest include documented infection, COVID-19 illness severity, admission to an intensive care unit (ICU), and cardiac complications. The effectiveness was reported as (1-relative risk)*100, with confounders balanced via propensity score stratification. RESULTS: During the Delta period, the estimated effectiveness of the BNT162b2 vaccine was 98.4% (95% CI, 98.1% to 98.7%) against documented infection among adolescents, with no statistically significant waning after receipt of the first dose. An analysis of cardiac complications did not suggest a statistically significant difference between vaccinated and unvaccinated groups. During the Omicron period, the effectiveness against documented infection among children was estimated to be 74.3% (CI, 72.2% to 76.2%). Higher levels of effectiveness were seen against moderate or severe COVID-19 (75.5% [CI, 69.0% to 81.0%]) and ICU admission with COVID-19 (84.9% [CI, 64.8% to 93.5%]). Among adolescents, the effectiveness against documented Omicron infection was 85.5% (CI, 83.8% to 87.1%), with 84.8% (CI, 77.3% to 89.9%) against moderate or severe COVID-19, and 91.5% (CI, 69.5% to 97.6%) against ICU admission with COVID-19. The effectiveness of the BNT162b2 vaccine against the Omicron variant declined 4 months after the first dose and then stabilized. The analysis showed a lower risk for cardiac complications in the vaccinated group during the Omicron variant period. LIMITATION: Observational study design and potentially undocumented infection. CONCLUSION: This study suggests that BNT162b2 was effective for various COVID-19-related outcomes in children and adolescents during the Delta and Omicron periods, and there is some evidence of waning effectiveness over time. PRIMARY FUNDING SOURCE: National Institutes of Health.

Advanced Practice Providers in Pediatric Infectious Diseases.

Advanced Practice Providers (APPs) are a rapidly growing segment of the pediatric infectious diseases workforce. APPs offer many advantages to divisions that are struggling to counter a smaller fellowship applicant pool and faculty workforce transitions as a result of the pandemic. Many divisions still have yet to incorporate APPs into their inpatient or outpatient teams. This review will discuss the diverse pool of APPs, summarize how APPs are currently being used in the field, discuss the financial considerations of hiring APPs, and highlight future needs for embracing APPs as critical members of the pediatric ID workforce.

Vaccine Effectiveness Against Long COVID in Children.

OBJECTIVES: Vaccination reduces the risk of acute coronavirus disease 2019 (COVID-19) in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5 to 17 years. METHODS: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record program for visits after vaccine availability. We examined both probable (symptom-based) and diagnosed long COVID after vaccination. RESULTS: The vaccination rate was 67% in the cohort of 1 037 936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, whereas diagnosed long COVID was 0.8%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5-44.7) against probable long COVID and 41.7% (15.0-60.0) against diagnosed long COVID. VE was higher for adolescents (50.3% [36.6-61.0]) than children aged 5 to 11 (23.8% [4.9-39.0]). VE was higher at 6 months (61.4% [51.0-69.6]) but decreased to 10.6% (-26.8% to 37.0%) at 18-months. CONCLUSIONS: This large retrospective study shows moderate protective effect of severe acute respiratory coronavirus 2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including electronic health record sources and prospective data.

The association between influenza vaccine effectiveness and egg-based manufacturing technology: literature review and US expert consensus.

BACKGROUND: Influenza is associated with significant disease burden in the US and is currently best controlled by vaccination programs. Influenza vaccine effectiveness (VE) is low and may be reduced by several factors, including egg adaptations. Although non-egg-based influenza vaccines reportedly have greater VE in egg-adapted seasons, evidence for egg adaptations' reduction of VE is indirect and dissociated, apart from two previous European consensuses. METHODS: This study replicated the methodology used in a 2020 literature review and European consensus, providing an updated review and consensus opinion of 10 US experts on the evidence for a mechanistic basis for reduction of VE due to egg-based manufacturing methods. A mechanistic basis was assumed if sufficient evidence was found for underlying principles proposed to give rise to such an effect. Evidence for each principle was brought forward from the 2020 review and identified here by structured literature review and expert panel. Experts rated the strength of support for each principle and a mechanistic basis for reduction of VE due to egg-based influenza vaccine manufacture in a consensus method (consensus for strong/very strong evidence = ≥ 3.5 on 5-point Likert scale). RESULTS: Experts assessed 251 references (from previous study: 185; this study: 66). The majority of references for all underlying principles were rated as strong or very strong supporting evidence (52-86%). Global surveillance, WHO candidate vaccine virus selection, and manufacturing stages involving eggs were identified as most likely to impact influenza VE. CONCLUSION: After review of extensive evidence for reduction of VE due to egg-based influenza vaccine manufacture, influenza experts in the US joined those in Europe in unanimous agreement for a mechanistic basis for the effect. Vaccine providers and administrators should consider use of non-egg-based influenza vaccine manufacture to reduce the risk of egg adaptations and likely impact on VE.

Post-Exposure Prophylaxis for Varicella-Zoster Virus Exposure in High-Risk Children.

BACKGROUND: Post-exposure prophylaxis (PEP) with varicella immunoglobulin is recommended to minimize risk of varicella complications for high-risk children. However, providers frequently use alternatives like acyclovir or intravenous immunoglobulin. METHODS: A retrospective cohort study was conducted of PEP for varicella in children from January 2009 to December 2019. Data were provided by 47 children's hospitals who participate in the Pediatric Health Information Systems database. Patients with clinical encounters for varicella exposure were reviewed. Choice of varicella PEP regimens, including differences by underlying condition and institution, and incidence of varicella disease were determined. RESULTS: A total of 1704 patients with first clinical encounters for varicella met inclusion criteria. Of these patients, 509 (29.9%) were prescribed PEP after varicella exposure, and 65 (3.8%) ultimately had a subsequent encounter for varicella disease. Of 509 patients who received PEP, acyclovir was most frequently prescribed (n = 195, 38.3%), followed by varicella immunoglobulin (n = 146, 28.7%), IVIG (n = 115, 22.6%), and combination therapy (n = 53, 10.4%). The highest proportion of varicella immunoglobulin use (10/20, 50%) was amongst children with diagnoses of rheumatological/gastrointestinal conditions. The highest proportion of acyclovir use (29/684, 4.2%) was amongst children with diagnoses of oncology/stem cell transplant conditions. The proportion of patients who subsequently had clinical encounters for varicella disease was highest for Acyclovir (30/195, 15.4%) followed by varicella immunoglobulin (5/146, 3.4%), combination therapy (2/53, 3.8%), and intravenous immunoglobulin alone (0/115) (P < .0001). CONCLUSIONS: Varicella PEP in high-risk children was highly varied among children's hospitals. In our dataset, use of acyclovir was associated with a higher rate of subsequent encounters for Varicella disease.

A pilot recruitment strategy to enhance ethical and equitable access to Covid-19 pediatric vaccine trials.

BACKGROUND/AIMS: The SARS-CoV-2 pandemic disproportionately impacted communities with lower access to health care in the United States, particularly before vaccines were widely available. These same communities are often underrepresented in clinical trials. Efforts to ensure equitable enrollment of participants in trials related to treatment and prevention of Covid-19 can raise concerns about exploitation if communities with lower access to health care are targeted for recruitment. METHODS: To enhance equity while avoiding exploitation, our site developed and implemented a three-part recruitment strategy for pediatric Covid-19 vaccine studies. First, we publicized a registry for potentially interested participants. Next, we applied public health community and social vulnerability indices to categorize the residence of families who had signed up for the registry into three levels to reflect the relative impact of the pandemic on their community: high, medium, and low. Finally, we preferentially offered study participation to interested families living in areas categorized by these indices as having high impact of the Covid-19 pandemic on their community. RESULTS: This approach allowed us to meet goals for study recruitment based on public health metrics related to disease burden, which contributed to a racially diverse study population that mirrored the surrounding community demographics. While this three-part recruitment strategy improved representation of minoritized groups from areas heavily impacted by the Covid-19 pandemic, important limitations were identified that would benefit from further study. CONCLUSION: Future use of this approach to enhance equitable access to research while avoiding exploitation should test different methods to build trust and communicate with underserved communities more effectively.

Real-world Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents.

Background: The efficacy of the BNT162b2 vaccine in pediatrics was assessed by randomized trials before the Omicron variant's emergence. The long-term durability of vaccine protection in this population during the Omicron period remains limited. Objective: To assess the effectiveness of BNT162b2 in preventing infection and severe diseases with various strains of the SARS-CoV-2 virus in previously uninfected children and adolescents. Design: Comparative effectiveness research accounting for underreported vaccination in three study cohorts: adolescents (12 to 20 years) during the Delta phase, children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase. Setting: A national collaboration of pediatric health systems (PEDSnet). Participants: 77,392 adolescents (45,007 vaccinated) in the Delta phase, 111,539 children (50,398 vaccinated) and 56,080 adolescents (21,180 vaccinated) in the Omicron period. Exposures: First dose of the BNT162b2 vaccine vs. no receipt of COVID-19 vaccine. Measurements: Outcomes of interest include documented infection, COVID-19 illness severity, admission to an intensive care unit (ICU), and cardiac complications. The effectiveness was reported as (1-relative risk)*100% with confounders balanced via propensity score stratification. Results: During the Delta period, the estimated effectiveness of BNT162b2 vaccine was 98.4% (95% CI, 98.1 to 98.7) against documented infection among adolescents, with no significant waning after receipt of the first dose. An analysis of cardiac complications did not find an increased risk after vaccination. During the Omicron period, the effectiveness against documented infection among children was estimated to be 74.3% (95% CI, 72.2 to 76.2). Higher levels of effectiveness were observed against moderate or severe COVID-19 (75.5%, 95% CI, 69.0 to 81.0) and ICU admission with COVID-19 (84.9%, 95% CI, 64.8 to 93.5). Among adolescents, the effectiveness against documented Omicron infection was 85.5% (95% CI, 83.8 to 87.1), with 84.8% (95% CI, 77.3 to 89.9) against moderate or severe COVID-19, and 91.5% (95% CI, 69.5 to 97.6)) against ICU admission with COVID-19. The effectiveness of the BNT162b2 vaccine against the Omicron variant declined after 4 months following the first dose and then stabilized. The analysis revealed a lower risk of cardiac complications in the vaccinated group during the Omicron variant period. Limitations: Observational study design and potentially undocumented infection. Conclusions: Our study suggests that BNT162b2 was effective for various COVID-19-related outcomes in children and adolescents during the Delta and Omicron periods, and there is some evidence of waning effectiveness over time. Primary Funding Source: National Institutes of Health.

Spectrum of severity of multisystem inflammatory syndrome in children: an EHR-based cohort study from the RECOVER program.

Multi-system inflammatory syndrome in children (MIS-C) is a severe post-acute sequela of SARS-CoV-2 infection in children, and there is a critical need to unfold its highly heterogeneous disease patterns. Our objective was to characterize the illness spectrum of MIS-C for improved recognition and management. We conducted a retrospective cohort study using data from March 1, 2020-September 30, 2022, in 8 pediatric medical centers from PEDSnet. We included 1139 children hospitalized with MIS-C and used their demographics, symptoms, conditions, laboratory values, and medications for analyses. We applied heterogeneity-adaptive latent class analyses and identified three latent classes. We further characterized the sociodemographic and clinical characteristics of the latent classes and evaluated their temporal patterns. Class 1 (47.9%) represented children with the most severe presentation, with more admission to the ICU, higher inflammatory markers, hypotension/shock/dehydration, cardiac involvement, acute kidney injury and respiratory involvement. Class 2 (23.3%) represented a moderate presentation, with 4-6 organ systems involved, and some overlapping features with acute COVID-19. Class 3 (28.8%) represented a mild presentation. Our results indicated that MIS-C has a spectrum of clinical severity ranging from mild to severe and the proportion of severe or critical MIS-C decreased over time.

Vaccine Effectiveness Against Long COVID in Children: A Report from the RECOVER EHR Cohort.

Objective: Vaccination reduces the risk of acute COVID-19 in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5-17 years. Methods: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record (EHR) Program for visits between vaccine availability, and October 29, 2022. Conditional logistic regression was used to estimate VE against long COVID with matching on age group (5-11, 12-17) and time period and adjustment for sex, ethnicity, health system, comorbidity burden, and pre-exposure health care utilization. We examined both probable (symptom-based) and diagnosed long COVID in the year following vaccination. Results: The vaccination rate was 56% in the cohort of 1,037,936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, while diagnosed long COVID was 0.7%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5 - 44.5) against probable long COVID and 41.7% (15.0 - 60.0) against diagnosed long COVID. VE was higher for adolescents 50.3% [36.3 - 61.0]) than children aged 5-11 (23.8% [4.9 - 39.0]). VE was higher at 6 months (61.4% [51.0 - 69.6]) but decreased to 10.6% (-26.8 - 37.0%) at 18-months. Discussion: This large retrospective study shows a moderate protective effect of SARS-CoV-2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including EHR sources and prospective data. Article Summary: Vaccination against COVID-19 has a protective effect against long COVID in children and adolescents. The effect wanes over time but remains significant at 12 months. What's Known on This Subject: Vaccines reduce the risk and severity of COVID-19 in children. There is evidence for reduced long COVID risk in adults who are vaccinated, but little information about similar effects for children and adolescents, who have distinct forms of long COVID. What This Study Adds: Using electronic health records from US health systems, we examined large cohorts of vaccinated and unvaccinated patients <18 years old and show that vaccination against COVID-19 is associated with reduced risk of long COVID for at least 12 months. Contributors' Statement: Drs. Hanieh Razzaghi and Charles Bailey conceptualized and designed the study, supervised analyses, drafted the initial manuscript, and critically reviewed and revised the manuscript.Drs. Christopher Forrest and Yong Chen designed the study and critically reviewed and revised the manuscript.Ms. Kathryn Hirabayashi, Ms. Andrea Allen, and Dr. Qiong Wu conducted analyses, and critically reviewed and revised the manuscript.Drs. Suchitra Rao, H Timothy Bunnell, Elizabeth A. Chrischilles, Lindsay G. Cowell, Mollie R. Cummins, David A. Hanauer, Benjamin D. Horne, Carol R. Horowitz, Ravi Jhaveri, Susan Kim, Aaron Mishkin, Jennifer A. Muszynski, Susanna Nagie, Nathan M. Pajor, Anuradha Paranjape, Hayden T. Schwenk, Marion R. Sills, Yacob G. Tedla, David A. Williams, and Ms. Miranda Higginbotham critically reviewed and revised the manuscript.All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Authorship statement: Authorship has been determined according to ICMJE recommendations.

A machine learning-based phenotype for long COVID in children: An EHR-based study from the RECOVER program.

As clinical understanding of pediatric Post-Acute Sequelae of SARS CoV-2 (PASC) develops, and hence the clinical definition evolves, it is desirable to have a method to reliably identify patients who are likely to have post-acute sequelae of SARS CoV-2 (PASC) in health systems data. In this study, we developed and validated a machine learning algorithm to classify which patients have PASC (distinguishing between Multisystem Inflammatory Syndrome in Children (MIS-C) and non-MIS-C variants) from a cohort of patients with positive SARS- CoV-2 test results in pediatric health systems within the PEDSnet EHR network. Patient features included in the model were selected from conditions, procedures, performance of diagnostic testing, and medications using a tree-based scan statistic approach. We used an XGboost model, with hyperparameters selected through cross-validated grid search, and model performance was assessed using 5-fold cross-validation. Model predictions and feature importance were evaluated using Shapley Additive exPlanation (SHAP) values. The model provides a tool for identifying patients with PASC and an approach to characterizing PASC using diagnosis, medication, laboratory, and procedure features in health systems data. Using appropriate threshold settings, the model can be used to identify PASC patients in health systems data at higher precision for inclusion in studies or at higher recall in screening for clinical trials, especially in settings where PASC diagnosis codes are used less frequently or less reliably. Analysis of how specific features contribute to the classification process may assist in gaining a better understanding of features that are associated with PASC diagnoses.

Hard to Swallow: A Review of Interventions to Improve Swallowing Solid Medication.

Solid oral medications are preferred over intravenous or liquid formulations; however, difficulty swallowing solid medication remains a common barrier to adherence. Previous reviews have demonstrated limited evidence on interventions to improve solid medication swallowing abilities. PubMed, Medline (OVID), CINAHL, Scopus, and Web of Science databases were searched for interventions to improve the pediatric population's ability to swallow solid medications. We included studies in English published after the latest review, from January 2014 through April 2022, with pediatric patients not having comorbid conditions affecting swallowing ability. The authors independently reviewed each study's sampling strategy, study design, and the strength of outcome measures and assigned a numerical rating representing "poor," "fair," or "good" for each category. Individual ratings were averaged per category and a final quality rating score given based on the average of all 3 categories. Our search identified 581 unique records; 10 were included in the final review. Interventions varied and included behavioral therapies and novel products or medication formulations. Three received a "good" quality rating, 5 were "fair," and 2 were "poor." All studies showed their intervention(s) to be successful in improving a child's ability to swallow solid oral medications. Despite the availability of several different effective interventions, pediatric providers do not routinely address patients' difficulty with swallowing solid oral medications. Patients would benefit from implementation of a universal screening process followed by a guideline for appropriate patient-centered interventions; the opportunity exists to use this process as a national quality benchmark reflecting institutional commitment to high-value care.

Understanding pediatric long COVID using a tree-based scan statistic approach: an EHR-based cohort study from the RECOVER Program.

Objectives: Post-acute sequalae of SARS-CoV-2 infection (PASC) is not well defined in pediatrics given its heterogeneity of presentation and severity in this population. The aim of this study is to use novel methods that rely on data mining approaches rather than clinical experience to detect conditions and symptoms associated with pediatric PASC. Materials and Methods: We used a propensity-matched cohort design comparing children identified using the new PASC ICD10CM diagnosis code (U09.9) (N = 1309) to children with (N = 6545) and without (N = 6545) SARS-CoV-2 infection. We used a tree-based scan statistic to identify potential condition clusters co-occurring more frequently in cases than controls. Results: We found significant enrichment among children with PASC in cardiac, respiratory, neurologic, psychological, endocrine, gastrointestinal, and musculoskeletal systems, the most significant related to circulatory and respiratory such as dyspnea, difficulty breathing, and fatigue and malaise. Discussion: Our study addresses methodological limitations of prior studies that rely on prespecified clusters of potential PASC-associated diagnoses driven by clinician experience. Future studies are needed to identify patterns of diagnoses and their associations to derive clinical phenotypes. Conclusion: We identified multiple conditions and body systems associated with pediatric PASC. Because we rely on a data-driven approach, several new or under-reported conditions and symptoms were detected that warrant further investigation.

Can Multisystem Inflammatory Syndrome in Children Be Managed in the Outpatient Setting? An EHR-Based Cohort Study From the RECOVER Program.

Using electronic health record data combined with primary chart review, we identified seven children across nine participant pediatric medical centers with a diagnosis of Multisystem Inflammatory Syndrome in Children (MIS-C) managed exclusively as outpatients. These findings should raise awareness of mild presentations of MIS-C and the option of outpatient management.