Estimation of reference curves for the urinary steroid metabolome in the first year of life in healthy children: tracing the complexity of human postnatal steroidogenesis, Journal of Steroid Biochemistry and Molecular Biology http://dx.doi.org/10. 1016/j.jsbmb.2015.07.024 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 of 24 Page 2 of 24 Graphical abstract HighlightsThe steroid metabolome during fetal-neonatal transition varies with sex and postnatal age.For 67 urinary steroid compounds normative values have been quantified by GC-MS for the first year of life.Highest concentrations are found for progesterone metabolites and glucocorticoids.In both sexes, most compounds peak at week 3 and decrease to 20% by week 25.Normative data for the urine steroid metabolome provide a powerful diagnostic tool. AbstractContext: Complex steroid disorders such as P450 oxidoreductase deficiency or apparent cortisone reductase deficiency may be recognized by steroid profiling using chromatographic mass spectrometric methods. These methods are highly specific and sensitive, and provide a complete spectrum of steroid metabolites in a single measurement of one sample which makes them superior to immunoassays. The steroid metabolome during the fetal-neonatal transition is characterized by a) the metabolites of the fetal-placental unit at birth, b) the fetal adrenal androgens until its involution 3-6 months postnatally, and c) the steroid metabolites produced by the developing endocrine organs. All these developmental events change the steroid metabolome in an age-and sex-dependent manner during the first year of life.Objective: The aim of this study was to provide normative values for the urinary steroid metabolome of healthy newborns at short time intervals in the first year of life. Methods:We conducted a prospective, longitudinal study to measure 67 urinary steroid metabolites in 21 male and 22 female term healthy newborn infants at 13 time-points from week 1 to week 49 of life. Urine samples were collected from newborn infants before discharge from hospital and from healthy infants at home. Steroid metabolites were measured by gas chromatography-mass spectrometry (GC-MS) and steroid concentrations corrected for urinary creatinine excretion were calculated.Results: 61 steroids showed age and 15 steroids sex specificity. Highest urinary steroid concentrations were found in both sexes for progesterone derivatives, in particular 20α-DH-5α-DH-progesterone, and for highly polar 6α-hydroxylated glucocorticoids. The steroids peaked at week 3 and decreased by ~80% at week 25 in both sexes. The decline of progestins, andro...

Definition of SARS-CoV-2 antibody responses is essential to verify protective immunity following infection and vaccination. Here, we devised a versatile serological test, named ABCORA, that is based on a multifactorial analysis of SARS-CoV-2 and circulating human coronavirus (HCoV) antibody responses. Utilizing empirical tailored cut-offs and computational approaches based on training and validation cohorts comprising pre-pandemic (N=825) and SARS-CoV-2 infected plasma donors (N=389), we defined several analysis strategies that allow a highly accurate definition of SARS-CoV-2 seroconversion and prediction of neutralization activity. Intriguingly, HCoV reactivity was significantly higher in SARS-CoV-2 negative donors. Amongst SARS-CoV-2 infected individuals, elevated SARS-CoV-2 responses were linked to higher HCoV activity suggesting that pre-existing HCoV immunity may confer protection against SARS-CoV-2 acquisition and promote development of SARS-CoV-2 specific antibody responses. Deciphering interdependencies between SARS-CoV-2 and HCoV immunity should be enforced as understanding their impact on infection may allow soliciting cross-protective activities for broader coronavirus prevention.