Abatacept Pharmacokinetics and Exposure Response in Patients Hospitalized With COVID-19: A Secondary Analysis of the ACTIV-1 IM Randomized Clinical Trial.

Importance: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown. Objective: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments. Design, Setting, and Participants: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 and February 2024. Exposure: Single intravenous infusion of abatacept (10 mg/kg with a maximum dose of 1000 mg). Main Outcomes and Measures: Mortality at day 28 was the primary outcome of interest, and time to recovery at day 28 was the secondary outcome. Drug exposure was assessed using the projected area under the serum concentration time curve over 28 days (AUC0-28). Logistic regression modeling was used to analyze the association between drug exposure and 28-day mortality, adjusted for age, sex, and disease severity. The association between time to recovery and abatacept exposure was examined using Fine-Gray modeling with death as a competing risk, and was adjusted for age, sex, and disease severity. Results: Of the 509 patients who received abatacept, 395 patients with 848 serum samples were included in the population pharmacokinetic analysis. Their median age was 55 (range, 19-89) years and most (250 [63.3%]) were men. Abatacept clearance increased with body weight and more severe disease activity at baseline. Drug exposure was higher in patients who survived vs those who died, with a median AUC0-28 of 21 428 (range, 8462-43 378) mg × h/L vs 18 262 (range, 9628-27 507) mg × h/L (P < .001). Controlling for age, sex, and disease severity, an increase of 5000 units in AUC0-28 was associated with lower odds of mortality at day 28 (OR, 0.52 [95% CI, 0.35-0.79]; P = .002). For an AUC0-28 of 19 400 mg × h/L or less, there was a higher probability of recovery at day 28 (hazard ratio, 2.63 [95% CI, 1.70-4.08] for every 5000-unit increase; P < .001). Controlling for age, sex, and disease severity, every 5000-unit increase in AUC0-28 was also associated with lower odds of a composite safety event at 28 days (OR, 0.46 [95% CI, 0.33-0.63]; P < .001). Using the dosing regimen studied in the ACTIV-1 IM trial, 121 of the 395 patients (30.6%) would not achieve an abatacept exposure of at least 19 400 mg × h/L, particularly at the extremes of body weight. Using a modified, higher-dose regimen, only 12 patients (3.0%) would not achieve the hypothesized target abatacept exposure. Conclusions and Relevance: In this study, patients who were hospitalized with severe COVID-19 and achieved higher projected abatacept exposure had reduced mortality and a higher probability of recovery with fewer safety events. However, abatacept clearance was high in this population, and the current abatacept dosing (10 mg/kg intravenously with a maximum of 1000 mg) may not achieve optimal exposure in all patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04593940.

Direct-to-participant recruitment of mothers and infants: A strategic approach during challenging pandemic times.

Under traditional circumstances, most clinical trials rely on in-person operations to identify, recruit, and enroll study participants and to complete study-related visits. During unusual circumstances, such as the COVID-19 pandemic, the typical clinical trial model is challenged and forced to explore alternative approaches to implementing study recruitment, participant enrollment, and data collection strategies. One such alternative is a direct-to-participant approach which leverages electronic resources and relevant technological devices (e.g., smart phones) available to researchers and patients. This approach functions under the assumption that a participant has access to a device that connects to the internet such as a smart phone, tablet, or computer. Researchers are then able to transition a typical paper-based, in-person model to an electronic-based, siteless, remote study. This article describes the challenges clinicians and researchers faced when implementing a direct-to-participant study approach during the COVID-19 pandemic. The lessons learned during this study of infant populations could help increase efficiency of future trials, specifically, by lessening the burden on participants and clinicians as well as streamlining the process for enrollment and data collection. While direct-to-adult participant recruitment is not a novel approach, our findings suggest that studies attempting to recruit the infant population may benefit from such a direct-to-participant approach.

Morbidity and mortality of twins and triplets compared to singleton infants delivered between 26-34 weeks gestation in the United States.

OBJECTIVE: To describe in-hospital morbidities and mortality among twins and triplets delivered at ≥26 to ≤34 weeks gestational age (GA) while controlling for prematurity and growth restriction. STUDY DESIGN: Retrospective analysis of inborn infants discharged from a neonatal intensive care unit (NICU) managed by the Pediatrix Medical Group between 2010 and 2018. RESULT: Among 247 437 infants included, 27.4% were multiples. Adjusted for GA and other factors typically known prior to delivery, in-hospital morbidities varied by plurality and generally were more common in singletons. The odds of death prior to discharge were less for twins at 0.74 (95% CI: 0.67-0.83) and triplets at 0.69 (95% CI: 0.51-0.92) compared to singletons. CONCLUSION: Singletons experience greater morbidity and mortality compared to twins and triplets born ≥26 weeks to ≤34 weeks GA, except PDA requiring procedural intervention, ROP requiring treatment, and longer length of stay.

Trends in COVID-19 diagnoses and outcomes in infants hospitalized in the neonatal intensive care unit.

OBJECTIVE: Characterize the prevalence of coronavirus disease 2019 (COVID-19) diagnosis among mothers with infants hospitalized in 294 neonatal intensive care units (NICUs), and demographics and outcomes of infants with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure in utero. STUDY DESIGN: Cohort study of infants discharged from NICUs 01/2020-09/2021. We defined groups based on infant diagnosis, infant testing, and maternal SARS-CoV-2 infection status. We compared demographics, clinical characteristics, and outcomes. RESULTS: Of 150,924 infants, 94% had no COVID-related diagnosis or test; 247 (0.2%) infants tested positive for COVID-19 and were more likely to require mechanical ventilation. Infants with unknown maternal status and negative testing were more commonly premature, outborn, and had longer hospitalizations. CONCLUSION: In this large cohort of hospitalized infants, most had no known exposure to COVID-19. Adverse outcomes and mortality were rare. Further studies are needed to evaluate the long-term effects of COVID-19 in this population.

Risk factors and epidemiology of spontaneous intestinal perforation among infants born at 22-24 weeks' gestational age.

OBJECTIVE: To describe the epidemiology, risk factors, and timing of spontaneous intestinal perforation (SIP) among infants born at 22-24 weeks' gestational age (GA). STUDY DESIGN: Observational cohort study among infants born at 22-24 weeks' GA in 446 neonatal intensive care units. RESULTS: We identified 9712 infants, of whom 379 (3.9%) developed SIP. SIP incidence increased with decreasing GA (P < 0.001). Antenatal magnesium (odds ratio (OR) 1.42; 95% confidence interval (CI), 1.09-1.85), antenatal indomethacin (OR 1.40; 95% CI, 1.06-1.85), postnatal indomethacin (OR 1.61; 95% CI, 1.23-2.11), and postnatal hydrocortisone exposure (OR 2.02; 95% CI 1.50-2.73) were associated with SIP. Infants who lost 15-20% (OR 1.77; 95% CI, 1.28-2.44) or >20% (OR 2.04; 95% CI, 1.46-2.85) of birth weight had higher odds of SIP than infants with weight loss <10%. CONCLUSIONS: Antenatal magnesium exposure, antenatal indomethacin exposure, postnatal hydrocortisone exposure, postnatal indomethacin exposure, and weight loss ≥15% were associated with SIP.

Impact of the COVID-19 Pandemic on Pediatric Preventive Health Care Among North Carolina Children Enrolled in Medicaid.

BACKGROUND: Children enrolled in private insurance had reduced preventive health care during the coronavirus disease 2019 (COVID-19) pandemic. However, the impact of the pandemic on children enrolled in Medicaid has been minimally described. METHODS: We used an administrative claims database from North Carolina Medicaid to evaluate the rates of well-child visits and immunization administration for children ≤14 months of age, and used a quasi-Poisson regression model to estimate the rate ratio (RR) of each outcome during the pandemic period (3/15/2020 through 3/15/2021) compared with the pre-pandemic period (3/15/2019 through 3/14/2020). RESULTS: We included 83 442 children during the pre-pandemic period and 96 634 children during the pandemic period. During the pre-pandemic period, 405 295 well-child visits and 715 100 immunization administrations were billed; during the pandemic period, 287 285 well-child visits and 457 144 immunization administrations were billed. The rates of well-child visits (RR 0.64; 95% CI, 0.64-0.64) and vaccine administration (RR 0.55; 95% CI, 0.55-0.55) were lower during the pandemic compared with the pre-pandemic period. CONCLUSIONS: The rates of well-child visits and immunization administrations among North Carolina children enrolled in public insurance substantially decreased during the first year of the COVID-19 pandemic.

Trends in Pediatric Emergency and Inpatient Healthcare Use for Mental and Behavioral Health Among North Carolinians During the Early COVID-19 Pandemic.

BACKGROUND: Widespread school closures and health care avoidance during the COVID-19 pandemic led to disruptions in access to pediatric mental health care. METHODS: We conducted a retrospective study of emergency and inpatient administrative claims from privately insured children aged 6-20 years in North Carolina between January 2019 and December 2020. We compared rates of emergency department (ED) visits (per 100 000 person-days) and risks of hospitalizations (per 100 000 persons) with diagnosis codes in each category (mental/behavioral health; suicidal ideation, suicide attempt, and intentional self-harm [SI/SA/ISH]; and social issues) across 3 time periods (pre-pandemic, lockdown, and reopening). We calculated the proportion and 95% confidence intervals (CI) of total ED visits and total hospitalizations attributable to mental/behavioral health and SI/SA/ISH across the 3 time periods. RESULTS: Rates of all categories of ED visits decreased from pre-pandemic to the lockdown period; from pre-pandemic to the reopening period, mental/behavioral health visits decreased but rates of SI/SA/ISH visits were unchanged. The proportion of ED visits attributable to mental/behavioral health increased from 3.5% (95% CI 3.2%-3.7%) pre-pandemic to 4.0% (95% CI 3.7%-4.3%) during reopening, and the proportion of SI/SA/ISH diagnoses increased from 1.6% (95% CI 1.4%-1.8%) pre-pandemic to 2.4% (95% CI 2.1%-2.7%) during the reopening period. Emergency care use for social issues and hospital admissions for mental/behavioral health and SI/SA/ISH diagnoses were unchanged across the study periods. CONCLUSIONS: In the early pandemic, pediatric mental health care and acute suicidal crises accounted for increased proportions of emergency care. During pandemic recovery, understanding the populations most impacted and increasing access to preventative mental health care is critical.

Leveraging School Infection Data to Address Community COVID-19 Data Gaps.

BACKGROUND: At-home COVID-19 tests became available in the USA in April 2021 with widespread use by January 2022; however, the lack of infrastructure to report test results to public health agencies created a gap in public health data. Kindergarten through grade 12 (K-12) schools often tracked COVID-19 cases among students and staff; leveraging school data may have helped bridge data gaps. METHODS: We examined infection rates reported by school districts to ABC Science Collaborative with corresponding community rates from March 15, 2021 to June 3, 2022. We computed weekly ratios of community-to-district-reported rates (reporting ratios) across 3 study periods (spring 2021, fall 2021, and spring 2022) and estimated the difference and 95% confidence intervals (CIs) in the average reporting ratio between study periods. RESULTS: In spring 2021, before approval or widespread use of at-home testing, the community-reported infection rate was higher than the school-reported infection rate (reporting ratio: 1.40). In fall 2021 and spring 2022, as at-home testing rapidly increased, school-reported rates were higher than community-reported rates (reporting ratios: 0.82 and 0.66). Average reporting ratios decreased between spring 2021 and fall 2021 (-0.58, 95% CI -0.84, -0.32) and spring 2021 and spring 2022 (-0.73, 95% CI -0.96, -0.48); there was no significant change between fall 2021 and spring 2022 (-0.15, 95% CI -0.36, 0.06). CONCLUSIONS: At-home COVID-19 testing resulted in significant data gaps; K-12 data could have supplemented community data. In future public health emergencies, reporting of school data could minimize data gaps, but requires additional resources including funding to track infections and standardized data reporting methods.

Comparative Effectiveness of Dual- Versus Mono-Sedative Therapy on Opioid Administration, Sedative Administration, and Sedation Level in Mechanically Ventilated, Critically Ill Children.

OBJECTIVE: We estimated the effect of early initiation of dual therapy vs monotherapy on drug administration and related outcomes in mechanically ventilated, critically ill children. METHODS: We used the electronic medical record at a single tertiary medical center to conduct an active comparator, new user cohort study. We included children <18 years of age who were exposed to a sedative or analgesic within 6 hours of intubation. We used stabilized inverse probability of treatment weighting to account for confounding at baseline. We estimated the average effect of initial dual therapy vs monotherapy on outcomes including cumulative opioid, benzodiazepine, and dexmedetomidine dosing; sedation scores; time to double the opioid or benzodiazepine infusion rate; initiation of neuromuscular blockade within the first 7 days of follow-up; time to extubation; and 7-day all-cause in-hospital death. RESULTS: The cohort included 640 patients. Children receiving dual therapy received 0.03 mg/kg (95% CI, 0.02-0.04) more dexmedetomidine over the first 7 days after initiation of mechanical ventilation than did monotherapy patients. Dual therapy patients had similar sedation scores, time to double therapy, initiation of neuromuscular blockade, and time to extubation as monotherapy patients. Dual therapy patients had a lower incidence of death. CONCLUSIONS: In this study, initial dual therapy compared with monotherapy does not reduce overall drug administration during mechanical ventilation. The identified effect of dual therapy on mortality deserves further investigation.

Diagnostic Utility of Cerebrospinal Fluid White Blood Cell Components for the Identification of Bacterial Meningitis in Infants.

BACKGROUND: To evaluate the diagnostic and predictive utility of cerebrospinal fluid (CSF) white blood cell (WBC) components in the diagnosis of bacterial meningitis in infants discharged from the neonatal intensive care unit (NICU). METHODS: We identified a cohort of infants discharged from a Pediatrix NICU between 1997 and 2020 who did not have an immunodeficiency, had at least 1 CSF culture collected within the first 120 days of life, and at least 1 CSF laboratory specimen obtained on the day of culture collection. We only included an infant's first CSF culture and excluded cultures from CSF reservoirs and those growing contaminants or nonbacterial organisms. We examined the utility of CSF WBC components to diagnose or predict bacterial meningitis by calculating sensitivity, specificity, positive and negative predictive values, likelihood ratios, and area under the receiver operating curve (AUC) at different cutoff values for each parameter. We performed subgroup analysis excluding infants treated with antibiotics the day before CSF culture collection. RESULTS: Of the 20 756 infants that met the study inclusion criteria, 320 (2%) were diagnosed with bacterial meningitis. We found (AUC [95% CI]) CSF WBC count (0.76 [0.73-0.79]), CSF neutrophil count (0.74 [0.70-0.78]), and CSF neutrophil percent (0.71 [0.67-0.75]) had the highest predictive values for bacterial meningitis, even when excluding infants with early antibiotic administration. CONCLUSIONS: No single clinical prediction rule had the optimal discriminatory power for predicting culture-proven bacterial meningitis, and clinicians should be cautious when interpreting CSF WBC parameters in infants with suspected meningitis.

School Absenteeism as a Marker for Community COVID-19 Rates.

BACKGROUND: Reported community transmission rates of coronavirus disease 2019 (COVID-19) may not be accurate, particularly since at-home testing has become widely available. School absenteeism may serve as a marker of broader community COVID-19 transmission. METHODS: We performed an observational study of North Carolina kindergarten through 12th grade schools participating in the ABC Science Collaborative that offered in-school instruction, and contributed severe acute respiratory syndrome coronavirus 2 data for at least 2 of 4 weeks monthly for the 2021-2022 academic year. Additionally, we analyzed publicly available databases including the North Carolina Department of Public Instruction, Centers for Disease Control and Prevention COVID-19 Data Repository, and National Center for Education Statistics. We described community and school COVID-19 infection rates compared with student monthly absenteeism rates to determine if the relationship between community COVID-19 infection rates and student absenteeism varied over time. RESULTS: We included 500 192 students from 27 school districts. For the 2021-2022 academic year, the student and community COVID-19 infection rates did not show a significant difference (P > .05) across each month of comparison. Student absenteeism rates and community COVID-19 infection rates by month showed a similar trend across the academic year. For every 1% increase in community infection percentage, we found a 1.68% (1.12-2.25%) increase in absenteeism (P < .001); for every 1 month change in time, we found a 0.12% (0.01-0.24%) increase in absenteeism (P < .05). CONCLUSIONS: Student absenteeism and infection rates may be a useful marker of COVID-19 community infection rates when testing frequency and results reporting are inconsistent.

Late-Onset Sepsis Evaluation and Empiric Therapy in Extremely Low Gestational Age Newborns.

BACKGROUND: Little is known about late-onset sepsis (LOS) evaluations in extremely low gestational age newborns (ELGANs). We describe frequencies of LOS evaluation in ELGANs, infant characteristics, and empiric therapy choices during evaluations. METHODS: Cohort study of infants 22-28 weeks gestational age (GA) discharged from 243 centers from 2009 to 2018, excluding infants with congenital anomalies, discharged or deceased prior to postnatal day (PND) 2, or admitted after PND 2. A new LOS evaluation was defined as the first blood culture obtained between PND 3 and 90, or one obtained ≥1 day following a negative culture and ≥10 days from prior positive cultures. We determined numbers of evaluations and percentage positive by GA, center, and over time. We described characteristics associated with positive evaluations, infants with LOS, and empiric antimicrobials. We calculated descriptive and comparative statistics using Wilcoxon rank sum, Fisher's exact, or Pearson chi-square tests, as appropriate. RESULTS: Of 47,187 included infants, 67% had ≥1 LOS evaluation and 21% of evaluated infants had ≥1 LOS (culture positive) episode; 1.6 evaluations occurred per infant and 10% were positive. The percentage of infants evaluated and positive for LOS was higher at earlier GA. LOS was associated with inotrope support (15% vs. 9%; p < .001) and invasive mechanical ventilation (66% vs. 51%; p < .001). Infants with positive cultures were more likely than infants with negative cultures to receive empiric antimicrobials during the LOS evaluation (95% vs. 73%; p < .001). CONCLUSIONS: Among ELGANs, earlier GA and postnatal age were associated with LOS evaluation and positive cultures. Most infants undergoing evaluation were started on empiric antimicrobials.

Association Between Hypoglycemia and the Occurrence of Early Onset Sepsis in Premature Infants.

BACKGROUND: We examined the association between hypoglycemia and the occurrence of early onset sepsis (EOS) in premature infants admitted to the neonatal intensive care unit (NICU). METHODS: We included infants discharged from 358 NICUs between 1997 and 2020 with gestational age <34 weeks, ≥1 culture collected in the first 3 days of life, and ≥1 serum glucose value recorded on the day of or day prior to culture collection. We used multivariable logistic regression and inverse probability weighting (IPW) and constructed models for three definitions of hypoglycemia: American Academy of Pediatrics (AAP), Pediatric Endocrine Society, and a definition based on neurodevelopmental studies. We performed subgroup analysis in EOS episodes caused by Gram-negative and Gram-positive organisms. RESULTS: Of the 62,178 infants and 64,559 cultures that met study inclusion criteria, 739 (1%) cultures were positive. The median (25th, 75th percentile) glucose value was 75 mg/dL (50, 106) on the day of or day prior to a positive culture versus 70 mg/dL (50, 95) on the day of or day prior to a negative culture. We found that hypoglycemia was not associated with the occurrence of EOS for all organisms and Gram-positive organisms, whereas there was a small but significant association between the lower AAP glucose cutoff value and EOS due to Gram-negative organisms (logistic regression: risk difference [RD] 0.24% [95% CI, 0.01-0.47]; IPW: RD 0.22% [95% CI, 0.00-0.43]). CONCLUSIONS: Hypoglycemia may be an early marker of EOS, particularly in episodes caused by Gram-negative organisms and when using a stricter definition of hypoglycemia.

Approaches for enhancing the informativeness and quality of clinical trials: Innovations and principles for implementing multicenter trials from the Trial Innovation Network.

One challenge for multisite clinical trials is ensuring that the conditions of an informative trial are incorporated into all aspects of trial planning and execution. The multicenter model can provide the potential for a more informative environment, but it can also place a trial at risk of becoming uninformative due to lack of rigor, quality control, or effective recruitment, resulting in premature discontinuation and/or non-publication. Key factors that support informativeness are having the right team and resources during study planning and implementation and adequate funding to support performance activities. This communication draws on the experience of the National Center for Advancing Translational Science (NCATS) Trial Innovation Network (TIN) to develop approaches for enhancing the informativeness of clinical trials. We distilled this information into three principles: (1) assemble a diverse team, (2) leverage existing processes and systems, and (3) carefully consider budgets and contracts. The TIN, comprised of NCATS, three Trial Innovation Centers, a Recruitment Innovation Center, and 60+ CTSA Program hubs, provides resources to investigators who are proposing multicenter collaborations. In addition to sharing principles that support the informativeness of clinical trials, we highlight TIN-developed resources relevant for multicenter trial initiation and conduct.

In-Person Instruction and Educational Outcomes of K-8 Students During the COVID-19 Pandemic.

OBJECTIVES: Quantify the relationship between district policy permitting in-person instruction and educational outcomes during the 2020 to 2021 academic year for kindergarten through eighth grade students. METHODS: An ecological, repeated cross-sectional analysis of grade-level proficiency of students enrolled in public school districts in North Carolina (n = 115 school districts) was conducted. Univariate and multivariate analyses were performed to evaluate the association between the proportion of the school year a district spent in-person and 2020 to 2021 end-of-year student proficiency in the district. We then fit a multivariable linear regression model, weighted by district size, and adjusted for district-level 2018 to 2019 proficiency and district-level factors (rural or urban, area deprivation). RESULTS: Compared to 2018 to 2019, there was a 12.1% decrease (95% confidence interval [CI]: 16.8-19.3) in mathematics and an 18.1% decrease (95% CI: 10.8-13.4) in reading proficiency across the state at the end of 2020 to 2021. Compared to a district that remained entirely remote for the 2020 to 2021 school year, a district offering full in-person instruction had 12% (95% CI: 11%-12.9%) and 4.1% (95% CI: 3.5%-4.8%) more students achieve grade-level proficiency in mathematics and reading, respectively. In-person instruction was associated with greater increases in mathematics proficiency than reading, and greater increases in elementary-level students' proficiency than middle school-level. CONCLUSIONS: The proportion of students achieving grade-level proficiency in 2020 to 2021 fell below prepandemic levels at each evaluated time point in the academic year. Increased time spent in-person by a school district was associated with an increased proportion of students achieving grade-level end-of-grade proficiency in both mathematics and reading.

Common Data Element Collection in Underserved School Communities: Challenges and Recommendations.

OBJECTIVES: To provide recommendations for future common data element (CDE) development and collection that increases community partnership, harmonizes data interpretation, and continues to reduce barriers of mistrust between researchers and underserved communities. METHODS: We conducted a cross-sectional qualitative and quantitative evaluation of mandatory CDE collection among Rapid Acceleration of Diagnostics-Underserved Populations Return to School project teams with various priority populations and geographic locations in the United States to: (1) compare racial and ethnic representativeness of participants completing CDE questions relative to participants enrolled in project-level testing initiatives and (2) identify the amount of missing CDE data by CDE domain. Additionally, we conducted analyses stratified by aim-level variables characterizing CDE collection strategies. RESULTS: There were 15 study aims reported across the 13 participating Return to School projects, of which 7 (47%) were structured so that CDEs were fully uncoupled from the testing initiative, 4 (27%) were fully coupled, and 4 (27%) were partially coupled. In 9 (60%) study aims, participant incentives were provided in the form of monetary compensation. Most project teams modified CDE questions (8/13; 62%) to fit their population. Across all 13 projects, there was minimal variation in the racial and ethnic distribution of CDE survey participants from those who participated in testing; however, fully uncoupling CDE questions from testing increased the proportion of Black and Hispanic individuals participating in both initiatives. CONCLUSIONS: Collaboration with underrepresented populations from the early study design process may improve interest and participation in CDE collection efforts.

Utilization and Impact of Symptomatic and Exposure SARS-CoV-2 Testing in K-12 Schools.

OBJECTIVES: The Centers for Disease Control and Prevention recommend that schools can offer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic (on-demand) testing for students and staff with coronavirus disease 2019 symptoms or exposures. Data related to the uptake, implementation, and effect of school-associated on-demand diagnostic testing have not been described. METHODS: The Rapid Acceleration of Diagnostics Underserved Populations Return to School program provided resources to researchers to implement on-demand SARS-CoV-2 testing in schools. This study describes the strategies used and uptake among the different testing programs. Risk of positivity was compared for symptomatic and exposure testing during the δ and ο variant periods. We estimated the number of school absence days saved with school-based diagnostic testing. RESULTS: Of the 16 eligible programs, 7 provided school-based on-demand testing. The number of persons that participated in these testing programs is 8281, with 4134 (49.9%) receiving >1 test during the school year. Risk of positivity was higher for symptomatic testing compared with exposure testing and higher during the ο variant predominant period compared with the δ variant predominant period. Overall, access to testing saved an estimated 13 806 absent school days. CONCLUSIONS: School-based on-demand SARS-CoV-2 testing was used throughout the school year, and nearly half the participants accessed testing on more than 1 occasion. Future studies should work to understand participant preferences around school-based testing and how these strategies can be used both during and outside of pandemics.

Building School-Academic Partnerships to Implement COVID-19 Testing in Underserved Populations.

OBJECTIVE: In April 2021, the US government made substantial investments in students' safe return to school by providing resources for school-based coronavirus disease 2019 (COVID-19) mitigation strategies, including COVID-19 diagnostic testing. However, testing uptake and access among vulnerable children and children with medical complexities remained unclear. METHODS: The Rapid Acceleration of Diagnostics Underserved Populations program was established by the National Institutes of Health to implement and evaluate COVID-19 testing programs in underserved populations. Researchers partnered with schools to implement COVID-19 testing programs. The authors of this study evaluated COVID-19 testing program implementation and enrollment and sought to determine key implementation strategies. A modified Nominal Group Technique was used to survey program leads to identify and rank testing strategies to provide a consensus of high-priority strategies for infectious disease testing in schools for vulnerable children and children with medical complexities. RESULTS: Among the 11 programs responding to the survey, 4 (36%) included prekindergarten and early care education, 8 (73%) worked with socioeconomically disadvantaged populations, and 4 focused on children with developmental disabilities. A total of 81 916 COVID-19 tests were performed. "Adapting testing strategies to meet the needs, preferences, and changing guidelines," "holding regular meetings with school leadership and staff," and "assessing and responding to community needs" were identified as key implementation strategies by program leads. CONCLUSIONS: School-academic partnerships helped provide COVID-19 testing in vulnerable children and children with medical complexities using approaches that met the needs of these populations. Additional work is needed to develop best practices for in-school infectious disease testing in all children.