Browsing by Author "Babbitt, Christopher J."
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Item Changes in Distribution of Severe Neurologic Involvement in US Pediatric Inpatients With COVID-19 or Multisystem Inflammatory Syndrome in Children in 2021 vs 2020(American Medical Association, 2023) LaRovere, Kerri L.; Poussaint, Tina Y.; Young, Cameron C.; Newhams, Margaret M.; Kucukak, Suden; Irby, Katherine; Kong, Michele; Schwartz, Stephanie P.; Walker, Tracie C.; Bembea, Melania M.; Wellnitz, Kari; Havlin, Kevin M.; Cvijanovich, Natalie Z.; Hall, Mark W.; Fitzgerald, Julie C.; Schuster, Jennifer E.; Hobbs, Charlotte V.; Halasa, Natasha B.; Singh, Aalok R.; Mack, Elizabeth H.; Bradford, Tamara T.; Gertz, Shira J.; Schwarz, Adam J.; Typpo, Katri V.; Loftis, Laura L.; Giuliano, John S., Jr.; Horwitz, Steven M.; Biagas, Katherine V.; Clouser, Katharine N.; Rowan, Courtney M.; Maddux, Aline B.; Soma, Vijaya L.; Babbitt, Christopher J.; Aguiar, Cassyanne L.; Kolmar, Amanda R.; Heidemann, Sabrina M.; Harvey, Helen; Zambrano, Laura D.; Campbell, Angela P.; Randolph, Adrienne G.; Overcoming COVID-19 Investigators; Pediatrics, School of MedicineImportance: In 2020 during the COVID-19 pandemic, neurologic involvement was common in children and adolescents hospitalized in the United States for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complications. Objective: To provide an update on the spectrum of SARS-CoV-2-related neurologic involvement among children and adolescents in 2021. Design, setting, and participants: Case series investigation of patients reported to public health surveillance hospitalized with SARS-CoV-2-related illness between December 15, 2020, and December 31, 2021, in 55 US hospitals in 31 states with follow-up at hospital discharge. A total of 2253 patients were enrolled during the investigation period. Patients suspected of having multisystem inflammatory syndrome in children (MIS-C) who did not meet criteria (n = 85) were excluded. Patients (<21 years) with positive SARS-CoV-2 test results (reverse transcriptase-polymerase chain reaction and/or antibody) meeting criteria for MIS-C or acute COVID-19 were included in the analysis. Exposure: SARS-CoV-2 infection. Main outcomes and measures: Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening neurologic involvement was adjudicated by experts based on clinical and/or neuroradiological features. Type and severity of neurologic involvement, laboratory and imaging data, vaccination status, and hospital discharge outcomes (death or survival with new neurologic deficits). Results: Of 2168 patients included (58% male; median age, 10.3 years), 1435 (66%) met criteria for MIS-C, and 476 (22%) had documented neurologic involvement. Patients with neurologic involvement vs without were older (median age, 12 vs 10 years) and more frequently had underlying neurologic disorders (107 of 476 [22%] vs 240 of 1692 [14%]). Among those with neurologic involvement, 42 (9%) developed acute SARS-CoV-2-related life-threatening conditions, including central nervous system infection/demyelination (n = 23; 15 with possible/confirmed encephalitis, 6 meningitis, 1 transverse myelitis, 1 nonhemorrhagic leukoencephalopathy), stroke (n = 11), severe encephalopathy (n = 5), acute fulminant cerebral edema (n = 2), and Guillain-Barré syndrome (n = 1). Ten of 42 (24%) survived with new neurologic deficits at discharge and 8 (19%) died. Among patients with life-threatening neurologic conditions, 15 of 16 vaccine-eligible patients (94%) were unvaccinated. Conclusions and relevance: SARS-CoV-2-related neurologic involvement persisted in US children and adolescents hospitalized for COVID-19 or MIS-C in 2021 and was again mostly transient. Central nervous system infection/demyelination accounted for a higher proportion of life-threatening conditions, and most vaccine-eligible patients were unvaccinated. COVID-19 vaccination may prevent some SARS-CoV-2-related neurologic complications and merits further study.Item Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19(AMA, 2021-02) Feldstein, Leora R.; Tenforde, Mark W.; Friedman, Kevin G.; Newhams, Margaret; Rose, Erica Billig; Dapul, Heda; Soma, Vijaya L.; Maddux, Aline B.; Mourani, Peter M.; Bowens, Cindy; Maamari, Mia; Hall, Mark W.; Riggs, Becky J.; Giuliano, John S.; Singh, Aalok R.; Li, Simon; Kong, Michele; Schuster, Jennifer E.; McLaughlin, Gwenn E.; Schwartz, Stephanie P.; Walker, Tracie C.; Loftis, Laura L.; Hobbs, Charlotte V.; Halasa, Natasha B.; Doymaz, Sule; Babbitt, Christopher J.; Hume, Janet R.; Gertz, Shira J.; Irby, Katherine; Clouser, Katharine N.; Cvijanovich, Natalie Z.; Bradford, Tamara T.; Smith, Lincoln S.; Heidemann, Sabrina M.; Zackai, Sheemon P.; Wellnitz, Kari; Nofziger, Ryan A.; Horwitz, Steven M.; Carroll, Ryan W.; Rowan, Courtney M.; Tarquinio, Keiko M.; Mack, Elizabeth H.; Fitzgerald, Julie C.; Coates, Bria M.; Jackson, Ashley M.; Young, Cameron C.; Son, Mary Beth F.; Patel, Manish M.; Newburger, Jane W.; Randolph, Adrienne G.; Overcoming COVID-19 Investigators; Pediatrics, School of MedicineImportance Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. Objective To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). Setting, Design, and Participants Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase–polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement. Exposure SARS-CoV-2. Main Outcomes and Measures Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19. Results Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), and lower platelet count (<150 ×103 cells/μL [212/523 {41%} vs 84/486 {17%}, P < .001]). A total of 398 patients (73.8%) with MIS-C and 253 (43.8%) with COVID-19 were admitted to the intensive care unit, and 10 (1.9%) with MIS-C and 8 (1.4%) with COVID-19 died during hospitalization. Among patients with MIS-C with reduced left ventricular systolic function (172/503, 34.2%) and coronary artery aneurysm (57/424, 13.4%), an estimated 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days. Conclusions and Relevance This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19.Item Community-Onset Bacterial Coinfection in Children Critically Ill With Severe Acute Respiratory Syndrome Coronavirus 2 Infection(Oxford University Press, 2023-03-06) Moffitt, Kristin L.; Nakamura, Mari M.; Young, Cameron C.; Newhams, Margaret M.; Halasa, Natasha B.; Reed, J. Nelson; Fitzgerald, Julie C.; Spinella, Philip C.; Soma, Vijaya L.; Walker, Tracie C.; Loftis, Laura L.; Maddux, Aline B.; Kong, Michele; Rowan, Courtney M.; Hobbs, Charlotte V.; Schuster, Jennifer E.; Riggs, Becky J.; McLaughlin, Gwenn E.; Michelson, Kelly N.; Hall, Mark W.; Babbitt, Christopher J.; Cvijanovich, Natalie Z.; Zinter, Matt S.; Maamari, Mia; Schwarz, Adam J.; Singh, Aalok R.; Flori, Heidi R.; Gertz, Shira J.; Staat, Mary A.; Giuliano, John S., Jr.; Hymes, Saul R.; Clouser, Katharine N.; McGuire, John; Carroll, Christopher L.; Thomas, Neal J.; Levy, Emily R.; Randolph, Adrienne G.; Pediatrics, School of MedicineBackground: 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.Item Data-driven clustering identifies features distinguishing multisystem inflammatory syndrome from acute COVID-19 in children and adolescents(Elsevier, 2021-08-31) Geva, Alon; Patel, Manish M.; Geva, Alon; Patel, Manish M.; Newhams, Margaret M.; Young, Cameron C.; Son, Mary Beth F.; Kong, Michele; Maddux, Aline B.; Hall, Mark W.; Riggs, Becky J.; Singh, Aalok R.; Giuliano, John S.; Hobbs, Charlotte V.; Loftis, Laura L.; McLaughlin, Gwenn E.; Schwartz, Stephanie P.; Schuster, Jennifer E.; Babbitt, Christopher J.; Halasa, Natasha B.; Gertz, Shira J.; Doymaz, Sule; Hume, Janet R.; Bradford, Tamara T.; Irby, Katherine; Carroll, Christopher L.; McGuire, John K.; Tarquinio, Keiko M.; Rowan, Courtney M.; Mack, Elizabeth H.; Cvijanovich, Natalie Z.; Fitzgerald, Julie C.; Spinella, Philip C.; Staat, Mary A.; Clouser, Katharine N.; Soma, Vijaya L.; Dapul, Heda; Maamari, Mia; Bowens, Cindy; Havlin, Kevin M.; Mourani, Peter M.; Heidemann, Sabrina M.; Horwitz, Steven M.; Feldstein, Leora R.; Tenforde, Mark W.; Newburger, Jane W.; Mandl, Kenneth D.; Randolph, Adrienne G.; Overcoming COVID-19 Investigators; Pediatrics, School of MedicineBackground Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia. Methods We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians) <21 years old hospitalized with COVID-19-related illness admitted between 15 March 2020 and 31 December 2020. We compared prevalence of assigned MIS-C labels and clinical features among clusters, followed by recursive feature elimination to identify characteristics of potentially misclassified MIS-C-labeled patients. Findings Of 94 clinical features tested, 46 were retained for clustering. Cluster 1 patients (N = 498; 92% labeled MIS-C) were mostly previously healthy (71%), with mean age 7·2 ± 0·4 years, predominant cardiovascular (77%) and/or mucocutaneous (82%) involvement, high inflammatory biomarkers, and mostly SARS-CoV-2 PCR negative (60%). Cluster 2 patients (N = 445; 27% labeled MIS-C) frequently had pre-existing conditions (79%, with 39% respiratory), were similarly 7·4 ± 2·1 years old, and commonly had chest radiograph infiltrates (79%) and positive PCR testing (90%). Cluster 3 patients (N = 583; 19% labeled MIS-C) were younger (2·8 ± 2·0 y), PCR positive (86%), with less inflammation. Radiographic findings of pulmonary infiltrates and positive SARS-CoV-2 PCR accurately distinguished cluster 2 MIS-C labeled patients from cluster 1 patients. Interpretation Using a data driven, unsupervised approach, we identified features that cluster patients into a group with high likelihood of having MIS-C. Other features identified a cluster of patients more likely to have acute severe COVID-19 pulmonary disease, and patients in this cluster labeled by clinicians as MIS-C may be misclassified. These data driven phenotypes may help refine the diagnosis of MIS-C.Item A Description of COVID-19-Directed Therapy in Children Admitted to US Intensive Care Units 2020(Oxford University Press, 2022) Schuster, Jennifer E.; Halasa, Natasha B.; Nakamura, Mari; Levy, Emily R.; Fitzgerald, Julie C.; Young, Cameron C.; Newhams, Margaret M.; Bourgeois, Florence; Staat, Mary A.; Hobbs, Charlotte V.; Dapul, Heda; Feldstein, Leora R.; Jackson, Ashley M.; Mack, Elizabeth H.; Walker, Tracie C.; Maddux, Aline B.; Spinella, Philip C.; Loftis, Laura L.; Kong, Michele; Rowan, Courtney M.; Bembea, Melania M.; McLaughlin, Gwenn E.; Hall, Mark W.; Babbitt, Christopher J.; Maamari, Mia; Zinter, Matt S.; Cvijanovich, Natalie Z.; Michelson, Kelly N.; Gertz, Shira J.; Carroll, Christopher L.; Thomas, Neal J.; Giuliano, John S., Jr.; Singh, Aalok R.; Hymes, Saul R.; Schwarz, Adam J.; McGuire, John K.; Nofziger, Ryan A.; Flori, Heidi R.; Clouser, Katharine N.; Wellnitz, Kari; Cullimore, Melissa L.; Hume, Janet R.; Patel, Manish; Randolph, Adrienne G.; Overcoming COVID-19 Investigators; Pediatrics, School of MedicineBackground: 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.Item Frequency, Characteristics and Complications of COVID-19 in Hospitalized Infants(Wolters Kluwer, 2022) Hobbs, Charlotte V.; Woodworth, Kate; Young, Cameron C.; Jackson, Ashley M.; Newhams, Margaret M.; Dapul, Heda; Maamari, Mia; Hall, Mark W.; Maddux, Aline B.; Sing, Aalok R.; Schuster, Jennifer E.; Rowan, Courtney M.; Fitzgerald, Julie C.; Irby, Katherine; Kong, Michele; Mack, Elizabeth H.; Staat, Mary A.; Cvijanovich, Natalie Z.; Bembea, Melania M.; Coates, Bria M.; Halasa, Natasha B.; Walker, Tracie C.; McLaughlin, Gwenn E.; Babbitt, Christopher J.; Nofziger, Ryan A.; Loftis, Laura L.; Bradford, Tamara T.; Campbell, Angela P.; Patel, Manish M.; Randolph, Adrienne G.; Overcoming COVID-19 Investigators; Pediatrics, School of MedicineBackground: Previous studies of severe acute respiratory syndrome coronavirus 2 infection in infants have incompletely characterized factors associated with severe illness or focused on infants born to mothers with coronavirus disease 2019 (COVID-19). Here we highlight demographics, clinical characteristics and laboratory values that differ between infants with and without severe acute COVID-19. Methods: Active surveillance was performed by the Overcoming COVID-19 network to identify children and adolescents with severe acute respiratory syndrome coronavirus 2-related illness hospitalized at 62 sites in 31 states from March 15 to December 27, 2020. We analyzed patients >7 days to <1 year old hospitalized with symptomatic acute COVID-19. Results: We report 232 infants >7 days to <1 year of age hospitalized with acute symptomatic COVID-19 from 37 US hospitals in our cohort from March 15 to December 27, 2020. Among 630 cases of severe COVID-19 in patients >7 days to <18 years old, 128 (20.3%) were infants. In infants with severe illness from the entire study period, the median age was 2 months, 66% were from racial and ethnic minority groups, 66% were previously healthy, 73% had respiratory complications, 13% received mechanical ventilation and <1% died. Conclusions: Infants accounted for over a fifth of children <18 years of age hospitalized for severe acute COVID-19, commonly manifesting with respiratory symptoms and complications. Although most infants hospitalized with COVID-19 did not suffer significant complications, longer term outcomes remain unclear. Notably, 75% of infants with severe disease were <6 months of age in this cohort study period, which predated maternal COVID-19 vaccination, underscoring the importance of maternal vaccination for COVID-19 in protecting the mother and infant.Item Infants Admitted to US Intensive Care Units for RSV Infection During the 2022 Seasonal Peak(American Medical Association, 2023-08-01) Halasa, Natasha; Zambrano, Laura D.; Amarin, Justin Z.; Stewart, Laura S.; Newhams, Margaret M.; Levy, Emily R.; Shein, Steven L.; Carroll, Christopher L.; Fitzgerald, Julie C.; Michaels, Marian G.; Bline, Katherine; Cullimore, Melissa L.; Loftis, Laura; Montgomery, Vicki L.; Jeyapalan, Asumthia S.; Pannaraj, Pia S.; Schwarz, Adam J.; Cvijanovich, Natalie Z.; Zinter, Matt S.; Maddux, Aline B.; Bembea, Melania M.; Irby, Katherine; Zerr, Danielle M.; Kuebler, Joseph D.; Babbitt, Christopher J.; Glas Gaspers, Mary; Nofziger, Ryan A.; Kong, Michele; Coates, Bria M.; Schuster, Jennifer E.; Gertz, Shira J.; Mack, Elizabeth H.; White, Benjamin R.; Harvey, Helen; Hobbs, Charlotte V.; Dapul, Heda; Butler, Andrew D.; Bradford, Tamara T.; Rowan, Courtney M.; Wellnitz, Kari; Allen Staat, Mary; Aguiar, Cassyanne L.; Hymes, Saul R.; Randolph, Adrienne G.; Campbell, Angela P.; RSV-PIC Investigators; Pediatrics, School of MedicineImportance: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide. Objective: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission. Design, setting, and participants: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection. Exposure: Respiratory syncytial virus. Main outcomes and measures: Data were captured on demographics, clinical characteristics, signs and symptoms, laboratory values, severity measures, and clinical outcomes, including receipt of noninvasive respiratory support, invasive mechanical ventilation, vasopressors or extracorporeal membrane oxygenation, and death. Mixed-effects multivariable log-binomial regression models were used to assess associations between intubation status and demographic factors, gestational age, and underlying conditions, including hospital as a random effect to account for between-site heterogeneity. Results: The first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonintubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days. Conclusions and relevance: In this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness.Item Investigating Health Disparities Associated With Multisystem Inflammatory Syndrome in Children After SARS-CoV-2 Infection(Wolters Kluwer, 2022) Zambrano, Laura D.; Ly, Kathleen N.; Link-Gelles, Ruth; Newhams, Margaret M.; Akande, Manzilat; Wu, Michael J.; Feldstein, Leora R.; Tarquinio, Keiko M.; Sahni, Leila C.; Riggs, Becky J.; Singh, Aalok R.; Fitzgerald, Julie C.; Schuster, Jennifer E.; Giuliano, John S., Jr.; Englund, Janet A.; Hume, Janet R.; Hall, Mark W.; Osborne, Christina M.; Doymaz, Sule; Rowan, Courtney M.; Babbitt, Christopher J.; Clouser, Katharine N.; Horwitz, Steven M.; Chou, Janet; Patel, Manish M.; Hobbs, Charlotte; Randolph, Adrienne G.; Campbell, Angela P.; Overcoming COVID-19 Investigators; Pediatrics, School of MedicineBackground: 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. Methods: 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. Results: 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). Conclusions: 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.Item Life-Threatening Complications of Influenza vs Coronavirus Disease 2019 (COVID-19) in US Children(Oxford University Press, 2023) Halasa, Natasha B.; Spieker, Andrew J.; Young, Cameron C.; Olson, Samantha M.; Newhams, Margaret M.; Amarin, Justin Z.; Moffitt, Kristin L.; Nakamura, Mari M.; Levy, Emily R.; Soma, Vijaya L.; Talj, Rana; Weiss, Scott L.; Fitzgerald, Julie C.; Mack, Elizabeth H.; Maddux, Aline B.; Schuster, Jennifer E.; Coates, Bria M.; Hall, Mark W.; Schwartz, Stephanie P.; Schwarz, Adam J.; Kong, Michele; Spinella, Philip C.; Loftis, Laura L.; McLaughlin, Gwenn E.; Hobbs, Charlotte V.; Rowan, Courtney M.; Bembea, Melania M.; Nofziger, Ryan A.; Babbitt, Christopher J.; Bowens, Cindy; Flori, Heidi R.; Gertz, Shira J.; Zinter, Matt S.; Giuliano, John S.; Hume, Janet R.; Cvijanovich, Natalie Z.; Singh, Aalok R.; Crandall, Hillary A.; Thomas, Neal J.; Cullimore, Melissa L.; Patel, Manish M.; Randolph, Adrienne G.; Pediatric Intensive Care Influenza; Overcoming COVID-19 Investigators; Pediatrics, School of MedicineBackground: Clinical differences between critical illness from influenza infection vs coronavirus disease 2019 (COVID-19) have not been well characterized in pediatric patients. Methods: We compared demographics, clinical characteristics, and outcomes of US children (aged 8 months to 17 years) admitted to the intensive care or high-acuity unit with influenza or COVID-19. Using mixed-effects models, we assessed the odds of death or requiring life support for influenza vs 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 years 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%), and a shorter hospital stay (median, 5 days vs 7 days). 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% confidence interval, .78-2.15; P = .32). 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.Item Multisystem Inflammatory Syndrome in Children — Initial Therapy and Outcomes(Massachusetts Medical Society, 2021-07-01) Son, Mary Beth F.; Murray, Nancy; Friedman, Kevin; Young, Cameron C.; Newhams, Margaret M.; Feldstein, Leora R.; Loftis, Laura L.; Tarquinio, Keiko M.; Singh, Aalok R.; Heidemann, Sabrina M.; Soma, Vijaya L.; Riggs, Becky J.; Fitzgerald, Julie C.; Kong, Michele; Doymaz, Sule; Giuliano, John S., Jr.; Keenaghan, Michael A.; Hume, Janet R.; Hobbs, Charlotte V.; Schuster, Jennifer E.; Clouser, Katharine N.; Hall, Mark W.; Smith, Lincoln S.; Horwitz, Steven M.; Schwartz, Stephanie P.; Irby, Katherine; Bradford, Tamara T.; Maddux, Aline B.; Babbitt, Christopher J.; Rowan, Courtney M.; McLaughlin, Gwenn E.; Yager, Phoebe H.; Maamari, Mia; Mack, Elizabeth H.; Carroll, Christopher L.; Montgomery, Vicki L.; Halasa, Natasha B.; Cvijanovich, Natalie Z.; Coates, Bria M.; Rose, Charles E.; Newburger, Jane W.; Patel, Manish M.; Randolph, Adrienne G.; Pediatrics, School of MedicineBackground: The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. Methods: We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. Results: A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis. Conclusions: Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.).