An immune-protein score combining TRAIL, IP-10 and CRP for predicting severe COVID-19 disease.

COVID-19 patients are oftentimes over- or under-treated due to a deficit in predictive management tools. This study reports derivation of an algorithm that integrates the host levels of TRAIL, IP-10, and CRP into a single numeric score that is an early indicator of severe outcome for COVID-19 patients and can identify patients at-risk to deteriorate. 394 COVID-19 patients were eligible; 29% meeting a severe outcome (intensive care unit admission/non-invasive or invasive ventilation/death). The score's area under the receiver operating characteristic curve (AUC) was 0.86, superior to IL-6 (AUC 0.77; p = 0.033) and CRP (AUC 0.78; p < 0.001). Likelihood of severe outcome increased significantly (p < 0.001) with higher scores. The score differentiated severe patients who further deteriorated from those who improved (p = 0.004) and projected 14-day survival probabilities (p < 0.001). The score accurately predicted COVID-19 patients at-risk for severe outcome, and therefore has potential to facilitate timely care escalation and de-escalation and appropriate resource allocation.

Pediatric Hospitalizations After School Reopening During the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Alpha (B.1.1.7) Variant Spread: A Multicenter Cross-sectional Study in Israel.

This multicenter, cross-sectional study provides evidence on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated emergency department visits and hospitalizations in pediatric wards and intensive care units after school reopening during the SARS-CoV-2 Alpha (B.1.1.7) variant spread in Israel. Study findings suggest that school reopening was not followed by an increase in SARS-CoV-2-related pediatric morbidity.

Factors Associated With Referral of Children With a Femur Fracture to a Social Worker by an Orthopedist for Suspected Child Abuse.

OBJECTIVES: This article explores factors associated with referral of children with a femur fracture to a social worker by an orthopedist for suspected child abuse. METHODS: This retrospective chart review study included 131 children younger than 5 years who sustained a femur fracture and were hospitalized in a major 495-bed hospital located in the northern-central Israel from 2009 to 2021. Data on children who were referred to a social worker by the treating orthopedist and those who were not were compared. RESULTS: More than half the children studied (58.8%, n = 77) were referred to a social worker by an orthopedist for suspected child abuse. However, only a fifth of these cases were eventually reported to the authorities. Male sex (odds ratio [OR], 2.44), younger age of the child (OR, 0.95), and spiral femur fracture type (OR, 5.30) increased the likelihood of referral. In addition, treatment of the child by an orthopedic specialist (as compared with an orthopedic resident; OR, 3.12) and lengthier professional experience of the treating orthopedist (OR, 1.08) increased the likelihood of referral. CONCLUSIONS: Younger male children presenting with a spiral femur fracture have a higher likelihood to be referred to a social worker because of suspected child abuse by treating orthopedic specialists with lengthier professional experience. The findings point to the need to improve the capacity of orthopedic residents to report child abuse.

Antibiotic misuse in respiratory tract infections in children and adults-a prospective, multicentre study (TAILORED Treatment).

Respiratory tract infections (RTI) are more commonly caused by viral pathogens in children than in adults. Surprisingly, little is known about antibiotic use in children as compared to adults with RTI. This prospective study aimed to determine antibiotic misuse in children and adults with RTI, using an expert panel reference standard, in order to prioritise the target age population for antibiotic stewardship interventions. We recruited children and adults who presented at the emergency department or were hospitalised with clinical presentation of RTI in The Netherlands and Israel. A panel of three experienced physicians adjudicated a reference standard diagnosis (i.e. bacterial or viral infection) for all the patients using all available clinical and laboratory information, including a 28-day follow-up assessment. The cohort included 284 children and 232 adults with RTI (median age, 1.3 years and 64.5 years, respectively). The proportion of viral infections was larger in children than in adults (209(74%) versus 89(38%), p < 0.001). In case of viral RTI, antibiotics were prescribed (i.e. overuse) less frequently in children than in adults (77/209 (37%) versus 74/89 (83%), p < 0.001). One (1%) child and three (2%) adults with bacterial infection were not treated with antibiotics (i.e. underuse); all were mild cases. This international, prospective study confirms major antibiotic overuse in patients with RTI. Viral infection is more common in children, but antibiotic overuse is more frequent in adults with viral RTI. Together, these findings support the need for effective interventions to decrease antibiotic overuse in RTI patients of all ages.

[PREFERENCES OF PARENTS FOR PEDIATRIC INPATIENT WARD PHYSICIAN'S ATTIRE].

BACKGROUND: The preferred attire for physicians has not been defined to date. In Israel, where casual attire is acceptable in most circumstances, patients' preferences have not yet been systematically evaluated. METHODS: This is a cross-sectional study that was designed to evaluate parents' preferences for physicians' attire in a pediatric inpatient ward. A volunteer was dressed in four types of clothes sets: elegant attire, sportive attire, careless attire and scrubs - all of which were displayed, with or without a white coat. Parents were asked whether or not they felt the physician was an important component of the medical encounter; they were also asked to choose the picture of the doctor they preferred to care for their child. RESULTS: A total of 250 parents participated in the study; 68% of the parents believe that the physician's attire is an important component of the medical encounter; 41% of the parents preferred the doctor to wear scrubs with a white coat, 22% preferred scrubs without a white coat. Careless attire was the least preferred attire. CONCLUSIONS: The physicians' attire was important for most of the participants. We recommend that doctors in inpatient wards wear scrubs.

A host-protein signature is superior to other biomarkers for differentiating between bacterial and viral disease in patients with respiratory infection and fever without source: a prospective observational study.

Bacterial and viral infections often present with similar symptoms. Etiologic misdiagnosis can alter the trajectory of patient care, including antibiotic overuse. A host-protein signature comprising tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) was validated recently for differentiating bacterial from viral disease. However, a focused head-to-head comparison of its diagnostic performance against other biomarker candidates for this indication was lacking in patients with respiratory infection and fever without source. We compared the signature to other biomarkers and prediction rules using specimens collected prospectively at two secondary medical centers from children and adults. Inclusion criteria included fever > 37.5 °C, symptom duration ≤ 12 days, and presentation with respiratory infection or fever without source. Comparator method was based on expert panel adjudication. Signature and biomarker cutoffs and prediction rules were predefined. Of 493 potentially eligible patients, 314 were assigned unanimous expert panel diagnosis and also had sufficient specimen volume. The resulting cohort comprised 175 (56%) viral and 139 (44%) bacterial infections. Signature sensitivity 93.5% (95% CI 89.1-97.9%), specificity 94.3% (95% CI 90.7-98.0%), or both were significantly higher (all p values < 0.01) than for CRP, procalcitonin, interleukin-6, human neutrophil lipocalin, white blood cell count, absolute neutrophil count, and prediction rules. Signature identified as viral 50/57 viral patients prescribed antibiotics, suggesting potential to reduce antibiotic overuse by 88%. The host-protein signature demonstrated superior diagnostic performance in differentiating viral from bacterial respiratory infections and fever without source. Future utility studies are warranted to validate potential to reduce antibiotic overuse.

Travelling beyond time: shared brain system for self-projection in the temporal, political and moral domains.

Mental time travel (MTT), a cornerstone of human cognition, enables individuals to mentally project themselves into their past or future. It was shown that this self-projection may extend beyond the temporal domain to the spatial and social domains. What about higher cognitive domains? Twenty-eight participants underwent functional magnetic resonance imaging (fMRI) while self-projecting to different political, moral and temporal perspectives. For each domain, participants were asked to judge their relationship to various people (politicians, moral figures, personal acquaintances) from their actual or projected self-location. Findings showed slower, less accurate responses during self-projection across all domains. fMRI analysis revealed self-projection elicited brain activity at the precuneus, medial and dorsolateral prefrontal cortex, temporoparietal junction and anterior insula, bilaterally and right lateral temporal cortex. Notably, 23.5% of active voxels responded to all three domains and 27% to two domains, suggesting a shared brain system for self-projection. For ordinality judgement (self-reference), 52.5% of active voxels corresponded to the temporal domain specifically. Self-projection activity overlapped mostly with the frontoparietal control network, followed by the default mode network, while self-reference showed a reversed pattern, demonstrating MTT's implication in spontaneous brain activity. MTT may thus be regarded as a 'mental-experiential travel', with self-projection as a domain-general construct and self-reference related mostly to time. This article is part of the theme issue 'Elements of episodic memory: lessons from 40 years of research'.

Associations of High-Sensitive Cardiac Troponin T in Healthy Newborns and Prolonged Second Stage of Labor, Neonatal and Maternal Factors: A Prospective Study.

INTRODUCTION: High-sensitivity cardiac troponin T (hs-cTnT) is not used routinely as a diagnostic biomarker in newborns. The high precision of hs-cTnT assays increases the ability to determine small differences in cTnT over time and to detect troponin T elevation; thus, we believe that hs-cTnT assays might improve clinical care. We explored the plausible association between hs-cTnT levels (ng/L) in healthy newborns and prolonged second stage of labor, neonatal, and maternal factors. METHODS: A prospective study was performed among healthy newborns in the Obstetrics and Gynecology Department at Hillel Yaffe Medical Center in Israel in January-June 2021. The sociodemographic characteristics of the participants, maternal age, gravidity, parity, Pitocin use, epidural analgesia, and neonatal anemia were obtained from the electronic medical records. Gestational age was determined by ultrasound biometric measurements. We classified second-stage labor as normal or prolonged using the WHO guidelines. Samples from umbilical cord blood were drawn using syringes rinsed with anticoagulant by a specialist in pediatrics. The remaining blood was used to determine hs-cTnT levels (ng/L), which was defined as a continuous quantitative variable with the median value and the 25th-75th percentiles. RESULTS: Overall, 184 cord blood samples were performed from healthy newborns (60.6% males) with a median hs-cTnT of 39.03 (25th-75th percentiles = 30.53-54.09) ng/L. A multivariable linear regression model showed no significant association between neonatal anemia and hs-cTnT levels (ng/L) (p = 0.8). Gestational age (B coefficient -4.24, p < 0.001) and gravidity (B coefficient -2.41, p = 0.03) were negatively associated with hs-cTnT levels (ng/L), while Pitocin use (B coefficient 6.91, p = 0.04) and prolonged second stage of labor (B coefficient 18.07, p = 0.02) were positively associated with hs-cTnT levels (ng/L). CONCLUSIONS: High hs-cTnT levels (ng/L) were documented in the cord blood of healthy newborns. Hs-cTnT levels were positively correlated with a prolonged second stage of labor and Pitocin use and negatively correlated with longer gestational age and higher gravidity. Hs-cTnT may signify labor-related fetal distress. A larger surveillance study is mandatory to establish this correlation and assess for possible prognostic significance of elevated hs-cTnT in this context.

When all computers shut down: the clinical impact of a major cyber-attack on a general hospital.

Importance: Healthcare organizations operate in a data-rich environment and depend on digital computerized systems; thus, they may be exposed to cyber threats. Indeed, one of the most vulnerable sectors to hacks and malware is healthcare. However, the impact of cyberattacks on healthcare organizations remains under-investigated. Objective: This study aims to describe a major attack on an entire medical center that resulted in a complete shutdown of all computer systems and to identify the critical actions required to resume regular operations. Setting: This study was conducted on a public, general, and acute care referral university teaching hospital. Methods: We report the different recovery measures on various hospital clinical activities and their impact on clinical work. Results: The system malfunction of hospital computers did not reduce the number of heart catheterizations, births, or outpatient clinic visits. However, a sharp drop in surgical activities, emergency room visits, and total hospital occupancy was observed immediately and during the first postattack week. A gradual increase in all clinical activities was detected starting in the second week after the attack, with a significant increase of 30% associated with the restoration of the electronic medical records (EMR) and laboratory module and a 50% increase associated with the return of the imaging module archiving. One limitation of the present study is that, due to its retrospective design, there were no data regarding the number of elective internal care hospitalizations that were considered crucial. Conclusions and relevance: The risk of ransomware cyberattacks is growing. Healthcare systems at all levels of the hospital should be aware of this threat and implement protocols should this catastrophic event occur. Careful evaluation of steady computer system recovery weekly enables vital hospital function, even under a major cyberattack. The restoration of EMR, laboratory systems, and imaging archiving modules was found to be the most significant factor that allowed the return to normal clinical hospital work.

A rapid host-protein test for differentiating bacterial from viral infection: Apollo diagnostic accuracy study.

Objectives: To determine the diagnostic accuracy of a rapid host-protein test for differentiating bacterial from viral infections in patients who presented to the emergency department (ED) or urgent care center (UCC). Methods: This was a prospective multicenter, blinded study. MeMed BV (MMBV), a test based on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-inducible protein-10 (IP-10), and C-reactive protein (CRP), was measured using a rapid measurement platform. Patients were enrolled from 9 EDs and 3 UCCs in the United States and Israel. Patients >3 months of age presenting with fever and clinical suspicion of acute infection were considered eligible. MMBV results were not provided to the treating clinician. MMBV results (bacterial/viral/equivocal) were compared against a reference standard method for classification of infection etiology determined by expert panel adjudication. Experts were blinded to MMBV results. They were provided with comprehensive patient data, including laboratory, microbiological, radiological and follow-up. Results: Of 563 adults and children enrolled, 476 comprised the study population (314 adults, 162 children). The predominant clinical syndrome was respiratory tract infection (60.5% upper, 11.3% lower). MMBV demonstrated sensitivity of 90.0% (95% confidence interval [CI]: 80.3-99.7), specificity of 92.8% (90.0%-95.5%), and negative predictive value of 98.8% (96.8%-99.6%) for bacterial infections. Only 7.2% of cases yielded equivocal MMBV scores. Area under the curve for MMBV was 0.95 (0.90-0.99). Conclusions: MMBV had a high sensitivity and specificity relative to reference standard for differentiating bacterial from viral infections. Future implementation of MMBV for patients with suspected acute infections could potentially aid with appropriate antibiotic decision-making.

Diagnostic Accuracy of a Real-Time Host-Protein Test for Infection.

OBJECTIVE: Determining infection etiology can be difficult because viral and bacterial diseases often manifest similarly. A host protein test that computationally integrates the circulating levels of TNF-related apoptosis-induced ligand, interferon γ-induced protein-10, and C-reactive protein to differentiate between bacterial and viral infection (called MMBV) demonstrated high performance in multiple prospective clinical validation studies. Here, MMBV's diagnostic accuracy is evaluated in febrile children for whom physicians were uncertain about etiology when applied at the physician's discretion. METHODS: Patients aged 3 months to 18 years were retrospectively recruited (NCT03075111; SPIRIT study; 2014-2017). Emergency department physician's etiological suspicion and certainty level were recorded in a questionnaire at blood-draw. MMBV results are based on predefined score thresholds: viral/non-bacterial etiology (0 ≤ score <35), equivocal (35 ≤ score ≤65), and bacterial or coinfection (65 < score ≤100). Reference standard etiology (bacterial/viral/indeterminate) was adjudicated by 3 independent experts based on all available patient data. Experts were blinded to MMBV. MMBV and physician's etiological suspicion were assessed against the reference standard. RESULTS: Of 3003 potentially eligible patients, the physicians were uncertain about infection etiology for 736 of the cases assigned a reference standard (128 bacterial, 608 viral). MMBV performed with sensitivity 89.7% (96/107; 95% confidence interval 82.4-94.3) and specificity 92.6% (498/538; 95% confidence interval 90.0-94.5), significantly outperforming physician's etiological suspicion (sensitivity 49/74 = 66.2%, specificity 265/368 = 72.0%; P < .0001). MMBV equivocal rate was 12.4% (91/736). CONCLUSIONS: MMBV was more accurate in determining etiology compared with physician's suspicion and had high sensitivity and specificity according to the reference standard.

Analysis of Prognostic Factors Impacting Pediatric Acute Mastoiditis Outcomes.

BACKGROUND: This study aimed to investigate the outcomes of pediatric patients with acute mastoiditis while examining the role of intravenous steroid therapy, patient demographics, and serum inflammatory values as prognostic factors. METHODS: This study is a single-center retrospective observational study including 73 consecutive patients treated for acute mastoiditis in the course of the 10-year study period (January 2010 to December 2019). RESULTS: Data analysis showed that patients requiring surgical treatment (14%) had a 3-fold higher C-reactive protein value at admission compared to those treated conservatively (P < .001). Receiver operating characteristic analysis revealed that a C-reactive protein cut-off of ≥98.7 had a sensitivity and specificity of 100% and 74.6%, respectively, for predicting the need for surgery (area under the curve=0.927, P < .001). The duration of symptoms before hospitalization was nearly 2 days shorter in male patients (P=.031), and the use of intravenous steroid therapy significantly shortened the length of hospitalization (P=.023), by 1.4 days on average. CONCLUSION: Intravenous steroid therapy may be useful in decreasing the length of hospital stay. Mastoiditis tends to present more severely in male patients, and monitoring C-reactive protein values during treatment correlated well with the need for surgery.

When the lights go down in the delivery room: Lessons from a ransomware attack.

OBJECTIVE: To describe the challenges facing the obstetric division following a cyberattack and discuss ways of preparing for and overcoming another one. METHODS: A retrospective descriptive study conducted in a mid-sized medical center. Division activities, including the number of deliveries, cesarean sections, emergency room visits, admissions, maternal-fetal medicine department occupancy, and ambulatory encounters, from 2 weeks before the attack to 8 weeks following it (a total of 11 weeks), were compared with the retrospective period in 2019 (pre-COVID-19). In addition, we present the challenges and adaptation measures taken at the division and hospital levels leading up to the resumption of full division activity. RESULTS: On the day of the cyberattack, critical decisions were made. The media announced the event, calling on patients not to come to our hospital. Also, all elective activities other than cesarean deliveries were stopped. The number of deliveries, admissions, and both emergency room and ambulatory clinic visits decreased by 5%-10% overall for 11 weeks, reflecting the decrease in division activity. Nevertheless, in all stations, there were sufficient activities and adaptation measures to ensure patient safety, decision-making, and workflow of patients were accounted for. CONCLUSIONS: The risk of ransomware cyberattacks is growing. Healthcare systems at all levels should recognize this threat and have protocols for dealing with them once they occur.

BV score differentiates viral from bacterial-viral co-infection in adenovirus PCR positive children.

Background and objectives: Adenovirus causes acute respiratory illness that can mimic bacterial infection, making it challenging to differentiate adenoviral infection from adenoviral-bacterial co-infection. A host-protein score (BV score) for differentiating bacterial from viral infection that combines the expression levels of TNF-related apoptosis-induced ligand, interferon gamma-induced protein-10, and C-reactive protein exhibited a negative predictive value (NPV) of 98% in prior studies. Here we evaluate BV score's diagnostic accuracy in pediatrics with adenovirus PCR detection. Methods: This is a sub-analysis of children aged 3 months to 20 years with adenovirus PCR-positive infection recruited prospectively in two previous cohort studies. Reference standard diagnosis (bacterial, viral or indeterminate) was based on expert adjudication. BV score ranges from 0 to 100 and provides three results based on predefined cutoffs: viral or other non-bacterial etiology (0 ≤ score < 35), equivocal (35 ≤ score ≤ 65), and bacterial or co-infection (65 < score ≤ 100). Experts were blinded to BV results. Results: Out of 1,779 children, 142 had an adenovirus PCR-positive nasopharyngeal swab. Median age was 1.2 years (interquartile range 0.6-1.8), 50.7% were male and 52.8% were hospitalized. 12 cases were reference standard bacterial, 115 reference standard viral and 15 were indeterminate. BV score attained sensitivity of 100.0% (no false negatives), specificity of 89.5% (95% confidence interval: 83.2-95.8), and NPV of 100.0% (92.6-100.0). Equivocal rate was 19.7%. Conclusions: BV score accurately differentiated between adenoviral and bacterial-adenoviral co-infection in this cohort of children with PCR-positive adenovirus detection. This performance supports a potential to improve appropriate antibiotic use.

The diagnostic value of nasal microbiota and clinical parameters in a multi-parametric prediction model to differentiate bacterial versus viral infections in lower respiratory tract infections.

BACKGROUND: The ability to accurately distinguish bacterial from viral infection would help clinicians better target antimicrobial therapy during suspected lower respiratory tract infections (LRTI). Although technological developments make it feasible to rapidly generate patient-specific microbiota profiles, evidence is required to show the clinical value of using microbiota data for infection diagnosis. In this study, we investigated whether adding nasal cavity microbiota profiles to readily available clinical information could improve machine learning classifiers to distinguish bacterial from viral infection in patients with LRTI. RESULTS: Various multi-parametric Random Forests classifiers were evaluated on the clinical and microbiota data of 293 LRTI patients for their prediction accuracies to differentiate bacterial from viral infection. The most predictive variable was C-reactive protein (CRP). We observed a marginal prediction improvement when 7 most prevalent nasal microbiota genera were added to the CRP model. In contrast, adding three clinical variables, absolute neutrophil count, consolidation on X-ray, and age group to the CRP model significantly improved the prediction. The best model correctly predicted 85% of the 'bacterial' patients and 82% of the 'viral' patients using 13 clinical and 3 nasal cavity microbiota genera (Staphylococcus, Moraxella, and Streptococcus). CONCLUSIONS: We developed high-accuracy multi-parametric machine learning classifiers to differentiate bacterial from viral infections in LRTI patients of various ages. We demonstrated the predictive value of four easy-to-collect clinical variables which facilitate personalized and accurate clinical decision-making. We observed that nasal cavity microbiota correlate with the clinical variables and thus may not add significant value to diagnostic algorithms that aim to differentiate bacterial from viral infections.

T-cell compartment in synovial fluid of pediatric patients with JIA correlates with disease phenotype.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is an autoimmune disease where T cells are key players. It can be classified into two main clinical diseases: polyarticular and pauciarticular, based on the number of joints involved. Oligoarthritis, which is considered a pauciarticular subtype since it involves up to four joints upon presentation, is further divided into persistent or extended forms based on disease progression. METHODOLOGY/PRINCIPAL FINDINGS: Here we assessed the T-cell compartment in synovial fluid obtained from 33 JIA patients with active disease and correlated the analyzed parameters with the patients' clinical characteristics. The T-cell compartment was determined by the representation of T-cell receptor (TCR) repertoires and the amount of TCR excision circles (TRECs). RESULTS: Patients with polyarticular disease have more a clonal pattern of their TCR repertoire. These findings were consistent in all tested TCR-Vγ consensus primers. Similarly, patients with polyarticular disease had lower TREC levels than patients with pauciarticular disease. A predictive value of TRECs may be suggested, as lower TREC levels were observed in patients in whom disease modifying anti rheumatic drugs were initiated subsequently during the follow-up. CONCLUSION: In pediatric JIA patients, we showed an alteration in the T cells from synovial fluid, which correlated with disease phenotype, assumedly secondary to enhanced proliferation, clonal TCR restriction, and reduced T-cell production, possibly reflecting a different disease or a different course of disease progression.

National COVID-19 vaccine program progress and parents' willingness to vaccinate their children.

Vaccinating children against COVID-19 is critical as a public health strategy in order to reach herd immunity and prevent illness among children and adults. The aim of the study was to identify correlation between willingness to vaccinate children under 12 years old, and vaccination rate for adult population in Canada, the United States, and Israel. This was a secondary analysis of a cross-sectional survey study (COVID-19 Parental Attitude Study) of parents of children 12 years and younger presenting to 12 pediatric emergency departments (EDs). Parental reports of willingness to vaccinate against COVID-19 when vaccines for children will be approved was correlated to country-specific rate of vaccination during December 2020-March 2021, obtained from ourworldindata.org. Logistic regression models were fit with covariates for week and the corresponding vaccine rate. A total of 720 surveys were analyzed. In Canada, administering mostly first dose to the adult population, willingness to vaccinate children was trending downward (correlation = -0.28), in the United States, it was trending upwards (correlation = 0.21) and in Israel, initially significant increase with decline shortly thereafter (correlation = 0.06). Odds of willingness to vaccinate in Canada, the United States, and Israel was OR = 0.82, 95% CI = 0.63-1.07, OR = 1.24, 95% CI = 0.99-1.56, and OR = 1.03, 95% CI = 0.95-1.12, respectively. A robust population-based vaccination program as in Israel, and to a lesser degree the United States, led to increasing willingness by parents to vaccinate their children younger than 12 years against COVID-19. In Canada, slow rate of vaccination of the adult population was associated with lower willingness to vaccinate children.

Caregiver Willingness to Vaccinate Their Children against COVID-19 after Adult Vaccine Approval.

Vaccines against COVID-19 are likely to be approved for children under 12 years in the near future. Understanding vaccine hesitancy in parents is essential for reaching herd immunity. A cross-sectional survey of caregivers in 12 emergency departments (ED) was undertaken in the U.S., Canada, and Israel. We compared reported willingness to vaccinate children against COVID-19 with an initial survey and post-adult COVID-19 vaccine approval. Multivariable logistic regression models were performed for all children and for those <12 years. A total of 1728 and 1041 surveys were completed in phases 1 and 2, respectively. Fewer caregivers planned to vaccinate against COVID-19 in phase 2 (64.5% and 59.7%, respectively; p = 0.002). The most significant positive predictor of willingness to vaccinate against COVID-19 was if the child was vaccinated per recommended local schedules. Fewer caregivers plan to vaccinate their children against COVID-19, despite vaccine approval for adults, compared to what was reported at the peak of the pandemic. Older caregivers who fully vaccinated their children were more likely to adopt vaccinating children. This study can inform target strategy design to implement adherence to a vaccination campaign.