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. (Funded by the Centers for Disease Control and Prevention.)

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Objective The epidemiology and outcomes of Multiple Organ Dysfunction Syndrome (MODS) are incompletely characterized in the pediatric population due to small sample size and conflicting diagnoses of organ failure. We sought to describe the epidemiology and outcomes of early MODS in a large clinical database of PICU patients based on consensus definitions of organ failure. Design Retrospective analysis of a contemporaneously collected clinical PICU database. Setting VPICU Performance System (VPS) database patient admissions from 1/2004-12/2005 for 35 US children’s hospitals. Patients We evaluated 63,285 consecutive PICU admissions from 1/2004-12/2005 in the VPS database. We excluded patients <1 month or >18 years of age, and hospitals with >10% missing values for MODS variables. We identified day 1 MODS by International Pediatric Sepsis Consensus Conference (IPSCC) criteria with day 1 laboratory and vital sign values. We evaluated functional status using Pediatric Overall Performance Category (POPC) and Pediatric Cerebral Performance Category (PCPC) scores from PICU admission and discharge. Interventions Analysis: Student’s t-test, Χ2, Mann-Whitney rank sum, Kruskal-Wallis, linear and logistic regression. Measurements and Main Results We analyzed 44,693 admissions from 28 hospitals meeting inclusion criteria. Overall PICU mortality was 2.8%. We identified day 1 MODS in 18.6% of admissions. Patients with day 1 MODS had higher mortality (10.0% v. 1.2%, p<0.001), longer PICU length of stay (3.6 v. 1.3 days, p<0.001) and larger change from baseline POPC and PCPC scores at time of PICU discharge (p<0.001). Infants had the highest incidence of day 1 MODS (25.2% vs. 16.5%, p<0.001) compared to other age groups. Conclusions Using the largest clinical dataset to date and consensus definitions for organ failure, we found that children with MODS present on day one of ICU admission have worse functional outcomes, higher mortality, and longer PICU length of stay than children who do not have MODS on day one. Infants are disproportionally affected by MODS.