Prevalence of Respiratory Viral Infections in Deceased Persons during the COVID-19 Pandemic Season 2021-2022: A Population-Based Observational Study.

Although the omicron variant of SARS-CoV-2 circulated intensely during the 2021-2022 season, many patients with severe acute respiratory disease tested negative for COVID-19. The aim of this study was to assess the presence of different respiratory viruses in deceased persons. The proportion of deceased persons with respiratory viral infections in the 2021-2022 season in Navarre, Spain, was estimated considering all deaths caused by confirmed COVID-19 according to the epidemiological surveillance and the results of multiplex PCR tests for respiratory viruses performed in a sample of deceased persons with a cause of death other than COVID-19. Of 3578 deaths, 324 (9.1%) were initially reported as caused by pre-mortem confirmed COVID-19. A sample of 242 persons who died by causes other than COVID-19 were tested post-mortem; 64 (26.4%) of them were positive for any respiratory virus: 11.2% for SARS-CoV-2, 5.8% for rhinovirus, 3.7% for human coronavirus, 2.5% for metapneumovirus, 1.7% for respiratory syncytial virus, 1.7% for parainfluenza, 1.2% for influenza, and less than 1% each for adenovirus and bocavirus. Combining both approaches, we estimated that 34.4% of all deceased persons during the study period had a respiratory viral infection and 19.2% had SARS-CoV-2. Only 33.3% (9/27) of SARS-CoV-2 and 5.0% (2/40) of other viruses detected post-mortem had previously been confirmed pre-mortem. In a period with very intense circulation of SARS-CoV-2 during the pandemic, other respiratory viruses were also frequently present in deceased persons. Some SARS-CoV-2 infections and most other viral infections were not diagnosed pre-mortem. Several respiratory viruses may contribute to excess mortality in winter.

Adults with excess weight or obesity, but not with overweight, report greater pain intensities than individuals with normal weight: a systematic review and meta-analysis.

Context: Over 1.9 billion adult people have overweight or obesity. Considered as a chronic disease itself, obesity is associated with several comorbidities. Chronic pain affects approximately 60 million people and its connection with obesity has been displayed in several studies. However, controversial results showing both lower and higher pain thresholds in subjects with obesity compared to individuals with normal weight and the different parameters used to define such association (e.g., pain severity, frequency or duration) make it hard to draw straight forward conclusions in the matter. The objective of this article is to examine the relationship between overweight and obesity (classified with BMI as recommended by WHO) and self-perceived pain intensity in adults. Methods: A literature search was conducted following PRISMA guidelines using the databases CINAHL, Cochrane Library, EMBASE, PEDro, PubMed, Scopus and Web of Science to identify original studies that provide BMI values and their associated pain intensity assessed by self-report scales. Self-report pain scores were normalized and pooled within meta-analyses. The Cochrane's Q test and I2 index were used to clarify the amount of heterogeneity; meta-regression was performed to explore the relationship between each outcome and the risk of bias. Results: Of 2194 studies, 31 eligible studies were identified and appraised, 22 of which provided data for a quantitative analysis. The results herein suggested that adults with excess weight (BMI ≥ 25.0) or obesity (BMI ≥ 30.0) but not with overweight (pre-obesity) alone (BMI 25.0-29.9), are more likely to report greater intensities of pain than individuals of normal weight (BMI 18.5-24.9). Subgroup analyses regarding the pathology of the patients showed no statistically significant differences between groups. Also, influence of age in the effect size, evaluated by meta-regression, was only observed in one of the four analyses. Furthermore, the robustness of the findings was supported by two different sensitivity analyses. Conclusion: Subjects with obesity and excess weight, but not overweight, reported greater pain intensities than individuals with normal weight. This finding encourages treatment of obesity as a component of pain management. More research is required to better understand the mechanisms of these differences and the clinical utility of the findings. Systematic Review Registration: https://doi.org/10.17605/OSF.IO/RF2G3, identifier OSF.IO/RF2G3.

Hospitalisations and Deaths Averted by COVID-19 Vaccination in Navarre, Spain, 2021-2022.

In 2021-2022, most of the Spanish population received COVID-19 vaccines and a high proportion of them had SARS-CoV-2 infection. We estimated the rate of hospitalisations and deaths that were averted by risk reduction among vaccinated COVID-19 cases. Hospitalisations and deaths were analysed among COVID-19 cases confirmed in 2021 and 2022 in Navarre, Spain. To calculate the number of prevented outcomes by sex, age, comorbidities, and semester, the difference in the risk of each outcome between unvaccinated and vaccinated cases was multiplied by the number of vaccinated cases. COVID-19 vaccination coverage with any dose reached 88%, 86% with full vaccination, and 56% with a booster dose. The cumulative rates per 1000 inhabitants were 382 COVID-19 confirmed cases, 6.70 hospitalisations, and 1.15 deaths from COVID-19. The estimated rates of prevented events by vaccination were 16.33 hospitalisations and 3.39 deaths per 1000 inhabitants, which was 70.9% and 74.7% of expected events without vaccination, respectively. People aged 80 years and older or with major chronic conditions accounted for the majority of hospitalizations and deaths prevented by COVID-19 vaccination. One hospitalisation and death due to COVID-19 were averted for every 53 and 258 people vaccinated, respectively. The high COVID-19 vaccine effect in reducing the risk of severe outcomes and the high vaccination coverage in risk populations prevented three out of four hospitalisations and deaths due to COVID-19 during a period of intense circulation of SARS-CoV-2.

Multicenter clinical evaluation of a novel transcription-mediated amplification assay for SARS-CoV-2 molecular testing / Evaluación clínica multicéntrica de un nuevo ensayo de amplificación mediada por transcripción para la detección molecular de SARS-CoV-2

Introduction The onset and spread of COVID-19 pandemic has forced clinical laboratories to rapidly expand testing capacity for SARS-CoV-2. This study evaluates the clinical performance of the TMA Procleix SARS-CoV-2 assay in comparison to the RT-PCR assay Allplex™ SARS-CoV-2 for the qualitative detection of SARS-CoV-2 RNA. Methods Between November 2020 and February 2021, 610 upper-respiratory specimens received for routine SARS-CoV-2 molecular testing were prospectively collected and selected at the Hospital Universitari Vall d’Hebron and the Hospital Universitari Bellvitge in Barcelona, Spain. All samples were processed in parallel with the TMA and the RT-PCR assays, and results were compared. Discrepancies were retested by an additional RT-PCR method and the clinical history of these patients was reviewed. Results Overall, the level of concordance between both assays was 92.0% (κ, 0.772). Most discordant results (36/38, 94.7%) corresponded to samples testing positive with the TMA assay and negative with the RT-PCR method. Of these discrepant cases, most (28/36, 77.8%) were finally classified as confirmed or probable SARS-CoV-2 cases according to the discrepant analysis. Conclusion In conclusion, the TMA Procleix SARS-CoV-2 assay performed well for the qualitative detection of SARS-CoV-2 RNA in a multisite clinical setting. This novel TMA assay demonstrated a greater sensitivity in comparison to RT-PCR methods for the molecular detection of SARS-CoV-2. This higher sensitivity but also the qualitative feature of this detection of SARS-CoV-2 should be considered when making testing algorithm decisions (AU)

Introducción El inicio y la expansión de la pandemia por COVID-19 han forzado a los laboratorios clínicos a ampliar rápidamente la capacidad de detección de SARS-CoV-2. Evaluamos el rendimiento clínico del ensayo de TMA Procleix SARS-CoV-2 en comparación con el ensayo de RT-PCR Allplex™ SARS-CoV-2 para la detección cualitativa de ARN de SARS-CoV-2. Métodos Entre noviembre de 2020 y febrero de 2021 se seleccionaron prospectivamente 610 muestras del tracto respiratorio superior recibidas de rutina en el Hospital Universitario Vall d’Hebron y el Hospital Universitario de Bellvitge en Barcelona, España, para el diagnóstico molecular de SARS-CoV-2. Todas las muestras fueron procesadas en paralelo con los ensayos de TMA y RT-PCR, y se compararon los resultados. Las discrepancias se estudiaron por un método adicional de RT-PCR y se revisaron las historias clínicas de los pacientes. Resultados En general, la concordancia entre ambos ensayos fue del 92,0% (κ, 0,772). La mayoría de los casos discrepantes (36/38, 94,7%) correspondían a muestras positivas con el ensayo de TMA y negativas con el método de RT-PCR. De estos, la mayoría (28/36, 77,8%) fueron finalmente clasificados como casos confirmados o probables de SARS-CoV-2 de acuerdo al análisis de discrepantes. Conclusión El ensayo de TMA Procleix SARS-CoV-2 funcionó bien para la detección cualitativa de ARN de SARS-CoV-2 en un entorno clínico multicéntrico. Este ensayo TMA demostró una mayor sensibilidad en comparación con métodos de RT-PCR para la detección molecular de SARS-CoV-2. Esta mayor sensibilidad, pero también el carácter cualitativo de esta detección de SARS-CoV-2, se deben considerar en el diagnóstico de la infección (AU)

Influenza Vaccine Effectiveness in Preventing Laboratory-Confirmed Influenza Cases and Hospitalizations in Navarre, Spain, 2022-2023.

We estimated influenza vaccine effectiveness (IVE) in preventing outpatient and hospitalized cases in the 2022-2023 season. A test-negative design included a representative sample of outpatients and all hospitalized patients with influenza-like illness (ILI) from October 2022 to May 2023 in Navarre, Spain. ILI patients were tested by PCR for influenza virus. Influenza vaccination status was compared between confirmed influenza cases and test-negative controls. Among 3321 ILI patients tested, IVE to prevent influenza cases was 34% (95% confidence interval (CI): 16 to 48) overall, 85% (95%CI: 63 to 94) against influenza B, and 28% (95%CI: 3 to 46) against A(H3N2). Among 558 outpatients, 222 (40%) were confirmed for influenza: 55% A(H3N2), 11% A(H1N1), and 31% B. Overall, IVE to prevent outpatient cases was 48% (95%CI: 8 to 70), 88% (95%CI: 3 to 98) against influenza B, and 50% (95%CI: -4 to 76) against A(H3N2). Of 2763 hospitalized patients, 349 (13%) were positive for influenza: 64% A(H3N2), 17% A(H1N1), and 8% B. IVE to prevent hospitalization was 24% (95%CI: -1 to 42) overall, 82% (95%CI: 49 to 93) against influenza B, and 16% (95%CI: -17 to 40) against A(H3N2). No IVE was observed in preventing influenza A(H1N1). IVE was high to prevent influenza B, moderate against A(H3N2) and null against A(H1N1). A lower proportion of influenza B cases may explain the smaller IVE in hospitalized patients than in outpatients. The null IVE against A(H1N1) was consistent with the observed antigenic drift and supports the new composition of the 2023-2024 influenza vaccine.

Sigma-1 receptor agonism exacerbates immune-driven nociception: Role of TRPV1 + nociceptors.

The analgesic effects of sigma-1 antagonists are undisputed, but the effects of sigma-1 agonists on pain are not well studied. Here, we used a mouse model to show that the administration of the sigma-1 agonists dextromethorphan (a widely used antitussive drug), PRE-084 (a standard sigma-1 ligand), and pridopidine (a selective drug being investigated in clinical trials for the treatment of neurodegenerative diseases) enhances PGE2-induced mechanical hyperalgesia. Superficial plantar incision induced transient weight-bearing asymmetry at early time points, but the mice appeared to recover at 24 h, despite noticeable edema and infiltration of neutrophils (a well-known cellular source of PGE2) at the injured site. Sigma-1 agonists induced a relapse of weight bearing asymmetry in a manner dependent on the presence of neutrophils. The effects of sigma-1 agonists were all reversed by administration of the sigma-1 antagonist BD-1063 in wild-type mice, and were absent in sigma-1 knockout mice, supporting the selectivity of the effects observed. The proalgesic effects of sigma-1 agonism were also abolished by the TRP antagonist ruthenium red and by in vivo resiniferatoxin ablation of TRPV1 + peripheral sensory neurons. Therefore, sigma-1 agonism exacerbates pain-like responses in mice with a mild inflammatory state through the action of TRPV1 + nociceptors. We also show that sigma-1 receptors are present in most (if not all) mouse and human DRG neurons. If our findings translate to humans, further studies will be needed to investigate potential proalgesic effects induced by sigma-1 agonism in patients treated with sigma-1 agonists.

Investigational Drugs for the Treatment of Postherpetic Neuralgia: Systematic Review of Randomized Controlled Trials.

The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical development are addressed in this review. A systematic literature search was conducted in three electronic databases (Medline, Web of Science, Scopus) and in the ClinicalTrials.gov register from 1 January 2016 to 1 June 2023 to identify Phase II, III and IV clinical trials evaluating drugs for the treatment of PHN. A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). In brief, there are several drugs in advanced clinical development for treating PHN with some of them reporting promising results. AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN.

Assessing the Influence of COVID-19 Vaccination Coverage on Excess Mortality across 178 Countries: A Cross-Sectional Study.

The COVID-19 pandemic has had a devastating impact on global health, necessitating urgent and effective strategies to mitigate its consequences. Vaccination programs have been implemented worldwide to combat virus transmission and reduce the disease burden. This study aimed to investigate the relationship between COVID-19 vaccination coverage and all-cause excess mortality in 178 nations during the first two years of the pandemic. Multiple regression analysis, after adjusting for life expectancy at birth, confirmed a significant association between higher vaccination coverage and lower all-cause mortality rates (ß = -106.8, 95% CI -175.4 to -38.2, p = 0.002). These findings underscore the importance of vaccination campaigns in reducing overall mortality during the COVID-19 pandemic. Evidence-based decision making and resource allocation can benefit from this information, facilitating the optimization of vaccination strategies for maximal impact on mortality reduction. Further research and continuous monitoring are crucial to understanding the long-term effects of vaccination coverage on population health in the ongoing pandemic.

Assessing the relationship between energy-related methane emissions and the burden of cardiovascular diseases: a cross-sectional study of 73 countries.

The energy industry significantly contributes to anthropogenic methane emissions, which add to global warming and have been linked to an increased risk of cardiovascular diseases (CVD). This study aims to evaluate the relationship between energy-related methane emissions and the burden of CVD, measured in disability-adjusted life years (DALYs), in 2019. We conducted a cross-sectional analysis of datasets from 73 countries across all continents. The analyzed datasets included information from 2019 on environmental energy-related methane emissions, burden of DALYs due to CVD. The age-standardized prevalence of obesity in adults and life expectancy at birth were retrieved. The relationship between the variables of interest was evaluated using multiple linear regression models. In the multiple model, we observed a positive linear association between methane emissions and the log-transformed count of DALYs related to CVD. Specifically, for each unit increase in energy-related methane emissions, the burden of CVD increased by 0.06% (95% CI 0.03-0.09%, p < 0.001). The study suggests that reducing methane emissions from the energy industry could improve public health for those at risk of CVD. Policymakers can use these findings to develop strategies to reduce methane emissions and protect public health.

Urinary epidermal growth factor in kidney disease: A systematic review / Factor de crecimiento epidérmico urinario en la enfermedad renal: una revisión sistemática

Urinary epidermal growth factor (uEGF) is primarily produced by the kidney, and alterations of it have been associated with several kidney diseases. The aim of this review was to describe uEGF levels in presence or progression of kidney diseases. We conducted a systematic review of observational studies with uEGF determination, patients with acute kidney injury, chronic kidney disease, primary or secondary nephropathy, or renal cancer were included. Studies were searched in Medline, Google Scholar, Science Direct, and EBSCO up to August 2, 2021. Participants and measurements characteristics from which uEGF were determined as the specificity, sensitivity, and the area under the ROC curve, whenever available, were gathered. 53 studies were included, the most frequent kidney diseases studied were acute kidney injury, chronic kidney disease, and diabetic nephropathy. In most studies, uEGF levels were lower in cases than in controls. Studies showed that uEGF levels can predict presence or progression of acute kidney injury, chronic kidney disease, and nephropathy. Heterogeneity in the reported uEGF values can be attributed to the different techniques, sampling, and ways of reporting uEGF values. Although uEGF values are lower in patients with almost all kidney diseases and their progression, uEGF evaluation methods should be standardised to be used as a biomarker in clinical practice. (AU)

El factor de crecimiento epidérmico urinario (uEGF) es producido principalmente por el riñón, y sus alteraciones se han asociado con varias enfermedades renales. El objetivo de esta revisión fue describir los niveles de uEGF en presencia o progresión de enfermedades renales. Realizamos una revisión sistemática de estudios observacionales con determinación de uEGF en la que se incluyeron pacientes con insuficiencia renal aguda, enfermedad renal crónica, nefropatía primaria o secundaria, o cáncer renal. Se realizaron búsquedas de estudios en Medline, Google Scholar, Science Direct y EBSCO hasta el 2 de agosto de 2021. Se extrajeron las características de los participantes y de las mediciones del uEGF, así como la especificidad, la sensibilidad y el área bajo la curva ROC, siempre que estuvieran disponibles. Se incluyeron 53 estudios, y las enfermedades renales más frecuentes estudiadas fueron la insuficiencia renal aguda, la enfermedad renal crónica y la nefropatía diabética. En la mayoría de los estudios los niveles de uEGF fueron más bajos en los casos que en los controles. Los estudios demostraron que los niveles de uEGF pueden predecir la presencia o la progresión de la lesión renal aguda, la enfermedad renal crónica y la nefropatía. La heterogeneidad en los valores de uEGF informados se puede atribuir a las diferentes técnicas, muestreo y formas de informar los valores de uEGF. Aunque los valores de uEGF son más bajos en pacientes con casi todas las enfermedades renales y su progresión, los métodos de evaluación de uEGF deben estandarizarse para ser utilizados como biomarcadores en la práctica clínica. (AU)

Assessing the Relationship between Annual Surface Temperature Changes and the Burden of Dengue: Implications for Climate Change and Global Health Outcomes.

Dengue fever remains a significant global health concern, imposing a substantial burden on public health systems worldwide. Recent studies have suggested that climate change, specifically the increase in surface temperatures associated with global warming, may impact the transmission dynamics of dengue. This study aimed to assess the relationship between annual surface temperature changes from 1961 to 2019 and the burden of dengue in 185 countries. The dengue burden was evaluated for 2019 using disability-adjusted life years (DALYs) and the annual rate of change (ARC) in DALY rates assessed from 1990 to 2019. A cross-sectional and ecological analysis was conducted using two publicly available datasets. Regression coefficients (ß) and 95% confidence intervals (CI) were used to examine the relationship between annual surface temperature changes and the burden of dengue. The results revealed a significant negative relationship between mean surface temperatures and DALY rates in 2019 (ß = -16.9, 95% CI -26.9 to -6.8). Similarly, a significant negative relationship was observed between the temperature variable and the ARC (ß = -0.99, 95% CI -1.66 to -0.32). These findings suggest that as temperatures continue to rise, the burden of dengue may globally decrease. The ecology of the vector and variations in seasons, precipitation patterns, and humidity levels may partially contribute to this phenomenon. Our study contributes to the expanding body of evidence regarding the potential implications of climate change for dengue dynamics. It emphasizes the critical importance of addressing climate change as a determinant of global health outcomes.

Animal models of kidney iron overload and ferroptosis: a review of the literature.

In recent years, it has been identified that excess iron contributes to the development of various pathologies and their complications. Kidney diseases do not escape the toxic effects of iron, and ferroptosis is identified as a pathophysiological mechanism that could be a therapeutic target to avoid damage or progression of kidney disease. Ferroptosis is cell death associated with iron-dependent oxidative stress. To study the effects of iron overload (IOL) in the kidney, numerous animal models have been developed. The methodological differences between these models should reflect the IOL-generating mechanisms associated with human IOL diseases. A careful choice of animal model should be considered for translational purposes.

Efficacy and Security of Tetrodotoxin in the Treatment of Cancer-Related Pain: Systematic Review and Meta-Analysis.

The pharmacological treatment of cancer-related pain is unsatisfactory. Tetrodotoxin (TTX) has shown analgesia in preclinical models and clinical trials, but its clinical efficacy and safety have not been quantified. For this reason, our aim was to perform a systematic review and meta-analysis of the clinical evidence that was available. A systematic literature search was conducted in four electronic databases (Medline, Web of Science, Scopus, and ClinicalTrials.gov) up to 1 March 2023 in order to identify published clinical studies evaluating the efficacy and security of TTX in patients with cancer-related pain, including chemotherapy-induced neuropathic pain. Five articles were selected, three of which were randomized controlled trials (RCTs). The number of responders to the primary outcome (≥30% improvement in the mean pain intensity) and those suffering adverse events in the intervention and placebo groups were used to calculate effect sizes using the log odds ratio. The meta-analysis showed that TTX significantly increased the number of responders (mean = 0.68; 95% CI: 0.19-1.16, p = 0.0065) and the number of patients suffering non-severe adverse events (mean = 1.13; 95% CI: 0.31-1.95, p = 0.0068). However, TTX did not increase the risk of suffering serious adverse events (mean = 0.75; 95% CI: -0.43-1.93, p = 0.2154). In conclusion, TTX showed robust analgesic efficacy but also increased the risk of suffering non-severe adverse events. These results should be confirmed in further clinical trials with higher numbers of patients.

Multicenter clinical evaluation of a novel transcription-mediated amplification assay for SARS-CoV-2 molecular testing.

INTRODUCTION: The onset and spread of COVID-19 pandemic has forced clinical laboratories to rapidly expand testing capacity for SARS-CoV-2. This study evaluates the clinical performance of the TMA Procleix SARS-CoV-2 assay in comparison to the RT-PCR assay Allplex™ SARS-CoV-2 for the qualitative detection of SARS-CoV-2 RNA. METHODS: Between November 2020 and February 2021, 610 upper-respiratory specimens received for routine SARS-CoV-2 molecular testing were prospectively collected and selected at the Hospital Universitari Vall d'Hebron and the Hospital Universitari Bellvitge in Barcelona, Spain. All samples were processed in parallel with the TMA and the RT-PCR assays, and results were compared. Discrepancies were retested by an additional RT-PCR method and the clinical history of these patients was reviewed. RESULTS: Overall, the level of concordance between both assays was 92.0% (κ, 0.772). Most discordant results (36/38, 94.7%) corresponded to samples testing positive with the TMA assay and negative with the RT-PCR method. Of these discrepant cases, most (28/36, 77.8%) were finally classified as confirmed or probable SARS-CoV-2 cases according to the discrepant analysis. CONCLUSION: In conclusion, the TMA Procleix SARS-CoV-2 assay performed well for the qualitative detection of SARS-CoV-2 RNA in a multisite clinical setting. This novel TMA assay demonstrated a greater sensitivity in comparison to RT-PCR methods for the molecular detection of SARS-CoV-2. This higher sensitivity but also the qualitative feature of this detection of SARS-CoV-2 should be considered when making testing algorithm decisions.

Assessing the Burden of Dengue during the COVID-19 Pandemic in Mexico.

The transmission of the dengue virus in Mexico has historically been high, and its burden during the COVID-19 pandemic is currently not well understood. Our objective was to assess the burden of dengue-related disability-adjusted life years (DALYs) between 2020 and 2022. We conducted a cross-sectional analysis of databases resulting from an epidemiological surveillance of vector-borne diseases and computed DALYs using the protocol of the Global Burden of Disease (GBD) study 2019. Our results showed that there were 218,807 incident cases of dengue during the study period, resulting in 951 deaths. The calculated DALYs (and their 95% confidence intervals) were 8121 (7897-8396), 4733 (4661-4820), and 8461 (8344-8605) in 2020, 2021, and 2022, respectively. The DALY rates (per 100,000) were 6.5 (6.3-6.6), 3.8 (3.7-3.9), and 6.7 (6.6-6.8), respectively. The rates for 2020 and 2022 were similar to the historical mean (6.4, p = 0.884), whereas the rate for 2021 was lower than the mean. Premature mortality (years of life lost, YLL) contributed to 91% of the total burden. Our findings suggest that dengue fever remained a significant cause of disease burden during the COVID-19 pandemic, especially in terms of premature mortality.

Predictors of Recurrent Laboratory-Confirmed Symptomatic SARS-CoV-2 Infections in a Cohort of Healthcare Workers.

BACKGROUND: Repeated SARS-CoV-2 infections are plausible and related published data are scarce. We aimed to identify factors associated with the risk of recurrent (three episodes) laboratory-confirmed symptomatic SARS-CoV-2 infections. METHODS: A retrospective cohort study was conducted, and 1,700 healthcare workers were enrolled. We used risk ratios (RR) and 95% confidence intervals (CI) to evaluate the factors associated with symptomatic SARS-CoV-2 infections. RESULTS: We identified 14 participants with recurrent illness episodes. Therefore, the incidence rate was 8.5 per 10,000 person months. In a multiple-model study, vaccinated adults (vs. unvaccinated, RR = 1.05 [1.03-1.06]) and those with a severe first illness episode (vs. mild disease, RR = 1.05 [1.01-1.10]) were at increased risk for repeated symptomatic SARS-CoV-2 reinfections. Increasing age showed a protective effect (per each additional year of age: RR = 0.98 [0.97-0.99]). CONCLUSIONS: Our results suggest that recurrent SARS-CoV-2 infections are rare events in adults, and they seem to be determined, partially, by vaccination status and age.

Effect of COVID-19 vaccination on the SARS-CoV-2 transmission among social and household close contacts: A cohort study.

BACKGROUND: COVID-19 vaccination was expected to reduce SARS-CoV-2 transmission, but the relevance of this effect remains unclear. We aimed to estimate the effectiveness of COVID-19 vaccination of the index cases and their close contacts in reducing the probability of SARS-CoV-2 transmission. METHODS: Transmission of SARS-CoV-2 infection was evaluated in two cohorts of adult close contacts of COVID-19 confirmed cases (social and household settings) by COVID-19 vaccination status of the index case and the close contact, from April to November 2021 in Navarre, Spain. The effects of vaccination of the index case and the close contact were estimated as (1-adjusted relative risk) × 100%. RESULTS: Among 19,631 social contacts, 3257 (17%) were confirmed with SARS-CoV-2. COVID-19 vaccination of the index case reduced infectiousness by 44% (95% CI, 27-57%), vaccination of the close contact reduced susceptibility by 69% (95% CI, 65-73%), and vaccination of both reduced transmissibility by 74% (95% CI, 70-78%) in social settings, suggesting some synergy of effects. Among 20,708 household contacts, 6269 (30%) were infected, and vaccine effectiveness estimates were 13% (95% CI, -5% to 28%), 61% (95% CI, 58-64%), and 52% (95% CI, 47-56%), respectively. These estimates were lower in older people and had not relevant differences between the Alpha (April-June) and Delta (July-November) variant periods. CONCLUSIONS: COVID-19 vaccination reduces infectiousness and susceptibility; however, these effects are insufficient for complete control of SARS-CoV-2 transmission, especially in older people and household setting. Relaxation of preventive behaviors after vaccination may counteract part of the vaccine effect on transmission.

Comparison of the Risk of Hospitalization and Severe Disease Among Co-circulating Severe Acute Respiratory Syndrome Coronavirus 2 Variants.

BACKGROUND: We compare the risk of coronavirus disease 2019 (COVID-19) outcomes among co-circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants between January 2021 and May 2022 in Navarra, Spain. METHODS: We compared the frequency of hospitalization and severe disease (intensive care unit admission or death) due to COVID-19 among the co-circulating variants. Variants analyzed were nonvariants of concern (non-VOCs), Alpha, Delta, Omicron BA.1, and Omicron BA.2. Logistic regression models were used to estimate adjusted odds ratio (aOR). RESULTS: The Alpha variant had a higher risk of hospitalization (aOR, 1.86 [95 confidence interval {CI}, 1.282.71]) and severe disease (aOR, 2.40 [95 CI, 1.314.40]) than non-VOCs. The Delta variant did not show a significantly different risk of hospitalization (aOR, 0.73 [95 CI, .401.30]) and severe disease (aOR, 3.04 [95 CI, .5716.22]) compared to the Alpha variant. The Omicron BA.1 significantly reduced both risks relative to the Delta variant (aORs, 0.28 [95 CI, .16.47] and 0.23 [95 CI, .12.46], respectively). The Omicron BA.2 reduced the risk of hospitalization compared to BA.1 (aOR, 0.52 [95 CI, .29.95]). CONCLUSIONS: The Alpha and Delta variants showed an increased risk of hospitalization and severe disease, which decreased considerably with the Omicron BA.1 and BA.2. Surveillance of variants can lead to important differences in severity.

Increased Frequency of Giant Miniature End-Plate Potentials at the Neuromuscular Junction in Diabetic Rats.

There is a need for research addressing the functional characteristics of the motor end-plate in diabetes to identify mechanisms contributing to neuromuscular dysfunction. Here, we investigated the effect of diabetes on spontaneous acetylcholine release in the rat neuromuscular junction. We studied two randomized groups of male Wistar rats (n = 7 per group, 350 ± 50 g, 12-16 weeks of age): one with streptozotocin-induced experimental diabetes, and a healthy control group without diabetes. After 8 weeks of monitoring after diabetes induction, rats in both groups were anesthetized with pentobarbital. Then, the diaphragm muscle was dissected for electrophysiological recordings of miniature end-plate potentials (MEPPs) using a single electrode located at the region of the muscle end-plate. All experiments were conducted at environmental temperature (20-22 °C) in rat Ringer solution with constant bubbling carbogen (95% O2, 5% CO2). Compared to healthy controls, in the diaphragm neuromuscular end-plate derived from diabetic rats, the MEPPs were higher in amplitude and frequency, and the proportion of giant MEPPs was elevated (7.09% vs. 1.4% in controls). Our results showed that diabetes affected the acetylcholine MEPP pattern and increased the number of giant potentials compared to healthy controls.