Metabolic signature of the pathogenic 22q11.2 deletion identifies carriers and provides insight into systemic dysregulation.

Large deletions at chromosome 22q11.2 are known to cause severe clinical conditions collectively known as 22q11.2 deletion syndrome.

Multi-omic analyses of triptan-treated migraine attacks gives insight into molecular mechanisms.

Migraine is a common, polygenic disorder that is characterized by moderate to severe headache attacks. Migraine attacks are commonly treated with triptans, i.e.

Patterns of testing in the extensive Danish national SARS-CoV-2 test set-up.

Background: The Danish national SARS-CoV-2 mass test system was among the most ambitious worldwide. We describe its set-up and analyse differences in patterns of testing per demography and time period in relation to the three waves of SARS-CoV-2 transmission in Denmark.

Methods: We included all reported PCR- and rapid antigen-tests performed between 27 February 2020 and 10 March 2022 among all residents aged 2 years or above.

Evaluation of four laboratory-based high-throughput SARS-CoV-2 automated antigen tests compared to RT-PCR on nasal and oropharyngeal samples.

Background: The demand for RT-PCR testing has been unprecedented during the SARS-CoV-2 pandemic. Fully automated antigen tests (AAT) are less cumbersome than RT-PCR, but data on performance compared to RT-PCR are scarce.

Methods: The study consists of two parts.

Effects of Long-Term Storage on the Biobanked Neonatal Dried Blood Spot Metabolome.

Over 2.5 million neonatal dried blood spots (DBS) are stored at the Danish National Biobank. These samples offer extraordinary possibilities for metabolomics research, including prediction of disease and understanding of underlying molecular mechanisms of disease development.

Diet-associated vertically transferred metabolites and risk of asthma, allergy, eczema, and infections in early childhood.

Background: Evidence suggests maternal pregnancy dietary intake and nutrition in the early postnatal period to be of importance for the newborn child's health. However, studies investigating diet-related metabolites transferred from mother to child on disease risk in childhood are lacking. We sought to investigate the influence of vertically transferred metabolites on risk of atopic diseases and infections during preschool age.

Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots.

The vitamin D binding protein (DBP), encoded by the group-specific component (GC) gene, is a component of the vitamin D system. In a genome-wide association study of DBP concentration in 65,589 neonates we identify 26 independent loci, 17 of which are in or close to the GC gene, with fine-mapping identifying 2 missense variants on chromosomes 12 and 17 (within SH2B3 and GSDMA, respectively). When adjusted for GC haplotypes, we find 15 independent loci distributed over 10 chromosomes.

Rapid and Flexible RT-qPCR Surveillance Platforms To Detect SARS-CoV-2 Mutations.

Multiple mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) increase transmission, disease severity, and immune evasion and facilitate zoonotic or anthropozoonotic infections. Four such mutations, ΔH69/V70, L452R, E484K, and N501Y, occurred in the SARS-CoV-2 spike glycoprotein in combinations that allow the simultaneous detection of VOCs. Here, we present two flexible reverse transcription-quantitative PCR (RT-qPCR) platforms for small- and large-scale screening (also known as variant PCR) to detect these mutations and schemes for adapting the platforms to future mutations.

Combined nasal- and oropharyngeal self-swab provides equivalent performance compared to professionally collected oropharyngeal swabs in detecting SARS-CoV-2 in a real-life setting.

Purpose: To investigate the performance of a combined nasal midturbinate- and oropharyngeal (NAOP) self-swab compared to a deep oropharyngeal (OP) swab by health care workers (HCW) in detecting SARS-CoV-2 in a real-life setting.

Methods: Paired swabs from 1119 participants were included. RT-PCR were used to detect SARS-CoV-2 in both swab samples.

Vitamin D status and severity of COVID-19.

We explored the association between COVID-19 severity and vitamin D status using information from Danish nation-wide health registers, the COVID-19 surveillance database and stored blood samples from the national biobank. 25-hydroxyvitamin D (25(OH)D) was measured using tandem mass spectroscopy. The association between 25(OH)D levels and COVID-19 severity, classified hierarchical as non-hospitalized, hospitalized but not admitted to an intensive care unit (ICU), admitted to ICU, and death, was evaluated by proportional odds ratios (POR) assuming proportionality between the four degrees of severity.

A RT-qPCR system using a degenerate probe for specific identification and differentiation of SARS-CoV-2 Omicron (B.1.1.529) variants of concern.

Fast surveillance strategies are needed to control the spread of new emerging SARS-CoV-2 variants and gain time for evaluation of their pathogenic potential. This was essential for the Omicron variant (B.1.

Household transmission of the SARS-CoV-2 Omicron variant in Denmark.

In late 2021, the Omicron SARS-CoV-2 variant overtook the previously dominant Delta variant, but the extent to which this transition was driven by immune evasion or a change in the inherent transmissibility is currently unclear. We estimate SARS-CoV-2 transmission within Danish households during December 2021. Among 26,675 households (8,568 with the Omicron VOC), we identified 14,140 secondary infections within a 1-7-day follow-up period.

Effect of vaccination on household transmission of SARS-CoV-2 Delta variant of concern.

Effective vaccines protect individuals by not only reducing the susceptibility to infection, but also reducing the infectiousness of breakthrough infections in vaccinated cases. To disentangle the vaccine effectiveness against susceptibility to infection (VE) and vaccine effectiveness against infectiousness (VE), we took advantage of Danish national data comprising 24,693 households with a primary case of SARS-CoV-2 infection (Delta Variant of Concern, 2021) including 53,584 household contacts. In this setting, we estimated VE as 61% (95%-CI: 59-63), when the primary case was unvaccinated, and VE as 31% (95%-CI: 26-36), when the household contact was unvaccinated.

A method to correct for the influence of bovine serum albumin-associated vitamin D metabolites in protein extracts from neonatal dried blood spots.

Objective: We developed an assay to measure the concentration of 25 hydroxyvitamin D and D in protein extracts derived from stored neonatal dried blood spots. During this study, we postulated that these samples had been contaminated with exogenous vitamin D metabolites because of the addition of bovine serum albumin (BSA) as part of an extraction step undertaken 7 years earlier. The aim of the current study was to develop methods in order to adjust for this contamination.

Vitamin D Concentrations at Birth and the Risk of Rheumatoid Arthritis in Early Adulthood: A Danish Population-Based Case-Cohort Study.

Background: Low vitamin D in pregnancy may impair the development of the fetal immune system and influence the risk of later development of rheumatoid arthritis (RA) in the offspring. The aim was to examine whether lower 25-hydroxyvitamin D3 (25(OH)D) concentrations at birth were associated with the risk of developing RA in early adulthood. Methods: This case-cohort study obtained data from Danish registers and biobanks.

Neonatal Screening for Congenital Adrenal Hyperplasia in Denmark: 10 Years of Experience.

Introduction: Early detection of salt-wasting congenital adrenal hyperplasia (SW-CAH) is important to reduce CAH-related morbidity. However, neonatal screening has shown to have a low positive predictive value (PPV), especially among preterm newborns. Here, the Danish CAH screening is evaluated by comparing incidence and morbidity of SW-CAH 10 years before and after introduction of screening.

Sensitive and Robust LC-MS/MS Assay to Quantify 25-Hydroxyvitamin D in Leftover Protein Extract from Dried Blood Spots.

Neonatal dried blood spots (DBS) provide a remarkable resource for biobanks. These microsamples can provide information related to the genetic correlates of disease and can be used to quantify a range of analytes, such as proteins and small molecules. However, after routine neonatal screening, the amount of DBS sample available is limited.

Epidemiological characterisation of the first 785 SARS-CoV-2 Omicron variant cases in Denmark, December 2021.

By 9 December 2021, 785 SARS-CoV-2 Omicron variant cases have been identified in Denmark. Most cases were fully (76%) or booster-vaccinated (7.1%); 34 (4.

Neonatal metabolome of caesarean section and risk of childhood asthma.

Background: Birth by caesarean section is linked to an increased risk of developing asthma, but the underlying mechanisms are unclear.

Objective: To elucidate the link between birth by caesarean section and asthma using newborn metabolomic profiles and integrating early-life gut microbiome data and cord blood immunology.

Methods: We investigated the influence of caesarean section on liquid chromatography mass spectrometry metabolomic profiles of dried blood spots from newborns of the two independent Copenhagen Prospective Studies on Asthma in Childhood cohorts, COPSAC2010 (n=677) and COPSAC2000 (n=387).

SARS-CoV-2 RNA stability in dry swabs for longer storage and transport at different temperatures.

During the current COVID-19 pandemic, different methods have been used to evaluate patients with suspected SARS-CoV-2 infection. In this study, we experimentally evaluate the ability of spiked saliva-moist swabs and spiked swabs without any transport medium to retain SARS-CoV-2 for storage and transport at different environmental settings during different incubation time periods. Our results show that at ambient temperature of 20°C, SARS-CoV-2 RNA remains stable for up to 9 days allowing a long-time span for transport and storage without compromising clinical results.

Genetic regulation of spermine oxidase activity and cancer risk: a Mendelian randomization study.

Spermine oxidase (SMOX) catalyzes the oxidation of spermine to spermidine. Observational studies have reported SMOX as a source of reactive oxygen species associated with cancer, implying that inhibition of SMOX could be a target for chemoprevention. Here we test causality of SMOX levels with cancer risk using a Mendelian randomization analysis.