Viral shedding and antibody response in 37 patients with MERS-coronavirus infection

Background. The Middle East respiratory syndrome (MERS) coronavirus causes isolated cases and outbreaks of severe respiratory disease. Essential features of the natural history of disease are poorly understood. Methods. We studied 37 adult patients infected with MERS coronavirus for viral load in the lower and upper respiratory tracts (LRT and URT, respectively), blood, stool, and urine. Antibodies and serum neutralizing activities were determined over the course of disease. Results. One hundred ninety-nine LRT samples collected during the 3 weeks following diagnosis yielded virus RNA in 93% of tests. Average (maximum) viral loads were 5 × 106 (6 × 1010) copies/mL. Viral loads (positive detection frequencies) in 84 URT samples were 1.9 × 104 copies/mL (47.6%). Thirty-three percent of all 108 serum samples tested yielded viral RNA. Only 14.6% of stool and 2.4% of urine samples yielded viral RNA. All seroconversions occurred during the first 2 weeks after diagnosis, which corresponds to the second and third week after symptom onset. Immunoglobulin M detection provided no advantage in sensitivity over immunoglobulin G (IgG) detection. All surviving patients, but only slightly more than half of all fatal cases, produced IgG and neutralizing antibodies. The levels of IgG and neutralizing antibodies were weakly and inversely correlated with LRT viral loads. Presence of antibodies did not lead to the elimination of virus from LRT. Conclusions. The timing and intensity of respiratory viral shedding in patients with MERS closely matches that of those with severe acute respiratory syndrome. Blood viral RNA does not seem to be infectious. Extrapulmonary loci of virus replication seem possible. Neutralizing antibodies do not suffice to clear the infection

New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57

Genome-wide association study identifies 74 loci associated with educational attainment

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals1. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample1,2 of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases

New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P <5 x 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.Peer reviewe

Evaluation of Confirmatory Strategies for Detection of Type-Specific Antibodies against Herpes Simplex Virus Type 2

In this study, the optimal combination of three commercial glycoprotein G-2 (gG-2)-based herpes simplex virus type 2 (HSV-2) type-specific enzyme-linked immunosorbent assays (Euroimmun anti-HSV-2 immunoglobulin G [IgG] ELISA [Eu2], Gull HSV-2-specific IgG ELISA [Gu2], and Radim HSV-2 IgG ELISA [Ra2]) and one gG-2-based HSV-2-specific immunoblot (Euroimmun anti-HSV-1/HSV-2 gG Western blot [EuW]) was determined with regard to diagnostic performance and cost efficiency. Two hundred fifty serum samples were included in this study, 194 of which were from female prostitutes. When a formal primary “gold standard” was defined based on majority agreement of the commercial tests, with EuW being decisive in stand-off situations, the sensitivity and specificity of the assays in the samples from prostitutes were as follows: Eu2, 100 and 89.22%; Gu2, 94.44 and 96.08%; Ra2, 61.18 and 95.10%; and EuW, 98.90 and 100%. The most cost-effective confirmatory strategy in the samples from prostitutes was screening with Eu2, retesting positive and equivocal samples with Gu2, and resolving the remaining discordant results with EuW (estimated additional costs per sample, 79.02%; sensitivity, 100%; positive predictive value, 96.81%). Applying a self-developed gG-2-independent assay to the discordant and concordant negative samples in the samples from prostitutes suggested that the primary gold standard may have missed six HSV-2-positive samples. In conclusion, confirmatory strategies based on commercial gG-2-dependent seroassays result in an increase in the specificity of HSV-2-specific serology. However, further improvement of the sensitivity of current HSV-2-specific serology may require the additional exploitation of the gG-2-independent type-specific antibody response

Humoral Immune Response to CoronaVac in Turkish Adults

While most approved vaccines are based on the viral spike protein or its immunogenic regions, inactivated whole-virion vaccines (e.g., CoronaVac) contain additional antigens that may enhance protection. This study analyzes short-term humoral responses against the SARS-CoV-2 spike (S1) and nucleocapsid (NCP) protein in 50 Turkish adults without previous SARS-CoV-2 infection after CoronaVac immunization. Samples were collected before vaccination (t0), 28&ndash;29 days after the first vaccine dose and prior to the second dose (t1), as well as 14&ndash;15 days after the second dose (t2). Anti-S1 IgG and IgA as well as anti-NCP IgG were quantified using ELISA. At t1, seroconversion rates for anti-S1 IgG, anti-S1 IgA and anti-NCP IgG were 30.0%, 28.0% and 4.0%, respectively, increasing significantly to 98.0%, 78.0% and 40.0% at t2. The anti-NCP IgG median (t2) was below the positivity cut-off, while anti-S1 IgG and IgA medians were positive. Anti-S1 IgG levels strongly correlated with anti-S1 IgA (rs = 0.767, p &lt; 0.001) and anti-NCP IgG (rs = 0.683, p &lt; 0.001). In conclusion, two CoronaVac doses induced significant increases in antibodies against S1 and NCP. Despite strong correlations between the antibody concentrations, the median levels and seroconversion rates of S1-specific responses exceed those of NCP-specific responses as early as two weeks after the second vaccine dose