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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveys can estimate cumulative incidence for monitoring epidemics, requiring assessment of serologic assays to inform testing algorithm development and interpretation of results. We conducted a multilaboratory evaluation of 21 commercial high-throughput SARS-CoV-2 serologic assays using blinded panels of 1,000 highly characterized specimens. Assays demonstrated a range of sensitivities (96%-63%), specificities (99%-96%), and precision (intraclass correlation coefficient 0.55-0.99). Durability of antibody detection was dependent on antigen and immunoglobulin targets; antispike and total Ig assays demonstrated more stable longitudinal reactivity than antinucleocapsid and IgG assays. Assays with high sensitivity, specificity, and durable antibody detection are ideal for serosurveillance, but assays demonstrating waning reactivity are appropriate for other applications, including correlation with neutralizing activity and detection of anamnestic boosting by reinfections. Assay performance must be evaluated in context of intended use, particularly in the context of widespread vaccination and circulation of SARS-CoV-2 variants.

Serosurveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical to monitor the course of the evolving pandemic and local outbreaks and can provide data on infection-fatality ratios, [...]

Background: Less discriminatory donor selection policies for men who have sex with men (MSM) may impact transfusion safety in terms of higher residual risks for known transfusion‐transmitted infections (TTIs), increased vulnerability toward new TTIs that are also transmitted via sex, and HIV infections masked by pre‐exposure prophylaxis (PrEP). Study Design and Methods: TTI trends in Dutch donors were studied over a 13‐year period (2011–2023), characterized by successive relaxations of MSM deferral criteria. Structured posttest counseling was performed to determine risk factors in TTI‐positive donors. PrEP drug levels were measured in 9977 donations from male donors living in urban areas and in 67 donors with active or resolved syphilis. Results: HIV incidence (from 5.8 to 1.5 per 1,000,000 donor years (DY)) and HBV incidence (from 12.4 to 4.5 per 1,000,000 DY) in Dutch donors decreased with less stringent MSM deferral criteria, while syphilis prevalence (from 26.4 to 44.1 per 100,000 new donors) and syphilis incidence (from 18.3 to 46.3 per 1,000,000 DY) increased over time. The proportion of MSM‐related syphilis rose from 2% to 32% in new donors and from 12% to 27% in repeat donors. PrEP was detected in 2 of 9977 (0.02%) donations from male donors living in urban areas, and in 1 of 39 (2.6%) male donors with syphilis. Discussion: To date, phasing out donor deferral for MSM had no significant impact on transfusion safety in the Netherlands. However, rising syphilis rates and (recent) PrEP use in the blood donor population, albeit rare, suggest an influx of donors with higher sexual risk profiles and requires intensified TTI surveillance in donors. [ABSTRACT FROM AUTHOR]

Introduction: Serological surveillance is useful for assessing SARS-CoV-2 immunity in populations. To effectively study the presence and persistence of antibodies, it is necessary to distinguish between persons with past infection, and persons who only received vaccination. Knowledge of the duration of antibody persistence is essential for correct interpretation of surveillance results. Methods: Starting in April 2020, waning of SARS-CoV-2 antibodies was studied in a longitudinal cohort study of 495 SARS-CoV-2 antibody-positive Dutch blood donors, not pre-selected by PCR testing or disease severity. Additionally, in May 2021, a sample of donors representative for the Dutch population was tested for antibodies against the SARS-CoV-2 spike (S) protein, using the Wantai Ab ELISA and the Elecsys® Anti-SARS-CoV-2 S assay; and for antibodies against the nucleocapsid protein, which indicate past infection, using the Elecsys® Anti-SARS-CoV-2 assay. Results: The anti-S response in donors that were infected in April or May 2020 remained positive in 100% of donors in the Elecsys® Anti-SARS-CoV-2 S assay one year after infection, after which follow up of waning was no longer possible because of large scale vaccination. The anti-nucleocapsid response results were still positive in approximately 80% of donors two years after infection. In May 2021, 51% of the donors showed anti-S reactivity and 16.8% tested positive for anti-nucleocapsid antibodies. Conclusion: Infection with SARS-CoV-2 resulted in spike and nucleocapsid antibody levels still detectable in the majority of donors 1–2 years after infection. In May 2021, 51% of donors were vaccinated and 16.8% had had an infection. Thus, both Elecsys® SARS-CoV-2 antibody assays can be used to reliably assess the vaccination and infection status of individuals. [ABSTRACT FROM AUTHOR]

UnlabelledExposure to hepatitis E virus (HEV) is common in the United States, but there are few data on prevalence of HEV/human immunodeficiency virus (HIV) coinfection in U.S.PopulationsWe tested 2,919 plasma samples collected from HIV-infected (HIV(+)) women and men enrolled in U.S. cohort studies for HEV viremia using a high-throughput nucleic acid testing (NAT) platform. NAT(+) samples were confirmed by real-time polymerase chain reaction. Samples were selected for testing primarily on the basis of biomarkers of liver disease and immune suppression. Prevalence of HEV viremia was 3 of 2,606 and 0 of 313 in tested plasma samples collected from HIV(+) women and men, respectively. All HEV isolates were genotype 3a. Based on follow-up testing of stored samples, 1 woman had chronic HEV infection for >4 years whereas 2 women had acute HEV detectable at only a single study visit.ConclusionsTo our knowledge, this is the first reported case of chronic HEV infection in an HIV(+) U.S. individual. We also confirm that chronic HEV infection can persist despite a CD4(+) count >200 cells/mm(3). Overall, though, these data suggest that HEV infection is rare in the HIV(+) U.S. population.

The epithelial anion channel CFTR interacts with multiple PDZ domain--containing proteins. Heterologous expression studies have demonstrated that the [Na.sup.+]/[H.sup.+] exchanger regulatory factors, NHERF1, NHERF2, and PDZK1 (NHERF3), modulate CFTR membrane retention, conductivity, and interactions with other transporters. To study their biological roles in vivo, we investigated CFTR-dependent duodenal HC[O.sub.3]- secretion in mouse models of Nherf1, Nherf2, and Pdzk1 loss of function. We found that Nherf1 ablation strongly reduced basal as well as forskolin-stimulated (FSK-stimulated) HC[O.sub.3]- secretory rates and blocked [[beta].sub.2]-adrenergic receptor ([[beta].sub.2]-AR) stimulation. Conversely, Nherf2-/- mice displayed augmented FSK-stimulated HC[O.sub.3]- secretion. Furthermore, although lysophosphatidic acid (LPA) inhibited FSK-stimulated HC[O.sub.3]- secretion in WT mice, this effect was lost in Nherf2-/- mice. Pdzk1 ablation reduced basal, but not FSK-stimulated, HC[O.sub.3]- secretion. In addition, laser microdissection and quantitative PCR revealed that the [[beta].sub.2]-AR and the type 2 LPA receptor were expressed together with CFTR in duodenal crypts and that colocalization of the [[beta].sub.2]-AR and CFTR was reduced in the Nherf1-/- mice. These data suggest that the NHERF proteins differentially modulate duodenal HC[O.sub.3]- secretion: while NHERF1 is an obligatory linker for [[beta].sub.2]-AR stimulation of CFTR, NHERF2 confers inhibitory signals by coupling the LPA receptor to CFTR., Introduction The epithelial anion channel CFTR has been recognized as a hub protein, connecting to many other proteins and thus able to form protein-protein networks and affecting an astonishingly large [...]

The adaptor proteins sodium/hydrogen exchanger regulatory factor (NHERF)-I and NHERF-2 have overlapping tissue distribution in renal cells and overlapping specificity in their binding to renal transporters and other proteins. To compare the kidney-specific differences in the function of these adaptor proteins, NHERF-1 and NHERF-2 null mice were compared with wild-type control mice. In NHERF-2 null mice, the renal proximal tubule abundance and distribution of NHERF-1 and NHERF-3 were not different from those in wild-type animals. The glomerular expression of podocalyxin and ZO-1 also did not differ. NHERF-1 null mice had increased urinary excretion of phosphate, calcium, and uric acid compared with wild-type control and NHERF-2 null mice. Because of the association between NHERF-2 and podocalyxin in glomeruli and C1C-5 in the renal proximal tubule, the urinary excretion of protein was determined. There were no differences in the urinary excretion of protein or low-molecular-weight proteins between wild-type control, NHERF-[1.sup.-/-], and NHERF-[2.sup.- /-] mice. These studies indicate that the increased urinary excretion of phosphate and uric acid are specific to NHERF-1 null mice and highlight the fact that predictions about the role of adaptor proteins such as the NHERF proteins obtained from studies of model cell systems must be confirmed in whole animals. mouse kidney; PDZ proteins; sodium/hydrogen exchanger regulatory factor