Late Identification of Perinatal Transmission of HIV in an Infant at High Risk.

The focus of this case study is the delayed diagnosis of a perinatal HIV transmission, which was identified when the infant reached 4 months of age, and the social conditions and structural determinants that contributed to the increased transmission risk. Despite adhering to the diagnostic testing protocols and neonatal antiretroviral (ARV) guidelines of the New York State Department of Health, this transmission still occurred. This transmission event prompted strategies to address criminalization of substance use during pregnancy and a reevaluation of the HIV testing and treatment protocols, including the timing of testing. Obtaining a diagnostic specimen at birth before initiating prophylactic or presumptive therapy, without causing delays in therapy, and incorporating HIV-1 DNA or RNA testing 2 to 6 weeks after discontinuing ARV therapy might have facilitated earlier detection and a quicker resumption of ARV therapy for this high-risk infant. Subsequently, the New York State HIV perinatal testing guidelines were updated. These changes included the recommendation to obtain a diagnostic specimen at birth before initiating ARV medications, whenever feasible, without causing delays in ARV initiation. Additionally, an extra virologic diagnostic test is recommended at 2 to 6 weeks after discontinuing ARVs for infants at high risk of perinatal HIV transmission, especially those with possible DNA or RNA suppression due to ARV prophylaxis or presumptive HIV therapy.

Lower Prevalence of Asymptomatic Alzheimer's Disease Among Healthy African Americans.

OBJECTIVE: Alzheimer's disease (AD) is believed to be more common in African Americans (AA), but biomarker studies in AA populations are limited. This report represents the largest study to date examining cerebrospinal fluid AD biomarkers in AA individuals. METHODS: We analyzed 3,006 cerebrospinal fluid samples from controls, AD cases, and non-AD cases, including 495 (16.5%) self-identified black/AA and 2,456 (81.7%) white/European individuals using cutoffs derived from the Alzheimer's Disease Neuroimaging Initiative, and using a data-driven multivariate Gaussian mixture of regressions. RESULTS: Distinct effects of race were found in different groups. Total Tauand phospho181-Tau were lower among AA individuals in all groups (p < 0.0001), and Aß42 was markedly lower in AA controls compared with white controls (p < 0.0001). Gaussian mixture of regressions modeling of cerebrospinal fluid distributions incorporating adjustments for covariates revealed coefficient estimates for AA race comparable with 2-decade change in age. Using Alzheimer's Disease Neuroimaging Initiative cutoffs, fewer AA controls were classified as biomarker-positive asymptomatic AD (8.0% vs 13.4%). After adjusting for covariates, our Gaussian mixture of regressions model reduced this difference, but continued to predict lower prevalence of asymptomatic AD among AA controls (9.3% vs 13.5%). INTERPRETATION: Although the risk of dementia is higher, data-driven modeling indicates lower frequency of asymptomatic AD in AA controls, suggesting that dementia among AA populations may not be driven by higher rates of AD. ANN NEUROL 2024;96:463-475.

Quantitating SARS-CoV-2 Neutralizing Antibodies from Human Dried Blood Spots.

Background: In the earliest days of COVID-19 pandemic, the collection of dried blood spots (DBS) enabled public health laboratories to undertake population-scale seroprevalence studies to estimate rates of SARS-CoV-2 exposure. With SARS-CoV-2 seropositivity levels now estimated to exceed 94% in the United States, attention has turned to using DBS to assess functional (neutralizing) antibodies within cohorts of interest. Methods: Contrived DBS eluates from convalescent, fully vaccinated and pre-COVID-19 serum samples were evaluated in SARS-CoV-2 plaque reduction neutralization titer (PRNT) assays, a SARS-CoV-2 specific 8-plex microsphere immunoassay, a cell-based pseudovirus assay, and two different spike-ACE2 inhibition assays, an in-house Luminex-based RBD-ACE2 inhibition assay and a commercial real-time PCR-based inhibition assay (NAB-Sure™). Results: DBS eluates from convalescent individuals were compatible with the spike-ACE2 inhibition assays, but not cell-based pseudovirus assays or PRNT. However, the insensitivity of cell-based pseudovirus assays was overcome with DBS eluates from vaccinated individuals with high SARS-CoV-2 antibody titers. Conclusion: SARS-CoV-2 neutralizing titers can be derived with confidence from DBS eluates, thereby opening the door to the use of these biospecimens for the analysis of vulnerable populations and normally hard to reach communities.

Characterization of African-American Super-Agers in the National Alzheimer's Coordinating Center cohort.

BACKGROUND: "Super-agers" are adults aged ≥80 with cognitive performance similar to persons two to three decades younger. Characteristics such as larger hippocampal volume, APOE-ε4 allele absence, higher educational attainment, female sex, and lifelong cognitive stimulation are associated with cognitive performance compatible with super-aging. These findings are based on predominantly white research samples. Limited data are available on African-American super-agers. To fill this gap, we explored potential factors associated with super-aging in older African-American adults. METHODS: Data from African-American participants aged ≥80 in the National Alzheimer's Coordinating Center (NACC) dataset were analyzed. Using global Clinical Dementia Rating (CDR) scores, participants were first categorized as impaired (score ≥0.5) or non-impaired/normal cognition (NC) (score = 0). From the NC group, super-agers were identified using NACC-data-driven cutoffs. Participants were considered super-agers if their memory performance was similar to persons aged 50-60 with NC, and their performance on other domains was within one standard deviation of the mean for persons aged ≥80. We examined group characteristics (NC, super-ager, impaired) using chi-square and ANOVA with pairwise comparisons. Multinomial logistic regression, adjusted for sex and education, evaluated correlates of super-ager group assignment. RESULTS: Data for 1285 African-American participants aged ≥80 were analyzed. We identified 24.7% (n = 316) NC, 4.8% (n = 61) super-agers, and 70.6% (n = 905) impaired. Super-agers were mostly female and more educated, had similar vascular comorbidities as the other groups, and had less sleep disorders, depression, and alcohol use. After adjusting for sex and education, super-ager group assignment was associated with less sleep disorders, less depression, and moderate alcohol use. CONCLUSIONS: Participants with controlled vascular risk, mental health, alcohol use, and sleep disorders tended to be in the super-ager group. These factors may be important focus areas in clinical practice to support cognitive resilience with aging in older African-American adults.

Demographic and Clinical Factors Associated With SARS-CoV-2 Spike 1 Antibody Response Among Vaccinated US Adults: the C4R Study.

This study investigates correlates of anti-S1 antibody response following COVID-19 vaccination in a U.S. population-based meta-cohort of adults participating in longstanding NIH-funded cohort studies. Anti-S1 antibodies were measured from dried blood spots collected between February 2021-August 2022 using Luminex-based microsphere immunoassays. Of 6245 participants, mean age was 73 years (range, 21-100), 58% were female, and 76% were non-Hispanic White. Nearly 52% of participants received the BNT162b2 vaccine and 48% received the mRNA-1273 vaccine. Lower anti-S1 antibody levels are associated with age of 65 years or older, male sex, higher body mass index, smoking, diabetes, COPD and receipt of BNT16b2 vaccine (vs mRNA-1273). Participants with a prior infection, particularly those with a history of hospitalized illness, have higher anti-S1 antibody levels. These results suggest that adults with certain socio-demographic and clinical characteristics may have less robust antibody responses to COVID-19 vaccination and could be prioritized for more frequent re-vaccination.