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During the omicron wave of the COVID-19 pandemic and with SARS-CoV-2 vaccines becoming available, seroprevalence rates rose in children and adolescents. This study investigated the impact of both SARS-CoV-2 infections and vaccinations on the incidence of acute and prolonged symptoms in real-world conditions during the transition from the pandemic to the endemic phase. Participants from a pediatric population based seroprevalence study (CorKID study) were followed up at least two and for almost four years by survey of health status features and symptoms suggestive of post-COVID syndrome (PCS). In a subgroup (n = 259) SARS-CoV-2 antibody serology was further investigated. 789 participants of the original CorKID study cohort (n = 2.121; 37.2%) were included. 67.9% reported at least one SARS-CoV2 infection. 46.6% had received one or more SARS-CoV-2 vaccinations. In the vast majority of serologically tested participants antibodies again SARS-CoV-2 spike (98.9%) or nucleocapsid (93.3%) antigen were detected following infection and/or vaccination. At least 30% experienced one unrecognized SARS-CoV-2 infection. The overall health status was comparable between children, irrespective of SARS-CoV-2 infections and similar to pre-pandemic assessment. However, a subset of young adolescents exhibited a decline in physical performance compared to pre-pandemic conditions. After infection, PCS-like symptoms persisted in 7% of the respondents for more than three months and up to four years. SARS-CoV-2 vaccinated participants (47%) reported 12% less acute flu-like infections other than SARS-CoV-2. Nearly all participants developed SARS-CoV-2 antibodies in this longitudinal study through either vaccination or infection during the Omicron wave. About 7% of participants suffered from PCS symptoms, predominately fatigue and exhaustion. Furthermore, participants who received vaccinations against SARS-CoV-2 reported a lower frequency of acute infections during follow-up.

The transmission of hepatitis E virus (HEV) genotype 3 remains unclear. Up to date, it is predominantly considered a foodborne disease. However, there is growing evidence that other transmission pathways exist. The aim of this study was to analyze risk factors for anti-HEV IgG titers in the Study of Health in Pomerania, a population-based cohort located in Northeast Germany. We performed cross-sectional analyses using quantile and logistic regression. Spatial location was included as an interaction term to explore whether residential location of the participant acts as an effect modifier. The risk factors assessed were consumption frequency of meat, sausage, fish and raw vegetables, high-risk occupation and animal contact. The estimated seroprevalence of anti-HEV IgG was 27.3% (95% confidence interval [CI] 26.0%, 28.6%). Participants living in rural coastal areas had 14.5 U/ml higher antibody titers both for high meat (95% CI 3.9, 25.2; P  = 0.008) and high sausage consumption (95% CI 4.1, 24.9; P  = 0.006) in comparison with low consumption. In urban areas, participants who had contact with domestic carnivores had higher antibody titers (by 12.8 U/ml; 95% CI 0.3, 25.3; P  = 0.046). Our results imply that risk factors of HEV exposure might differ among geographical regions. More research is needed to clarify the mechanisms underlying these findings.

Background Measurement of gylcated hemoglobin A1c (HbA1c) plays a central role in monitoring quality of antidiabetic therapy and in the diagnosis of diabetes. Several studies report increased levels of HbA1c in nondiabetic elderly. However, this observation did not reach incorporation into daily clinical practice or the respective guidelines. The present study aimed to evaluate HbA1c levels in relation to age in two independent population-based cohorts and to derive age-specific reference intervals. Methods Four thousand two hundred sixty three participants from the Study of Health in Pomerania (SHIP-0) and 4402 participants from the independent study SHIP-Trend were included. HbA1c was determined by means of high-performance liquid chromatography. Multivariable linear regression models were performed. Reference intervals for HbA1c were determined. Results Reference intervals were derived from a healthy subpopulation with the upper reference limit (URL) for HbA1c of 42.1 mmol/Mol (6.0%) for individuals aged 20–39 years increasing to 43.2 mmol/Mol (6.1%) for individuals aged 40–59 years. For people aged ≥60 years the URL was 47.5 mmol/Mol (6.5%). In both study populations an increase in HbA1c with age was observed. ANOVA revealed up to 8.5 mmol/Mol (0.77%) or 7.3 mmol/Mol (0.68%) higher estimated mean levels of HbA1c in the oldest compared to the youngest age group in SHIP-0 or SHIP-trend, respectively. Linear regression analyses confirmed the positive associations of HbA1c with age which was independent of BMI Conclusion The present study confirmed the previously observed increase of HbA1c with increasing age in non-diabetic individuals. As a consequence age-dependent reference values for HbA1c were derived from two large and well defined reference populations. Implementation of them into daily practice may improve patient care and diagnosis of diabetes and reduce the risk of misdiagnosis and subsequent overtreatment of diabetes in elderly patients.

Auricular stimulation (AS) is a promising method in the treatment of situational anxiety. Expressive writing (EW) is an established psychological method, which reduces test anxiety and improves exam results. The aim of this crossover trial was to compare AS with EW, and with the no intervention (NI) condition, for treatment of exam anxiety. Healthy medical students underwent 3 comparable anatomy exams with an interval of one month, either performing EW, receiving AS or NI prior to the exam; the order of interventions was randomized. AS was applied using indwelling fixed needles bilaterally at the areas innervated mostly by the auricular branch of the vagal nerve on the day before the exam. Anxiety level, measured using State-Trait-Anxiety Inventory (STAI) before and after the interventions and immediately before exam, was the primary outcome. Quality of night sleep, blood pressure, heart rate and activity of salivary alpha-amylase (sAA) were analyzed across 3 conditions. All 37 included participants completed the study. Anxiety level (STAI) decreased immediately after AS in comparison with baseline (P = 0.02) and remained lower in comparison with that after EW and NI (P<0.01) on the day of exam. After EW and NI anxiety increased on the day of exam in comparison with baseline (P<0.01). Quality of sleep improved after AS in comparison with both control conditions (P<0.01). The activity of sAA decreased after EW and after AS (P<0.05) but not after NI condition. Auricular stimulation, but not expressive writing, reduced exam anxiety and improved quality of sleep in medical students. These changes might be due to reduced activity of the sympathetic nervous system.

Platelet count is known to be associated with sex, age and mean platelet volume (MPV). Sex and age were proposed for adjustment of platelet count reference intervals, but MPV is currently not used for further adjustment. We investigated the association of MPV, age and sex with platelet counts and established individualized reference ranges respecting MPV. The association of platelet count with age, sex and MPV was assessed in healthy participants (n = 3,033 individuals; 1,542 women) in the cross-sectional population-based cohort Study of Health in Pomerania. Reference intervals respecting age, sex, and MPV were estimated using quantile regressions for the 2.5th and 97.5th percentile. Women had higher platelet counts than men (239 vs. 207 x109/L, p<0.001). Platelet counts correlated with age (p<0.001) and MPV (p<0.001). Quantile regression of lower and upper platelet count limits correlated less with age in female (p = 0.047 for 2.5th percentile; p = 0.906 for 97.5th percentile) and male subjects (p = 0.029 for 2.5th percentile; p = 0.195 for 97.5th percentile) compared to MPV (p<0.001 for upper and lower limit for both sexes). After adjustment for MPV, age did no longer correlate with the 2.5th (p = 0.165) or 97.5th percentile (p = 0.999) of platelet count. In contrast, after adjustment for age, MPV levels still significantly correlated with 2.5th, 50th and 97.5th percentile (p<0.001). MPV and sex have a stronger association with platelet count than age. MPV should be considered to adjust platelet count reference intervals and needs to be respected as confounder for platelet counts in epidemiological studies and clinical practice.

Background There continues to be a great need for better biomarkers and host-directed treatment targets for community-acquired pneumonia (CAP). Alterations in phospholipid metabolism may constitute a source of small molecule biomarkers for acute infections including CAP. Evidence from animal models of pulmonary infections and sepsis suggests that inhibiting acid sphingomyelinase (which releases ceramides from sphingomyelins) may reduce end-organ damage. Methods We measured concentrations of 105 phospholipids, 40 acylcarnitines, and 4 ceramides, as well as acid sphingomyelinase activity, in plasma from patients with CAP (n = 29, sampled on admission and 4 subsequent time points), chronic obstructive pulmonary disease exacerbation with infection (COPD, n = 13) as a clinically important disease control, and 33 age- and sex-matched controls. Results Phospholipid concentrations were greatly decreased in CAP and normalized along clinical improvement. Greatest changes were seen in phosphatidylcholines, followed by lysophosphatidylcholines, sphingomyelins and ceramides (three of which were upregulated), and were least in acylcarnitines. Changes in COPD were less pronounced, but also differed qualitatively, e.g. by increases in selected sphingomyelins. We identified highly accurate biomarkers for CAP (AUC ≤ 0.97) and COPD (AUC ≤ 0.93) vs. Controls, and moderately accurate biomarkers for CAP vs. COPD (AUC ≤ 0.83), all of which were phospholipids. Phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins were also markedly decreased in S. aureus -infected human A549 and differentiated THP1 cells. Correlations with C-reactive protein and procalcitonin were predominantly negative but only of mild-to-moderate extent, suggesting that these markers reflect more than merely inflammation. Consistent with the increased ceramide concentrations, increased acid sphingomyelinase activity accurately distinguished CAP (fold change = 2.8, AUC = 0.94) and COPD (1.75, 0.88) from Controls and normalized with clinical resolution. Conclusions The results underscore the high potential of plasma phospholipids as biomarkers for CAP, begin to reveal differences in lipid dysregulation between CAP and infection-associated COPD exacerbation, and suggest that the decreases in plasma concentrations are at least partially determined by changes in host target cells. Furthermore, they provide validation in clinical blood samples of acid sphingomyelinase as a potential treatment target to improve clinical outcome of CAP.

Early diagnosis of myocardial infarction (MI) with cardiac troponin (cTn) assays at the point-of-care (POC) is suggested to shorten turn-around-time in the emergency department (ED). The present study aimed at comparing the diagnostic performance of two POC cTn assays with that of a central laboratory high-sensitivity (hs) method, under routine ED conditions. In 2,163 non-selected ED patients suspected for MI, the diagnostic performance of the POC troponin I (TnI), troponin T (TnT), and hs-TnT assay for the prediction of MI was evaluated based on receiver operating characteristic (ROC) analyses and compared with the performance based on the manufacturers' cut-offs. Due to an observed association between renal function as determined by estimated glomerular filtration rate (eGFR) and cTn concentrations, all analyses were stratified by renal function. In patients with normal renal function (eGFR > 60 mL/min/1.73m2), POC and hs assays showed a comparable diagnostic performance as quantified by the area under the ROC curve (AUC) of about 0.88. The ROC-derived optimal cut-off (OCO) levels for the different cTn assays clearly changed with decreasing kidney function. Impaired kidney function required OCO to be three to five times higher to achieve a comparable performance. Particularly cTnT concentrations were strongly associated with renal function. The three cTn assays demonstrated equivalent diagnostic performance in ED-patients admitted with suspected ACS in relation to the release diagnosis, supporting the use of POC testing in this setting. The present results implicate that application of eGFR-specific OCOs may decrease false-positives among patients with impaired renal function. Providing individual cut-offs depending on patients' eGFR might be an appropriate add-on tool to improve specificity in the diagnosis of MI.

Background Currently total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are used in clinical practice to estimate future cardiovascular risk. We assessed whether other lipoprotein subclasses also contribute to cause-specific and all-cause mortality in the general population. Methods Two independent cohorts of the Study of Health in Pomerania (SHIP-START and SHIP-TREND) were used. Participants were selected from population registration offices. The primary outcomes were all-cause, cardiovascular and cancer mortality. TC, total triglycerides (TG), phospholipids as well as the fractional concentrations of cholesterol, TG, phospholipids, and apolipoproteins of all lipoprotein subclasses were measured using nuclear magnetic resonance spectroscopy. Cox proportional hazard regression models were applied to assess the association between lipoprotein subclasses and mortality. Additionally, cause-specific hazards for cardiovascular disease (CVD) and cancer mortality were modelled considering competing events. Results Data from 3,579 SHIP-START and 4,267 SHIP-TREND individuals were included. During follow-up, 946 (26.4%) SHIP-START and 387 (9.1%) SHIP-TREND participants died. In both cohorts, total LDL-TG and LDL1-TG to LDL6-TG but not total TG were positively or U-shaped related with all-cause mortality. In SHIP-START, total TG, VLDL-TG, IDL-TG and LDL-TG (including subclasses) were associated with CVD mortality. HDL4-C as well as small and dense LDL-C (e.g. LDL6-C) represented risk factors for mortality with mutually enhancing effects. Conclusions The findings suggest that lipoprotein subclasses, especially LDL-TGs or HDL4-C/LDL6-C, provide information beyond the established TC and LDL-C levels and therefore might be of use for an early identification of subjects at risk.

Background Dyslipidemia has been associated with reduced bone mineral density and osteoporotic fractures, but the relation between lipid and bone metabolism remains poorly understood. Analysing the effects of lipoprotein subclasses on bone turnover may provide valuable insights into this association. We therefore examined whether lipoprotein subclasses, measured by proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy, are associated with bone turnover markers (BTMs) and with the ultrasound-based bone stiffness index. Methods Data from 1.349 men and 1.123 women, who participated in the population-based Study of Health in Pomerania-TREND were analysed. Serum intact amino-terminal propeptide of type I procollagen (P1NP, bone formation) and carboxy-terminal telopeptide of type I collagen (CTX, bone resorption) concentrations were measured. Associations between the lipoprotein data and the BTMs or the stiffness index were investigated using linear regression models. Results The triglyceride or cholesterol content in very-low-density lipoprotein and intermediate-density lipoprotein particles was inversely associated with both BTMs, with effect estimates being slightly higher for CTX than for P1NP. The triglyceride content in low-density lipoprotein and high-density lipoprotein particles and the Apo-A2 content in high-density lipoprotein particles was further inversely associated with the BTMs. Associations with the ultrasound-based bone stiffness index were absent. Conclusions Consistent inverse associations of triglycerides with bone turnover were observed, which argue for a protective effect on bone health, at least in the normal range. Yet, the presented associations did not translate into effects on the ultrasound-based bone stiffness. Further, there was no relevant gain of information by assessing the lipoprotein subclasses. Nevertheless, our study highlights the close relations between lipid and bone metabolism in the general population.

In this retrospective, monocentric cohort study, we tested if an intrathecal free light chain kappa (FLC-k) synthesis reflects not only an IgG but also IgA and IgM synthesis. We also analysed if FLC-k can help to distinguish between an inflammatory process and a blood contamination of cerebrospinal fluid (CSF). A total of 296 patient samples were identified and acquired from patients of the department of Neurology, University Medicine Greifswald (Germany). FLC-k were analysed in paired CSF and serum samples using the Siemens FLC-k kit. To determine an intrathecal FLC-k and immunoglobulin (Ig) A/-M-synthesis we analysed CSF/serum quotients in quotient diagrams, according to Reiber et al. Patient samples were grouped into three cohorts: cohort I (n = 41), intrathecal IgA and/or IgM synthesis; cohort II (n = 16), artificial blood contamination; and the control group (n = 239), no intrathecal immunoglobulin synthesis. None of the samples had intrathecal IgG synthesis, as evaluated with quotient diagrams or oligoclonal band analysis. In cohort I, 98% of patient samples presented an intrathecal synthesis of FLC-k. In cohort II, all patients lacked intrathecal FLC-k synthesis. In the control group, 6.5% presented an intrathecal synthesis of FLC-k. The data support the concept that an intrathecal FLC-k synthesis is independent of the antibody class produced. In patients with an artificial intrathecal Ig synthesis due to blood contamination, FLC-k synthesis is lacking. Thus, additional determination of FLC-k in quotient diagrams helps to discriminate an inflammatory process from a blood contamination of CSF.