Abstract
Comparative analyses of the immunogenicity and reactogenicity of homologous and heterologous SARS-CoV-2 vaccine-regimens will inform optimized vaccine strategies. Here we analyze the humoral ...and cellular immune response following heterologous and homologous vaccination strategies in a convenience cohort of 331 healthy individuals. All regimens induce immunity to the vaccine antigen. Immunity after vaccination with ChAdOx1-nCoV-19 followed by either BNT162b2 (
n
= 66) or mRNA-1273 (
n
= 101) is equivalent to or more pronounced than homologous mRNA-regimens (
n
= 43 BNT162b2,
n
= 59 mRNA-1273) or homologous ChAdOx1-nCoV-19 vaccination (
n
= 62). We note highest levels of spike-specific CD8 T-cells following both heterologous regimens. Among mRNA-containing combinations, spike-specific CD4 T-cell levels in regimens including mRNA-1273 are higher than respective combinations with BNT162b2. Polyfunctional T-cell levels are highest in regimens based on ChAdOx1-nCoV-19-priming. All five regimens are well tolerated with most pronounced reactogenicity upon ChAdOx1-nCoV-19-priming, and ChAdOx1-nCoV-19/mRNA-1273-boosting. In conclusion, we present comparative analyses of immunogenicity and reactogenicity for heterologous vector/mRNA-boosting and homologous mRNA-regimens.
Context: Low-grade inflammation is associated with insulin resistance and precedes the onset of type 2 diabetes mellitus in adults, but there are no comparable data in youth.
Objective: The objective ...of the study was to characterize the pattern of subclinical immune activation that is associated with indices of obesity and insulin resistance in youth and analyze whether this association is explained by obesity.
Design: This was a cross-sectional study.
Setting: Medical check-up of schoolchildren was conducted by the Public Health Office in Düsseldorf (Germany).
Participants: Participants included 519 adolescents (mean age 15.5 ± 0.8 yr).
Main Outcome Measures: Measures included body mass index (BMI) and waist circumference (WC) as indices of obesity; fasting glucose, insulin, and homeostasis model assessment of insulin resistance; serum concentrations of TNFα, IL-6, IL-8, IL-18, monocyte chemoattractant protein-1, interferon-γ-inducible protein (IP)-10 and adiponectin as immunological variables.
Results: In age-, sex-, and lipid-adjusted analyses, IL-6, IL-18, IP-10, and adiponectin (inversely) were associated with both BMI and WC (all P ≤ 0.002). None of the immune markers was related to glucose, but IL-6, IL-18, and adiponectin (inversely) were associated with insulin and homeostasis model assessment of insulin resistance in age- and sex-adjusted models. Adjustment for BMI or WC indicated that a considerable proportion of these associations may be mediated by obesity.
Conclusions: We found that a differential low-grade immune activation is associated with parameters of obesity in adolescents. Moreover, there is evidence that IL-6, IL-18, IP-10, and adiponectin (inversely) are associated with insulin resistance and that these associations can mainly be attributed to obesity.
Knowledge is limited as to how prior SARS-CoV-2 infection influences cellular and humoral immunity after booster-vaccination with bivalent BA.4/5-adapted mRNA-vaccines, and whether vaccine-induced ...immunity may indicate subsequent infection. In this observational study, individuals with prior infection (n = 64) showed higher vaccine-induced anti-spike IgG-antibodies and neutralizing titers, but the relative increase was significantly higher in non-infected individuals (n = 63). In general, both groups showed higher neutralizing activity towards the parental strain than towards Omicron-subvariants BA.1, BA.2 and BA.5. In contrast, CD4 or CD8 T cell levels towards spike from the parental strain and the Omicron-subvariants, and cytokine expression profiles were similar irrespective of prior infection. Breakthrough infections occurred more frequently among previously non-infected individuals, who had significantly lower vaccine-induced spike-specific neutralizing activity and CD4 T cell levels. In summary, we show that immunogenicity after BA.4/5-bivalent vaccination differs between individuals with and without prior infection. Moreover, our results may help to improve prediction of breakthrough infections.
BACKGROUNDPatients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) differ in the severity of disease. We hypothesized that characteristics of SARS-CoV-2-specific immunity ...correlate with disease severity.METHODSIn this study, SARS-CoV-2-specific T cells and antibodies were characterized in uninfected controls and patients with different coronavirus disease 2019 (COVID-19) disease severity. SARS-CoV-2-specific T cells were flow cytometrically quantified after stimulation with SARS-CoV-2 peptide pools and analyzed for expression of cytokines (IFN-γ, IL-2, and TNF-α) and markers for activation, proliferation, and functional anergy. SARS-CoV-2-specific IgG and IgA antibodies were quantified using ELISA. Moreover, global characteristics of lymphocyte subpopulations were compared between patient groups and uninfected controls.RESULTSDespite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2-specific T cells as compared with convalescent individuals. SARS-CoV-2-specific CD4+ T cells dominated over CD8+ T cells and closely correlated with the number of plasmablasts and SARS-CoV-2-specific IgA and IgG levels. Unlike in convalescent patients, SARS-CoV-2-specific T cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4+ and CD8+ T cells in general.CONCLUSIONGiven the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered characteristics may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung.FUNDINGThe study was supported by institutional funds to MS and in part by grants of Saarland University, the State of Saarland, and the Rolf M. Schwiete Stiftung.
Background Liver diseases of infectious and non-infectious etiology cause considerable morbidity and mortality, particularly in low- and middle-income countries (LMICs). However, data on the ...prevalence of liver diseases and underlying risk factors in LMICs are scarce. The objective of this study was to elucidate the occurrence of infectious diseases among individuals with chronic liver damage in a rural setting of Côte d'Ivoire. Methodology In 2021, we screened 696 individuals from four villages in the southern part of Côte d'Ivoire for hepatic fibrosis and steatosis, employing transient elastography (TE) and controlled attenuation parameter (CAP). We classified CAP greater than or equal to248 dB/m as steatosis, TE greater than or equal to7.2 kPa as fibrosis, and did subgroup analysis for participants with TE ranging from 7.2 kPa to 9.1 kPa. Clinical and microbiologic characteristics were compared to an age- and sex-matched control group (TE <6.0 kPa; n = 109). Stool samples were subjected to duplicate Kato-Katz thick smears for diagnosis of Schistosoma mansoni. Venous blood samples were examined for hepatitis B and hepatitis C virus. Additionally, an abdominal ultrasound examination was performed. Principal findings Among 684 individuals with valid TE measurements, TE screening identified hepatic pathologies in 149 participants (17% with fibrosis and 6% with steatosis). 419 participants were included for further analyses, of which 261 had complete microbiologic analyses available. The prevalence of S. mansoni, hepatitis B, and hepatitis C were 30%, 14%, and 7%, respectively. Logistic regression analysis revealed higher odds for having TE results between 7.2 kPa and 9.1 kPa in individuals with S. mansoni infection (odds ratio OR = 3.02, 95% confidence interval CI = 1.58-5.76, P = 0.001), while HCV infection (OR = 5.02, 95% CI = 1.72-14.69, P = 0.003) and steatosis (OR = 4.62, 95% CI = 1.60-13.35, P = 0.005) were found to be risk factors for TE greater than or equal to9.2 kPa. Conclusions/significance Besides viral hepatitis, S. mansoni also warrants consideration as a pathogen causing liver fibrosis in Côte d'Ivoire. In-depth diagnostic work-up among individuals with abnormal TE findings might be a cost-effective public health strategy.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•We identified multiple New Delhi metallo-beta-lactamase 1 Klebsiella pneumoniae isolates in Ukrainian patients.•We detected isolates co-carrying OXA-48 and New Delhi metallo-beta-lactamase-1 ...carbapenemases.•Treatment choices were limited by the occurrence of multiresistant co-infections.•Sequencing results suggest partial transmission during primary care in Ukraine.
We analyzed consecutive clinical cases of infections due to carbapenemase-producing gram-negative bacteria detected in war-wounded patients from Ukraine who were treated at one university medical center in southwest Germany between June and December 2022. The isolates of multiresistant gram-negative bacteria were subjected to a thorough microbiological characterization and whole genome sequencing (WGS). We identified five war-wounded Ukrainian patients who developed infections with New Delhi metallo-β-lactamase 1-positive Klebsiella pneumoniae. Two isolates also carried OXA-48 carbapenemases. The bacteria were resistant to novel antibiotics, such as ceftazidime/avibactam and cefiderocol. The used treatment strategies included combinations of ceftazidime/avibactam + aztreonam, colistin, or tigecycline. WGS suggested transmission during primary care in Ukraine. We conclude that there is an urgent need for thorough surveillance of multiresistant pathogens in patients from war zones.
Digitalization affects all areas of society, including the health care sector. However, the digitalization of health care provision is progressing slowly compared to other sectors. In the ...professional and political literature, physicians are partially portrayed as digitalization sceptics. Thus, the role of physicians in this process requires further investigation. The theory of "digital natives" suggests a lower hurdle for younger generations to engage with digital technologies.
The objective of this study was to investigate the role of physicians in the process of digitalizing health care provision in Germany and to assess the age factor.
We conducted a large-scale study to assess the role of this professional group in the progress of the digital transformation of the German health care sector. Therefore, in an anonymous online survey, we inquired about the current digital penetration of the personal working environment, expectations, attitude toward, and concerns regarding digitalization. Based on these data, we studied associations with the nominal variable age and variations across 2 age groups.
The 1274 participants included in the study generally showed a high affinity towards digitalization with a mean of 3.88 on a 5-point Likert scale; 723 respondents (56.75%) stated they personally use mobile apps in their everyday working life, with a weak tendency to be associated with the respondents' age (η=0.26). Participants saw the most noticeable existing benefits through digitalization in data quality and readability (882/1274, 69.23%) and the least in patient engagement (213/1274, 16.72%). Medical practitioners preponderantly expect further improvements through increased digitalization across almost all queried areas but the most in access to medical knowledge (1136/1274, 89.17%), treatment of orphan diseases (1016/1274, 79.75%), and medical research (1023/1274, 80.30%).
Respondents defined their role in the digitalization of health care provision as ambivalent: "scrutinizing" on the one hand but "active" and "open" on the other. A gap between willingness to participate and digital sovereignty was indicated. Thus, education on digitalization as a means to support health care provision should not only be included in the course of study but also in the continuing process of further and advanced training.
Dengue virus (DENV) antibody assays frequently cross-react with sera from individuals who have been infected with or vaccinated against related flaviviruses. The goal of this study was to determine ...the specificity of two DENV ELISAs with sera from individuals vaccinated against yellow fever virus (YFV) and Japanese encephalitis virus (JEV). The Panbio and the Novatec Dengue IgG ELISAs were tested with sera obtained 3-4 weeks or 0.5-6 years after YFV or JEV vaccination and the diagnostic specificity of the assays was determined. As controls, the sera were tested using DENV, YFV, JEV, Zika and West Nile virus neutralization assays. The diagnostic specificity of the Panbio and the Novatec ELISA with sera from YFV-vaccinated subjects was 98.2% and 88.2%, respectively. Cross-reactions were rare in the first 4 weeks despite high YFV-neutralizing antibody titers and were mostly found later. The specificity of the Panbio and Novatec assays with sera from JEV-vaccinated individuals was 100% and 92.9%. Cross-reactions occurred in the early time period after vaccination. The measurement values of the two ELISAs correlated strongly. Thus, the Panbio ELISA showed higher diagnostic specificity and may be suitable for seroprevalence studies in areas with high disease prevalence.
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