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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 Extracorporeal Membrane Oxygenation Characteristics and Outcomes in Children and Adolescents With COVID-19 or Multisystem Inflammatory Syndrome Admitted to U.S. ICUs(Wolters Kluwer, 2023) Bembea, Melania M.; Loftis, Laura L.; Thiagarajan, Ravi R.; Young, Cameron C.; McCadden, Timothy P.; Newhams, Margaret M.; Kucukak, Suden; Mack, Elizabeth H.; Fitzgerald, Julie C.; Rowan, Courtney M.; Maddux, Aline B.; Kolmar, Amanda R.; Irby, Katherine; Heidemann, Sabrina; Schwartz, Stephanie P.; Kong, Michele; Crandall, Hillary; Havlin, Kevin M.; Singh, Aalok R.; Schuster, Jennifer E.; Hall, Mark W.; Wellnitz, Kari A.; Maamari, Mia; Gaspers, Mary G.; Nofziger, Ryan A.; Lim, Peter Paul C.; Carroll, Ryan W.; Munoz, Alvaro Coronado; Bradford, Tamara T.; Cullimore, Melissa L.; Halasa, Natasha B.; McLaughlin, Gwenn E.; Pannaraj, Pia S.; Cvijanovich, Natalie Z.; Zinter, Matt S.; Coates, Bria M.; Horwitz, Steven M.; Hobbs, Charlotte V.; Dapul, Heda; Graciano, Ana Lia; Butler, Andrew D.; Patel, Manish M.; Zambrano, Laura D.; Campbell, Angela P.; Randolph, Adrienne G.; Overcoming COVID-19 Investigators; Pediatrics, School of MedicineObjectives: Extracorporeal membrane oxygenation (ECMO) has been used successfully to support adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cardiac or respiratory failure refractory to conventional therapies. Comprehensive reports of children and adolescents with SARS-CoV-2-related ECMO support for conditions, including multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19, are needed. Design: Case series of patients from the Overcoming COVID-19 public health surveillance registry. Setting: Sixty-three hospitals in 32 U.S. states reporting to the registry between March 15, 2020, and December 31, 2021. Patients: Patients less than 21 years admitted to the ICU meeting Centers for Disease Control criteria for MIS-C or acute COVID-19. Interventions: None. Measurements and main results: The final cohort included 2,733 patients with MIS-C ( n = 1,530; 37 [2.4%] requiring ECMO) or acute COVID-19 ( n = 1,203; 71 [5.9%] requiring ECMO). ECMO patients in both groups were older than those without ECMO support (MIS-C median 15.4 vs 9.9 yr; acute COVID-19 median 15.3 vs 13.6 yr). The body mass index percentile was similar in the MIS-C ECMO versus no ECMO groups (89.9 vs 85.8; p = 0.22) but higher in the COVID-19 ECMO versus no ECMO groups (98.3 vs 96.5; p = 0.03). Patients on ECMO with MIS-C versus COVID-19 were supported more often with venoarterial ECMO (92% vs 41%) for primary cardiac indications (87% vs 23%), had ECMO initiated earlier (median 1 vs 5 d from hospitalization), shorter ECMO courses (median 3.9 vs 14 d), shorter hospital length of stay (median 20 vs 52 d), lower in-hospital mortality (27% vs 37%), and less major morbidity at discharge in survivors (new tracheostomy, oxygen or mechanical ventilation need or neurologic deficit; 0% vs 11%, 0% vs 20%, and 8% vs 15%, respectively). Most patients with MIS-C requiring ECMO support (87%) were admitted during the pre-Delta (variant B.1.617.2) period, while most patients with acute COVID-19 requiring ECMO support (70%) were admitted during the Delta variant period. Conclusions: ECMO support for SARS-CoV-2-related critical illness was uncommon, but type, initiation, and duration of ECMO use in MIS-C and acute COVID-19 were markedly different. Like pre-pandemic pediatric ECMO cohorts, most patients survived to hospital discharge.Item Health Impairments in Children and Adolescents After Hospitalization for Acute COVID-19 or MIS-C(American Academy of Pediatrics, 2022) Maddux, Aline B.; Berbert, Laura; Young, Cameron C.; Feldstein, Leora R.; Zambrano, Laura D.; Kucukak, Suden; Newhams, Margaret M.; Miller, Kristen; FitzGerald, Madyson M.; He, Jie; Halasa, Natasha B.; Cvijanovich, Natalie Z.; Loftis, Laura L.; Walker, Tracie C.; Schwartz, Stephanie P.; Gertz, Shira J.; Tarquinio, Keiko M.; Fitzgerald, Julie C.; Kong, Michele; Schuster, Jennifer E.; Mack, Elizabeth H.; Hobbs, Charlotte V.; Rowan, Courtney M.; Staat, Mary A.; Zinter, Matt S.; Irby, Katherine; Crandall, Hillary; Flori, Heidi; Cullimore, Melissa L.; Nofziger, Ryan A.; Shein, Steven L.; Glas Gaspers, Mary; Hume, Janet R.; Levy, Emily R.; Chen, Sabrina R.; Patel, Manish M.; Tenforde, Mark W.; Weller, Edie; Campbell, Angela P.; Randolph, Adrienne G.; Overcoming COVID-19 Investigators; Pediatrics, School of MedicineObjectives: To evaluate risk factors for postdischarge sequelae in children and adolescents hospitalized for acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome in children (MIS-C). Methods: Multicenter prospective cohort study conducted in 25 United States pediatric hospitals. Patients <21-years-old, hospitalized May 2020 to May 2021 for acute COVID-19 or MIS-C with follow-up 2 to 4 months after admission. We assessed readmissions, persistent symptoms or activity impairment, and new morbidities. Multivariable regression was used to calculate adjusted risk ratios (aRR) and 95% confidence intervals (CI). Results: Of 358 eligible patients, 2 to 4 month survey data were available for 119 of 155 (76.8%) with acute COVID-19 and 160 of 203 (78.8%) with MIS-C. Thirteen (11%) patients with acute COVID-19 and 12 (8%) with MIS-C had a readmission. Thirty-two (26.9%) patients with acute COVID-19 had persistent symptoms (22.7%) or activity impairment (14.3%) and 48 (30.0%) with MIS-C had persistent symptoms (20.0%) or activity impairment (21.3%). For patients with acute COVID-19, persistent symptoms (aRR, 1.29 [95% CI, 1.04-1.59]) and activity impairment (aRR, 1.37 [95% CI, 1.06-1.78]) were associated with more organ systems involved. Patients with MIS-C and pre-existing respiratory conditions more frequently had persistent symptoms (aRR, 3.09 [95% CI, 1.55-6.14]) and those with obesity more frequently had activity impairment (aRR, 2.52 [95% CI, 1.35-4.69]). New morbidities were infrequent (9% COVID-19, 1% MIS-C). Conclusions: Over 1 in 4 children hospitalized with acute COVID-19 or MIS-C experienced persistent symptoms or activity impairment for at least 2 months. Patients with MIS-C and respiratory conditions or obesity are at higher risk of prolonged recovery.Item Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome(AMA, 2021-03) LaRovere, Kerri L.; Riggs, Becky J.; Poussaint, Tina Y.; Young, Cameron C.; Newhams, Margaret M.; Maamari, Mia; Walker, Tracie C.; Singh, Aalok R.; Dapul, Heda; Hobbs, Charlotte V.; McLaughlin, Gwenn E.; Son, Mary Beth F.; Maddux, Aline B.; Clouser, Katharine N.; Rowan, Courtney M.; McGuire, John K.; Fitzgerald, Julie C.; Gertz, Shira J.; Shein, Steven L.; Munoz, Alvaro Coronado; Thomas, Neal J.; Irby, Katherine; Levy, Emily R.; Staat, Mary A.; Tenforde, Mark W.; Feldstein, Leora R.; Halasa, Natasha B.; Giuliano, John S.; Hall, Mark W.; Kong, Michele; Carroll, Christopher L.; Schuster, Jennifer E.; Doymaz, Sule; Loftis, Laura L.; Tarquinio, Keiko M.; Babbitt, Christopher J.; Nofziger, Ryan A.; Kleinman, Lawrence C.; Keenaghan, Michael A.; Cvijanovich, Natalie Z.; Spinella, Philip C.; Hume, Janet R.; Wellnitz, Kari; Mack, Elizabeth H.; Michelson, Kelly N.; Flori, Heidi R.; Patel, Manish M.; Randolph, Adrienne G.; Overcoming COVID-19 Investigators; Gaspers, Mary G; Typpo, Katri V; Sanders, Ronald C; Schwarz, Adam J; Harvey, Helen; Zinter, Matt S; Mourani, Peter M; Coates, Bria M; Bhoojhawon, Guru; Havlin, Kevin M; Montgomery, Vicki L; Sullivan, Janice E; Bradford, Tamara T; Bembea, Melania M; Lipton, Susan V; Graciano, Ana Lia; Chen, Sabrina R; Kucukak, Suden; Newburger, Jane W; Carroll, Ryan W; Fernandes, Neil D; Yager, Phoebe H; Marohn, Kimberly L; Heidemann, Sabrina M; Cullimore, Melissa L; McCulloh, Russell J; Horwitz, Steven M; Li, Simon; Walsh, Rowan F; Ratner, Adam J; Soma, Vijaya L; Gillen, Jennifer K; Zackai, Sheemon P; Ackerman, Kate G; Cholette, Jill M; Harwayne-Gidansky, Ilana; Hymes, Saul R; Overby, Philip J; Schwartz, Stephanie P; Lansell, Amanda N; Koncicki, Monica L; Carcillo, Joseph; Fink, Ericka; Kimura, Dai; Bowens, Cindy; Crandall, Hillary; Smith, Lincoln S; Cengiz, Pelin; Pediatrics, School of MedicineImportance 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.Item Neurological and Psychological Sequelae Associated With Multisystem Inflammatory Syndrome in Children(American Medical Association, 2023-07-03) Rollins, Caitlin K.; Calderon, Johanna; Wypij, David; Taylor, Alex M.; Kanjiker, Tahera Sultana Davalji; Rohde, Julia S.; Maiman, Moshe; Zambrano, Laura D.; Newhams, Margaret M.; Rodriguez, Susan; Hart, Nicholas; Worhach, Jennifer; Kucukak, Suden; Poussaint, Tina Y.; Son, Mary Beth F.; Friedman, Matthew L.; Gertz, Shira J.; Hobbs, Charlotte V.; Kong, Michele; Maddux, Aline B.; McGuire, Jennifer L.; Licht, Paul A.; Allen Staat, Mary; Yonker, Lael M.; Mazumdar, Maitreyi; Randolph, Adrienne G.; Campbell, Angela P.; Newburger, Jane W.; Overcoming COVID-19 Investigators; Pediatrics, School of MedicineImportance: Acute neurological involvement occurs in some patients with multisystem inflammatory syndrome in children (MIS-C), but few data report neurological and psychological sequelae, and no investigations include direct assessments of cognitive function 6 to 12 months after discharge. Objective: To characterize neurological, psychological, and quality of life sequelae after MIS-C. Design, setting, and participants: This cross-sectional cohort study was conducted in the US and Canada. Participants included children with MIS-C diagnosed from November 2020 through November 2021, 6 to 12 months after hospital discharge, and their sibling or community controls, when available. Data analysis was performed from August 2022 to May 2023. Exposure: Diagnosis of MIS-C. Main outcomes and measures: A central study site remotely administered a onetime neurological examination and in-depth neuropsychological assessment including measures of cognition, behavior, quality of life, and daily function. Generalized estimating equations, accounting for matching, assessed for group differences. Results: Sixty-four patients with MIS-C (mean [SD] age, 11.5 [3.9] years; 20 girls [31%]) and 44 control participants (mean [SD] age, 12.6 [3.7] years; 20 girls [45%]) were enrolled. The MIS-C group exhibited abnormalities on neurological examination more frequently than controls (15 of 61 children [25%] vs 3 of 43 children [7%]; odds ratio, 4.7; 95% CI, 1.3-16.7). Although the 2 groups performed similarly on most cognitive measures, the MIS-C group scored lower on the National Institutes of Health Cognition Toolbox List Sort Working Memory Test, a measure of executive functioning (mean [SD] scores, 96.1 [14.3] vs 103.1 [10.5]). Parents reported worse psychological outcomes in cases compared with controls, particularly higher scores for depression symptoms (mean [SD] scores, 52.6 [13.1] vs 47.8 [9.4]) and somatization (mean [SD] scores, 55.5 [15.5] vs 47.0 [7.6]). Self-reported (mean [SD] scores, 79.6 [13.1] vs 85.5 [12.3]) and parent-reported (mean [SD] scores, 80.3 [15.5] vs 88.6 [13.0]) quality of life scores were also lower in cases than controls. Conclusions and relevance: In this cohort study, compared with contemporaneous sibling or community controls, patients with MIS-C had more abnormal neurologic examinations, worse working memory scores, more somatization and depression symptoms, and lower quality of life 6 to 12 months after hospital discharge. Although these findings need to be confirmed in larger studies, enhanced monitoring may be warranted for early identification and treatment of neurological and psychological symptoms.Item NFKB2 haploinsufficiency identified via screening for IFN-α2 autoantibodies in children and adolescents hospitalized with SARS-CoV-2-related complications(Elsevier, 2023) Bodansky, Aaron; Vazquez, Sara E.; Chou, Janet; Novak, Tanya; Al-Musa, Amer; Young, Cameron; Newhams, Margaret; Kucukak, Suden; Zambrano, Laura D.; Mitchell, Anthea; Wang, Chung-Yu; Moffitt, Kristin; Halasa, Natasha B.; Loftis, Laura L.; Schwartz, Stephanie P.; Walker, Tracie C.; Mack, Elizabeth H.; Fitzgerald, Julie C.; Gertz, Shira J.; Rowan, Courtney M.; Irby, Katherine; Sanders, Ronald C., Jr.; Kong, Michele; Schuster, Jennifer E.; Staat, Mary A.; Zinter, Matt S.; Cvijanovich, Natalie Z.; Tarquinio, Keiko M.; Coates, Bria M.; Flori, Heidi R.; Dahmer, Mary K.; Crandall, Hillary; Cullimore, Melissa L.; Levy, Emily R.; Chatani, Brandon; Nofziger, Ryan; Overcoming COVID-19 Network Study Group Investigators; Geha, Raif S.; DeRisi, Joseph; Campbell, Angela P.; Anderson, Mark; Randolph, Adrienne G.; Pediatrics, School of MedicineBackground: Autoantibodies against type I IFNs occur in approximately 10% of adults with life-threatening coronavirus disease 2019 (COVID-19). The frequency of anti-IFN autoantibodies in children with severe sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. Objective: We quantified anti-type I IFN autoantibodies in a multicenter cohort of children with severe COVID-19, multisystem inflammatory syndrome in children (MIS-C), and mild SARS-CoV-2 infections. Methods: Circulating anti-IFN-α2 antibodies were measured by a radioligand binding assay. Whole-exome sequencing, RNA sequencing, and functional studies of peripheral blood mononuclear cells were used to study any patients with levels of anti-IFN-α2 autoantibodies exceeding the assay's positive control. Results: Among 168 patients with severe COVID-19, 199 with MIS-C, and 45 with mild SARS-CoV-2 infections, only 1 had high levels of anti-IFN-α2 antibodies. Anti-IFN-α2 autoantibodies were not detected in patients treated with intravenous immunoglobulin before sample collection. Whole-exome sequencing identified a missense variant in the ankyrin domain of NFKB2, encoding the p100 subunit of nuclear factor kappa-light-chain enhancer of activated B cells, aka NF-κB, essential for noncanonical NF-κB signaling. The patient's peripheral blood mononuclear cells exhibited impaired cleavage of p100 characteristic of NFKB2 haploinsufficiency, an inborn error of immunity with a high prevalence of autoimmunity. Conclusions: High levels of anti-IFN-α2 autoantibodies in children and adolescents with MIS-C, severe COVID-19, and mild SARS-CoV-2 infections are rare but can occur in patients with inborn errors of immunity.Item Risk factors for health impairments in children after hospitalization for acute COVID-19 or MIS-C(Frontiers Media, 2023-10-18) Maddux, Aline B.; Young, Cameron C.; Kucukak, Suden; Zambrano, Laura D.; Newhams, Margaret M.; Rollins, Caitlin K.; Halasa, Natasha B.; Gertz, Shira J.; Mack, Elizabeth H.; Schwartz, Stephanie; Kong, Michele; Loftis, Laura L.; Irby, Katherine; Rowan, Courtney M.; Tarquinio, Keiko M.; Zinter, Matt S.; Crandall, Hillary; Cvijanovich, Natalie Z.; Schuster, Jennifer E.; Fitzgerald, Julie C.; Staat, Mary A.; Hobbs, Charlotte V.; Nofziger, Ryan A.; Shein, Steven; Flori, Heidi; Cullimore, Melissa L.; Chatani, Brandon M.; Levy, Emily R.; Typpo, Katri V.; Hume, Janet R.; Campbell, Angela P.; Randolph, Adrienne G.; Overcoming COVID-19 Investigators; Pediatrics, School of MedicineObjective: To identify risk factors for persistent impairments after pediatric hospitalization for acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic. Methods: Across 25 U.S. Overcoming COVID-19 Network hospitals, we conducted a prospective cohort study of patients <21-years-old hospitalized for acute COVID-19 or MIS-C (May 2020 to March 2022) surveyed 2- to 4-months post-admission. Multivariable regression was used to calculate adjusted risk ratios (aRR) and 95% confidence intervals (CI). Results: Of 232 children with acute COVID-19, 71 (30.6%) had persistent symptoms and 50 (21.6%) had activity impairments at follow-up; for MIS-C (n = 241), 56 (23.2%) had persistent symptoms and 58 (24.1%) had activity impairments. In adjusted analyses of patients with acute COVID-19, receipt of mechanical ventilation was associated with persistent symptoms [aRR 1.83 (95% CI: 1.07, 3.13)] whereas obesity [aRR 2.18 (95% CI: 1.05, 4.51)] and greater organ system involvement [aRR 1.35 (95% CI: 1.13, 1.61)] were associated with activity impairment. For patients with MIS-C, having a pre-existing respiratory condition was associated with persistent symptoms [aRR 3.04 (95% CI: 1.70, 5.41)] whereas obesity [aRR 1.86 (95% CI: 1.09, 3.15)] and greater organ system involvement [aRR 1.26 (1.00, 1.58)] were associated with activity impairments. Discussion: Among patients hospitalized, nearly one in three hospitalized with acute COVID-19 and one in four hospitalized with MIS-C had persistent impairments for ≥2 months post-hospitalization. Persistent impairments were associated with more severe illness and underlying health conditions, identifying populations to target for follow-up.Item Risk Factors for Multisystem Inflammatory Syndrome in Children: A Case-Control Investigation(Wolters Kluwer, 2023) Zambrano, Laura D.; Wu, Michael J.; Martin, Lora; Malloch, Lacy; Chen, Sabrina; Newhams, Margaret M.; Kucukak, Suden; Son, Mary Beth; Sanders, Cameron; Patterson, Kayla; Halasa, Natasha; Fitzgerald, Julie C.; Leroue, Matthew K.; Hall, Mark; Irby, Katherine; Rowan, Courtney M.; Wellnitz, Kari; Sahni, Leila C.; Loftis, Laura; Bradford, Tamara T.; Staat, Mary; Babbitt, Christopher; Carroll, Christopher L.; Pannaraj, Pia S.; Kong, Michele; Schuster, Jennifer E.; Chou, Janet; Patel, Manish M.; Randolph, Adrienne G.; Campbell, Angela P.; Hobbs, Charlotte V.; Overcoming COVID-19 investigators; Pediatrics, School of MedicineBackground: In a 2020 pilot case-control study using medical records, we reported that non-Hispanic Black children were more likely to develop multisystem inflammatory syndrome in children (MIS-C) after adjustment for sociodemographic factors and underlying medical conditions. Using structured interviews, we investigated patient, household, and community factors underlying MIS-C likelihood. Methods: MIS-C case patients hospitalized in 2021 across 14 US pediatric hospitals were matched by age and site to outpatient controls testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 3 months of the admission date. Caregiver interviews queried race/ethnicity, medical history, and household and potential community exposures 1 month before MIS-C hospitalization (case-patients) or after SARS-CoV-2 infection (controls). We calculated adjusted odds ratios (aOR) using mixed-effects multivariable logistic regression. Results: Among 275 case patients and 496 controls, race/ethnicity, social vulnerability and patient or family history of autoimmune/rheumatologic disease were not associated with MIS-C. In previously healthy children, MIS-C was associated with a history of hospitalization for an infection [aOR: 4.8; 95% confidence interval (CI): 2.1-11.0]. Household crowding (aOR: 1.7; 95% CI: 1.2-2.6), large event attendance (aOR: 1.7; 95% CI: 1.3-2.1), school attendance with limited masking (aOR: 2.6; 95% CI: 1.1-6.6), public transit use (aOR: 1.8; 95% CI: 1.4-2.4) and co-resident testing positive for SARS-CoV-2 (aOR: 2.2; 95% CI: 1.3-3.7) were associated with increased MIS-C likelihood, with risk increasing with the number of these factors. Conclusions: From caregiver interviews, we clarify household and community exposures associated with MIS-C; however, we did not confirm prior associations between sociodemographic factors and MIS-C.Item Tachyarrhythmias During Hospitalization for COVID-19 or Multisystem Inflammatory Syndrome in Children and Adolescents(American Heart Association, 2022) Dionne, Audrey; Friedman, Kevin G.; Young, Cameron C.; Newhams, Margaret M.; Kucukak, Suden; Jackson, Ashley M.; Fitzgerald, Julie C.; Smallcomb, Laura S.; Heidemann, Sabrina; McLaughlin, Gwenn E.; Irby, Katherine; Bradford, Tamara T.; Horwitz, Steven M.; Loftis, Laura L.; Soma, Vijaya L.; Rowan, Courtney M.; Kong, Michele; Halasa, Natasha B.; Tarquinio, Keiko M.; Schwarz, Adam J.; Hume, Janet R.; Gertz, Shira J.; Clouser, Katharine N.; Carroll, Christopher L.; Wellnitz, Kari; Cullimore, Melissa L.; Doymaz, Sule; Levy, Emily R.; Typpo, Katri V.; Lansell, Amanda N.; Butler, Andrew D.; Kuebler, Joseph D.; Zambrano, Laura D.; Campbell, Angela P.; Patel, Manish M.; Randolph, Adrienne G.; Newburger, Jane W.; Overcoming COVID-19 Investigators; Pediatrics, School of MedicineBackground: Cardiac complications related to COVID‐19 in children and adolescents include ventricular dysfunction, myocarditis, coronary artery aneurysm, and bradyarrhythmias, but tachyarrhythmias are less understood. The goal of this study was to evaluate the frequency, characteristics, and outcomes of children and adolescents experiencing tachyarrhythmias while hospitalized for acute severe COVID‐19 or multisystem inflammatory syndrome in children. Methods and Results: This study involved a case series of 63 patients with tachyarrhythmias reported in a public health surveillance registry of patients aged <21 years hospitalized from March 15, 2020, to December 31, 2021, at 63 US hospitals. Patients with tachyarrhythmias were compared with patients with severe COVID‐19–related complications without tachyarrhythmias. Tachyarrhythmias were reported in 22 of 1257 patients (1.8%) with acute COVID‐19 and 41 of 2343 (1.7%) patients with multisystem inflammatory syndrome in children. They included supraventricular tachycardia in 28 (44%), accelerated junctional rhythm in 9 (14%), and ventricular tachycardia in 38 (60%); >1 type was reported in 12 (19%). Registry patients with versus without tachyarrhythmia were older (median age, 15.4 [range, 10.4–17.4] versus 10.0 [range, 5.4–14.8] years) and had higher illness severity on hospital admission. Intervention for treatment of tachyarrhythmia was required in 37 (59%) patients and included antiarrhythmic medication (n=31, 49%), electrical cardioversion (n=11, 17%), cardiopulmonary resuscitation (n=8, 13%), and extracorporeal membrane oxygenation (n=9, 14%). Patients with tachyarrhythmias had longer hospital length of stay than those who did not, and 9 (14%) versus 77 (2%) died. Conclusions: Tachyarrhythmias were a rare complication of acute severe COVID‐19 and multisystem inflammatory syndrome in children and adolescents and were associated with worse clinical outcomes, highlighting the importance of close monitoring, aggressive treatment, and postdischarge care.Item Tachyarrhythmias During Hospitalization for COVID-19 or Multisystem Inflammatory Syndrome in Children and Adolescents(American Heart Association, 2022-10-18) Dionne, Audrey; Friedman, Kevin G.; Young, Cameron C.; Newhams, Margaret M.; Kucukak, Suden; Jackson , Ashley M.; Fitzgerland , Julie C.; Smallcomb, Laura S.; Heidemann, Sabrina; McLaughlin , Gwenn E.; Irby, Katherine; Bradford, Tamara T.; Horwitz, Steven M.; Loftis, Laura L.; Soma, Vijaya L.; Rowan, Courtney M.; Kong, Michele; Halasa, Natasha B.; Tarquinio, Keiko M.; Schwartz, Adam J.; Hume, Janet R.; Gertz, Shira J.; Clouser, Katharine N.; Carroll, Christopher L.; Wellnitz, Kari; Cullimore , Melissa L.; Doymaz, Sule; Levy, Emily R.; Typpo, Katri V.; Lansell, Amanda N.; Butler, Andrew D.; Kuebler, Joseph D.; Zambrano, Laura D.; Campbell, Angela P.; Patel, Manish M.; Randolph, Andrienne G.; Newburger, Jane W.; Overcoming COVID‐19 Investigators; Pediatrics, School of MedicineBackground Cardiac complications related to COVID‐19 in children and adolescents include ventricular dysfunction, myocarditis, coronary artery aneurysm, and bradyarrhythmias, but tachyarrhythmias are less understood. The goal of this study was to evaluate the frequency, characteristics, and outcomes of children and adolescents experiencing tachyarrhythmias while hospitalized for acute severe COVID‐19 or multisystem inflammatory syndrome in children. Methods and Results This study involved a case series of 63 patients with tachyarrhythmias reported in a public health surveillance registry of patients aged <21 years hospitalized from March 15, 2020, to December 31, 2021, at 63 US hospitals. Patients with tachyarrhythmias were compared with patients with severe COVID‐19–related complications without tachyarrhythmias. Tachyarrhythmias were reported in 22 of 1257 patients (1.8%) with acute COVID‐19 and 41 of 2343 (1.7%) patients with multisystem inflammatory syndrome in children. They included supraventricular tachycardia in 28 (44%), accelerated junctional rhythm in 9 (14%), and ventricular tachycardia in 38 (60%); >1 type was reported in 12 (19%). Registry patients with versus without tachyarrhythmia were older (median age, 15.4 [range, 10.4–17.4] versus 10.0 [range, 5.4–14.8] years) and had higher illness severity on hospital admission. Intervention for treatment of tachyarrhythmia was required in 37 (59%) patients and included antiarrhythmic medication (n=31, 49%), electrical cardioversion (n=11, 17%), cardiopulmonary resuscitation (n=8, 13%), and extracorporeal membrane oxygenation (n=9, 14%). Patients with tachyarrhythmias had longer hospital length of stay than those who did not, and 9 (14%) versus 77 (2%) died. Conclusions Tachyarrhythmias were a rare complication of acute severe COVID‐19 and multisystem inflammatory syndrome in children and adolescents and were associated with worse clinical outcomes, highlighting the importance of close monitoring, aggressive treatment, and postdischarge care.