CONTEXT: International Classification of Diseases (ICD) codes are used for billing but also for surveillance for injuries such as traumatic brain injuries (TBI). While specificity is possible in the ICD-10-CM scheme, use of the code for unspecified injury of head (SO9.9) remains high. OBJECTIVES: This process evaluation sought to understand medical ICD-10-CM coding behaviors for TBI in emergency department (ED) settings. DESIGN: Semi-structured interviews explored the processes that facilitate or hinder ED physicians from selecting specific ICD codes for TBI and potential points of intervention for increased coding specificity and reducing the use of unspecified codes. SETTING: Video interviews were conducted with a nationwide sample in the United States. PARTICIPANTS: A purposive snowball sampling strategy was used to recruit 26 ED physicians with experience diagnosing TBI. INTERVENTION: Semi-structured interviews identified factors related to the selection of specific ICD codes for head injury. MAIN OUTCOME MEASURE: Thematic analysis of transcribed data. RESULTS: Four main themes emerged from the data: the impact of training and expertise, factors related to diagnosis, unclear connections with medical coders, and actionable recommendations. Interviews underscored the context surrounding "unspecified" codes for TBI, including demands from patient care, time pressures, issues around how a diagnosis may impact patient management decisions, and considerations related to mapping within the electronic medical record (EMR) where options may default to an unspecified code. CONCLUSIONS: Findings from this analysis indicate that ED providers may benefit from more robust training on how documentation can better support ICD-10-CM coding for this type of trauma. Revised EMR structures could support efficient coding specificity and clarity.

BACKGROUND: Cesarean delivery rates have increased globally resulting in a public health concern. We estimate rates of cesarean deliveries among Thai women using the World Health Organization (WHO) Robson Classification system and compare rates by Robson group to the Robson guideline for acceptable rates to identify groups that might benefit most from interventions for rate reduction. METHODS: In 2017 and 2018, we established cohorts of pregnant women aged ≥ 18 years seeking prenatal care at two tertiary Thai hospitals and followed them until 6-8 weeks postpartum. Three in-person interviews (enrollment, end of pregnancy, and postpartum) were conducted using structured questionnaires to obtain demographic characteristics, health history, and delivery information. Cesarean delivery indication was classified based on core obstetric variables (parity, previous cesarean delivery, number of fetuses, fetal presentation, gestational week, and onset of labor) assigned to 10 groups according to the Robson Classification. Logistic regression was used to identify factors associated with cesarean delivery among nulliparous women with singleton, cephalic, term pregnancies. RESULTS: Of 2,137 participants, 970 (45%) had cesarean deliveries. The median maternal age at delivery was 29 years (interquartile range, 25-35); 271 (13%) participants had existing medical conditions; and 446 (21%) had pregnancy complications. The cesarean delivery rate varied by Robson group. Multiparous women with > 1 previous uterine scar, with a single cephalic pregnancy, ≥ 37 weeks gestation (group 5) contributed the most (14%) to the overall cesarean rate, whereas those with a single pregnancy with a transverse or oblique lie, including women with previous uterine scars (group 9) contributed the least (< 1%). Factors independently associated with cesarean delivery included age ≥ 25 years, pre-pregnancy obesity, new/worsen medical condition during pregnancy, fetal distress, abnormal labor, infant size for gestational age ≥ 50(th) percentiles, and self-pay for delivery fees. Women with existing blood conditions were less likely to have cesarean delivery. CONCLUSIONS: Almost one in two pregnancies among women in our cohorts resulted in cesarean deliveries. Compared to WHO guidelines, cesarean delivery rates were elevated in selected Robson groups indicating that tailored interventions to minimize non-clinically indicated cesarean delivery for specific groups of pregnancies may be warranted.

BACKGROUND: Recent studies explored which pathogens drive the global burden of pneumonia hospitalizations among young children. However, the etiology of broader acute lower respiratory tract infections (ALRIs) remains unclear. METHODS: Using a multicountry study (Albania, Jordan, Nicaragua, and the Philippines) of hospitalized infants and non-ill community controls between 2015 and 2017, we assessed the prevalence and severity of viral infections and coinfections. We also estimated the proportion of ALRI hospitalizations caused by 21 respiratory pathogens identified via multiplex real-time reverse transcription polymerase chain reaction with bayesian nested partially latent class models. RESULTS: An overall 3632 hospitalized infants and 1068 non-ill community controls participated in the study and had specimens tested. Among hospitalized infants, 1743 (48.0%) met the ALRI case definition for the etiology analysis. After accounting for the prevalence in non-ill controls, respiratory syncytial virus (RSV) was responsible for the largest proportion of ALRI hospitalizations, although the magnitude varied across sites-ranging from 65.2% (95% credible interval, 46.3%-79.6%) in Albania to 34.9% (95% credible interval, 20.0%-49.0%) in the Philippines. While the fraction of ALRI hospitalizations caused by RSV decreased as age increased, it remained the greatest driver. After RSV, rhinovirus/enterovirus (range, 13.4%-27.1%) and human metapneumovirus (range, 6.3%-12.0%) were the next-highest contributors to ALRI hospitalizations. CONCLUSIONS: We observed substantial numbers of ALRI hospitalizations, with RSV as the largest source, particularly in infants aged <3 months. This underscores the potential for vaccines and long-lasting monoclonal antibodies on the horizon to reduce the burden of ALRI in infants worldwide.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous throughout the United States. Previous studies have shown PFAS exposure to be associated with a reduced immune response. However, the relationship between serum PFAS and antibody levels following SARS-CoV-2 infection or COVID-19 vaccination has not been examined. We examined differences in peak immune response and the longitudinal decline of antibodies following SARS-CoV-2 infection and COVID-19 vaccination by serum PFAS levels in a cohort of essential workers in the United States. We measured serum antibodies using an in-house semi-quantitative enzyme-linked immunosorbent assay (ELISA). Two cohorts contributed blood samples following SARS-CoV-2 infection or COVID-19 vaccination. We used linear mixed regression models, adjusting for age, race/ethnicity, gender, presence of chronic conditions, location, and occupation, to estimate differences in immune response with respect to serum PFAS levels. Our study populations included 153 unvaccinated participants that contributed 316 blood draws over a 14-month period following infection, and 860 participants and 2451 blood draws over a 12-month period following vaccination. Higher perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) concentrations were associated with a lower peak antibody response after infection (p = 0.009, 0.031, 0.015). Higher PFOS, perfluorooctanoic acid (PFOA), PFHxS, and PFNA concentrations were associated with slower declines in antibodies over time after infection (p = 0.003, 0.014, 0.026, 0.025). PFOA, PFOS, PFHxS, and PFNA serum concentrations prior to vaccination were not associated with differences in peak antibody response after vaccination or with differences in decline of antibodies over time after vaccination. These results suggest that elevated PFAS may impede potential immune response to SARS-CoV-2 infection by blunting peak antibody levels following infection; the same finding was not observed for immune response to vaccination.

In the United States, injury is the leading cause of death for persons aged 1--44 years, and the approximately 800,000 emergency medical services (EMS) providers have a substantial impact on the care of injured persons and on public health. At an injury scene, EMS providers determine the severity of injury, initiate medical management, and identify the most appropriate facility to which to transport the patient through a process called "field triage." Although basic emergency services generally are consistent across hospital emergency departments (EDs), certain hospitals have additional expertise, resources, and equipment for treating severely injured patients. Such facilities, called "trauma centers," are classified from Level I (centers providing the highest level of trauma care) to Level IV (centers providing initial trauma care and transfer to a higher level of trauma care if necessary) depending on the scope of resources and services available. The risk for death of a severely injured person is 25% lower if the patient receives care at a Level I trauma center. However, not all patients require the services of a Level I trauma center; patients who are injured less severely might be served better by being transported to a closer ED capable of managing milder injuries. Transferring all injured patients to Level I trauma centers might overburden the centers, have a negative impact on patient outcomes, and decrease cost effectiveness. In 1986, the American College of Surgeons developed the Field Triage Decision Scheme (Decision Scheme), which serves as the basis for triage protocols for state and local EMS systems across the United States. The Decision Scheme is an algorithm that guides EMS providers through four decision steps (physiologic, anatomic, mechanism of injury, and special considerations) to determine the most appropriate destination facility within the local trauma care system. Since its initial publication in 1986, the Decision Scheme has been revised four times. In 2005, with support from the National Highway Traffic Safety Administration, CDC began facilitating revision of the Decision Scheme by hosting a series of meetings of the National Expert Panel on Field Triage, which includes injury-care providers, public health professionals, automotive industry representatives, and officials from federal agencies. The Panel reviewed relevant literature, presented its findings, and reached consensus on necessary revisions. The revised Decision Scheme was published in 2006. This report describes the process and rationale used by the Expert Panel to revise the Decision Scheme.

In the United States, injury is the leading cause of death for persons aged 1-44 years. In 2008, approximately 30 million injuries were serious enough to require the injured person to visit a hospital emergency department (ED); 5.4 million (18%) of these injured patients were transported by Emergency Medical Services (EMS). On arrival at the scene of an injury, the EMS provider must determine the severity of injury, initiate management of the patient's injuries, and decide the most appropriate destination hospital for the individual patient. These destination decisions are made through a process known as "field triage," which involves an assessment not only of the physiology and anatomy of injury but also of the mechanism of the injury and special patient and system considerations. Since 1986, the American College of Surgeons Committee on Trauma (ACS-COT) has provided guidance for the field triage process through its "Field Triage Decision Scheme." This guidance was updated with each version of the decision scheme (published in 1986, 1990, 1993, and 1999). In 2005, CDC, with financial support from the National Highway Traffic Safety Administration, collaborated with ACS-COT to convene the initial meetings of the National Expert Panel on Field Triage (the Panel) to revise the decision scheme; the revised version was published in 2006 by ACS-COT (American College of Surgeons. Resources for the optimal care of the injured patient: 2006. Chicago, IL: American College of Surgeons; 2006). In 2009, CDC published a detailed description of the scientific rationale for revising the field triage criteria (CDC. Guidelines for field triage of injured patients: recommendations of the National Expert Panel on Field Triage. MMWR 2009;58[No. RR-1]). In 2011, CDC reconvened the Panel to review the 2006 Guidelines in the context of recently published literature, assess the experiences of states and local communities working to implement the Guidelines, and recommend any needed changes or modifications to the Guidelines. This report describes the dissemination and impact of the 2006 Guidelines; outlines the methodology used by the Panel for its 2011 review; explains the revisions and modifications to the physiologic, anatomic, mechanism-of-injury, and special considerations criteria; updates the schematic of the 2006 Guidelines; and provides the rationale used by the Panel for these changes. This report is intended to help prehospital-care providers in their daily duties recognize individual injured patients who are most likely to benefit from specialized trauma center resources and is not intended as a mass casualty or disaster triage tool. The Panel anticipates a review of these Guidelines approximately every 5 years.

The Whole School, Whole Community, Whole Child (WSCC) framework advances an intentional and integrated vision of policies, practices, and programs that support students' health and academic success across 10 components within school settings. WSCC promotes family and community engagement with schools and recognizes schools as key locations for equitable access to services for addressing health disparities and increasing healthy options for all students.1-3 This approach has some formal recognition in the United States; 18 states and the District of Columbia have statutes or regulations addressing WSCC or a coordinated school health approach, and another 17 include these concepts in noncodified policy language, such as nonbinding guidance, agreements, or procedures from state agencies.4 | | This special issue presents a decade of school-based physical activity (PA) and nutrition intervention research conducted across multiple WSCC components. Individually and collectively, these articles identified evidence-based strategies that can be implemented within schools and highlighted opportunities for future research focused on school-based PA and nutrition interventions. Here, we use the terms interventions and strategies interchangeably to describe changes to school policies, practices, or infrastructure.

BACKGROUND: We introduce the Whole School, Whole Community, Whole Child approach to supporting student and school staff physical activity and nutrition and describe the methods used to generate the evidence synthesized across the special issue articles. METHODS: A 2-phase literature review search included a search of systematic reviews (2010-2018) for individual qualifying articles (Phase 1) and a search for individual articles on topics not addressed by a review (2010-2020) or that needed an update because they were in a review that was older (2010-2016) or showed insufficient evidence (Phase 2). Research librarians developed search strategies. In each phase, pairs of subject matter experts applied criteria to review abstracts and full-text articles and extracted data using standardized forms. We included 314 articles, describing 293 studies. FINDINGS: Most of the included studies looked at elementary or secondary school level interventions; 51% were rated poor quality, and few took place in a rural setting. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Most of the identified studies engaged majority minority or racially/ethnically diverse schools, suggesting that these interventions are feasible in a variety of settings. CONCLUSIONS: This collection of 10 articles identifies evidence-based interventions, gaps in research, and implications for health equity.

Recent disease events have heightened awareness for the need for collaboration between the nation's public health and veterinary infectious disease communities to improve preparedness for current and future biological threats. To address this need, the U.S. Department of Agriculture's National Bio- and Agro-Defense Facility (USDA NBAF) has partnered with Texas A&M University through its Global Health Research Complex (TAMGHRC) to establish the Research Alliance for Veterinary Science and Biodefense BSL-3 Network (RAV3N). As a collaborative network of U.S. university and federal BSL-3Ag/BSL-3/BSL-4 laboratory research facilities, the objective of RAV3N is to establish strategic and coordinated approaches for harnessing collective large-animal biocontainment infrastructure and research capacity to improve bio-surveillance, diagnostics, and countermeasure development against high-consequence pathogens of veterinary and zoonotic importance. Here, we describe the origin and development of RAV3N, detail phase I activities, and summarize the proceedings of its first membership meeting held in August 2022.

BACKGROUND Information is limited on messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection or attenuating disease when administered in real-world conditions.METHODS Prospective cohorts of 3,975 healthcare personnel, first responders, and other essential and frontline workers completed weekly SARS-CoV-2 testing during December 14 2020—April 10 2021. Self-collected mid-turbinate nasal swabs were tested by qualitative and quantitative reverse-transcription–polymerase-chain-reaction (RT-PCR). VE was calculated as 100%×(1−hazard ratio); adjusted VE was calculated using vaccination propensity weights and adjustments for site, occupation, and local virus circulation.RESULTS SARS-CoV-2 was detected in 204 (5.1%) participants; 16 were partially (≥14 days post-dose-1 to 13 days after dose-2) or fully (≥14 days post-dose-2) vaccinated, and 156 were unvaccinated; 32 with indeterminate status (&lt;14 days after dose-1) were excluded. Adjusted mRNA VE of full vaccination was 91% (95% confidence interval [CI]=76%–97%) against symptomatic or asymptomatic SARS-CoV-2 infection; VE of partial vaccination was 81% (95% CI=64%-90%). Among partially or fully vaccinated participants with SARS-CoV-2 infection, mean viral RNA load (Log10 copies/mL) was 40% lower (95% CI=16%-57%), the risk of self-reported febrile COVID-19 was 58% lower (Risk Ratio=0.42, 95% CI=0.18-0.98), and 2.3 fewer days (95% CI=0.8-3.7) were spent sick in bed compared to unvaccinated infected participants.CONCLUSIONS Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infections when administered in real-world conditions and attenuated viral RNA load, febrile symptoms, and illness duration among those with breakthrough infection despite vaccination.Competing Interest StatementAllison L. Naleway reported funding from Pfizer for a meningococcal B vaccine study unrelated to the submitted work. Kurt T. Hegmann serves at the Editor of the American College of Occupational and Environmental Medicine evidence-based practice guidelines. Matthew S. These reported grants and personal fees from Reed Group and the American College of Occupational and Environmental Medicine, outside the submitted work. Other authors have reported no conflicts of interest.Funding StatementFunding provided in whole or in part by federal funds from the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention under contract numbers 75D30120R68013 awarded to Marshfield Clinic Research Laboratory, 75D30120C08379 to University of Arizona, and 75D30120C08150 awarded to Abt Associates, Inc.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This study was reviewed and approved by the University of Arizona IRB as the single IRB for this studyAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesSummary data will be available once all study objectives are met.

Larval mosquitoes are aquatic omnivorous scavengers which scrape food from submerged surfaces and collect suspended food particles with their mouth brushes. The composition of diets that have been used in insectaries varies widely though necessarily provides sufficient nutrition to allow colonies to be maintained. Issues such as cost, availability and experience influence which diet is selected. One component of larval diets, essential fatty acids, appears to be necessary for normal flight though deficiencies may not be evident in laboratory cages and are likely more important when mosquitoes are reared for release into the field in e.g. mark-release-recapture and genetic control activities.In this study, four diets were compared for rearing Anopheles gambiae and Aedes aegypti, all of which provide these essential fatty acids. Two diets were custom formulations specifically designed for mosquitoes (Damiens) and two were commercially available fish foods: Doctors Foster and Smith Koi Staple Diet and TetraMin Plus Flakes. Development rate, survival, dry weight and adult longevity of mosquitoes reared with these four diets were measured. The method of presentation of one diet, Koi pellets, was additionally fed in two forms, pellets or a slurry, to determine any effect of food presentation on survival and development rate.While various criteria might be selected to choose ‘the best’ food, the readily-available Koi pellets resulted in development rates and adult longevity equal to the other diets, high survival to the adult stage and, additionally, this is available at low cost.

Law Enforcement Officers (LEOs), firefighters, and other first responders are at increased risk of SARS-CoV-2 infection compared to healthcare personnel but have relatively low COVID-19 vaccine uptake. Resistance to COVID-19 vaccine mandates among first responders has the potential to disrupt essential public services and threaten public health and safety. Using data from the HEROES-RECOVER prospective cohorts, we report on the increased illness burden of COVID-19 among unvaccinated first responders. From January to September 2021, first responders contributed to weekly active surveillance for COVID-19-like illness (CLI). Self-collected respiratory specimens collected weekly, irrespective of symptoms, and at the onset CLI were tested by Reverse Transcription Polymerase Chain Reaction (RT-PCR) assay for SARSCoV-2. Among 1415 first responders, 17% were LEOs, 68% firefighters, and 15% had other first responder occupations. Unvaccinated (41%) compared to fully vaccinated (59%) first responders were less likely to believe COVID-19 vaccines are very or extremely effective (17% versus 54%) or very or extremely safe (15% versus 54%). From January through September 2021, among unvaccinated LEOs, the incidence of COVID-19 was 11.9 per 1,000 person-weeks (95%CI=7.0-20.1) compared to only 0.6 (95%CI=0.2-2.5) among vaccinated LEOs. Incidence of COVID-19 was also higher among unvaccinated firefighters (9.0 per 1,000 person-weeks; 95%CI=6.4-12.7) compared to those vaccinated (1.8 per 1,000; 95%CI=1.1-2.8). Once they had laboratory-confirmed COVID-19, unvaccinated first responders were sick for a mean+/-SD of 14.7+/-21.7 days and missed a mean of 38.0+/-46.0 hours of work. These findings suggest that state and local governments with large numbers of unvaccinated first responders may face major disruptions in their workforce due to COVID-19 illness. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Background: Persons living with HIV (PLHIV) who are also infected with Kaposi sarcoma-associated herpesvirus (KSHV) constitute a group among the highest risk for Kaposi sarcoma (KS). As such, understanding KSHV prevalence amongst PLHIV is important for the control of KS. To date, data on KSHV prevalence amongst PLHIV in East Africa - one of the world's hotbeds for KS - is both sparse and variable. Method(s): In a cross-sectional design, we studied consecutive adult PLHIV identified just prior to starting antiretroviral therapy at an ambulatory HIV clinic in Mbarara, Uganda. Results from two enzyme immunoassays (with synthetic K8.1 and ORF 65 antigens as targets) and one immunofluorescence assay (using induced BCBL cells) to detect antibodies to KSHV were combined to classify KSHV antibody positivity. Result(s): We evaluated 727 PLHIV between 2005 to 2013; median age was 34 years (interquartile range (IQR): 28-40), 69% were women, and median CD4 count was 167 cells/microl (IQR: 95-260). Prevalence of KSHV antibody positivity was 42% (95% CI: 38%-46%), with little substantive change after several correction approaches, including Rogan-Gladen. Adjusted prevalence of KSHV antibody positivity was 1.6 times (95% CI: 1.3-1.9) higher in men than women; adjusted absolute prevalence difference was +0.20 (95% CI: +0.11 to +0.30). Lack of formal education (prevalence ratio=1.6 comparing no school to >= 4 years of secondary school; 95% CI: 1.1-2.3) was also associated with KSHV infection. We found no strong evidence for a role for age, alcohol use, or other measurements of sexual behavior, SES, or well-being in the occurrence of KSHV antibody positivity. Conclusion(s): Among adult PLHIV in western Uganda, KSHV prevalence is estimated at 42%, with little change after several approaches to correction for antibody detection inaccuracy. This estimate differs from several others in the region (up to 83%), highlighting need for inter-assay comparison studies using identical local specimens. To the extent HIV does not influence KSHV acquisition, the findings may also represent KSHV prevalence in the general population. The large-magnitude effect of sex and education on KSHV acquisition motivates an accelerated search for mechanisms. The sex effect, in part, may explain the higher incidence of KS among men. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

BACKGROUND: Emerging data suggest that second-generation influenza vaccines with higher hemagglutinin (HA) antigen content and/or different production methods may induce stronger antibody responses to HA than standard-dose egg-based influenza vaccines in adults. We compared antibody responses to high-dose egg-based inactivated (HD-IIV3), recombinant (RIV4), and cell culture-based (ccIIV4) vs standard-dose egg-based inactivated influenza vaccine (SD-IIV4) among health care personnel (HCP) aged 18-65 years in 2 influenza seasons (2018-2019, 2019-2020). METHODS: In the second trial season, newly and re-enrolled HCPs who received SD-IIV4 in season 1 were randomized to receive RIV4, ccIIV4, or SD-IIV4 or were enrolled in an off-label, nonrandomized arm to receive HD-IIV3. Prevaccination and 1-month-postvaccination sera were tested by hemagglutination inhibition (HI) assay against 4 cell culture propagated vaccine reference viruses. Primary outcomes, adjusted for study site and baseline HI titer, were seroconversion rate (SCR), geometric mean titers (GMTs), mean fold rise (MFR), and GMT ratios that compared vaccine groups to SD-IIV4. RESULTS: Among 390 HCP in the per-protocol population, 79 received HD-IIV3, 103 RIV4, 106 ccIIV4, and 102 SD-IIV4. HD-IIV3 recipients had similar postvaccination antibody titers compared with SD-IIV4 recipients, whereas RIV4 recipients had significantly higher 1-month-postvaccination antibody titers against vaccine reference viruses for all outcomes. CONCLUSIONS: HD-IIV3 did not induce higher antibody responses than SD-IIV4, but, consistent with previous studies, RIV4 was associated with higher postvaccination antibody titers. These findings suggest that recombinant vaccines rather than vaccines with higher egg-based antigen doses may provide improved antibody responses in highly vaccinated populations.

BACKGROUND: The World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear. METHODS: We obtained whole-genome sequences and associated phenotypes of resistance or susceptibility to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for isolates from 16 countries across six continents. For each isolate, mutations associated with drug resistance and drug susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These profiles were predicted to be susceptible to all four drugs (i.e., pansusceptible) if they were predicted to be susceptible to isoniazid and to the other drugs or if they contained mutations of unknown association in genes that affect susceptibility to the other drugs. We simulated the way in which the negative predictive value changed with the prevalence of drug resistance. RESULTS: A total of 10,209 isolates were analyzed. The largest proportion of phenotypes was predicted for rifampin (9660 [95.4%] of 10,130) and the smallest was predicted for ethambutol (8794 [89.8%] of 9794). Resistance to isoniazid, rifampin, ethambutol, and pyrazinamide was correctly predicted with 97.1%, 97.5%, 94.6%, and 91.3% sensitivity, respectively, and susceptibility to these drugs was correctly predicted with 99.0%, 98.8%, 93.6%, and 96.8% specificity. Of the 7516 isolates with complete phenotypic drug-susceptibility profiles, 5865 (78.0%) had complete genotypic predictions, among which 5250 profiles (89.5%) were correctly predicted. Among the 4037 phenotypic profiles that were predicted to be pansusceptible, 3952 (97.9%) were correctly predicted. CONCLUSIONS: Genotypic predictions of the susceptibility of M. tuberculosis to first-line drugs were found to be correlated with phenotypic susceptibility to these drugs. (Funded by the Bill and Melinda Gates Foundation and others.).

Messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines have been shown to be effective in preventing symptomatic COVID-19 in randomized placebo-controlled Phase III trials (1,2); however, the benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood. Using prospective cohorts of health care personnel, first responders, and other essential and frontline workers* in eight U.S. locations during December 14, 2020-March 13, 2021, CDC routinely tested for SARS-CoV-2 infections every week regardless of symptom status and at the onset of symptoms consistent with COVID-19-associated illness. Among 3,950 participants with no previous laboratory documentation of SARS-CoV-2 infection, 2,479 (62.8%) received both recommended mRNA doses and 477 (12.1%) received only one dose of mRNA vaccine.(†) Among unvaccinated participants, 1.38 SARS-CoV-2 infections were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) per 1,000 person-days.(§) In contrast, among fully immunized (≥14 days after second dose) persons, 0.04 infections per 1,000 person-days were reported, and among partially immunized (≥14 days after first dose and before second dose) persons, 0.19 infections per 1,000 person-days were reported. Estimated mRNA vaccine effectiveness for prevention of infection, adjusted for study site, was 90% for full immunization and 80% for partial immunization. These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions. COVID-19 vaccination is recommended for all eligible persons.

OBJECTIVE: To improve patient safety and pain management, the Centers for Disease Control and Prevention (CDC) released the Guideline for Prescribing Opioids for Chronic Pain (CDC Guideline). Recognizing that issuing a guideline alone is insufficient for transforming practice, CDC supported an Opioid Quality Improvement (QI) Collaborative, consisting of 10 health care systems that represented more than 120 practices across the United States. The research team identified factors related to implementation success using domains described by the integrated Promoting Action on Research Implementation in Health Services (iPARIHS) implementation science framework. METHODS: Data from interviews, notes from check-in calls, and documents provided by systems were used. The researchers collected data throughout the project through interviews, meeting notes, and documents. RESULTS: The iPARIHS framework was used to identify factors that affected implementation related to the context, innovation (implementing recommendations from the CDC Guideline), recipient (clinicians), and facilitation (QI team). Contextual characteristics were at the clinic, health system, and broader external context, including staffing and leadership support, previous QI experience, and state laws. Characteristics of the innovation were its adaptability and challenges operationalizing the measures. Recipient characteristics included belief in the importance of the innovation but challenges engaging in the initiative. Finally, facilitation characteristics driving differential outcomes included staffing and available time of the QI team, the ability to make changes, and experience with QI. CONCLUSION: As health care systems continue to implement the CDC Guideline, these insights can advance successful implementation efforts by describing common implementation challenges and identifying strategies to prepare for and overcome them.

CONTEXT.—: Lower Anogenital Squamous Terminology (LAST) standardization recommended p16(INK4a) immunohistochemistry (p16 IHC) for biopsies diagnosed morphologically as cervical intraepithelial neoplasia (CIN) grade 2 (CIN2) to classify them as low-grade or high-grade squamous intraepithelial lesions (HSILs). OBJECTIVE.—: To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses. DESIGN.—: A statewide, stratified sample of cervical biopsies diagnosed by community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available. RESULTS.—: Biopsies were more likely to test p16 IHC positive with increasing severity of CP diagnoses, overall (P(trend) ≤ .001) and within each HPV risk group (P(trend) ≤ .001 except for low-risk HPV [P(trend) < .010]). All abnormal grades of CP-diagnosed biopsies were more likely to test p16 IHC positive with a higher HPV risk group (P(trend) < .001), and testing p16 IHC positive was associated with higher HPV risk group than testing p16 IHC negative for each grade of CP-diagnosed biopsies (P < .001). p16 IHC-positive, CP-diagnosed CIN2 biopsies were less likely than CP-diagnosed CIN3 biopsies to test HPV16 positive, have an antecedent HSIL(+) cytology, or to be diagnosed as CIN3(+) by the EP (P < .001 for all). p16 IHC-positive, CP-diagnosed CIN1 biopsies had lower HPV risk groups than p16 IHC-negative, CP-diagnosed CIN2 biopsies (P < .001). CONCLUSIONS.—: p16 IHC-positive, CP-diagnosed CIN2 appears to be lower cancer risk than CP-diagnosed CIN3. LAST classification of "HSIL" diagnosis, which includes p16 IHC-positive CIN2, should annotate the morphologic diagnosis (CIN2 or CIN3) to inform all management decisions, which is especially important for young (<30 years) women diagnosed with CIN2 for whom surveillance rather than treatment is recommended.

BACKGROUND: Minimal data exist on HIV drug resistance patterns and prevalence among paediatric patients failing ART in resource-limited settings. We assessed levels of HIV drug resistance in children with virological failure. METHODS: This cross-sectional study, performed from March 2017 to March 2019 in South Africa, enrolled HIV-positive children aged ≤19 years, receiving ART through public health facilities with recent evidence suggestive of virological failure (at least one viral load ≥1000 copies/mL), across 45 randomly selected high-volume clinics from all nine provinces. Resistance genotyping was performed using next-generation sequencing technologies. Descriptive analysis taking into account survey design was used to determine outcomes. RESULTS: Among 899 participants enrolled, the adjusted proportion of HIV drug resistance among children with virological failure was 87.5% (95% CI 83.0%-90.9%). Resistance to NNRTIs was detected in 77.4% (95% CI 72.5%-81.7%) of participants, and resistance to NRTIs in 69.5% (95% CI 62.9%-75.4%) of participants. Overall, resistance to PIs was detected in 7.7% (95% CI 4.4%-13.0%) of children. CONCLUSIONS: HIV drug resistance was highly prevalent in paediatric patients failing ART in South Africa, with 9 in 10 patients harbouring resistance to NNRTIs and/or NRTIs. PI-based regimens are predicted to be highly efficacious in achieving virological suppression amongst patients failing NNRTI-based regimens. Scaling up resistance testing amongst patients would facilitate access to second- and third-line regimens in South Africa.

BACKGROUND: Few studies have examined influenza vaccine effectiveness (VE) among women during pregnancy in middle-income countries. We used data from a prospective cohort of women who were pregnant in Peru to estimate effectiveness of the 2018 Southern Hemisphere influenza vaccine. METHODS: Women at <28 weeks gestation were enrolled from 4 tertiary level hospitals in Lima, Peru at the start of the 2018 influenza season and followed until the end of their pregnancies. Participants had mid-turbinate nasal swabs collected and tested for influenza by reverse-transcription polymerase chain reaction (RT-PCR) with onset of ≥1 of myalgia, cough, runny nose or nasal congestion, sore throat, or difficulty breathing. Time-varying Cox proportional hazard regression models were used to estimate the risk of RT-PCR-confirmed influenza infection after adjusting for inverse probability treatment weight. RESULTS: We followed 1896 women for a median of 127 days (interquartile range [IQR], 86-174). Participants had a median age of 29 years (IQR, 24-34). Among the 1896 women, 49% were vaccinated with the 2018 influenza vaccine and 1039 (55%) developed influenza-like illness, 76 (7%) of whom had RT-PCR-confirmed influenza. Incidence rates of RT-PCR-confirmed influenza were 36.6 and 15.3 per 100 000 person-days among women who were unvaccinated and vaccinated, respectively. Adjusted influenza VE was 22% (95% confidence interval, -64.1% to 62.9%). CONCLUSIONS: Participants vaccinated against influenza had more than 50% lower incidence of RT-PCR-confirmed influenza illness. Although the VE estimated through propensity weight-adjusted time-varying Cox regression did not reach statistical significance, our findings provide additional evidence about the value of maternal influenza vaccination in middle-income countries.

BACKGROUND: Three doses of coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines produce robust antibody responses, but data are limited among individuals previously infected with SARS-CoV-2. From a cohort of health care personnel (75.5%), first responders (4.6%), and other frontline workers (19.8%) in 6 US states, we longitudinally assessed antibody waning after dose-2, and response to dose-3, according to SARS-CoV-2 infection history. METHODS: Participants submitted sera every three months, after SARS-CoV-2 infection, and after each COVID-19 vaccine dose. Sera were tested for antibodies and reported quantitatively as area under the serial dilution curve (AUC). Changes in the AUC values over time were compared as fold-changes using a linear mixed model. RESULTS: Analysis included 388 participants who received dose-3 by November 2021. Three comparison groups: (1) vaccine only with no known prior SARS-CoV-2 infection (n = 224); (2) infection prior to dose-1 (n = 123); and (3) infection after dose 2 and before dose-3 (n = 41). The interval from dose 2 and dose 3 was approximately 8-months. After dose-3, antibody levels rose 2.5-fold (95%CI = 2.2-3.0) in group 2, and 2.9-fold (95%CI = 2.6-3.3) in group 1. Those infected within 90 days before dose-3 (and median 233 days (IQR = 213-246) after dose-2) did not increase significantly after dose-3. CONCLUSIONS: A third dose of mRNA vaccine typically elicited a robust humoral immune response among those with primary vaccination regardless of SARS-CoV-2 infection >3 months prior to boosting. Those with infection < 3 months prior to boosting did not have a significant increase in antibody concentrations in response to a booster.

For injury epidemiologists, the hunt for data is an | ongoing detective story. While there is a thrill in the | chase, there is even more satisfaction in using those | data to drive important public health research and | programming. The size of the U.S. agriculture workforce and the declining number of work-related agricultural injuries made annual data collection costly. | Therefore, in 2015, the National Institute for | Occupational Safety and Health (NIOSH) discontinued | interagency agreements with Department of Labor | (DOL) and United States Department of Agriculture | (USDA) to collect national agricultural worker injury | data and developed a plan to seek alternative methods | to obtain quality agricultural injury surveillance data. | However, those means were not the only tool to gather | agricultural injury data, and many alternative efforts | persisted.1 The ethos of the new model seeks to engage | with extramural partners to fill the many identified | gaps in agricultural injury data. While some may long | for the “good old days” of the national injury surveys, | we recognize several factors make such endeavors | impractical.

IMPORTANCE: Data on the epidemiology of mild to moderately severe COVID-19 are needed to inform public health guidance. OBJECTIVE: To evaluate associations between 2 or 3 doses of mRNA COVID-19 vaccine and attenuation of symptoms and viral RNA load across SARS-CoV-2 viral lineages. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of essential and frontline workers in Arizona, Florida, Minnesota, Oregon, Texas, and Utah with COVID-19 infection confirmed by reverse transcriptase-polymerase chain reaction testing and lineage classified by whole genome sequencing of specimens self-collected weekly and at COVID-19 illness symptom onset. This analysis was conducted among 1199 participants with SARS-CoV-2 from December 14, 2020, to April 19, 2022, with follow-up until May 9, 2022, reported. EXPOSURES: SARS-CoV-2 lineage (origin strain, Delta variant, Omicron variant) and COVID-19 vaccination status. MAIN OUTCOMES AND MEASURES: Clinical outcomes included presence of symptoms, specific symptoms (including fever or chills), illness duration, and medical care seeking. Virologic outcomes included viral load by quantitative reverse transcriptase-polymerase chain reaction testing along with viral viability. RESULTS: Among 1199 participants with COVID-19 infection (714 [59.5%] women; median age, 41 years), 14.0% were infected with the origin strain, 24.0% with the Delta variant, and 62.0% with the Omicron variant. Participants vaccinated with the second vaccine dose 14 to 149 days before Delta infection were significantly less likely to be symptomatic compared with unvaccinated participants (21/27 [77.8%] vs 74/77 [96.1%]; OR, 0.13 [95% CI, 0-0.6]) and, when symptomatic, those vaccinated with the third dose 7 to 149 days before infection were significantly less likely to report fever or chills (5/13 [38.5%] vs 62/73 [84.9%]; OR, 0.07 [95% CI, 0.0-0.3]) and reported significantly fewer days of symptoms (10.2 vs 16.4; difference, -6.1 [95% CI, -11.8 to -0.4] days). Among those with Omicron infection, the risk of symptomatic infection did not differ significantly for the 2-dose vaccination status vs unvaccinated status and was significantly higher for the 3-dose recipients vs those who were unvaccinated (327/370 [88.4%] vs 85/107 [79.4%]; OR, 2.0 [95% CI, 1.1-3.5]). Among symptomatic Omicron infections, those vaccinated with the third dose 7 to 149 days before infection compared with those who were unvaccinated were significantly less likely to report fever or chills (160/311 [51.5%] vs 64/81 [79.0%]; OR, 0.25 [95% CI, 0.1-0.5]) or seek medical care (45/308 [14.6%] vs 20/81 [24.7%]; OR, 0.45 [95% CI, 0.2-0.9]). Participants with Delta and Omicron infections who received the second dose 14 to 149 days before infection had a significantly lower mean viral load compared with unvaccinated participants (3 vs 4.1 log10 copies/L; difference, -1.0 [95% CI, -1.7 to -0.2] for Delta and 2.8 vs 3.5 log10 copies/L, difference, -1.0 [95% CI, -1.7 to -0.3] for Omicron). CONCLUSIONS AND RELEVANCE: In a cohort of US essential and frontline workers with SARS-CoV-2 infections, recent vaccination with 2 or 3 mRNA vaccine doses less than 150 days before infection with Delta or Omicron variants, compared with being unvaccinated, was associated with attenuated symptoms, duration of illness, medical care seeking, or viral load for some comparisons, although the precision and statistical significance of specific estimates varied.

OBJECTIVES: Determine whether Pre-Game Safety Huddles, a novel and low-resource approach to concussion education, increase the expected likelihood of concussion reporting for youth athletes. METHODS: A cluster-randomised trial compared Safety Huddles to usual care. Safety Huddles bring together athletes and coaches from both teams before the start of each game for coaches to briefly affirm the importance of speaking up if a concussion is suspected. Participants were athletes from 22 competitive community-based American football and girls and boys soccer teams (ages 9-14), and randomisation into intervention or control occurred at the level of the bracket (group of teams that compete against each other during the regular season). The primary outcome was expected likelihood of reporting concussion symptoms to the coach, measured via validated athlete survey at the beginning and end of the season. RESULTS: Of 343 eligible participants, 339 (99%) completed baseline surveys and 303 (88%) completed surveys at season end. The mean (SD) age was 11.4 (1.1) years, 26% were female soccer athletes, 27% were male soccer athletes and 47% were football athletes. In adjusted analyses accounting for baseline values and clustering by sport and team via random effects, expected likelihood of concussion reporting at the end of the season was significantly higher in the intervention group compared to controls (mean difference=0.49, 95% CI 0.11 to 0.88; Cohen's d=0.35). CONCLUSIONS AND RELEVANCE: Pre-Game Safety Huddles increased the expected likelihood of athletes reporting concussion symptoms. While further study is warranted, sport organisations should consider this approach a promising low-resource option for improving concussion safety in their setting. TRIAL REGISTRATION NUMBER: NCT04099329.

BACKGROUND: Antibody responses to non-egg-based standard-dose cell-culture influenza vaccine (containing 15 µg hemagglutinin (HA)/component) and recombinant vaccine (containing 45 µg HA/component) during consecutive seasons have not been studied in the United States. METHODS: In a randomized trial of immunogenicity of quadrivalent influenza vaccines among healthcare personnel (HCP) aged 18-64 years over two consecutive seasons, HCP who received recombinant-hemagglutinin (RIV) or cell-culture-based vaccine (ccIIV) during the first season (Y1) were re-randomized the second season of 2019-2020 (Y2) to receive ccIIV or RIV, resulting in four ccIIV-RIV combinations. In Y2, hemagglutination inhibition (HI) antibody titers against reference cell-grown vaccine viruses were compared in each ccIIV-RIV group with titers among HCP randomized both seasons to receive egg-based, standard-dose inactivated influenza vaccine (IIV), using geometric mean titer (GMT) ratios of Y2-post-vaccination titers. RESULTS: Y2 data from 414 HCPs were analyzed per-protocol. Compared to 60 IIV/IIV recipients, 74 RIV/RIV and 106 ccIIV/RIV recipients showed significantly elevated GMT ratios (Bonferroni corrected P <.007) against all components except A (H3N2). Post-vaccination GMT ratios for ccIIV/ccIIV and RIV/ccIIV were not significantly elevated compared to IIV/IIV except for RIV/ccIIV against A(H1N1)pdm09. CONCLUSIONS: In adult HCPs, receipt of RIV two consecutive seasons or the second season was more immunogenic than consecutive egg-based IIV for three of the four components of quadrivalent vaccine. Immunogenicity of ccIIV/ccIIV was similar to that of IIV/IIV. Differences in hemagglutinin antigen content may play a role in immunogenicity of influenza vaccination in consecutive seasons.

Toxoplasmosis is caused by infection with the zoonotic parasite Toxoplasma gondii. Although disease tends to be mild (e.g., self-limiting influenza-like symptoms) or asymptomatic in immunocompetent persons, toxoplasmosis is more severe in immunocompromised persons, who can develop potentially fatal encephalopathy (1). In addition, primary infections acquired during pregnancy might result in a range of adverse outcomes, including fetal ocular infection, cranial and neurologic deformities, stillbirth, and miscarriage (1,2). An estimated 11% of the U.S. population aged ≥6 years are seropositive for toxoplasmosis, based on analysis of sera collected through the National Health and Nutrition Examination Survey during 2011-2014 (3). Toxoplasmosis is not a nationally notifiable disease in the United States, and currently no national public health surveillance data are available; however, it is reportable in eight states. To better understand how surveillance data are collected and used, reviews of state-level toxoplasmosis surveillance were conducted during June-July 2021 using semistructured interviews with health officials in six states (Arkansas, Kentucky, Minnesota, Nebraska, Pennsylvania, and Wisconsin) where toxoplasmosis is currently reportable. Why or when toxoplasmosis became reportable could not be determined, and many of the states had limited capacity to respond to reported cases. Case definitions varied considerably in terms of clinical description, laboratory criteria, and case classification (i.e., confirmed, probable, or suspect), limiting disease estimates and comparisons among states. Implementation of a standardized case definition would help ensure that cases are counted consistently, enabling better use of surveillance data to characterize disease. Identifying newly acquired cases is challenging because most acute cases among immunocompetent persons (including pregnant women) are asymptomatic, disease among immunocompromised persons is likely reactivation of latent disease, and congenital infections might not manifest until later in life.

BACKGROUND: Frozen foods have rarely been linked to Listeria monocytogenes illness. We describe an outbreak investigation prompted both by hospital clustering of illnesses and product testing. METHODS: We identified outbreak-associated listeriosis cases using whole-genome sequencing (WGS), product testing results, and epidemiologic linkage to cases in the same Kansas hospital. We reviewed hospital medical and dietary records, product invoices, and molecular subtyping results. Federal and state officials tested product and environmental samples for L. monocytogenes. RESULTS: Kansas officials were investigating five cases of listeriosis at a single hospital when, simultaneously, unrelated sampling for a study in South Carolina identified L. monocytogenes in Company A ice cream products made in Texas. Isolates from four patients and Company A products were closely related by WGS, and the four patients with known exposures had consumed milkshakes made with Company A ice cream while hospitalized. Further testing identified L. monocytogenes in ice cream produced in a second Company A production facility in Oklahoma; these isolates were closely related by WGS to those from five patients in three other states. These ten illnesses, involving three deaths, occurred from 2010 through 2015. Company A ultimately recalled all products. CONCLUSION: In this U.S. outbreak of listeriosis linked to a widely distributed brand of ice cream, WGS and product sampling helped link cases spanning five years to two production facilities, indicating longstanding contamination. Comprehensive sanitation controls and environmental and product testing for L. monocytogenes, with regulatory oversight, should be implemented for ice cream production.

Concussion education is widely mandated and largely ineffective. Recent consensus guidance on concussion education asserts the importance of (1) theory-driven programming that targets the team as a system and (2) working with end users throughout the development process, and considering issues such as feasibility, acceptability, and sustainability. Consistent with this guidance, and in collaboration with youth sport stakeholders in two regions of the United States, we developed a novel approach to concussion education: Pre-game safety huddles. Safety huddles have the following two core components: (1) athletes, coaches, and other stakeholders come together before the start of each game and (2) opinion leaders (coaches, referees) affirm the importance of care seeking for suspected concussion. The aim of this article is to provide an overview of the collaborative process through which we refined the safety huddle concept into an acceptable and feasible intervention with potential for sustainable implementation in diverse youth sports settings with minimal resource demands. In describing our process and discussing challenges and opportunities, we hope to provide an example for others seeking to develop and implement injury prevention interventions in youth sports settings.

Upon request from tribal nations, and as part of the Centers for Disease Control and Prevention's (CDC's) emergency response, CDC staff provided both remote and on-site assistance to tribes to plan, prepare, and respond to the COVID-19 pandemic. From April 2, 2020, through June 11, 2021, CDC deployed a total of 275 staff to assist 29 tribal nations. CDC staff typically collaborated in multiple work areas including epidemiology and surveillance (86%), contact tracing (76%), infection prevention control (72%), community mitigation (72%), health communication (66%), incident command structure (55%), emergency preparedness (38%), and worker safety (31%). We describe the activities of CDC staff in collaboration with 4 tribal nations, Northern Cheyenne, Hoopa Valley, Shoshone-Bannock, and Oglala Sioux Tribe, to combat COVID-19 and lessons learned from the engagement.

BACKGROUND: Assessing the real-world effectiveness of COVID-19 vaccines and understanding the incidence and severity of SARS-CoV-2 illness in children is essential to inform policy and guide healthcare professionals advising parents and caregivers of children who test positive for SARS-CoV-2. OBJECTIVE: This report describes the objectives and methods for conducting the Pediatric Research Observing Trends and Exposures in COVID-19 Timelines (PROTECT) study. PROTECT is a longitudinal prospective pediatric cohort study designed to estimate SARS-CoV-2 incidence and COVID-19 vaccine effectiveness (VE) against infection among children aged 6 months to 17 years as well as differences in SARS-CoV-2 infection and vaccine response between children and adolescents. METHODS: The PROTECT multisite network was initiated in July 2021 and aims to enroll approximately 2,305 children across four U.S. locations and collect data over a two-year surveillance period; the enrollment target was based on prospective power calculations and account for expected attrition and nonresponse. Study sites recruit parents and legal guardians (PLGs) of age-eligible children participating in the existing HEROES-RECOVER network as well as from surrounding communities. Child demographics, medical history, COVID-19 exposure, vaccination history, and PLGs' knowledge and attitudes about COVID-19 are collected at baseline and throughout the study. Mid-turbinate nasal specimens are self- or PLG-collected weekly, regardless of symptoms, for SARS-CoV-2 and influenza testing via reverse transcription-polymerase chain reaction (RT-PCR) assay, and the presence of COVID-like-illness (CLI) is reported. Children who test positive for SARS-CoV-2 or influenza or report CLI are monitored weekly by online surveys to report exposure and medical utilization until no longer ill. Children, with their PLG's permission, may elect to contribute blood at enrollment, following SARS-CoV-2 infection, following COVID-19 vaccination, and at the end of the study period. PROTECT uses electronic medical records (EMR) linkages where available and verifies COVID-19 and influenza vaccinations through EMR or state vaccine registries. RESULTS: Data collection began in July 2021 and is expected to continue through Spring 2023. As of 05/13/2022, 2,371 children are enrolled in PROTECT. Enrollment is ongoing at all study sites. CONCLUSIONS: As COVID-19 vaccine products are authorized for use in pediatric populations, PROTECT study data will provide real-world estimates of VE in preventing infection. In addition, this prospective cohort provides a unique opportunity to further understand SARS-CoV-2 incidence, clinical course, and key knowledge gaps that may inform public health.