Browsing by Author "Irby, Katherine"

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    237. A Case-Control Study Investigating Household, Community, and Clinical Risk Factors Associated with Multisystem Inflammatory Syndrome in Children (MIS-C) after SARS-CoV-2 Infection
    (Oxford University Press, 2022) Zambrano, Laura D.; Wu, Michael J.; Martin, Lora M.; Malloch, Lacy; Newhams, Margaret M.; Son, Mary Beth; Sanders, Cameron; Patterson, Kayla; Halasa, Natasha B.; Fitzgerald, Julie C.; Leroue, Matthew; Hall, Mark; Irby, Katherine; Rowan, Courtney M.; Wellnitz, Kari; Loftis, Laura L.; Bradford, Tamara T.; Staat, Mary A.; Babbit, Christopher; Carroll, Christopher L.; Pannaraj, Pia S.; Kong, Michele; Chou, Janet; Patel, Manish M.; Randolph, Adrienne G.; Campbell, Angela P.; Hobbs, Charlotte V.; Medicine, School of Medicine
    Background: Risk factors for MIS-C, a rare but serious hyperinflammatory syndrome associated with SARS-CoV-2 infection, remain unclear. We evaluated household, clinical, and environmental risk factors potentially associated with MIS-C. Methods: This investigation included MIS-C cases hospitalized in 14 US pediatric hospitals in 2021. Outpatient controls were frequency-matched to case-patients by age group and site and had a positive SARS-CoV-2 viral test within 3 months of the admission of their matched MIS-C case (Figure 1). We conducted telephone surveys with caregivers and evaluated potential risk factors using mixed effects multivariable logistic regression, including site as a random effect. We queried regarding exposures within the month before hospitalization for MIS-C cases or the month after a positive COVID-19 test for controls. Enrollment scheme for MIS-C case-patients and SARS-CoV-2-positive outpatient controls. MIS-C case-patients were identified through hospital electronic medical records, while two outpatient controls per case were identified through registries of outpatient SARS-CoV-2 testing logs at facilities affiliated with that medical center. Caregivers of outpatient controls were interviewed at least four weeks after their positive test to ensure they did not develop MIS-C after their infection. Results: We compared 275 MIS-C case-patients with 494 outpatient SARS-CoV-2-positive controls. Race, ethnicity and social vulnerability indices were similar. MIS-C was more likely among persons who resided in households with >1 resident per room (aOR=1.6, 95% CI: 1.1–2.2), attended a large (≥10 people) event with little to no mask-wearing (aOR=2.2, 95% CI: 1.4–3.5), used public transportation (aOR=1.6, 95% CI: 1.2–2.1), attended school >2 days per week with little to no mask wearing (aOR=2.1, 95% CI: 1.0–4.4), or had a household member test positive for COVID-19 (aOR=2.1, 95% CI: 1.3–3.3). MIS-C was less likely among children with comorbidities (aOR=0.5, 95% CI: 0.3–0.9) and in those who had >1 positive SARS-CoV-2 test at least 1 month apart (aOR=0.4, 95% CI: 0.2–0.6). MIS-C was not associated with a medical history of recurrent infections or family history of underlying rheumatologic disease. Conclusion: Household crowding, limited masking at large indoor events or schools and use of public transportation were associated with increased likelihood of developing MIS-C after SARS-CoV-2 infection. In contrast, decreased likelihood of MIS-C was associated with having >1 SARS-CoV-2 positive test separated by at least a month. Our data suggest that additional studies are needed to determine if viral load, and/or recurrent infections in the month prior to MIS-C contribute to MIS-C risk. Medical and family history were not associated with MIS-C in our analysis.
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    Author Correction: Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C
    (Springer Nature, 2022-08-12) Tang, Juanjie; Novak, Tanya; Hecker, Julian; Grubbs, Gabrielle; Zahra, Fatema Tuz; Bellusci, Lorenza; Pourhashemi, Sara; Chou, Janet; Moffitt, Kristin; Halasa, Natasha B.; Schwartz, Stephanie P.; Walker, Tracie C.; Tarquinio, Keiko M.; Zinter, Matt S.; Staat, Mary A.; Gertz, Shira J.; Cvijanovich, Natalie Z.; Schuster, Jennifer E.; Loftis, Laura L.; Coates, Bria M.; Mack, Elizabeth H.; Irby, Katherine; Fitzgerald, Julie C.; Rowan, Courtney M.; Kong, Michele; Flori, Heidi R.; Maddux, Aline B.; Shein, Steven L.; Crandall, Hillary; Hume, Janet R.; Hobbs, Charlotte V.; Tremoulet, Adriana H.; Shimizu, Chisato; Burns, Jane C.; Chen, Sabrina R.; Moon, Hye Kyung; Lange, Christoph; Randolph, Adrienne G.; Khurana, Surender; Pediatrics, School of Medicine
    Correction to: Nature Communications 10.1038/s41467-022-30649-1, published online 27 May 2022
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    BNT162b2 mRNA Vaccination Against Coronavirus Disease 2019 is Associated With a Decreased Likelihood of Multisystem Inflammatory Syndrome in Children Aged 5-18 Years-United States, July 2021 - April 2022
    (Oxford University Press, 2023) Zambrano, Laura D.; Newhams, Margaret M.; Olson, Samantha M.; Halasa, Natasha B.; Price, Ashley M.; Orzel, Amber O.; Young, Cameron C.; Boom, Julie A.; Sahni, Leila C.; Maddux, Aline B.; Bline, Katherine E.; Kamidani, Satoshi; Tarquinio, Keiko M.; Chiotos, Kathleen; Schuster, Jennifer E.; Cullimore, Melissa L.; Heidemann, Sabrina M.; Hobbs, Charlotte V.; Nofziger, Ryan A.; Pannaraj, Pia S.; Cameron, Melissa A.; Walker, Tracie C.; Schwartz, Stephanie P.; Michelson, Kelly N.; Coates, Bria M.; Flori, Heidi R.; Mack, Elizabeth H.; Smallcomb, Laura; Gertz, Shira J.; Bhumbra, Samina S.; Bradford, Tamara T.; Levy, Emily R.; Kong, Michele; Irby, Katherine; Cvijanovich, Natalie Z.; Zinter, Matt S.; Bowens, Cindy; Crandall, Hillary; Hume, Janet R.; Patel, Manish M.; Campbell, Angela P.; Randolph, Adrienne G.; Overcoming COVID-19 Investigators; Pediatrics, School of Medicine
    Background: Multisystem inflammatory syndrome in children (MIS-C), linked to antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with considerable morbidity. Prevention of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) by vaccination might also decrease MIS-C likelihood. Methods: In a multicenter, case-control, public health investigation of children ages 5-18 years hospitalized from 1 July 2021 to 7 April 2022, we compared the odds of being fully vaccinated (2 doses of BNT162b2 vaccine ≥28 days before hospital admission) between MIS-C case-patients and hospital-based controls who tested negative for SARS-CoV-2. These associations were examined by age group, timing of vaccination, and periods of Delta and Omicron variant predominance using multivariable logistic regression. Results: We compared 304 MIS-C case-patients (280 [92%] unvaccinated) with 502 controls (346 [69%] unvaccinated). MIS-C was associated with decreased likelihood of vaccination (adjusted OR [aOR]: .16; 95% CI: .10-.26), including among children ages 5-11 years (aOR: .22; 95% CI: .10-.52), ages 12-18 years (aOR: .10; 95% CI: .05-.19), and during the Delta (aOR: .06; 95% CI: .02-.15) and Omicron (aOR: .22; 95% CI: .11-.42) variant-predominant periods. This association persisted beyond 120 days after the second dose (aOR: .08; 95% CI: .03-.22) in 12-18-year-olds. Among all MIS-C case-patients, 187 (62%) required intensive care unit admission and 280 (92%) vaccine-eligible case-patients were unvaccinated. Conclusions: Vaccination with 2 doses of BNT162b2 is associated with reduced likelihood of MIS-C in children ages 5-18 years. Most vaccine-eligible hospitalized patients with MIS-C were unvaccinated.
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    BNT162b2 Protection against the Omicron Variant in Children and Adolescents
    (Massachusetts Medical Society, 2022) Price, Ashley M.; Olson, Samantha M.; Newhams, Margaret M.; Halasa, Natasha B.; Boom, Julie A.; Sahni, Leila C.; Pannaraj, Pia S.; Irby, Katherine; Bline, Katherine E.; Maddux, Aline B.; Nofziger, Ryan A.; Cameron, Melissa A.; Walker, Tracie C.; Schwartz, Stephanie P.; Mack, Elizabeth H.; Smallcomb, Laura; Schuster, Jennifer E.; Hobbs, Charlotte V.; Kamidani, Satoshi; Tarquinio, Keiko M.; Bradford, Tamara T.; Levy, Emily R.; Chiotos, Kathleen; Bhumbra, Samina S.; Cvijanovich, Natalie Z.; Heidemann, Sabrina M.; Cullimore, Melissa L.; Gertz, Shira J.; Coates, Bria M.; Staat, Mary A.; Zinter, Matt S.; Kong, Michele; Chatani, Brandon M.; Hume, Janet R.; Typpo, Katri V.; Maamari, Mia; Flori, Heidi R.; Tenforde, Mark W.; Zambrano, Laura D.; Campbell, Angela P.; Patel, Manish M.; Randolph, Adrienne G.; Overcoming Covid-19 Investigators; Pediatrics, School of Medicine
    Background: Spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant, which led to increased U.S. hospitalizations for coronavirus disease 2019 (Covid-19), generated concern about immune evasion and the duration of protection from vaccines in children and adolescents. Methods: Using a case-control, test-negative design, we assessed vaccine effectiveness against laboratory-confirmed Covid-19 leading to hospitalization and against critical Covid-19 (i.e., leading to receipt of life support or to death). From July 1, 2021, to February 17, 2022, we enrolled case patients with Covid-19 and controls without Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2 messenger RNA vaccine) at least 14 days before illness among case patients and controls, according to time since vaccination for patients 12 to 18 years of age and in periods coinciding with circulation of B.1.617.2 (delta) (July 1, 2021, to December 18, 2021) and omicron (December 19, 2021, to February 17, 2022) among patients 5 to 11 and 12 to 18 years of age. Results: We enrolled 1185 case patients (1043 [88%] of whom were unvaccinated, 291 [25%] of whom received life support, and 14 of whom died) and 1627 controls. During the delta-predominant period, vaccine effectiveness against hospitalization for Covid-19 among adolescents 12 to 18 years of age was 93% (95% confidence interval [CI], 89 to 95) 2 to 22 weeks after vaccination and was 92% (95% CI, 80 to 97) at 23 to 44 weeks. Among adolescents 12 to 18 years of age (median interval since vaccination, 162 days) during the omicron-predominant period, vaccine effectiveness was 40% (95% CI, 9 to 60) against hospitalization for Covid-19, 79% (95% CI, 51 to 91) against critical Covid-19, and 20% (95% CI, -25 to 49) against noncritical Covid-19. During the omicron period, vaccine effectiveness against hospitalization among children 5 to 11 years of age was 68% (95% CI, 42 to 82; median interval since vaccination, 34 days). Conclusions: BNT162b2 vaccination reduced the risk of omicron-associated hospitalization by two thirds among children 5 to 11 years of age. Although two doses provided lower protection against omicron-associated hospitalization than against delta-associated hospitalization among adolescents 12 to 18 years of age, vaccination prevented critical illness caused by either variant.
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    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 Medicine
    Importance: 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.
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    Characteristics and Clinical Outcomes of Vaccine-Eligible US Children Under-5 Years Hospitalized for Acute COVID-19 in a National Network
    (Wolters Kluwer, 2024) Zambrano, Laura D.; Newhams, Margaret M.; Simeone, Regina M.; Fleming-Dutra, Katherine E.; Halasa, Natasha; Wu, Michael; Orzel-Lockwood, Amber O.; Kamidani, Satoshi; Pannaraj, Pia S.; Chiotos, Kathleen; Cameron, Melissa A.; Maddux, Aline B.; Schuster, Jennifer E.; Crandall, Hillary; Kong, Michele; Nofziger, Ryan A.; Staat, Mary A.; Bhumbra, Samina S.; Irby, Katherine; Boom, Julie A.; Sahni, Leila C.; Hume, Janet R.; Gertz, Shira J.; Maamari, Mia; Bowens, Cindy; Levy, Emily R.; Bradford, Tamara T.; Walker, Tracie C.; Schwartz, Stephanie P.; Mack, Elizabeth H.; Guzman-Cottrill, Judith A.; Hobbs, Charlotte V.; Zinter, Matt S.; Cvijanovich, Natalie Z.; Bline, Katherine E.; Hymes, Saul R.; Campbell, Angela P.; Randolph, Adrienne G.; Overcoming COVID-19 Investigators; Pediatrics, School of Medicine
    Background and objectives: In June 2022, the mRNA COVID-19 vaccination was recommended for young children. We examined clinical characteristics and factors associated with vaccination status among vaccine-eligible young children hospitalized for acute COVID-19. Methods: We enrolled inpatients 8 months to <5 years of age with acute community-acquired COVID-19 across 28 US pediatric hospitals from September 20, 2022 to May 31, 2023. We assessed demographic and clinical factors, including the highest level of respiratory support, and vaccination status defined as unvaccinated, incomplete, or complete primary series [at least 2 (Moderna) or 3 (Pfizer-BioNTech) mRNA vaccine doses ≥14 days before hospitalization]. Results: Among 597 children, 174 (29.1%) patients were admitted to the intensive care unit and 75 (12.6%) had a life-threatening illness, including 51 (8.5%) requiring invasive mechanical ventilation. Children with underlying respiratory and neurologic/neuromuscular conditions more frequently received higher respiratory support. Only 4.5% of children hospitalized for COVID-19 (n = 27) had completed their primary COVID-19 vaccination series and 7.0% (n = 42) of children initiated but did not complete their primary series. Among 528 unvaccinated children, nearly half (n = 251) were previously healthy, 3 of them required extracorporeal membrane oxygenation for acute COVID-19 and 1 died. Conclusions: Most young children hospitalized for acute COVID-19, including most children admitted to the intensive care unit and with life-threatening illness, had not initiated COVID-19 vaccination despite being eligible. Nearly half of these children had no underlying conditions. Of the small percentage of children who initiated a COVID-19 primary series, most had not completed it before hospitalization.
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    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 Medicine
    Importance 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.
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    Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C
    (Springer Nature, 2022-05-27) Tang, Juanjie; Novak, Tanya; Hecker, Julian; Grubbs, Gabrielle; Tuz Zahra, Fatema; Bellusci, Lorenza; Pourhashemi, Sara; Chou, Janet; Moffitt, Kristin; Halasa, Natasha B.; Schwartz, Stephanie P.; Walker, Tracie C.; Tarquinio, Keiko M.; Zinter, Matt S.; Staat, Mary A.; Gertz, Shira J.; Cvijanovich, Natalie Z.; Schuster, Jennifer E.; Loftis, Laura L.; Coates, Bria M.; Mack, Elizabeth H.; Irby, Katherine; Fitzgerald, Julie C.; Rowan, Courtney M.; Kong, Michele; Flori, Heidi R.; Maddux, Aline B.; Shein, Steven L.; Crandall, Hillary; Hume, Janet R.; Hobbs, Charlotte V.; Tremoulet, Adriana H.; Shimizu, Chisato; Burns, Jane C.; Chen, Sabrina R.; Moon, Hye Kyung; Lange, Christoph; Randolph, Adrienne G.; Khurana, Surender; Pediatrics, School of Medicine
    Neutralization capacity of antibodies against Omicron after a prior SARS-CoV-2 infection in children and adolescents is not well studied. Therefore, we evaluated virus-neutralizing capacity against SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants by age-stratified analyses (<5, 5-11, 12-21 years) in 177 pediatric patients hospitalized with severe acute COVID-19, acute MIS-C, and in convalescent samples of outpatients with mild COVID-19 during 2020 and early 2021. Across all patients, less than 10% show neutralizing antibody titers against Omicron. Children <5 years of age hospitalized with severe acute COVID-19 have lower neutralizing antibodies to SARS-CoV-2 variants compared with patients >5 years of age. As expected, convalescent pediatric COVID-19 and MIS-C cohorts demonstrate higher neutralization titers than hospitalized acute COVID-19 patients. Overall, children and adolescents show some loss of cross-neutralization against all variants, with the most pronounced loss against Omicron. In contrast to SARS-CoV-2 infection, children vaccinated twice demonstrated higher titers against Alpha, Beta, Gamma, Delta and Omicron. These findings can influence transmission, re-infection and the clinical disease outcome from emerging SARS-CoV-2 variants and supports the need for vaccination in children.
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    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 Medicine
    Background 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.
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    Effectiveness of BNT162b2 (Pfizer-BioNTech) mRNA Vaccination Against Multisystem Inflammatory Syndrome in Children Among Persons Aged 12–18 Years — United States, July–December 2021
    (U.S. Department of Health & Human Services, 2022-01-14) Zambrano, Laura D.; Newhams, Margaret M.; Olson, Samantha M.; Halasa, Natasha B.; Price, Ashley M.; Boom, Julie A.; Sahni, Leila C.; Kamidani, Satoshi; Tarquinio, Keiko M.; Maddux, Aline B.; Heidemann, Sabrina M.; Bhumbra, Samina S.; Bline, Katherine E.; Nofziger, Ryan A.; Hobbs, Charlotte V.; Bradford, Tamara T.; Cvijanovich , Natalie Z.; Irby, Katherine; Mack, Elizabeth H.; Cullimore, Melissa L.; Pannaraj, Pia S.; Kong, Michele; Walker, Tracie C.; Gertz, Shira J.; Michelson, Kelly N.; Cameron, Melissa A.; Chiotos, Kathleen; Maamari, Mia; Schuster, Jennifer E.; Orzel, Amber O.; Patel, Manish M.; Campbell, Angela P.; Randolph, Adrienne G.; Overcoming COVID-19 Investigators; Pediatrics, School of Medicine