Elevated risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variants compared with Alpha variant in vaccinated individuals

The extent to which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) break through infection- or vaccine-induced immunity is not well understood. We analyzed 28,578 sequenced SARS-CoV-2 samples from individuals with known immune status obtained through national community testing in the Netherlands from March to August 2021. We found evidence of an increased risk of infection by the Beta (B.1.351), Gamma (P.1), or Delta (B.1.617.2) variants compared with the Alpha (B.1.1.7) variant after vaccination. No clear differences were found between vaccines. However, the effect was larger in the first 14 to 59 days after complete vaccination compared with ≥60 days. In contrast to vaccine-induced immunity, there was no increased risk for reinfection with Beta, Gamma, or Delta variants relative to the Alpha variant in individuals with infection-induced immunity.</p

Comparison of genotyping and weight of evidence results when applying different genotyping strategies on samples from a DNA transfer experiment

In this study, we assessed to what extent data on the subject of TPPR (transfer, persistence, prevalence, recovery) that are obtained through an older STR typing kit can be used in an activity-level evaluation for a case profiled with a more modern STR kit. Newer kits generally hold more loci and may show higher sensitivity especially when reduced reaction volumes are used, and this could increase the evidential value at the source level. On the other hand, the increased genotyping information may invoke a higher number of contributors in the weight of evidence calculations, which could affect the evidential values as well. An activity scenario well explored in earlier studies [1,2] was redone using volunteers with known DNA profiles. DNA extracts were analyzed with three different approaches, namely using the optimal DNA input for (1) an older and (2) a newer STR typing system, and (3) using a standard, volume-based input combined with replicate PCR analysis with only the newer STR kit. The genotyping results were analyzed for various aspects such as percentage detected alleles and relative peak height contribution for background and the contributors known to be involved in the activity. Next, source-level LRs were calculated and the same trends were observed with regard to inclusionary and exclusionary LRs for persons who had or had not been in direct contact with the sampled areas. We subsequently assessed the impact on the outcome of the activity-level evaluation in an exemplary case by applying the assigned probabilities to a Bayesian network. We infer that data from different STR kits can be combined in the activity-level evaluations

Automating the Illumina DNA library preparation kit for whole genome sequencing applications on the flowbot ONE liquid handler robot

Abstract Whole-genome sequencing (WGS) is currently making its transition from research tool into routine (clinical) diagnostic practice. The workflow for WGS includes the highly labor-intensive library preparations (LP), one of the most critical steps in the WGS procedure. Here, we describe the automation of the LP on the flowbot ONE robot to minimize the risk of human error and reduce hands-on time (HOT). For this, the robot was equipped, programmed, and optimized to perform the Illumina DNA Prep automatically. Results obtained from 16 LP that were performed both manually and automatically showed comparable library DNA yields (median of 1.5-fold difference), similar assembly quality values, and 100% concordance on the final core genome multilocus sequence typing results. In addition, reproducibility of results was confirmed by re-processing eight of the 16 LPs using the automated workflow. With the automated workflow, the HOT was reduced to 25 min compared to the 125 min needed when performing eight LPs using the manual workflow. The turn-around time was 170 and 200 min for the automated and manual workflow, respectively. In summary, the automated workflow on the flowbot ONE generates consistent results in terms of reliability and reproducibility, while significantly reducing HOT as compared to manual LP

Socioeconomic status, financial stress, and glucocorticoid resistance among youth with asthma: Testing the moderation effects of maternal involvement and warmth

OBJECTIVES: Children who grow up in more socioeconomically disadvantaged homes experience greater levels of inflammation and worse asthma symptoms than children from more advantaged families. However, recent evidence suggests that certain family-level factors can mitigate health disparities associated with socioeconomic status (SES). In a sample of youth with asthma, we investigated the potential buffering effects of maternal involvement and warmth on SES disparities in asthma-related immune responses, assessed via glucocorticoid resistance (GR) of immune cells. METHODS: One hundred and forty-three youth (10-16 years of age) with asthma completed measures of maternal involvement and warmth, and their primary caregivers reported their levels of education, income, and financial stress. Peripheral blood mononuclear cells from youth\u27s blood were isolated, cultured, and assayed to determine mitogen-stimulated (PMA/INO + Etho) and mitogen/hydrocortisone-stimulated (PMA/INO + Cort) levels of two Th-2 cytokines (i.e., interleukin-5, interleukin-13) and one Th-1 cytokine (i.e., interferon-γ). GR was calculated by subtracting log-transformed cytokine concentration in the PMA/INO + Etho samples from log-transformed cytokine concentration in the PMA/INO + Cort samples. RESULTS: Both maternal involvement and warmth moderated the indirect pathway from family SES to GR of Th-2 cytokines via financial stress. Specifically, we found that low family SES was associated with elevated GR of Th-2 cytokines via increased financial stress among youth reporting low levels of maternal involvement and warmth, but not among those reporting high levels of maternal involvement or warmth. CONCLUSIONS: These results highlight the protective role of maternal involvement and warmth in health-related biological processes modulated by family SES among youth with asthma

Financial stress and glucocorticoid resistance: The moderating role of parental involvement

Objectives: Socioeconomic status (SES) health disparities have been documented among youth with asthma, with children growing in more socioeconomically disadvantaged homes experiencing worse asthma symptoms and greater levels of inflammation than children from well-off families. However, recent evidence suggests that certain individual and family-level factors can mitigate these health disparities. In a group of children affected by asthma, we investigated the potential moderating role of parental involvement on financial stress and asthma-related immune responses, assessed via leukocytes glucocorticoid resistance (GR). Methods: One hundred and forty-three youth (age 10-16) with asthma completed measures of parental involvement, while their primary caregiver reported their level of education, income, and financial stress, which was objectively assessed with the UCLA Life Stress Interview. Peripheral blood mononuclear cells from youth participants\u27 blood were isolated, cultured, and assayed to determine mitogen-stimulated (PMA/INO + Etho) and mitogen/hydrocortisone-stimulated (PMA/INO + Cort) levels of interleukin(IL)-5, IL-13, and interferon(IFN)-γ. GR was calculated by subtracting log-transformed cytokines concentration in the PMA/INO + Etho samples from log-transformed cytokines concentration in the PMA/INO + Cort samples. A composite of GR for Th-2 cytokines was derived by combining IL-13 and IL-5 (N = 143), while a separate measure of GR for IFN-γ, a Th-1 cytokine (N = 132), was derived. Results: Regression analyses showed significant interaction effects between parental involvement and financial stress on the GR Th-2 cytokines composite (b = -0.122, SE = 0.044, p \u3c .01), but not on GR for IFN-γ (b = -0.058, SE = 0.043, ns). Specifically, financial was negatively associated with Th-2 cytokines GR among children reporting low levels of parental involvement, but not among children reporting high levels of parental involvement. Further, moderated mediation analyses suggested that financial stress mediated the link between lower SES (income and education) and greater GR for Th-2 only for those children who reported lower levels of parental involvement. Conclusions: These results highlight the protective role of parental involvement on health-related biological processes modulated by SES among youth with asthma