Año 2024
Pre-print SSRN
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Background: It remains unclear which element of the immune response to SARS-CoV-2 vaccination best predicts protection from SARS-CoV-2 infection. We explored antibody, B cell and T cell responses to third-dose vaccine and relationship to incident SARS-CoV-2 infection. Methods: Adults in a prospective cohort provided blood samples at day 0, day 14 and 10 months post third-dose SARS-CoV-2 vaccine. Participants self-reported incident SARS-CoV-2 infection. Plasma anti-SARS-CoV-2 receptor binding domain (RBD) antibodies were measured. A sub-study assessed SARS-CoV-2-specific B cell and T cell responses in peripheral blood mononuclear cells by ELISpot. Comparative analysis between participants who developed incident infection and uninfected participants utilised non-parametric t-tests, Kaplan-Meier survival analysis and Cox proportional hazard ratios. Findings: Of 132 participants, 47(36%) reported incident SARS-CoV-2 infection at a median 16·5(16·25-21) weeks post third-dose vaccination. RBD titres, B cell responses, but not T cell responses, increased post third-dose vaccine. While no significant difference in day 14 RBD titres or T cell responses was observed between participants with and without incident SARS-CoV-2 infection, RBD memory B cell frequencies were significantly higher in those who did not develop infection (10·0%(4·5-16·0%) versus 4·9%(1·6-9·3%), p=0.01). RBD titres and memory B cell frequencies remained higher at 10 months than day 0 levels (p<0·01). Interpretations: Robust antibody and B cell responses persisted at 10 months following third-dose vaccination. Higher memory B cell frequencies, rather than antibody titres or T cell responses, predicted protection from subsequent infection, identifying memory B cells as a correlate of protection. Funding: Science Foundation Ireland, European Union’s Horizon 2020 research and innovation programme, Smurfit Kappa. Declaration of Interest: JS has received research support by the German Ministry of Education and Research (BMBF), Basilea Pharmaceuticals, Noscendo; has received speaker honoraria by AbbVie, Gilead, Hikma and Pfizer; has been a consultant to Gilead, Alvea Vax. and Micron Research PK reports grants or contracts from German Federal Ministry of Research and Education (BMBF) B-FAST (Bundesweites Forschungsnetz Angewandte Surveillance und Testung) and NAPKON (Nationales Pandemie Kohorten Netz, German National Pandemic Cohort Network) of the Network University Medicine (NUM) and the State of North Rhine-Westphalia; Consulting fees Ambu GmbH, Gilead Sciences, infill healthcare communication GmbH, Mundipharma Resarch Limited, Noxxon N.V. and Pfizer Pharma; Honoraria for lectures from Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, BioRad Laboratories Inc., Datamed GmbH, European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, HELIOS Kliniken GmbH, Jazz Pharmaceuticals Germany GmbH, LahnDill-Kliniken GmbH, medupdate GmbH, MedMedia GmbH, MSD Sharp & Dohme GmbH, Pfizer Pharma GmbH, Scilink Comunicación Científica SC, streamedup! GmbH, University Hospital and LMU Munich and VITIS GmbH; Participation on an Advisory Board from Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited and Pfizer Pharma; A filed patent at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); Other non-financial interests from Elsevier, Wiley and Taylor & Francis online outside the submitted work. SS has received financial support by Gilead Sciences, ViiV Healthcare, and MSD for attendance to international conferences. Ethical Approval: The All-Ireland Infectious Diseases (AIID) Cohort Study is a prospective, multicentre, observational study recruiting individuals with issues pertaining to infectious diseases (approved by the National Research Ethics Committee in Ireland, reference 20-NREC-COV056)

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Año 2024
Pre-print SSRN
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Immune memory is influenced by the frequency and type of antigenic challenges. Here, we compared immune responses to a BA.1 breakthrough infection in individuals with hybrid immunity (both prior infection and vaccination) versus those solely vaccinated. We found higher levels of serum anti-RBD antibodies and neutralizing antibodies post-infection in the vaccine-only group. Individuals in this group also showed a decrease in memory B cells against the ancestral strain but an increase in those specific to BA.1, suggesting a more limited immune imprinting. Reciprocally, hybrid immunity prevents the decrease in ADCC response, possibly by limiting IgG4 class-switching, and boosts anti-N responses post-infection. This highlights that BA.1 breakthrough infection induces different immune trajectories depending on prior immunization histories, which should be considered for further vaccination guidelines. Trial Registration: Registered on ClinicalTrials.gov (NCT04341142, NCT04648709, NCT04750720). Funding: This study was supported by ANRS-MIE (Emergen study, grant ANRS-0154 to BL), by ANR (ANRJCJC to TB), institutional grants from INSERM, CNRS, UCBL1, and ENS de Lyon. Declaration of Interest: The authors declare no competing interests. Ethical Approval: For the Covid-Ser cohort, written informed consent was obtained from all participants; ethics approval was obtained from the national review board for biomedical research in April 2020 (Comité de Protection des Personnes Sud Méditerranée I, Marseille, France; ID RCB 2020-A00932-37). Concerning, COVID-19-naive vaccinated individuals, they were included from two different cohorts. The first cohort, COVIMMUNITY, aimed to characterize the immune response in HCWs. Ethics approval was obtained from the national review board. The second cohort, ABCOVID, aimed to study the kinetics of COVID-19 antibodies in patients with confirmed SARS-CoV-2 infection as well as the kinetics of neutralizing antibodies post vaccination. This study was approved by the ILE DE FRANCE IV ethical committee. Written informed consent was collected at enrolment for all subjects.

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Año 2024
Revista BMC psychiatry
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BACKGROUND: The COVID-19 pandemic had and still have a major impact on adolescent mental health and consequently on suicidal behavior. However, few studies have investigated whether the pandemic has changed the patterns and the triggers of suicidality peaks in adolescents, e.g., seasonal patterns or family conflicts. We hypothesized that the pandemic modified suicidality rates: an increment of suicide attempts would be observed in the first semester of the academic year during COVID-19 pandemic compared to the same period of previous academic year; and the precipitating factors would be more related to social stressors during the pandemic school year. METHODS: A retrospective cross-sectional study was conducted to assess the precipitating factors, also including school-related factors and cognitive skills, of adolescent suicide attempters occurred in the first and second semesters of the year before the pandemic lockdown (study periods 1 and 2) and the year after (study periods 3 and 4). RESULTS: The sample consisted of 85 adolescents aged between 12 and 17 recruited consecutively from March 2019 to March 2021 at emergency ward because of suicide attempt. Forty-eight adolescents (55.3% of the sample) were attended before the lockdown (pre-pandemic group) and 38 (44.7%) the year after. The results showed a higher proportion of female suicide attempters in period 4 (Sept 2020-Feb 2021) respect to period 3 (Mar 2020-Aug 2020), i.e., pandemic semesters compared with the increment observed between period 2 and 1 (prepandemic semesters; Fisher's exact test = 4.73; p = 0.026). The multinomial regression models showed a significant effect in the frequency of adolescents who attempted suicide (ratio χ2 = 15.19, p = 0.019), accounted by the differences between period 4 (Sept 2020-Feb 2021) and period 1 (Mar 2019-Aug 2019), with depressive symptoms being a significant contributing factor (Exp(b) = 0.93; p = 0.04). Additionally, social triggers and age were found to be significant risk factors for suicide attempts in the first semester of the pandemic academic year (period 4) compared to the same semester of the pre-pandemic year (period 2; Exp(b) = 0.16, p = 0.01, and Exp(b) = 1.88, p = 0.006, respectively). CONCLUSIONS: During the pandemic, the decrement between first and second semester of the number of females attempting suicide was more pronounced than in the prepandemic school year -though this findings lacked statistical power due to very limited sample size-. Change in the frequency of adolescent attempting suicide in the different school periods was associated with greater severity of depressive symptoms. Social relations in back-to-school after the lockdown were also associated with the number of adolescents attempting suicide.

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Año 2024
Revista Scientific reports
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Cancers of the kidney and renal pelvis are among the most prevalent types of urinary cancers. We aimed to outline the incidence trends of kidney and renal pelvis cancers by age, sex, race/ethnicity, and histology in the United States (US) from 2000 to 2020. The data was obtained from the Surveillance, Epidemiology, and End Results (SEER) 22 database. The identification of patients with kidney and renal pelvis cancers with morphologies of renal cell carcinoma, nephroblastoma, sarcoma, and neuroendocrine tumor was conducted utilizing the International Classification of Diseases for Oncology version 3. The average annual percent change (AAPC) were presented. All estimates were given in the form of counts and delayed age-standardized incidence rates (ASIRs) per 100,000 people. From 2000 to 2019, a total of 490,481 cases of kidney and renal pelvic cancer were recorded across all age groups in the US. The majority of them were among Non-Hispanic Whites (NHWs) (69.75%) and those aged 55-69 years (39.96%). The ASIRs per 100,000 for kidney and pelvis cancers were 22.03 for men and 11.14 for women. Non-Hispanic Black men had the highest ASIR (24.53 [24.24, 24.81]), and increase in ASIR over the 2000-2019 period (AAPC: 2.19% [1.84, 2.84]). There was a noticeable increase in incidence of kidney and renal pelvis cancers. Individuals aged 70-84 years had the highest ASIR for kidney and renal pelvis cancers. The COVID-19 era has resulted in a significant reduction in incidence rates across all demographics.

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Año 2024
Revista Biologicals : journal of the International Association of Biological Standardization
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This study focuses on the development and initial assessment of an indirect IgG enzyme-linked immunosorbent assay (ELISA) specifically designed to detect of anti-SARS-CoV-2 antibodies. The unique aspect of this ELISA method lies in its utilization of a recombinant nucleocapsid (N) antigen, produced through baculovirus expression in insect cells. Our analysis involved 292 RT-qPCR confirmed positive serum samples and 54 pre-pandemic healthy controls. The process encompassed cloning, expression, and purification of the SARS-CoV-2 N gene in insect cells, with the resulted purified protein employed in our ELISA tests. Statistical analysis yielded an Area Under the Curve of 0.979, and the optimized cut-off exhibited 92 % sensitivity and 94 % specificity. These results highlight the ELISA's potential for robust and reliable serological detection of SARS-CoV-2 antibodies. Further assessments, including a larger panel size, reproducibility tests, and application in diverse populations, could enhance its utility as a valuable biotechnological solution for diseases surveillance.

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Año 2024
Autores Becker AP , Mang S , Rixecker T , Lepper PM - Más
Revista Pneumologie (Stuttgart, Germany)
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The acute respiratory failure as well as ARDS (acute respiratory distress syndrome) have challenged clinicians since the initial description over 50 years ago. Various causes can lead to ARDS and therapeutic approaches for ARDS/ARF are limited to the support or replacement of organ functions and the prevention of therapy-induced consequences. In recent years, triggered by the SARS-CoV-2 pathogen, numerous cases of acute lung failure (C-ARDS) have emerged. The pathophysiological processes of classical ARDS and C-ARDS are essentially similar. In their final stages of inflammation, both lead to a disruption of the blood-air barrier. Treatment strategies for C-ARDS, like classical ARDS, focus on supporting or replacing organ functions and preventing consequential damage. This article summarizes the treatment strategies in the intensive care unit.

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Año 2024
Revista Pulmonology
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INTRODUCTION AND OBJECTIVES: Quantifying breathing effort in non-intubated patients is important but difficult. We aimed to develop two models to estimate it in patients treated with high-flow oxygen therapy. PATIENTS AND METHODS: We analyzed the data of 260 patients from previous studies who received high-flow oxygen therapy. Their breathing effort was measured as the maximal deflection of esophageal pressure (ΔPes). We developed a multivariable linear regression model to estimate ΔPes (in cmH2O) and a multivariable logistic regression model to predict the risk of ΔPes being >10 cmH2O. Candidate predictors included age, sex, diagnosis of the coronavirus disease 2019 (COVID-19), respiratory rate, heart rate, mean arterial pressure, the results of arterial blood gas analysis, including base excess concentration (BEa) and the ratio of arterial tension to the inspiratory fraction of oxygen (PaO2:FiO2), and the product term between COVID-19 and PaO2:FiO2. RESULTS: We found that ΔPes can be estimated from the presence or absence of COVID-19, BEa, respiratory rate, PaO2:FiO2, and the product term between COVID-19 and PaO2:FiO2. The adjusted R2 was 0.39. The risk of ΔPes being >10 cmH2O can be predicted from BEa, respiratory rate, and PaO2:FiO2. The area under the receiver operating characteristic curve was 0.79 (0.73-0.85). We called these two models BREF, where BREF stands for BReathing EFfort and the three common predictors: BEa (B), respiratory rate (RE), and PaO2:FiO2 (F). CONCLUSIONS: We developed two models to estimate the breathing effort of patients on high-flow oxygen therapy. Our initial findings are promising and suggest that these models merit further evaluation.

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Año 2023
Autores Ernur D , Hanci V , Gökmen N - Más
Revista The National medical journal of India
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Background Although there are many studies on violence against physicians in the literature, there are few studies on violence against physicians working in intensive care units (ICUs). We aimed to investigate the frequency, type and underlying factors of violence against physicians working in ICUs in Turkey in the past 1 year. Methods We collected data by sending a questionnaire about violence against physicians working in ICUs via e-mail and WhatsApp between 1 and 15 May 2022. IBM SPSS Statistics V.24.0 was used for data analysis. The chi-square test and Fisher precision test were used to compare categorical data. Results Over one-third (38.6%) of the 354 physicians participating in our study reported that they had been exposed to violence in the past year, while 20.7% reported that they had been exposed to violence more than once in the past year. There was a significant relationship between the frequency of exposure to violence, female gender, age group, title, subspecialization status, working style and duration of working in the ICU (p<0.05). There was no relationship between the working area, type of hospital and ICU and exposure to violence (p>0.05). The presence of restriction and control points at the entrance to ICUs prevented violence (p<0.05). Conclusion Physicians working in ICUs encounter violence against them. The frequency of violence increased after the Covid-19 pandemic. A significant relationship was found between the frequency of violence and female gender, age group, title, subspecialization status, working style and duration of working in ICUs.

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Año 2024
Autores Pitchaimani M , Aswini U - Más
Revista Gene
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The actual ideal of the literature is to probe the effect of external undulation on prevalence of COVID-19. Owing to some environmental influences, we enhanced our model to the stochastic perturbations. In this article, we scrutinize a stochastic epidemic COVID-19 model with seven states of epidemiological classification. Incipiently, a sophisticated biological system with the effect of time lags put forward copious strategies. At the outset, aim of this work is to explore the existence and uniqueness of global positive solution. Moment exponential stability are upheld. By fabricating a suitable lyapunov function, the sufficient conditions for the persistence of the disease and the existence of an ergodic stationary distribution are established. To regulate the widespread of COVID-19 infection, the main intent is to curb the disease with the succor of three control measures. Finally, the theoretical results bring into being alive in the form of graphical visualization. By nurturing the comparison study, the parameters of the model system come up with real data of most afflicted countries that layout premier consequences.

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Año 2024
Revista The Lancet. Microbe
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BACKGROUND: Evolving SARS-CoV-2 variants and changing levels of pre-existing immunity require re-evaluation of antigen-detecting rapid diagnostic test (Ag-RDT) performance. We investigated possible associations between Ag-RDT sensitivity and various potential influencing factors, such as immunisation status and viral variant, in symptomatic hospital employees. METHODS: In this observational study, RT-PCR, Ag-RDT, and symptom-specific data were collected at three SARS-CoV-2 test centres for employees of the Charité-Universitätsmedizin Berlin hospital (Berlin, Germany). Employees reporting SARS-CoV-2-like symptoms, those at an increased risk of infection (eg, due to contact with an infected person), those testing positive in a previous self-administered Ag-RDT, or those seeking release-testing to return to work at least 7 days after a positive RT-PCR test were eligible for combined testing by RT-PCR and Ag-RDT. Only data from individuals with an ongoing SARS-CoV-2 infection as assessed by RT-PCR were used for further analysis. Bayesian regression analyses were done to evaluate possible differences in viral load and Ag-RDT sensitivity according to viral variant and immunisation status (previous vaccination or recovery from infection), using data from first RT-PCR positive samples in an infection. A comprehensive logistic regression analysis was used to investigate potential concomitant associations between Ag-RDT sensitivity and level of pre-existing immunity, time post symptom onset, viral load, gender, age, and Ag-RDT device. Ag-RDT performance was also compared between supernatants from cell cultures infected with the omicron variant of concern (VOC) or the wild-type strain (pre-VOC). FINDINGS: Between Nov 30, 2020 and Feb 11, 2022, a total of 14 773 samples from 7675 employees were tested for SARS-CoV-2 by both RT-PCR and Ag-RDT. We found a negative association between immunisation status and Ag-RDT sensitivity in symptomatic employees, with an observed sensitivity of 82% (94% highest posterior density interval [HPDI] 78-86) in immunologically naive participants compared with 73% (68-78) in multiply immunised individuals (ie, those with at least two vaccinations or recoveries from infection) and median log10 viral loads of 7·02 (IQR 5·83-8·07) and 8·08 (6·80-8·89), respectively. The dominant viral variant changed several times during the study period, from the pre-VOC period (sensitivity 80% [94% HPDI 75-85] in symptomatic participants) through the alpha variant (82% [70-94]), delta variant (75% [69-82]), and omicron variant (72% [65-79]) waves, concomitantly with a steep increase in vaccination coverage in our dataset. In a comparison of Ag-RDT performance on cell culture supernatants, we found no difference between the wild-type and omicron viral variants. INTERPRETATION: On the basis of our findings and data from other studies, we hypothesise that the observed reduction in clinical Ag-RDT sensitivity, despite higher SARS-CoV-2 RNA loads, is due to shorter incubation times later in our study period resulting from increased population immunity or changes in immune response dynamics caused by later SARS-CoV-2 VOCs. FUNDING: Berlin University Alliance, German Ministry of Education and Research, the EU (Projects EU4Health and ReCoVer), and the Berlin Institute of Health.

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