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Item 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 MedicineBackground: 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.Item 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 MedicineBackground: 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.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 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 MedicineBackground 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.Item 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 MedicineItem Effectiveness of BNT162b2 Vaccine against Critical Covid-19 in Adolescents(Massachusetts Medical Society, 2022) Olson, Samantha M.; Newhams, Margaret M.; Halasa, Natasha B.; Price, Ashley M.; Boom, Julie A.; Sahni, Leila C.; Pannaraj, Pia S.; Irby, Katherine; Walker, Tracie C.; Schwartz, Stephanie P.; Maddux, Aline B.; Mack, Elizabeth H.; Bradford, Tamara T.; Schuster, Jennifer E.; Nofziger, Ryan A.; Cameron, Melissa A.; Chiotos, Kathleen; Cullimore, Melissa L.; Gertz, Shira J.; Levy, Emily R.; Kong, Michele; Cvijanovich, Natalie Z.; Staat, Mary A.; Kamidani, Satoshi; Chatani, Brandon M.; Bhumbra, Samina S.; Bline, Katherine E.; Gaspers, Mary G.; Hobbs, Charlotte V.; Heidemann, Sabrina M.; Maamari, Mia; Flori, Heidi R.; Hume, Janet R.; Zinter, Matt S.; Michelson, Kelly N.; Zambrano, Laura D.; Campbell, Angela P.; Patel, Manish M.; Randolph, Adrienne G.; Pediatrics, School of MedicineBackground: The increasing incidence of pediatric hospitalizations associated with coronavirus disease 2019 (Covid-19) caused by the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United States has offered an opportunity to assess the real-world effectiveness of the BNT162b2 messenger RNA vaccine in adolescents between 12 and 18 years of age. Methods: We used a case-control, test-negative design to assess vaccine effectiveness against Covid-19 resulting in hospitalization, admission to an intensive care unit (ICU), the use of life-supporting interventions (mechanical ventilation, vasopressors, and extracorporeal membrane oxygenation), or death. Between July 1 and October 25, 2021, we screened admission logs for eligible case patients with laboratory-confirmed Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2) in case patients as compared with two hospital-based control groups: patients who had Covid-19-like symptoms but negative results on testing for SARS-CoV-2 (test-negative) and patients who did not have Covid-19-like symptoms (syndrome-negative). Results: A total of 445 case patients and 777 controls were enrolled. Overall, 17 case patients (4%) and 282 controls (36%) had been fully vaccinated. Of the case patients, 180 (40%) were admitted to the ICU, and 127 (29%) required life support; only 2 patients in the ICU had been fully vaccinated. The overall effectiveness of the BNT162b2 vaccine against hospitalization for Covid-19 was 94% (95% confidence interval [CI], 90 to 96); the effectiveness was 95% (95% CI, 91 to 97) among test-negative controls and 94% (95% CI, 89 to 96) among syndrome-negative controls. The effectiveness was 98% against ICU admission and 98% against Covid-19 resulting in the receipt of life support. All 7 deaths occurred in patients who were unvaccinated. Conclusions: Among hospitalized adolescent patients, two doses of the BNT162b2 vaccine were highly effective against Covid-19-related hospitalization and ICU admission or the receipt of life support. (Funded by the Centers for Disease Control and Prevention.).Item Effectiveness of Maternal Vaccination with mRNA COVID-19 Vaccine During Pregnancy Against COVID-19–Associated Hospitalization in Infants Aged <6 Months — 17 States, July 2021–January 2022(Center for Disease Control, 2022-02-18) Halasa, Natasha B.; Olson, Samantha M.; Staat, Mary A.; Newhams, Margaret M.; Price, Ashley M.; Boom, Julie A.; Sahni, Leila C.; Cameron, Melissa A.; Pannaraj, Pia S.; Bline, Katherine E.; Bhumbra, Samina S.; Bradford, Tamara T.; Chiotos, Kathleen; Coates, Bria M.; Cullimore, Melissa L.; Cvijanovich, Natalie Z.; Flori, Heidi R.; Gertz, Shira J.; Heidemann, Sabrina M.; Hobbs, Charlotte V.; Hume, Janet R.; Irby, Katherine; Kamidani, Satoshi; Kong, Michele; Levy, Emily R.; Mack, Elizabeth H.; Maddux, Aline B.; Michelson, Kelly N.; Nofziger, Ryan A.; Schuster, Jennifer E.; Schwartz, Stephanie P.; Smallcomb, Laura; Tarquinio, Keiko M.; Walker, Tracie C.; Zinter, Matt S.; Gilboa, Suzanne M.; Polen, Kara N.; Campbell, Angela P.; Randolph, Adrienne G.; Patel, Manish M.; Overcoming COVID-19 Investigators; Overcoming COVID-19 Network; Pediatrics, School of MedicineCOVID-19 vaccination is recommended for persons who are pregnant, breastfeeding, trying to get pregnant now, or who might become pregnant in the future, to protect them from COVID-19.§ Infants are at risk for life-threatening complications from COVID-19, including acute respiratory failure (1). Evidence from other vaccine-preventable diseases suggests that maternal immunization can provide protection to infants, especially during the high-risk first 6 months of life, through passive transplacental antibody transfer (2). Recent studies of COVID-19 vaccination during pregnancy suggest the possibility of transplacental transfer of SARS-CoV-2-specific antibodies that might provide protection to infants (3-5); however, no epidemiologic evidence currently exists for the protective benefits of maternal immunization during pregnancy against COVID-19 in infants. The Overcoming COVID-19 network conducted a test-negative, case-control study at 20 pediatric hospitals in 17 states during July 1, 2021-January 17, 2022, to assess effectiveness of maternal completion of a 2-dose primary mRNA COVID-19 vaccination series during pregnancy against COVID-19 hospitalization in infants. Among 379 hospitalized infants aged <6 months (176 with COVID-19 [case-infants] and 203 without COVID-19 [control-infants]), the median age was 2 months, 21% had at least one underlying medical condition, and 22% of case- and control-infants were born premature (<37 weeks gestation). Effectiveness of maternal vaccination during pregnancy against COVID-19 hospitalization in infants aged <6 months was 61% (95% CI = 31%-78%). Completion of a 2-dose mRNA COVID-19 vaccination series during pregnancy might help prevent COVID-19 hospitalization among infants aged <6 months.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 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 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.
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