ABSTRACT
Etripamil is a calcium channel blocker currently in Phase 3 trials for the treatment of paroxysmal supraventricular tachycardia (PSVT). Systemic and local toxicity following once-weekly intranasal administration of etripamil was evaluated in cynomolgus macaques to support clinical development. Groups of animals (N = 8, 4 males and 4 females) were administered etripamil into the left nostril weekly at dose levels of 0 (vehicle), 1.9, 3.8, or 5.7 mg/kg/dose for 26 doses. Persistence, reversibility, and progression of findings were examined following a 28-day recovery period. Clinical signs were transient and were related to the intranasal administration (e.g., nasal discharge, sneezing, etc.) of etripamil. There were no macroscopic or systemic microscopic findings at any dose. Etripamil-related adaptive and reactive local changes affecting the nasal cavity, larynx, and nasopharynx were observed at ≥1.9 mg/kg/dose. Minimal to severe dose-dependent nasal epithelial damage was observed, mainly affecting respiratory and transitional epithelium. Following the 28-day recovery period, microscopic changes were confined to the left nasal cavity and nasopharynx. These changes were significantly lower in incidence and severity, with noticeable reversal of the adaptive and reactive changes, indicating partial to complete recovery of the epithelial lining. Based on the lack of systemic toxicity and the minimal and transient nasal changes, the systemic, no observable adverse effect level (NOAEL) of etripamil in monkeys was the high dose, 5.7 mg/kg/dose. The NOAEL for local toxicity was 1.9 mg/kg/dose. Collectively, these data support further study of etripamil in human trials as a potential treatment for PSVT.
ABSTRACT
The automotive industry is entering a digital revolution, driven by the need to develop new products in less time that are high-quality and environmentally friendly. A proper manufacturing process influences the performance of the door grommet during its lifetime. In this work, uniaxial tensile tests based on molecular dynamics simulations have been performed on an ethylene-propylene-diene monomer (EPDM) material to investigate the effect of the crosslink density and its variation with temperature. The Mooney-Rivlin (MR) model is used to fit the results of molecular dynamics (MD) simulations in this paper and an exponential-type model is proposed to calculate the parameters C1(T) and C2T. The experimental results, confirmed by hardness tests of the cured part according to ASTM 1415-88, show that the free volume fraction and the crosslink density have a significant effect on the stiffness of the EPDM material in a deformed state. The results of molecular dynamics superposition on the MR model agree reasonably well with the macroscopically observed mechanical behavior and tensile stress of the EPDM at the molecular level. This work allows the accurate characterization of the stress-strain behavior of rubber-like materials subjected to deformation and can provide valuable information for their widespread application in the injection molding industry.
ABSTRACT
HER2, encoded by the ERBB2 gene, is an important druggable driver of human cancer gaining increasing importance as a therapeutic target in urothelial carcinoma (UC). The genomic underpinnings of HER2 overexpression in ERBB2 nonamplified UC are poorly defined. To address this knowledge gap, we investigated 172 UC tumors from patients treated at the University of California San Francisco, using immunohistochemistry and next-generation sequencing. We found that GATA3 and PPARG copy number gains individually predicted HER2 protein expression independently of ERBB2 amplification. To validate these findings, we interrogated the Memorial Sloan Kettering/The Cancer Genome Atlas (MSK/TCGA) dataset and found that GATA3 and PPARG copy number gains individually predicted ERBB2 mRNA expression independently of ERBB2 amplification. Our findings reveal a potential link between the luminal marker HER2 and the key transcription factors GATA3 and PPARG in UC and highlight the utility of examining GATA3 and PPARG copy number states to identify UC tumors that overexpress HER2 in the absence of ERBB2 amplification. In summary, we found that an increase in copy number of GATA3 and PPARG was independently associated with higher ERBB2 expression in patient samples of UC. This finding provides a potential explanation for HER2 overexpression in UC tumors without ERBB2 amplification and a way to identify these tumors for HER2-targeted therapies.
Subject(s)
DNA Copy Number Variations , GATA3 Transcription Factor , PPAR gamma , Receptor, ErbB-2 , Humans , GATA3 Transcription Factor/genetics , GATA3 Transcription Factor/metabolism , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Female , PPAR gamma/genetics , PPAR gamma/metabolism , Male , Urologic Neoplasms/genetics , Urologic Neoplasms/pathology , Aged , Middle Aged , Gene Amplification , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Gene Expression Regulation, NeoplasticABSTRACT
INTRODUCTION: Prophylactic meshes in high-risk patients prevent incisional hernias, although there are still some concerns about the best layer to place them in, the type of fixation, the mesh material, the significance of the level of contamination, and surgical complications. We aimed to provide answers to these questions and information about how the implanted material behaves based on its visibility under magnetic resonance imaging (MRI). METHOD: This is a prospective multicentre observational cohort study. Preliminary results from the first 3 months are presented. We included general surgical patients who had at least two risk factors for developing an incisional hernia. Multivariate logistic regression was used. A polyvinylidene fluoride (PVDF) mesh loaded with iron particles was used in an onlay position. MRIs were performed 6 weeks after treatment. RESULTS: Between July 2016 and June 2022, 185 patients were enrolled in the study. Surgery was emergent in 30.3% of cases, contaminated in 10.7% and dirty in 11.8%. A total of 5.6% of cases had postoperative wound infections, with the requirement of stoma being the only significant risk factor (OR = 7.59, p = 0.03). The formation of a seroma at 6 weeks detected by MRI, was associated with body mass index (OR = 1.13, p = 0.02). CONCLUSIONS: The prophylactic use of onlay PVDF mesh in midline laparotomies in high-risk patients was safe and effective in the short term, regardless of the type of surgery or the level of contamination. MRI allowed us to detect asymptomatic seromas during the early process of integration. STUDY REGISTRATION: This protocol was registered at ClinicalTrials.gov (NCT03105895).
Subject(s)
Fluorocarbon Polymers , Incisional Hernia , Magnetic Resonance Imaging , Polyvinyls , Surgical Mesh , Adult , Aged , Female , Humans , Male , Middle Aged , Incisional Hernia/prevention & control , Prospective Studies , Risk Factors , Time Factors , Treatment Outcome , Young Adult , Aged, 80 and overABSTRACT
In recent years, heterocyclic organic compounds have been explored as molecular electrocatalysts in relevant reactions for energy conversion and storage. Merging mimetics of biological systems that perform hydride transfer with rational synthetic chemical design has opened many opportunities for organic molecules to be tuned at the atomic level conferring them interesting reactivities. These molecular electrocatalysts represent an alternative to traditional metallic materials and metal complexes employed for water oxidation, hydrogen production, and carbon dioxide reduction. This minireview describes recent reports concerning design, catalytic activity and the mechanism of synthetic molecular electrocatalysts towards solar fuels production.
ABSTRACT
The Fifth Artificial Pancreas Workshop: Enabling Fully Automation, Access, and Adoption was held at the National Institutes of Health (NIH) Campus in Bethesda, Maryland on May 1 to 2, 2023. The organizing Committee included representatives of NIH, the US Food and Drug Administration (FDA), Diabetes Technology Society, Juvenile Diabetes Research Foundation (JDRF), and the Leona M. and Harry B. Helmsley Charitable Trust. In previous years, the NIH Division of Diabetes, Endocrinology, and Metabolic Diseases along with other diabetes organizations had organized periodic workshops, and it had been seven years since the NIH hosted the Fourth Artificial Pancreas in July 2016. Since then, significant improvements in insulin delivery have occurred. Several automated insulin delivery (AID) systems are now commercially available. The workshop featured sessions on: (1) Lessons Learned from Recent Advanced Clinical Trials and Real-World Data Analysis, (2) Interoperability, Data Management, Integration of Systems, and Cybersecurity, Challenges and Regulatory Considerations, (3) Adaptation of Systems Through the Lifespan and Special Populations: Are Specific Algorithms Needed, (4) Development of Adaptive Algorithms for Insulin Only and for Multihormonal Systems or Combination with Adjuvant Therapies and Drugs: Clinical Expected Outcomes and Public Health Impact, (5) Novel Artificial Intelligence Strategies to Develop Smarter, More Automated, Personalized Diabetes Management Systems, (6) Novel Sensing Strategies, Hormone Formulations and Delivery to Optimize Close-loop Systems, (7) Special Topic: Clinical and Real-world Viability of IP-IP Systems. "Fully automated closed-loop insulin delivery using the IP route," (8) Round-table Panel: Closed-loop performance: What to Expect and What are the Best Metrics to Assess it, and (9) Round-table Discussion: What is Needed for More Adaptable, Accessible, and Usable Future Generation of Systems? How to Promote Equitable Innovation? This article summarizes the discussions of the Workshop.
Subject(s)
Diabetes Mellitus, Type 1 , Pancreas, Artificial , Humans , Diabetes Mellitus, Type 1/drug therapy , Insulin/therapeutic use , Blood Glucose , Artificial Intelligence , Insulin Infusion Systems , Insulin, Regular, Human/therapeutic use , Automation , Hypoglycemic Agents/therapeutic useABSTRACT
La osteomielitis primaria de esternón es muy infrecuente en niños, con menos de 100 casos publicados hasta la actualidad. Su presentación clínica es a menudo inespecífica, lo que causa un retraso en el diagnóstico. Se presentan dos nuevos casos de osteomielitis primaria de esternón. Ambos referían un cuadro de fiebre, malestar general, dolor torácico y rechazo del decúbito, con eritema preesternal en uno de los casos. La velocidad de sedimentación globular y la proteína C-reactiva estaban elevadas en ambos casos. El diagnóstico se confirmó mediante estudios de imagen y en un caso se aisló Staphylococcus aureus sensible a meticilina en el hemocultivo. Ambos se recuperaron sin complicaciones con tratamiento antibiótico. Debe tenerse en cuenta la osteomielitis primaria de esternón en el diagnóstico diferencial del dolor torácico, especialmente si se acompaña de fiebre, signos inflamatorios locales, intolerancia al decúbito o elevación de reactantes de fase aguda.
Primary sternal osteomyelitis is very rare in children, with less than 100 cases published to date. Its clinical presentation is often non-specific, which results in a diagnostic delay. Here we describe 2 new cases of primary sternal osteomyelitis. Both referred fever, malaise, chest pain, and refusal to lie down, with pre-sternal erythema in one of the cases. The erythrocyte sedimentation rate and C-reactive protein values were high in both cases. The diagnosis was confirmed by imaging studies; methicillin-sensitive Staphylococcus aureus was isolated in the blood culture of one of them. Both recovered without complications with antibiotic treatment. Primary sternal osteomyelitis should be considered in the differential diagnosis of chest pain, especially if accompanied by fever, local inflammatory signs, intolerance to lying down, or increased acute phase reactants.
Subject(s)
Humans , Female , Infant , Child , Osteomyelitis/diagnosis , Osteomyelitis/drug therapy , Staphylococcal Infections/diagnosis , Staphylococcal Infections/drug therapy , Staphylococcus aureus , Chest Pain/drug therapy , Delayed Diagnosis , Fever , Anti-Bacterial Agents/therapeutic useABSTRACT
Diabetes Technology Society organized an expert consensus panel to develop metrics for research in the use of continuous glucose monitors (CGMs) in a hospital setting. The experts met virtually in small groups both before and after an April 13, 2023 virtual meeting of the entire panel. The goal of the panel was to develop consensus definitions in anticipation of greater use of CGMs in hospital settings in the future. Establishment of consensus definitions of inpatient analytical metrics will be easier to compare outcomes between studies. Panelists defined terms related to 10 dimensions of measurements related to the use of CGMs including (1) hospital hypoglycemia, (2) hospital hyperglycemia, (3) hospital time in range, (4) hospital glycemic variability, (5) hospital glycemia risk index, (6) accuracy of CGM devices and reference methods for CGMs in the hospital, (7) meaningful time blocks for hospital glycemic goals, (8) hospital CGM data sufficiency, (9) using CGM data for insulin dosing, and (10) miscellaneous factors. The panelists voted on 51 proposed recommendations. Based on the panel vote, 51 recommendations were classified as either strong (43) or mild (8). Additional research is needed on CGM performance in the hospital. This consensus report is intended to support that type of research intended to improve outcomes for hospitalized people with diabetes.
Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus , Hypoglycemia , Humans , Blood Glucose , Blood Glucose Self-Monitoring , Diabetes Mellitus/drug therapy , Diabetes Mellitus, Type 1/drug therapy , Hypoglycemia/drug therapy , Inpatients , Clinical Trials as TopicABSTRACT
The annual Virtual Hospital Diabetes Meeting was hosted by the Diabetes Technology Society on April 14 and 15, 2023, with the goal of reviewing the progress made in the hospital use of continuous glucose monitors (CGMs). Meeting topics included (1) Nursing Issues, Protocols, Order Sets, and Staff Education for Using CGMs, (2) Implementing CGM Programs for Use in the Wards, (3) Quality Metrics and Financial Implications of CGMs in the Hospital, (4) CGMs in the Critical Care Setting, (5) Special Situations: Labor/Delivery and Hemodialysis, (6) Research Session on CGMs in the Hospital, (7) Starting a CGM on Hospitalized Patients, (8) Automated Insulin Delivery Systems in the Hospital, (9) CGMs in Children, (10) Data Integration of CGMs for Inpatient Use and Telemetry, (11) Accuracy of CGMs/Comparison with Point-of-care Blood Glucose Testing, and (12) Discharge Planning with CGMs. Outcome data as well as shared collective real-life experiences were reviewed, and expert recommendations for CGM implementation were formulated.
Subject(s)
Blood Glucose , Diabetes Mellitus , Child , Humans , Blood Glucose Self-Monitoring/methods , Diabetes Mellitus/diagnosis , Hospitals , InpatientsABSTRACT
We present a case of a young man with complete atrioventricular block and aneurysm of the right sinus of Valsalva penetrating the interventricular septum and causing severe aortic regurgitation. Chest trauma and inflammatory or infectious diseases are potential causes. Bentall-de Bono surgical repair was performed. Anatomopathologic analysis demonstrated fibrosis, hyalinization, and extensive myxoid material. (Level of Difficulty: Beginner.).
ABSTRACT
BACKGROUND: Langerhan cell histiocytosis (LCH), although not a common cause, should be kept in the differential diagnosis for a patient that presents with a choroidal mass. CASE PRESENTATION: A 28-year-old female presented with a 4-day history of vision loss and associated pain in her right eye. EXAMINATION AND INVESTIGATIONS: A dilated fundus examination revealed a deep subretinal, orange, mottled lesion with associated serous retinal detachment. Ultrasonography demonstrated a solid mass at the posterior pole. Fluorescein angiography revealed corresponding, small, punctate, hyperfluorescent areas with leakage and pooling in the late phase outlining the subretinal fluid. Optical coherence tomography confirmed the choroidal elevation and subretinal fluid. In addition to starting oral steroids for addressing the patient's acute symptoms, a metastatic workup was ordered due to the lesion's appearance. Diagnosis: Computed tomography (CT) of the chest showed nodular lesions and subsequent lung biopsy was S-100 and CD1a positive, diagnostic of Langerhan's cell histiocytosis (LCH). TREATMENT AND OUTCOME: The patient was treated with six cycles of vinblastine and prednisolone therapy followed with a subsequent taper of steroids. Complete resolution of signs and symptoms was noted. DISCUSSION: A review of all reported cases of ophthalmic LCH with or without choroidal involvement was conducted. Diagnostic and therapeutic approaches described in these reportshave been summarized in the current manuscript. This case highlights the importance of pursuing a systemic workup in patients with uveal mass lesions. LCH should be considered in the differential of every choroidal mass.
ABSTRACT
BACKGROUND: Surgical site infection (SSI) surveillance is a labor-intensive endeavor. We present the design and validation of an algorithm for SSI detection after hip replacement surgery, and a report of its successful implementation in 4 public hospitals in Madrid, Spain. METHODS: We designed a multivariable algorithm, AI-HPRO, using natural language processing (NLP) and extreme gradient boosting to screen for SSI in patients undergoing hip replacement surgery. The development and validation cohorts included data from 19,661 health care episodes from 4 hospitals in Madrid, Spain. RESULTS: Positive microbiological cultures, the text variable "infection", and prescription of clindamycin were strong markers of SSI. Statistical analysis of the final model indicated high sensitivity (99.18%) and specificity (91.01%) with an F1-score of 0.32, AUC of 0.989, accuracy of 91.27%, and negative predictive value of 99.98%. DISCUSSION: Implementation of the AI-HPRO algorithm reduced the surveillance time from 975 person/hours to 63.5 person/hours and permitted an 88.95% reduction in the total volume of clinical records to be reviewed manually. The model presents a higher negative predictive value (99.98%) than algorithms relying on NLP alone (94%) or NLP and logistic regression (97%). CONCLUSIONS: This is the first report of an algorithm combining NLP and extreme gradient-boosting to permit accurate, real-time orthopedic SSI surveillance.
ABSTRACT
Mirror neurons have been found mainly in neocortical structures of primates and rodents; however, their functions are still debated. A new study has discovered mirror neurons for aggressive behaviors in the ventromedial hypothalamus of mice, an evolutionarily ancient structure, highlighting a new function key for survival.
Subject(s)
Mirror Neurons , Mice , Animals , Aggression/physiology , Hypothalamus/physiologyABSTRACT
ABSTRACT: We present a case of a young man with complete atrioventricular block and aneurysm of the right sinus of Valsalva penetrating the interventricular septum and causing severe aortic regurgitation. Chest trauma and inflammatory or infectious diseases are potential causes. Bentall-de Bono surgical repair was performed. Anatomopathologic analysis demonstrated fibrosis, hyalinization, and extensive myxoid material. (Level of Difficulty: Beginner.).
Subject(s)
Aortic Aneurysm , Pacemaker, Artificial , Sinus of Valsalva , Tomography, X-Ray Computed , Echocardiography , Heart VentriclesABSTRACT
Primary sternal osteomyelitis is very rare in children, with less than 100 cases published to date. Its clinical presentation is often non-specific, which results in a diagnostic delay. Here we describe 2 new cases of primary sternal osteomyelitis. Both referred fever, malaise, chest pain, and refusal to lie down, with pre-sternal erythema in one of the cases. The erythrocyte sedimentation rate and C-reactive protein values were high in both cases. The diagnosis was confirmed by imaging studies; methicillin-sensitive Staphylococcus aureus was isolated in the blood culture of one of them. Both recovered without complications with antibiotic treatment. Primary sternal osteomyelitis should be considered in the differential diagnosis of chest pain, especially if accompanied by fever, local inflammatory signs, intolerance to lying down, or increased acute phase reactants.
La osteomielitis primaria de esternón es muy infrecuente en niños, con menos de 100 casos publicados hasta la actualidad. Su presentación clínica es a menudo inespecífica, lo que causa un retraso en el diagnóstico. Se presentan dos nuevos casos de osteomielitis primaria de esternón. Ambos referían un cuadro de fiebre, malestar general, dolor torácico y rechazo del decúbito, con eritema preesternal en uno de los casos. La velocidad de sedimentación globular y la proteína C-reactiva estaban elevadas en ambos casos. El diagnóstico se confirmó mediante estudios de imagen y en un caso se aisló Staphylococcus aureus sensible a meticilina en el hemocultivo. Ambos se recuperaron sin complicaciones con tratamiento antibiótico. Debe tenerse en cuenta la osteomielitis primaria de esternón en el diagnóstico diferencial del dolor torácico, especialmente si se acompaña de fiebre, signos inflamatorios locales, intolerancia al decúbito o elevación de reactantes de fase aguda.
Subject(s)
Osteomyelitis , Staphylococcal Infections , Child , Humans , Delayed Diagnosis , Staphylococcus aureus , Anti-Bacterial Agents/therapeutic use , Staphylococcal Infections/diagnosis , Staphylococcal Infections/drug therapy , Osteomyelitis/diagnosis , Osteomyelitis/drug therapy , Fever , Chest Pain/drug therapyABSTRACT
In precision beekeeping, the automatic recognition of colony states to assess the health status of bee colonies with dedicated hardware is an important challenge for researchers, and the use of machine learning (ML) models to predict acoustic patterns has increased attention. In this work, five classification ML algorithms were compared to find a model with the best performance and the lowest computational cost for identifying colony states by analyzing acoustic patterns. Several metrics were computed to evaluate the performance of the models, and the code execution time was measured (in the training and testing process) as a CPU usage measure. Furthermore, a simple and efficient methodology for dataset prepossessing is presented; this allows the possibility to train and test the models in very short times on limited resources hardware, such as the Raspberry Pi computer, moreover, achieving a high classification performance (above 95%) in all the ML models. The aim is to reduce power consumption and improves the battery life on a monitor system for automatic recognition of bee colony states.
Subject(s)
Acoustics , Algorithms , Bees , Animals , Health Status , Machine Learning , Beekeeping/methodsABSTRACT
OBJECTIVES: Understanding the pathway by which neighbourhood factors influence glycaemic control may be crucial to addressing health disparities in diabetes. This study aimed to examine if the pathway between neighbourhood factors and glycaemic control is mediated by stress. DESIGN: Structured equation modelling (SEM) was used to investigate direct and indirect effects in the relationship between neighbourhood factors, stress and glycaemic control, with standardised estimates to allow comparison of paths. PARTICIPANTS: Data was obtained from 615 adults with type 2 diabetes in the Southeastern United States. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome variable was glycaemic control determined by glycated haemoglobin (HbA1c) within the prior 6 months. Neighbourhood factors included neighbourhood violence, aesthetic quality of the neighbourhood, access to healthy food, and social cohesion. Stress was measured using the perceived stress scale. RESULTS: In the final model (χ2(158)=406.97, p<0.001, root mean square error of approximation=0.05, p-close 0.38, Comparative Fit Index=0.97, Tucker-Lewis index=0.96, the coefficient of determination=1.0), violence (r=0.79, p=0.006), neighbourhood aesthetics (r=0.74, p=0.02) and social cohesion (r=0.57, p=0.04) were significantly associated with higher perceived stress. Stress (r=0.06, p=0.004) was directly associated with higher glycaemic control. Significant indirect effects existed between violence and higher HbA1c (r=0.05, p=0.04). After controlling for other neighbourhood factors, there was no significant relationship between access to healthy food and either stress or glycaemic control. CONCLUSIONS: While a number of neighbourhood factors were directly associated with stress, only neighbourhood violence had a significant indirect effect on glycaemic control via stress within the tested pathway. Future studies should examine individual-level stress management interventions and should consider community-level interventions targeting neighbourhood violence as strategies for addressing disparities in diabetes.
Subject(s)
Diabetes Mellitus, Type 2 , Adult , Humans , Glycated Hemoglobin/analysis , Diabetes Mellitus, Type 2/complications , Glycemic Control , Cross-Sectional Studies , Southeastern United States/epidemiology , Blood Glucose/metabolismABSTRACT
(1) Background: The COVID-19 pandemic and the implementation of restrictions and nonpharmaceutical interventions (NPIs) changed the trends in respiratory viral circulation and the pattern in pediatric healthcare utilization; (2) Methods: A retrospective, multicenter observational study designed to analyze the impact of the pandemic on pediatric healthcare utilization and the viral circulation pattern in children in a region in Northern Spain was carried out. Viral diagnostics data from all nasal or pharyngeal swabs collected in children in Asturias during the periods of March 2018−September 2019 and March 2020−September 2021 were analyzed, as well as the number of pediatric hospitalizations and emergency visits; (3) Results: A total of 14,640 samples were collected during the pandemic period. Of these, at least one respiratory virus was detected in 2940 (20.1%) while 5568/10,298 samples were positive in the pre-pandemic period (54.1%); p < 0.001. The detection of both enveloped and non-enveloped viruses decreased among periods (p < 0.001). After week 14, 2020, enveloped viruses were no longer detected until one year later, while non-enveloped viruses continued to be detected in children. Overall, a mean of 4946.8 (95% CI 4519.1−5374.4) pediatric emergency visits per month during the period 2018−2019 as compared to 2496.5 (95% CI 2086.4−2906.5) for 2020−2021 occurred (p < 0.001). The mean of pediatric hospitalizations also significantly decreased between periods, as follows: 346.6 (95% CI 313−380.2) in 2018−2019 vs. 161.1 (95% CI 138.4−183.8); p < 0.001; (4) Conclusions: Our study showed a remarkably reduction in pediatric hospitalizations and emergency visits and a change in the pattern of viral circulation during the COVID-19 pandemic in Asturias. The usual seasonal respiratory viruses, namely influenza or RSV were nearly absent in the pediatric population during the pandemic.
ABSTRACT
BACKGROUND: Updated seroprevalence estimates are important to describe the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) landscape and to guide public health decisions. The aims are to describe longitudinal changes in seroprevalence in children in a region in Northern Spain and to analyze factors associated with SARS-CoV-2 seropositivity. METHODS: Prospective multicenter longitudinal study with subjects recruited from July to September 2020. Children (up to 14 years old) were included and followed up until September 2021. Venous blood samples were collected every six months during three testing rounds and were analyzed for SARS-CoV-2 antibodies. The data regarding epidemiological features, contact tracing, symptoms, and virological tests were collected. The evolution of SARS-CoV-2 seroprevalence during the study and the differences between children with positive and negative SARS-CoV-2 antibody tests were analyzed. RESULTS: Two hundred children were recruited (50.5% girls, median age 9.7 years). The overall seroprevalence increased from round 1 [1.5%, 95% confidence interval (CI) 0.3%-4.3%] to round 2 (9.1%, 95% CI 4.6%-12.7%) and round 3 (16.6%, 95% CI 9.5%-19.6%) (P < 0.001). Main changes occurred in children aged zero to four years (P = 0.001) who lived in urban areas (P < 0.001). None of the children who were previously positive became seronegative. Following multivariable analysis, three variables independently associated with SARS-CoV-2 seropositivity were identified: close contact with coronavirus disease 2019 (COVID-19) confirmed or suspected cases [odds ratio (OR) = 3.9, 95% CI 1.2-12.5], previous positive virological test (OR = 17.1, 95% CI 3.7-78.3) and fatigue (OR = 18.1, 95% CI 1.7-193.4). CONCLUSIONS: SARS-CoV-2 seroprevalence in children has remarkably increased during the time of our study. Fatigue was the only COVID-19-compatible symptom that was more frequent in seropositive than in seronegative children.