Durability of Original Monovalent mRNA Vaccine Effectiveness Against COVID-19 Omicron-Associated Hospitalization in Children and Adolescents - United States, 2021-2023.

Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite the high frequency of reported underlying conditions associated with severe COVID-19. VE of the original monovalent vaccine against COVID-19-related hospitalizations was 52% (95% CI = 33%-66%) when the most recent dose was administered <120 days before hospitalization and 19% (95% CI = 2%-32%) if the interval was 120-364 days. VE of the original monovalent vaccine against COVID-19-related hospitalization was 31% (95% CI = 18%-43%) if the last dose was received any time within the previous year. VE against critical COVID-19-related illness, defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death, was 57% (95% CI = 21%-76%) when the most recent dose was received <120 days before hospitalization, 25% (95% CI = -9% to 49%) if it was received 120-364 days before hospitalization, and 38% (95% CI = 15%-55%) if the last dose was received any time within the previous year. VE was similar after excluding children and adolescents with documented immunocompromising conditions. Because of the low frequency of children who received updated COVID-19 vaccines and waning effectiveness of original monovalent doses, these data support CDC recommendations that all children and adolescents receive updated COVID-19 vaccines to protect against severe COVID-19.

Characteristics and Clinical Outcomes of Vaccine-Eligible US Children Under-5 Years Hospitalized for Acute COVID-19 in a National Network.

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.

Effectiveness of Maternal mRNA COVID-19 Vaccination During Pregnancy Against COVID-19-Associated Hospitalizations in Infants Aged <6 Months During SARS-CoV-2 Omicron Predominance - 20 States, March 9, 2022-May 31, 2023.

Infants aged <6 months are not eligible for COVID-19 vaccination. Vaccination during pregnancy has been associated with protection against infant COVID-19-related hospitalization. The Overcoming COVID-19 Network conducted a case-control study during March 9, 2022-May 31, 2023, to evaluate the effectiveness of maternal receipt of a COVID-19 vaccine dose (vaccine effectiveness [VE]) during pregnancy against COVID-19-related hospitalization in infants aged <6 months and a subset of infants aged <3 months. VE was calculated as (1 - adjusted odds ratio) x 100% among all infants aged <6 months and <3 months. Case-patients (infants hospitalized for COVID-19 outside of birth hospitalization and who had a positive SARS-CoV-2 test result) and control patients (infants hospitalized for COVID-19-like illness with a negative SARS-CoV-2 test result) were compared. Odds ratios were determined using multivariable logistic regression, comparing the odds of receipt of a maternal COVID-19 vaccine dose (completion of a 2-dose vaccination series or a third or higher dose) during pregnancy with maternal nonvaccination between case- and control patients. VE of maternal vaccination during pregnancy against COVID-19-related hospitalization was 35% (95% CI = 15%-51%) among infants aged <6 months and 54% (95% CI = 32%-68%) among infants aged <3 months. Intensive care unit admissions occurred in 23% of all case-patients, and invasive mechanical ventilation was more common among infants of unvaccinated (9%) compared with vaccinated mothers (1%) (p = 0.02). Maternal vaccination during pregnancy provides some protection against COVID-19-related hospitalizations among infants, particularly those aged <3 months. Expectant mothers should remain current with COVID-19 vaccination to protect themselves and their infants from hospitalization and severe outcomes associated with COVID-19.

Optimizing Education During Pediatric Resident Mock Code Sessions.

INTRODUCTION: Most pediatric residents have limited opportunities to manage cardiac arrest. We used simulation to fill that educational void. Given work hours and other obligations, resident education sessions must be high-yield. We examined the effectiveness of adding varying amounts of formal education to a mock code session on resident knowledge and confidence in managing pediatric cardiac arrest compared with participation alone. METHODS: Convenient groups of 3 to 8 pediatric residents completed a simulation session with the identical scenario: a 3-month-old infant with pulseless ventricular tachycardia and then pulseless electrical activity. All residents completed pretests and posttests, which consisted of open-ended knowledge questions from the American Heart Association Pediatric Advanced Life Support guidelines and confidence Likert scale assessments. Resident groups were assigned to 1 of 3 educational models: experiential-only: participation in the mock, traditional: mock code participation with standardized education after the mock code, or reinforced: standardized education before and after mock code participation. RESULTS: Ninety-five residents participated. Collectively, residents demonstrated a median 2-point (interquartile range, 1-4) increase in knowledge (test maximum score, 10) after they attended a mock code simulation session ( P < 0.0001); however, there were no statistically significant differences noted between educational modalities. All residents also demonstrated a 4-point median increase in confidence (test maximum score, 25) after completing their simulation session (interquartile range, 3-6) ( P < 0.001), but no differences were seen by type or amount of accompanying education. CONCLUSIONS: Residents had gains in confidence and knowledge of pediatric cardiac arrest management after participation in the mock code. Formal educational sessions and reinforced formal education sessions accompanying the mock code did not significantly increase knowledge or confidence.

Unpacking the renal system component of the "structure and function" core concept of physiology by an Australian team.

An Australia-wide consensus was reached on seven core concepts of physiology, one of which was "structure and function" with the descriptor "Structure and function are intrinsically related to all levels of the organism. In all physiological systems, the structure from a microscopic level to an organ level dictates its function." As a framework for the structure and function core concept, the renal system was unpacked by a team of 5 Australian Physiology educators from different universities with extensive teaching experience into hierarchical levels, with 5 themes and 25 subthemes up to 3 levels deep. Within theme 1, the structures that comprise the renal system were unpacked. Within theme 2, the physiological processes within the nephron such as filtration, reabsorption, and secretion were unpacked. Within theme 3, the processes involved in micturition were unpacked. In theme 4, the structures and processes involved in regulating renal blood flow and glomerular filtration were unpacked; and within theme 5, the role of the kidney in red blood cell production was unpacked. Twenty-one academics rated the difficulty and importance of each theme/subtheme, and results were analyzed using a one-way ANOVA. All identified themes were validated as "essential" to "important"/"moderately important" and rated between "difficult" to "not difficult." A similar framework consisting of structure, physiological processes, physical processes, and regulation can be used to unpack other body systems. Unpacking of the body systems will provide a list of what students should be taught in curricula across Australian universities and inform assessment and learning activities.NEW & NOTEWORTHY This is the first attempt to unpack and validate the "structure and function" core concept in physiology with all Australian educators. We unpacked the renal system into themes with hierarchical levels, which were validated by an experienced team of Australian physiology educators. Our unpacking of the "structure and function" core concept provides a specific framework for educators to apply this important concept in physiology education.

Establishing consensus for the core concepts of physiology in the Australian higher education context using the Delphi method.

A set of core concepts ("big ideas") integral to the discipline of physiology are important for students to understand and demonstrate their capacity to apply. We found poor alignment of learning outcomes in programs with physiology majors (or equivalent) from 17 Australian universities and the 15 core concepts developed by a team in the United States. The objective of this project was to reach Australia-wide consensus on a set of core concepts for physiology, which can be embedded in curricula across Australian universities. A four-phase Delphi method was employed, starting with the assembling of a Task Force of physiology educators with extensive teaching and curriculum development expertise from 25 Australian universities. After two online meetings and a survey, the Task Force reached agreement on seven core concepts of physiology and their descriptors, which were then sent out to the physiology educator community across Australia for agreement. The seven core concepts and their associated descriptions were endorsed through this process (n = 138). In addition, embedding the core concepts across the curriculum was supported by both Task Force members (85.7%) and educators (82.1%). The seven adopted core concepts of human physiology were Cell Membrane, Cell-Cell Communication, Movement of Substances, Structure and Function, Homeostasis, Integration, and Physiological Adaptation. The core concepts were subsequently unpacked into themes and subthemes. If adopted, these core concepts will result in consistency across curricula in undergraduate physiology programs and allow for future benchmarking.NEW & NOTEWORTHY This is the first time Australia-wide agreement has been reached on the core concepts of physiology with the Delphi method. Embedding of the core concepts will result in consistency in physiology curricula, improvements to teaching and learning, and benchmarking across Australian universities.

Factors Associated With COVID-19 Non-vaccination in Adolescents Hospitalized Without COVID-19.

BACKGROUND: Pfizer-BioNTech COVID-19 vaccine received emergency use authorization for persons ≥ 16 years in December 2020 and for adolescents 12-15 years in May 2021. Despite the clear benefits and favorable safety profile, vaccine uptake in adolescents has been suboptimal. We sought to assess factors associated with COVID-19 non-vaccination in adolescents 12-18 years of age. METHODS: Between June 1, 2021 and April 29, 2022, we assessed factors associated with COVID-19 non-vaccination in hospitalized adolescents ages 12-18 years enrolled in the Overcoming COVID-19 vaccine effectiveness network. Demographic characteristics and clinical information were captured through parent interviews and/or electronic medical record abstraction; COVID-19 vaccination was assessed through documented sources. We assessed associations between receipt of the COVID-19 vaccine and demographic and clinical factors using univariate and multivariable logistic regression and estimated adjusted odds ratios (aOR) for each factor associated with non-vaccination. RESULTS: Among 1665 hospitalized adolescents without COVID-19, 56% were unvaccinated. Unvaccinated adolescents were younger (median age 15.1 years vs. 15.4 years, p < .01) and resided in areas with higher social vulnerability index (SVI) scores (median 0.6 vs 0.5, p < .001) than vaccinated adolescents. Residence in the Midwest [aOR 2.60 (95% CI: 1.80, 3.79)] or South [aOR 2.49 (95% CI: 1.77, 3.54)] US census regions, rarely or never receiving influenza vaccine [aOR 5.31 (95% CI: 3.81, 7.47)], and rarely or never taking precautions against COVID-19 [aOR 3.17 (95% CI: 1.94, 5.31)] were associated with non-vaccination against COVID-19. CONCLUSIONS: Efforts to increase COVID-19 vaccination of adolescents should focus on persons with geographic, socioeconomic, and medical risk factors associated with non-vaccination.

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.

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.

Maternal Vaccination and Risk of Hospitalization for Covid-19 among Infants.

BACKGROUND: Infants younger than 6 months of age are at high risk for complications of coronavirus disease 2019 (Covid-19) and are not eligible for vaccination. Transplacental transfer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after maternal Covid-19 vaccination may confer protection against Covid-19 in infants. METHODS: We used a case-control test-negative design to assess the effectiveness of maternal vaccination during pregnancy against hospitalization for Covid-19 among infants younger than 6 months of age. Between July 1, 2021, and March 8, 2022, we enrolled infants hospitalized for Covid-19 (case infants) and infants hospitalized without Covid-19 (control infants) at 30 hospitals in 22 states. We estimated vaccine effectiveness by comparing the odds of full maternal vaccination (two doses of mRNA vaccine) among case infants and control infants during circulation of the B.1.617.2 (delta) variant (July 1, 2021, to December 18, 2021) and the B.1.1.259 (omicron) variant (December 19, 2021, to March 8, 2022). RESULTS: A total of 537 case infants (181 of whom had been admitted to a hospital during the delta period and 356 during the omicron period; median age, 2 months) and 512 control infants were enrolled and included in the analyses; 16% of the case infants and 29% of the control infants had been born to mothers who had been fully vaccinated against Covid-19 during pregnancy. Among the case infants, 113 (21%) received intensive care (64 [12%] received mechanical ventilation or vasoactive infusions). Two case infants died from Covid-19; neither infant's mother had been vaccinated during pregnancy. The effectiveness of maternal vaccination against hospitalization for Covid-19 among infants was 52% (95% confidence interval [CI], 33 to 65) overall, 80% (95% CI, 60 to 90) during the delta period, and 38% (95% CI, 8 to 58) during the omicron period. Effectiveness was 69% (95% CI, 50 to 80) when maternal vaccination occurred after 20 weeks of pregnancy and 38% (95% CI, 3 to 60) during the first 20 weeks of pregnancy. CONCLUSIONS: Maternal vaccination with two doses of mRNA vaccine was associated with a reduced risk of hospitalization for Covid-19, including for critical illness, among infants younger than 6 months of age. (Funded by the Centers for Disease Control and Prevention.).

BNT162b2 Protection against the Omicron Variant in Children and Adolescents.

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.).

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.

COVID-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.

Effectiveness of BNT162b2 Vaccine against Critical Covid-19 in Adolescents.

BACKGROUND: 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.).

Effectiveness of BNT162b2 (Pfizer-BioNTech) mRNA Vaccination Against Multisystem Inflammatory Syndrome in Children Among Persons Aged 12-18 Years - United States, July-December 2021.

Multisystem inflammatory syndrome in children (MIS-C) is a severe postinfectious hyperinflammatory condition, which generally occurs 2-6 weeks after a typically mild or asymptomatic infection with SARS-CoV-2, the virus that causes COVID-19 (1-3). In the United States, the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine is currently authorized for use in children and adolescents aged 5-15 years under an Emergency Use Authorization and is fully licensed by the Food and Drug Administration for persons aged ≥16 years (4). Prelicensure randomized trials in persons aged ≥5 years documented high vaccine efficacy and immunogenicity (5),§ and real-world studies in persons aged 12-18 years demonstrated high vaccine effectiveness (VE) against severe COVID-19 (6). Recent evidence suggests that COVID-19 vaccination is associated with lower MIS-C incidence among adolescents (7); however, VE of the 2-dose Pfizer-BioNTech regimen against MIS-C has not been evaluated. The effectiveness of 2 doses of Pfizer-BioNTech vaccine received ≥28 days before hospital admission in preventing MIS-C was assessed using a test-negative case-control design¶ among hospitalized patients aged 12-18 years at 24 pediatric hospitals in 20 states** during July 1-December 9, 2021, the period when most MIS-C patients could be temporally linked to SARS-CoV-2 B.1.617.2 (Delta) variant predominance. Patients with MIS-C (case-patients) and two groups of hospitalized controls matched to case-patients were evaluated: test-negative controls had at least one COVID-19-like symptom and negative SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) or antigen-based assay results, and syndrome-negative controls were hospitalized patients without COVID-19-like illness. Among 102 MIS-C case-patients and 181 hospitalized controls, estimated effectiveness of 2 doses of Pfizer-BioNTech vaccine against MIS-C was 91% (95% CI = 78%-97%). All 38 MIS-C patients requiring life support were unvaccinated. Receipt of 2 doses of the Pfizer-BioNTech vaccine is associated with a high level of protection against MIS-C in persons aged 12-18 years, highlighting the importance of vaccination among all eligible children.

Effectiveness of Pfizer-BioNTech mRNA Vaccination Against COVID-19 Hospitalization Among Persons Aged 12-18 Years - United States, June-September 2021.

Pfizer-BioNTech COVID-19 vaccine is authorized for use in children and adolescents aged 12-15 years and is licensed by the Food and Drug Administration (FDA) for persons aged ≥16 (1). A randomized placebo-controlled trial demonstrated an efficacy of 100% (95% confidence interval [CI] = 75.3%-100%) in preventing outpatient COVID-19 in persons aged 12-15 years (2); however, data among adolescents on vaccine effectiveness (VE) against COVID-19 in real-world settings are limited, especially among hospitalized patients. In early September 2021, U.S. pediatric COVID-19 hospitalizations reached the highest level during the pandemic (3,4). In a test-negative, case-control study at 19 pediatric hospitals in 16 states during June 1-September 30, 2021, the effectiveness of 2 doses of Pfizer-BioNTech vaccine against COVID-19 hospitalization was assessed among children and adolescents aged 12-18 years. Among 464 hospitalized persons aged 12-18 years (179 case-patients and 285 controls), the median age was 15 years, 72% had at least one underlying condition, including obesity, and 68% attended in-person school. Effectiveness of 2 doses of Pfizer-BioNTech vaccine against COVID-19 hospitalization was 93% (95% CI = 83%-97%), during the period when B.1.617.2 (Delta) was the predominant variant. This evaluation demonstrated that 2 doses of Pfizer-BioNTech vaccine are highly effective at preventing COVID-19 hospitalization among persons aged 12-18 years and reinforces the importance of vaccination to protect U.S. youths against severe COVID-19.

To Be or No B2: A Rare Cause of Stridor and Weakness in a Toddler.

We present a case of a young child with a rare metabolic disorder whose clinical presentation resembled that of autoimmune myasthenia gravis. The differential diagnosis was expanded when autoantibody testing was negative and the patient did not respond to standard immunomodulatory therapies. Rapid whole genome sequencing identified 2 rare variants of uncertain significance in the SLC52A3 gene shown to be in compound heterozygous state after parental testing. Biallelic mutations in SLC52A3 are associated with Riboflavin Transporter Deficiency, which in its untreated form, results in progressive neurodegeneration and death. Supplementation with oral riboflavin has been shown to limit disease progression and improve symptoms in some patients. When the diagnosis is suspected, patients should be started on supplementation immediately while awaiting results from genetic studies.

Distinct Effects of a High Fat Diet on Bone in Skeletally Mature and Developing Male C57BL/6J Mice.

Increased risks of skeletal fractures are common in patients with impaired glucose handling and type 2 diabetes mellitus (T2DM). The pathogenesis of skeletal fragility in these patients remains ill-defined as patients present with normal to high bone mineral density. With increasing cases of glucose intolerance and T2DM it is imperative that we develop an accurate rodent model for further investigation. We hypothesized that a high fat diet (60%) administered to developing male C57BL/6J mice that had not reached skeletal maturity would over represent bone microarchitectural implications, and that skeletally mature mice would better represent adult-onset glucose intolerance and the pre-diabetes phenotype. Two groups of developing (8 week) and mature (12 week) male C57BL/6J mice were placed onto either a normal chow (NC) or high fat diet (HFD) for 10 weeks. Oral glucose tolerance tests were performed throughout the study period. Long bones were excised and analysed for ex vivo biomechanical testing, micro-computed tomography, 2D histomorphometry and gene/protein expression analyses. The HFD increased fasting blood glucose and significantly reduced glucose tolerance in both age groups by week 7 of the diets. The HFD reduced biomechanical strength, both cortical and trabecular indices in the developing mice, but only affected cortical outcomes in the mature mice. Similar results were reflected in the 2D histomorphometry. Tibial gene expression revealed decreased bone formation in the HFD mice of both age groups, i.e., decreased osteocalcin expression and increased sclerostin RNA expression. In the mature mice only, while the HFD led to a non-significant reduction in runt-related transcription factor 2 (Runx2) RNA expression, this decrease became significant at the protein level in the femora. Our mature HFD mouse model more accurately represents late-onset impaired glucose tolerance/pre-T2DM cases in humans and can be used to uncover potential insights into reduced bone formation as a mechanism of skeletal fragility in these patients.

Osteocalcin and measures of adiposity: a systematic review and meta-analysis of observational studies.

Osteocalcin, the osteoblast-derived protein, has been shown to be modulated in patients with problematic glucose metabolism. Our systematic review and meta-analysis found that in humans, higher blood osteocalcin level is associated with lower body indices of fat. PURPOSE/INTRODUCTION: Osteocalcin (OC) was found to be inversely correlated with measures of glucose and energy metabolism, with some groups suggesting the undercarboxylated form (ucOC) to be metabolically active, although the link is not clear, especially in humans. Given obesity is a major risk factor for metabolic disorders, we aimed to assess the correlation between OC and two measures of body weight: body mass index (BMI) and percentage body fat (%BF). METHODS: MEDLINE and EMBASE were searched to identify observational studies in adult populations that reported the crude correlation coefficients (r) between OC and BMI and %BF. Pool r were obtained using random-effects models. RESULTS: Fifty-one publications were included in this analysis. Both total OC (TOC) (pooled r = - 0.151, 95% CI - 0.17, - 0.130; I2 = 52%) and ucOC (pooled r = - 0.060, 95% CI - 0.103, - 0.016; I2 = 54%) were inversely correlated with BMI. The pooled r between TOC and BMI in Caucasian-and-other-regions (r = - 0.187) were stronger than those in Asian populations (r = - 0.126; intra-group p = 0.002; R2 = 0.21). The mean/median BMI of the reported cohort was the major contributor to between-study heterogeneity in correlation between TOC/ucOC and BMI (R2 = 0.28 and 0.77, respectively). Both TOC and ucOC were also inversely correlated with %BF (TOC: pooled r = - 0.185, 95% CI - 0.257 to - 0.112; ucOC: pooled r = - 0.181, 95% CI - 0.258 to - 0.101). CONCLUSION: Higher OC and ucOC were correlated with lower BMI and %BF. The inverse correlations between TOC/ucOC and BMI appear to be affected by ethnicity and obesity status.

Female fertility preservation in DSD.

Disorders of sex development (DSD) are a group of complex conditions that can affect chromosomal, gonadal, and/or phenotypical sex with a highly variable fertility potential amongst affected individuals. In this review we discuss fertility issues facing patients affected by DSD and Turner syndrome and summarise the literature on fertility and reproductive outcomes. We will also discuss fertility preservation prior to gonadotoxic treatment in adolescent and prepubertal girls. Future directions in fertility preservation and ethical issues will also be addressed. Fertility preserving options that are established include ovarian tissue and oocyte cryopreservation. However, in many of the DSDs fertility is not possible and the discussion may need to move toward alternative methods of creating a family such as gamete donation or surrogacy.

Different vasodilator mechanisms in intermediate- and small-sized arteries from the hindlimb vasculature of the toad Rhinella marina.

In this study, myography was used to determine the effect of arterial size on nitric oxide (NO) vasodilatory mechanisms in the hindlimb vasculature of the toad Rhinella marina. Immunohistochemical analysis showed NO synthase (NOS) 1 immunoreactivity in perivascular nitrergic nerves in the iliac and sciatic arteries. Furthermore, NOS3 immunoreactivity was observed in the vascular smooth muscle of the sciatic artery, but not the endothelium. Acetylcholine (ACh) was used to facilitate intracellular Ca2+ signaling to activate vasodilatory pathways in the arteries. In the iliac artery, ACh-mediated vasodilation was abolished by blockade of the soluble guanylate cyclase pathway with the soluble guanylate cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, 10-5 M) and blockade of the prostaglandin signaling pathway with indomethacin (10-5 M). Furthermore, disruption of the endothelium had no effect on the ACh-mediated vasodilation in the iliac artery, and generic inhibition of NOS with Nω-nitro-l-arginine (3 × 10-4 M) significantly inhibited the vasodilation, indicating NO signaling. In contrast to the iliac artery, ACh-mediated vasodilation of the sciatic artery had a significant endothelium-dependent component. Interestingly, the vasodilation was not significantly affected by Nω-nitro-l-arginine, but it was significantly inhibited by the specific NOS1 inhibitor N5-(1-imino-3-butenyl)-l-ornithine (vinyl-l-NIO, 10-4 M). ODQ mostly inhibited the ACh-mediated vasodilation. In addition, indomethacin also significantly inhibited the ACh-mediated vasodilation, indicating a role for prostaglandins in the sciatic artery. This study found that the mechanisms of vasodilation in the hindlimb vasculature of R. marina vary with vessel size and that the endothelium is involved in vasodilation in the smaller sciatic artery.