To estimate the seroprevalence and temporal course of SARS-CoV-2 neutralizing antibodies, we embedded a multi-tiered seroprevalence survey within an ongoing community-based cohort study in Bonn, Germany. We first assessed anti-SARS-CoV-2 immunoglobulin G levels with an immunoassay, followed by confirmatory testing of borderline and positive test results with a recombinant spike-based immunofluorescence assay and a plaque reduction neutralization test (PRNT). Those with a borderline or positive immunoassay result were retested after 4 to 5 months. At baseline, 4771 persons participated (88% response rate). Between April 24th and June 30th, 2020, seroprevalence was 0.97% (95% CI: 0.72−1.30) by immunoassay and 0.36% (95% CI: 0.21−0.61) when considering only those with two additional positive confirmatory tests. Importantly, about 20% of PRNT+ individuals lost their neutralizing antibodies within five months. Here, we show that neutralizing antibodies are detectable in only one third of those with a positive immunoassay result, and wane relatively quickly.

Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.

Background and Objectives:While there is growing evidence that physical activity promotes neuronal health, studies examining the relation between physical activity and brain morphology remain inconclusive. We therefore examined whether objectively-quantified physical activity is related to brain volume, cortical thickness and grey matter density in a large cohort study. Additionally, we assessed molecular pathways that may underlie the effects of physical activity on brain morphology.Methods:We used cross-sectional baseline data from 2,550 eligible participants (57.6% women; mean age: 54.7 years, range: 30–94 years) of a prospective cohort study. Physical activity dose (metabolic equivalent hours and step counts) and intensity (sedentary, light-intensity and moderate-to-vigorous intensity activities) were recorded with accelerometers. Brain volumetric, grey matter density and cortical thickness measures were obtained from 3T MRI scans using FreeSurfer and Statistical Parametric Mapping. The relation of physical activity (independent variable) and brain structure (outcome) was examined with polynomial multivariable regression, while adjusting for age, sex, intracranial volume, education and smoking. Using gene expression profiles from the Allen Brain Atlas, we extracted molecular signatures associated with the effects of physical activity on brain morphology.Results:Physical activity dose and intensity were independently associated with larger brain volumes, grey matter density and cortical thickness of several brain regions. The effects of physical activity on brain volume were most pronounced at low physical activity quantities and differed between men and women and across age. For example, more time spent in moderate-to-vigorous intensity activities was associated with greater total grey matter volume, but the relation leveled off with more activity (standardized ß [95% confidence intervals]: 1.37 [0.35, 2.39] and -0.70 [-1.25, -0.15] for the linear and quadratic terms, respectively). The strongest effects of physical activity were observed in motor regions and cortical regions enriched for genes involved in mitochondrial respiration.Discussion:Our findings suggest that physical activity benefits brain health, with the strongest effects in motor regions and regions with a high oxidative demand. While young adults may particularly profit from additional high-intensity activities, older adults may already benefit from light-intensity activities. Physical activity and reduced sedentary time may be critical in the prevention of age-associated brain atrophy and neurodegenerative diseases.