Molecular Transducers of Physical Activity Consortium (MoTrPAC): Human Studies Design and Protocol.

Physical activity, including structured exercise, is associated with favorable health-related chronic disease outcomes. While there is evidence of various molecular pathways that affect these responses, a comprehensive molecular map of these molecular responses to exercise has not been developed. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a multi-center study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. MoTrPAC contains both a pre-clinical and human component. The details of the human studies component of MoTrPAC that include the design and methods are presented here. The human studies contain both an adult and pediatric component. In the adult component, sedentary participants are randomized to 12 weeks of Control, Endurance Exercise Training, or Resistance Exercise Training with outcomes measures completed before and following the 12 weeks. The adult component also includes recruitment of highly active endurance trained or resistance trained participants who only complete measures once. A similar design is used for the pediatric component; however, only endurance exercise is examined. Phenotyping measures include weight, body composition, vital signs, cardiorespiratory fitness, muscular strength, physical activity and diet, and other questionnaires. Participants also complete an acute rest period (adults only) or exercise session (adults, pediatrics) with collection of biospecimens (blood only for pediatrics) to allow for examination of the molecular responses. The design and methods of MoTrPAC may inform other studies. Moreover, MoTrPAC will provide a repository of data that can be used broadly across the scientific community.

Signal Variability Comparative Analysis of Healthy Early- and Late-Pubertal Children during Cardiopulmonary Exercise Testing.

PURPOSE: The kinetics of physiological responses to exercise have traditionally been characterized by estimating exponential equation parameters using iterative best-fit techniques of heart rate (HR) and gas exchange (respiratory rate, oxygen uptake (V̇O 2 ), carbon dioxide output, and ventilation). In this study, we present a novel approach to characterizing the maturation of physiological responses to exercise in children by accounting for response uncertainty and variability. METHODS: Thirty-seven early-pubertal (17 females, 20 males) and 44 late-pubertal (25 females, 19 males) participants performed three multiple brief exercise bouts (MBEB). MBEB consisted of ten 2-min bouts of cycle ergometry at constant work rate interspersed by 1-min rest. Exercise intensity was categorized as low, moderate, or high, corresponding to 40%, 60%, and 80% of peak work rate, and performed in random order on 3 separate days. We evaluated sample entropy (SampEn), approximate entropy, detrended fluctuation analysis, and average absolute local variability of HR and gas exchange. RESULTS: SampEn of HR and gas-exchange responses to MBEB was greater in early- compared with late-pubertal participants (e.g., V̇O 2 early-pubertal vs late-pubertal, 1.70 ± 0.023 vs 1.41 ± 0.027; P = 2.97 × 10 -14 ), and decreased as MBEB intensity increased (e.g., 0.37 ± 0.01 HR for low-intensity compared with 0.21 ± 0.014 for high intensity, P = 3.56 × 10 -17 ). Females tended to have higher SampEn than males (e.g., 1.61 ± 0.025 V̇O 2 for females vs 1.46 ± 0.031 for males, P = 1.28 × 10 -4 ). Average absolute local variability was higher in younger participants for both gas exchange and HR (e.g., early-pubertal vs late-pubertal V̇O 2 , 17.48 % ± 0.56% vs 10.24 % ± 0.34%; P = 1.18 × 10 -21 ). CONCLUSIONS: The greater entropy in signal response to a known, quantifiable exercise perturbation in the younger children might represent maturation-dependent, enhanced competition among physiological controlling mechanisms that originate at the autonomic, subconscious, and cognitive levels.

Formative Evaluation of a Student Symptom Decision Tree for COVID-19.

Objectives: In support of schools restarting during the COVID-19 pandemic, some schools partnered with local experts in academia, education, community, and public health to provide decision-support tools for determining what actions to take when presented with students at risk for spreading infection at school. Methods: The Student Symptom Decision Tree, developed in Orange County, California, is a flow chart consisting of branching logic and definitions to assist school personnel in making decisions regarding possible COVID-19 cases in schools which was repeatedly updated to reflect evolving evidence-based guidelines. A survey of 56 school personnel evaluated the frequency of use, acceptability, feasibility, appropriateness, usability, and helpfulness of the Decision Tree. Results: The tool was used at least 6 times a week by 66% of respondents. The Decision Tree was generally perceived as acceptable (91%), feasible (70%), appropriate (89%), usable (71%) and helpful (95%). Suggestions for improvement included reducing the complexity in content and formatting of the tool. Conclusions: The data suggest that school personnel found value in the Decision Tree, which was intended to assist them with making decisions in a challenging and rapidly evolving pandemic.

Real-world performance of SARS-Cov-2 serology tests in the United States, 2020.

BACKGROUND: Real-world performance of COVID-19 diagnostic tests under Emergency Use Authorization (EUA) must be assessed. We describe overall trends in the performance of serology tests in the context of real-world implementation. METHODS: Six health systems estimated the odds of seropositivity and positive percent agreement (PPA) of serology test among people with confirmed SARS-CoV-2 infection by molecular test. In each dataset, we present the odds ratio and PPA, overall and by key clinical, demographic, and practice parameters. RESULTS: A total of 15,615 people were observed to have at least one serology test 14-90 days after a positive molecular test for SARS-CoV-2. We observed higher PPA in Hispanic (PPA range: 79-96%) compared to non-Hispanic (60-89%) patients; in those presenting with at least one COVID-19 related symptom (69-93%) as compared to no such symptoms (63-91%); and in inpatient (70-97%) and emergency department (93-99%) compared to outpatient (63-92%) settings across datasets. PPA was highest in those with diabetes (75-94%) and kidney disease (83-95%); and lowest in those with auto-immune conditions or who are immunocompromised (56-93%). The odds ratios (OR) for seropositivity were higher in Hispanics compared to non-Hispanics (OR range: 2.59-3.86), patients with diabetes (1.49-1.56), and obesity (1.63-2.23); and lower in those with immunocompromised or autoimmune conditions (0.25-0.70), as compared to those without those comorbidities. In a subset of three datasets with robust information on serology test name, seven tests were used, two of which were used in multiple settings and met the EUA requirement of PPA ≥87%. Tests performed similarly across datasets. CONCLUSION: Although the EUA requirement was not consistently met, more investigation is needed to understand how serology and molecular tests are used, including indication and protocol fidelity. Improved data interoperability of test and clinical/demographic data are needed to enable rapid assessment of the real-world performance of in vitro diagnostic tests.

Real-world utilization of SARS-CoV-2 serological testing in RNA positive patients across the United States.

BACKGROUND: As diagnostic tests for COVID-19 were broadly deployed under Emergency Use Authorization, there emerged a need to understand the real-world utilization and performance of serological testing across the United States. METHODS: Six health systems contributed electronic health records and/or claims data, jointly developed a master protocol, and used it to execute the analysis in parallel. We used descriptive statistics to examine demographic, clinical, and geographic characteristics of serology testing among patients with RNA positive for SARS-CoV-2. RESULTS: Across datasets, we observed 930,669 individuals with positive RNA for SARS-CoV-2. Of these, 35,806 (4%) were serotested within 90 days; 15% of which occurred <14 days from the RNA positive test. The proportion of people with a history of cardiovascular disease, obesity, chronic lung, or kidney disease; or presenting with shortness of breath or pneumonia appeared higher among those serotested compared to those who were not. Even in a population of people with active infection, race/ethnicity data were largely missing (>30%) in some datasets-limiting our ability to examine differences in serological testing by race. In datasets where race/ethnicity information was available, we observed a greater distribution of White individuals among those serotested; however, the time between RNA and serology tests appeared shorter in Black compared to White individuals. Test manufacturer data was available in half of the datasets contributing to the analysis. CONCLUSION: Our results inform the underlying context of serotesting during the first year of the COVID-19 pandemic and differences observed between claims and EHR data sources-a critical first step to understanding the real-world accuracy of serological tests. Incomplete reporting of race/ethnicity data and a limited ability to link test manufacturer data, lab results, and clinical data challenge the ability to assess the real-world performance of SARS-CoV-2 tests in different contexts and the overall U.S. response to current and future disease pandemics.

Regulatory T-cells and GARP expression are decreased in exercise-associated chikungunya viral arthritis flares.

Objective: Chikungunya virus (CHIKV) causes persistent arthritis, and our prior study showed that approximately one third of CHIKV arthritis patients had exacerbated arthritis associated with exercise. The underlying mechanism of exercise-associated chikungunya arthritis flare (EACAF) is unknown, and this analysis aimed to examine the regulatory T-cell immune response related to CHIKV arthritis flares. Methods: In our study, 124 Colombian patients with a history of CHIKV infection four years prior were enrolled and 113 cases with serologically confirmed CHIKV IgG were used in this analysis. Patient information was gathered via questionnaires, and blood samples were taken to identify total live peripheral blood mononuclear cells, CD4+ cells, T regulatory cells, and their immune markers. We compared outcomes in CHIKV patients with (n = 38) vs. without (n = 75) EACAF using t-tests to assess means and the Fisher's exact test, chi-squared to evaluate categorical variables, and Kruskal-Wallis tests in the setting of skewed distributions (SAS 9.3). Results: 33.6% of CHIKV cases reported worsening arthritis with exercise. EACAF patients reported higher global assessments of arthritis disease ranging from 0-100 (71.2 ± 19.7 vs. 59.9 ± 28.0, p=0.03). EACAF patients had lower ratios of T regulatory (Treg)/CD4+ T-cells (1.95 ± 0.73 vs. 2.4 ± 1.29, p = 0.04) and lower percentage of GARP (glycoprotein-A repetitions predominant) expression per Treg (0.13 ± 0.0.33 vs. 0.16 ± 0.24 p= 0.020). Conclusion: These findings suggest relative decreases in GARP expression may indicate a decreased level of immune suppression. Treg populations in patients with CHIKV arthritis may contribute to arthritis flares during exercise, though current research is conflicting.

Functional Data Analysis for Predicting Pediatric Failure to Complete Ten Brief Exercise Bouts.

Physiological response to physical exercise through analysis of cardiopulmonary measurements has been shown to be predictive of a variety of diseases. Nonetheless, the clinical use of exercise testing remains limited because interpretation of test results requires experience and specialized training. Additionally, until this work no methods have identified which dynamic gas exchange or heart rate responses influence an individual's decision to start or stop physical activity. This research examines the use of advanced machine learning methods to predict completion of a test consisting of multiple exercise bouts by a group of healthy children and adolescents. All participants could complete the ten bouts at low or moderate-intensity work rates, however, when the bout work rates were high-intensity, 50% refused to begin the subsequent exercise bout before all ten bouts had been completed (task failure). We explored machine learning strategies to model the relationship between the physiological time series, the participant's anthropometric variables, and the binary outcome variable indicating whether the participant completed the test. The best performing model, a generalized spectral additive model with functional and scalar covariates, achieved 93.6% classification accuracy and an F1 score of 93.5%. Additionally, functional analysis of variance testing showed that participants in the 'failed' and 'success' groups have significantly different functional means in three signals: heart rate, oxygen uptake rate, and carbon dioxide uptake rate. Overall, these results show the capability of functional data analysis with generalized spectral additive models to identify key differences in the exercise-induced responses of participants in multiple bout exercise testing.

Heart rate and gas exchange dynamic responses to multiple brief exercise bouts (MBEB) in early- and late-pubertal boys and girls.

Natural patterns of physical activity in youth are characterized by brief periods of exercise of varying intensity interspersed with rest. To better understand systemic physiologic response mechanisms in children and adolescents, we examined five responses [heart rate (HR), respiratory rate (RR), oxygen uptake (V̇O2 ), carbon dioxide production (V̇CO2 ), and minute ventilation (V̇E), measured breath-by-breath] to multiple brief exercise bouts (MBEB). Two groups of healthy participants (early pubertal: 17 female, 20 male; late-pubertal: 23 female, 21 male) performed five consecutive 2-min bouts of constant work rate cycle-ergometer exercise interspersed with 1-min of rest during separate sessions of low- or high-intensity (~40% or 80% peak work, respectively). For each 2-min on-transient and 1-min off-transient we calculated the average value of each cardiopulmonary exercise testing (CPET) variable (Y̅). There were significant MBEB changes in 67 of 80 on- and off-transients. Y̅ increased bout-to-bout for all CPET variables, and the magnitude of increase was greater in the high-intensity exercise. We measured the metabolic cost of MBEB, scaled to work performed, for the entire 15 min and found significantly higher V̇O2 , V̇CO2 , and V̇E costs in the early-pubertal participants for both low- and high-intensity MBEB. To reduce breath-by-breath variability in estimation of CPET variable kinetics, we time-interpolated (second-by-second), superimposed, and averaged responses. Reasonable estimates of τ (<20% coefficient of variation) were found only for on-transients of HR and V̇O2 . There was a remarkable reduction in τHR following the first exercise bout in all groups. Natural patterns of physical activity shape cardiorespiratory responses in healthy children and adolescents. Protocols that measure the effect of a previous bout on the kinetics of subsequent bouts may aid in the clinical utility of CPET.

Diffuse optical spectroscopic method for tissue and body composition assessment.

SIGNIFICANCE: Growing levels of obesity and metabolic syndrome have driven demand for more advanced forms of body composition assessment. While various techniques exist to measure body composition, devices are typically expensive and not portable, involve radiation [in the case of dual-energy x-ray absorptiometry (DXA)], and are limited to analysis of adiposity while metabolic information from blood supply and oxygenation are not considered. AIM: We evaluate whether diffuse optical spectroscopic imaging (DOSI) can be used to predict site-specific adiposity and percent fat (whole body) while simultaneously providing information about local tissue hemoglobin levels and oxygenation. APPROACH: DOSI measures of tissue composition in gastrocnemius, quadriceps, abdomen, and biceps, DXA whole-body composition, and ultrasound-derived skin and adipose tissue thickness (SATT) in the quadriceps were obtained from 99 individuals aged 7 to 34 years old. RESULTS: Various DOSI-derived parameters were correlated with SATT and an optical method is proposed for estimating SATT using a newly defined parameter, the optical fat fraction (OFF), which considers all parameters that correlate with SATT. Broadband absorption and scattering spectra from study participants with the thinnest (SATT ≈ 0.25 ± 0.02 cm) and thickest SATT (SATT ≈ 1.55 ± 0.14 cm), representing best estimates for pure in vivo lean and fatty tissue, respectively, are reported. Finally, a trained prediction model is developed which allows DOSI assessment of OFF to predict DXA body-fat percentage, demonstrating that DOSI can be used to quantify body composition. CONCLUSIONS: This study shows that DOSI can be used to assess the adiposity of specific tissues or the entire human body, and the OFF parameter is defined for corroboration and further evaluation in future research.

Association of Congenital and Acquired Cardiovascular Conditions With COVID-19 Severity Among Pediatric Patients in the US.

Importance: Identifying the associations between severe COVID-19 and individual cardiovascular conditions in pediatric patients may inform treatment. Objective: To assess the association between previous or preexisting cardiovascular conditions and severity of COVID-19 in pediatric patients. Design, Setting, and Participants: This retrospective cohort study used data from a large, multicenter, electronic health records database in the US. The cohort included patients aged 2 months to 17 years with a laboratory-confirmed diagnosis of COVID-19 or a diagnosis code indicating infection or exposure to SARS-CoV-2 at 85 health systems between March 1, 2020, and January 31, 2021. Exposures: Diagnoses for 26 cardiovascular conditions between January 1, 2015, and December 31, 2019 (before infection with SARS-CoV-2). Main Outcomes and Measures: The main outcome was severe COVID-19, defined as need for supplemental oxygen or in-hospital death. Mixed-effects, random intercept logistic regression modeling assessed the significance and magnitude of associations between 26 cardiovascular conditions and COVID-19 severity. Multiple comparison adjustment was performed using the Benjamini-Hochberg false discovery rate procedure. Results: The study comprised 171 416 pediatric patients; the median age was 8 years (IQR, 2-14 years), and 50.28% were male. Of these patients, 17 065 (9.96%) had severe COVID-19. The random intercept model showed that the following cardiovascular conditions were associated with severe COVID-19: cardiac arrest (odds ratio [OR], 9.92; 95% CI, 6.93-14.20), cardiogenic shock (OR, 3.07; 95% CI, 1.90-4.96), heart surgery (OR, 3.04; 95% CI, 2.26-4.08), cardiopulmonary disease (OR, 1.91; 95% CI, 1.56-2.34), heart failure (OR, 1.82; 95% CI, 1.46-2.26), hypotension (OR, 1.57; 95% CI, 1.38-1.79), nontraumatic cerebral hemorrhage (OR, 1.54; 95% CI, 1.24-1.91), pericarditis (OR, 1.50; 95% CI, 1.17-1.94), simple biventricular defects (OR, 1.45; 95% CI, 1.29-1.62), venous embolism and thrombosis (OR, 1.39; 95% CI, 1.11-1.73), other hypertensive disorders (OR, 1.34; 95% CI, 1.09-1.63), complex biventricular defects (OR, 1.33; 95% CI, 1.14-1.54), and essential primary hypertension (OR, 1.22; 95% CI, 1.08-1.38). Furthermore, 194 of 258 patients (75.19%) with a history of cardiac arrest were younger than 12 years. Conclusions and Relevance: The findings suggest that some previous or preexisting cardiovascular conditions are associated with increased severity of COVID-19 among pediatric patients in the US and that morbidity may be increased among individuals children younger than 12 years with previous cardiac arrest.

Adolescent COVID-19 Vaccine Decision-Making among Parents in Southern California.

Adolescent COVID-19 vaccination has stalled at 53% in the United States. Vaccinating adolescents remains critical to preventing the continued transmission of COVID-19, the emergence of variants, and rare but serious disease in children, and it is the best preventive measure available to return to in-person schooling. We investigated parent-adolescent COVID-19 vaccine decision-making. Between 24 February and 15 March 2021, we conducted surveys and 12 focus groups with 46 parent-adolescent dyads in Southern California. Parents and adolescents completed a survey prior to participation in a focus group discussion, which focused on exploring COVID-19 vaccine acceptance or uncertainty and was guided by the 5C vaccine hesitancy model. Parents uncertain about vaccinating adolescents expressed low vaccine confidence and high COVID-19 disease risk complacency. Parents who accepted COVID-19 vaccination for adolescents expressed high confidence in health authority vaccine recommendations, high perceived COVID-19 risk, and collective responsibility to vaccinate children. Additionally, unique pandemic-related factors of vaccine acceptance included vaccinating for emotional health, resuming social activities, and vaccine mandates. Among parents, 46% were willing to vaccinate their adolescent, 11% were not, and 43% were unsure. Among adolescents, 63% were willing to vaccinate. Despite vaccine availability, 47% of adolescents remain unvaccinated against COVID-19. Factors associated with vaccine uncertainty and acceptability inform health care practitioner, school, community, and public health messaging to reach parents and adolescents.

Pediatric Cardiopulmonary Exercise Testing: Interoperability Through Domain Analysis Modeling and a National Survey.

PURPOSE: The electronic health record, data science advances, and dynamic environmental and infectious threats to child health highlight the need for harmonized and interoperable approaches to pediatric cardiopulmonary exercise testing (CPET). Accordingly, we developed a terminology harmonization in exercise medicine and exercise science domain analysis model (THEMES DAM) to structure CPET data elements. METHODS: THEMES DAM identified 114 data elements, including participant information, calibration, equipment, protocols, laboratory personnel, encouragement strategies, and analysis procedures. We used the THEMES DAM, vetted by the international data standards organization HL7, to construct a current-state survey of pediatric CPET centers in the United States. Forty-eight of 101 centers responded to a questionnaire covering seven major topic areas (38 items). RESULTS: Centers predominantly performed between 100 and 500 tests annually. Cardiac disease represented 55% of referrals. Almost all centers calibrated gas concentrations and flow daily, but 42% never calibrated their treadmill or cycle ergometers. All centers measured V̇O2peakbut calculated differently. Centers used a variety of protocols (e.g., for treadmill: 61%, Bruce; 43%, modified Bruce; 59%, other); 44% calculated CPET slopes from submaximal portions of CPET (e.g., V̇O2-HR). All centers verbally encouraged participants, but only 40% used a standardized approach. The interpretation of CPET was done by physicians (60%), exercise physiologists (25%), exercise technicians (10%), nurses (1%), or others (4%). Ninety-one percent would agree to collaborate in multicenter research, 89% to establish dynamic reference values, and 83% to better interpret CPET. CONCLUSIONS: The survey data and the implementation of THEMES DAM could accelerate interoperability across multiple centers. This would facilitate a nimble approach to create pediatric reference values responsive to the constantly changing health environment and stimulate novel approaches to CPET research and clinical application.

Self-Reported Physical Activity and Asthma Risk in Children.

BACKGROUND: Increased physical activity (PA) may protect against asthma but PA can trigger asthma symptoms. OBJECTIVE: To investigate relationships between moderate-to-vigorous PA (MVPA) assessed during routine care visits and incident asthma. METHODS: For this retrospective cohort, 542,486 children between 2 and 17 years from 2010 to 2017 were included who had an MVPA assessment (exercise vital sign) during routine care visits. The association of MVPA and asthma was analyzed using Cox proportional hazards regression models as a function of age, with MVPA and body mass index (BMI) being time-varying factors, adjusted for race and ethnicity, socioeconomic status, and air pollution. RESULTS: The mean MVPA was 5.4 (standard deviation: 4.4) hours/week. Crude asthma incidence density rate (IDR) was highest in children with <1 hour/week of MVPA (IDR: 9.07, 95% confidence interval [CI]: 8.79, 9.36) and lowest in children engaging in 4 to 7 hours/week of MVPA (IDR: 6.55, 95% CI: 6.33, 6.77). In adjusted models, an increase in MVPA was associated with lower asthma risk in children reporting 0 hour/week of MVPA (hazard ratio: 0.981, 95% CI: 0.973, 0.990). In children with ≥8 hours/week of MVPA, an increase in MVPA was associated with higher asthma risk (1.005, 95% CI: 1.002, 1.009). There was no significant BMI by MVPA interaction. CONCLUSION: Increasing MVPA in children with low activity levels is associated with lower asthma risk; children reporting high levels of activity may experience greater asthma risk as their activity levels increase further. Understanding the role of PA in the development of asthma and assessing MVPA during routine care visits in children may help to develop targeted interventions and guide asthma management.

Informatics education for translational research teams: An unrealized opportunity to strengthen the national research infrastructure.

Objective: To identify the informatics educational needs of clinical and translational research professionals whose primary focus is not informatics. Introduction: Informatics and data science skills are essential for the full spectrum of translational research, and an increased understanding of informatics issues on the part of translational researchers can alleviate the demand for informaticians and enable more productive collaborations when informaticians are involved. Identifying the level of interest in different topics among various types of of translational researchers will help set priorities for development and dissemination of informatics education. Methods: We surveyed clinical and translational science researchers in Clinical and Translational Science Award (CTSA) programs about their educational needs and preferences. Results: Researchers from 23 out of the 62 CTSA hubs responded to the survey. 67% of respondents across roles and topics expressed interest in learning about informatics topics. There was high interest in all 30 topics included in the survey, with some variation in interest depending on the role of the respondents. Discussion: Our data support the need to advance training in clinical and biomedical informatics. As the complexity and use of information technology and data science in research studies grows, informaticians will continue to be a limited resource for research collaboration, education, and training. An increased understanding of informatics issues across translational research teams can alleviate this burden and allow for more productive collaborations. To inform a roadmap for informatics education for research professionals, we suggest strategies to use the results of this needs assessment to develop future informatics education.

US School-Based Physical Fitness Assessments and Data Dissemination.

BACKGROUND: Low physical fitness (PF) levels during childhood affect healthy growth and development, and increase the risk of cardiovascular diseases. Physical education standards exist for nearly all states in the United States, but evaluation of PF in youth has yet to be systematic, reproducible, and harmonized. The purpose of this project was to describe publicly available data of school-based PF testing (SB-PFT). METHODS: A list of state-mandated SB-PFT programs published by SHAPE 2016 was confirmed by contacting appropriate authorities. SB-PFT data were obtained through each state's department of education. RESULTS: Sixteen states mandate SB-PFT, with 10 states providing publicly available data; 92% to 100% of states perform the pacer/mile, curl-up, and push-up; 54.2% to 78.5% of elementary and 44% to 66.5% of high-school youth are in the "healthy fitness zone" for aerobic capacity. CONCLUSIONS: SB-PFT provided PF data in children across the United States. The variability and inconsistency in reporting and in the values, however, raises questions about the current status of SB-PFT data and its utility in assessing PF in children. The critical nature of PF assessments is highlighted in the current COVID-19 pandemic, during which physical education has been curtailed, and emerging data demonstrate worsening of the already low levels of PF in youth.

Development of the systematic observation of COVID-19 mitigation (SOCOM): Assessing face covering and distancing in schools.

INTRODUCTION: During the COVID-19 pandemic, some K-12 schools resumed in-person classes with varying degrees of mitigation plans in the fall 2020. Physical distancing and face coverings can minimize SARS-CoV-2 spread, the virus that causes COVID-19. However, no research has focused on adherence to mitigation strategies during school days. Thus, we sought to develop a systematic observation protocol to capture COVID-19 mitigation strategy adherence in school environments: The Systematic Observation of COVID-19 Mitigation (SOCOM). METHODS: We extended previously validated and internationally used tools to develop the SOCOM training and implementation protocols to assess physical-distancing and face-covering behaviors. SOCOM was tested in diverse indoor and outdoor settings (classrooms, lunchrooms, physical education [PE], and recess) among diverse schools (elementary, secondary, and special needs). RESULTS: For the unique metrics of physical-distancing and face-covering behaviors, areas with less activity and a maximum of 10-15 students were more favorable for accurately capturing data. Overall proportion of agreement was high for physical distancing (90.9%), face covering (88.6%), activity type (89.2%), and physical activity level (87.9%). Agreement was lowest during active recess, PE, and observation areas with ≥20 students. CONCLUSIONS: Millions of children throughout the USA are likely to return to school in the months ahead. SOCOM is a relatively inexpensive research tool that can be implemented by schools to determine mitigation strategy adherence and to assess protocols that allow students return to school safely and slow the spread of COVID-19.

SARS-CoV-2 acquisition and immune pathogenesis among school-aged learners in four diverse schools.

BACKGROUND: Understanding SARS-CoV-2 infection in children is necessary to reopen schools safely. METHODS: We measured SARS-CoV-2 infection in 320 learners [10.5 ± 2.1 (sd); 7-17 y.o.] at four diverse schools with either remote or on-site learning. Schools A and B served low-income Hispanic learners; school C served many special-needs learners, and all provided predominantly remote instruction. School D served middle- and upper-income learners, with predominantly on-site instruction. Testing occurred in the fall (2020), and 6-8 weeks later during the fall-winter surge (notable for a tenfold increase in COVID-19 cases). Immune responses and mitigation fidelity were also measured. RESULTS: We found SARS-CoV-2 infections in 17 learners only during the surge. School A (97% remote learners) had the highest infection (10/70, 14.3%, p < 0.01) and IgG positivity rates (13/66, 19.7%). School D (93% on-site learners) had the lowest infection and IgG positivity rates (1/63, 1.6%). Mitigation compliance [physical distancing (mean 87.4%) and face-covering (91.3%)] was remarkably high at all schools. Documented SARS-CoV-2-infected learners had neutralizing antibodies (94.7%), robust IFN-γ + T cell responses, and reduced monocytes. CONCLUSIONS: Schools can implement successful mitigation strategies across a wide range of student diversity. Despite asymptomatic to mild SARS-CoV-2 infection, children generate robust humoral and cellular immune responses. IMPACT: Successful COVID-19 mitigation was implemented across a diverse range of schools. School-associated SARS-CoV-2 infections reflect regional rates rather than remote or on-site learning. Seropositive school-aged children with asymptomatic to mild SARS-CoV-2 infections generate robust humoral and cellular immunity.

SARS-CoV-2 Acquisition and Immune Pathogenesis Among School-Aged Learners in Four Diverse Schools.

BACKGROUND: Understanding SARS-CoV-2 infection in children is necessary to reopen schools safely. METHODS: We measured SARS-CoV-2 infection in 320 learners [10.5 ± 2.1(sd); 7-17 y.o.] at four diverse schools with either remote or on-site learning. Schools A and B served low-income Hispanic learners; school C served many special-needs learners; and all provided predominantly remote instruction. School D served middle- and upper-income learners, with predominantly on-site instruction. Testing occurred in the fall (2020), and 6-8 weeks later during the fall-winter surge (notable for a tenfold increase in COVID-19 cases). Immune responses and mitigation fidelity were also measured. RESULTS: We found SARS-CoV-2 infections in 17 learners only during the surge. School A (97% remote learners) had the highest infection (10/70, 14.3%, p<0.01) and IgG positivity rates (13/66, 19.7%). School D (93% on-site learners) had the lowest infection and IgG positivity rates (1/63, 1.6%). Mitigation compliance [physical distancing (mean 87.4%) and face covering (91.3%)] was remarkably high at all schools. Documented SARS-CoV-2-infected learners had neutralizing antibodies (94.7%), robust IFN-γ+ T cell responses, and reduced monocytes. CONCLUSION: Schools can implement successful mitigation strategies across a wide range of student diversity. Despite asymptomatic to mild SARS-CoV-2 infection, children generate robust humoral and cellular immune responses. KEY POINTS: Successful COVID-19 mitigation was implemented across a diverse range of schools.School-associated SARS-CoV-2 infections reflect regional rates rather than remote or on-site learning.Seropositive school-aged children with asymptomatic to mild SARS-CoV-2 infections generate robust humoral and cellular immunity.

SARS-CoV-2 vaccine testing and trials in the pediatric population: biologic, ethical, research, and implementation challenges.

As the nation implements SARS-CoV-2 vaccination in adults at an unprecedented scale, it is now essential to focus on the prospect of SARS-CoV-2 vaccinations in pediatric populations. To date, no children younger than 12 years have been enrolled in clinical trials. Key challenges and knowledge gaps that must be addressed include (1) rationale for vaccines in children, (2) possible effects of immune maturation during childhood, (3) ethical concerns, (4) unique needs of children with developmental disorders and chronic conditions, (5) health inequities, and (6) vaccine hesitancy. Because COVID-19 is minimally symptomatic in the vast majority of children, a higher acceptable risk threshold is required when evaluating pediatric clinical trials. Profound differences in innate and adaptive immunity during childhood and adolescence are known to affect vaccine responsiveness for a variety of childhood diseases. COVID-19 and the accompanying social disruption, such as the school shutdowns, has been disproportionately damaging to minority and low-income children. In this commentary, we briefly address each of these key issues, specify research gaps, and suggest a broader learning health system approach to accelerate testing and clinical trial development for an ethical and effective strategy to implement a pediatric SARS-CoV-2 vaccine as rapidly and safely as possible. IMPACT: As the US begins an unprecedented implementation of SARS-CoV-2 vaccination, substantial knowledge gaps have yet to be addressed regarding vaccinations in the pediatric population. Maturational changes in the immune system during childhood have influenced the effectiveness of pediatric vaccines for other diseases and conditions, and could affect SARS-CoV-2 vaccine responsiveness in children. Given that COVID-19 disease is far milder in the majority of children than in adults, the risk-benefit of a pediatric SARS-CoV-2 vaccine must be carefully weighed. The needs of children with developmental disabilities and with chronic disease must be addressed. Minority and low-income children have been disproportionately adversely affected by the COVID-19 pandemic; care must be taken to address issues of health equity regarding pediatric SARS-CoV-2 vaccine trials and allocation. Research and strategies to address general vaccine hesitancy in communities must be addressed in the context of pediatric SARS-CoV-2 vaccines.