Background: SARS-CoV-2 antibody levels have been proposed as a correlate of protection (CoP) from infection. Yet, large-scale prospective studies of cost-effective scalable antibody measures as predictors of infection under real-world conditions are limited. We examined whether antibody levels measured using high-throughput variant-specific SARS-CoV-2 anti-spike immunoglobulin G (IgG) and ACE2-neutralization assays correlate with cell-based neutralizing antibody (NAb) measurements, and whether they can serve as a reasonable CoP from SARS-CoV-2 infection.
View Article and Find Full Text PDFBackground: American Indian populations have experienced marked disparities in respiratory disease burden. Extracellular vesicle-encapsulated microRNAs (EV-miRNAs) are a novel class of biomarkers that may improve recognition of lung damage in indigenous populations in the United States.
Research Question: Are plasma EV-miRNAs viable biomarkers of respiratory health in American Indian populations?
Study Design And Methods: The Strong Heart Study is a prospective cohort study that enrolled American Indian patients aged 45 to 74 years.
Antibodies are critical tools for research into extracellular vesicles (EVs) and other extracellular nanoparticles (ENPs), where they can be used for their identification, characterization, and isolation. However, the lack of a centralized antibody platform where researchers can share validation results thus minimizing wasted personnel time and reagents, has been a significant obstacle. Moreover, because the performance of antibodies varies among assay types and conditions, detailed information on assay variables and protocols is also of value.
View Article and Find Full Text PDFBackground: Infection prevention (IP) measures are designed to mitigate the transmission of pathogens in healthcare. Using large-scale viral genomic and social network analyses, we determined if IP measures used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were adequate in protecting healthcare workers (HCWs) and patients from acquiring SARS-CoV-2.
Methods: We performed retrospective cross-sectional analyses of viral genomics from all available SARS-CoV-2 viral samples collected at UC San Diego Health and social network analysis using the electronic medical record to derive temporospatial overlap of infections among related viromes and supplemented with contact tracing data.
The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions.
View Article and Find Full Text PDFBackground: Immune changes that occur during pregnancy may place pregnant women at an increased risk for severe disease following viral infections like SARS-CoV-2. Whether these immunologic changes modify the immune response to SARS-CoV-2 infection during pregnancy is not well understood.
Objective: This study aimed to compare the humoral immune response to SARS-CoV-2 infection in pregnant and nonpregnant women.
Background: Schools are high-risk settings for SARS-CoV-2 transmission, but necessary for children's educational and social-emotional wellbeing. Previous research suggests that wastewater monitoring can detect SARS-CoV-2 infections in controlled residential settings with high levels of accuracy. However, its effective accuracy, cost, and feasibility in non-residential community settings is unknown.
View Article and Find Full Text PDFBackground: Aging-related cognitive decline is an early symptom of Alzheimer's disease and other dementias, and on its own can have substantial consequences on an individual's ability to perform important everyday functions. Despite increasing interest in the potential roles of extracellular microRNAs (miRNAs) in central nervous system (CNS) pathologies, there has been little research on extracellular miRNAs in early stages of cognitive decline. We leverage the longitudinal Normative Aging Study (NAS) cohort to investigate associations between plasma miRNAs and cognitive function among cognitively normal men.
View Article and Find Full Text PDFThe extracellular RNA communication consortium (ERCC) is an NIH-funded program aiming to promote the development of new technologies, resources, and knowledge about exRNAs and their carriers. After Phase 1 (2013-2018), Phase 2 of the program (ERCC2, 2019-2023) aims to fill critical gaps in knowledge and technology to enable rigorous and reproducible methods for separation and characterization of both bulk populations of exRNA carriers and single EVs. ERCC2 investigators are also developing new bioinformatic pipelines to promote data integration through the exRNA atlas database.
View Article and Find Full Text PDFAm J Respir Crit Care Med
January 2023
Early detection of respiratory diseases is critical to facilitate delivery of disease-modifying interventions. Extracellular vesicle-enriched microRNAs (EV-miRNAs) may represent reliable markers of early lung injury. Evaluate associations of plasma EV-miRNAs with lung function.
View Article and Find Full Text PDFSurface sampling for SARS-CoV-2 RNA detection has shown considerable promise to detect exposure of built environments to infected individuals shedding virus who would not otherwise be detected. Here, we compare two popular sampling media (VTM and SDS) and two popular workflows (Thermo and PerkinElmer) for implementation of a surface sampling program suitable for environmental monitoring in public schools. We find that the SDS/Thermo pipeline shows superior sensitivity and specificity, but that the VTM/PerkinElmer pipeline is still sufficient to support surface surveillance in any indoor setting with stable cohorts of occupants (e.
View Article and Find Full Text PDFAs SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing.
View Article and Find Full Text PDFBackground: Schools are high-risk settings for SARS-CoV-2 transmission, but necessary for children's educational and social-emotional wellbeing. Previous research suggests that wastewater monitoring can detect SARS-CoV-2 infections in controlled residential settings with high levels of accuracy. However, its effective accuracy, cost, and feasibility in non-residential community settings is unknown.
View Article and Find Full Text PDFEnvironmental monitoring in public spaces can be used to identify surfaces contaminated by persons with COVID-19 and inform appropriate infection mitigation responses. Research groups have reported detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on surfaces days or weeks after the virus has been deposited, making it difficult to estimate when an infected individual may have shed virus onto a SARS-CoV-2 positive surface, which in turn complicates the process of establishing effective quarantine measures. In this study, we determined that reverse transcription-quantitative polymerase chain reaction (RT-qPCR) detection of viral RNA from heat-inactivated particles experiences minimal decay over seven days of monitoring on eight out of nine surfaces tested.
View Article and Find Full Text PDFBiostatistics
December 2022
Medical research institutions have generated massive amounts of biological data by genetically profiling hundreds of cancer cell lines. In parallel, academic biology labs have conducted genetic screens on small numbers of cancer cell lines under custom experimental conditions. In order to share information between these two approaches to scientific discovery, this article proposes a "frequentist assisted by Bayes" (FAB) procedure for hypothesis testing that allows auxiliary information from massive genomics datasets to increase the power of hypothesis tests in specialized studies.
View Article and Find Full Text PDFTransmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is possible among symptom-free individuals. Patients are avoiding medically necessary healthcare visits for fear of becoming infected in the healthcare setting. We screened 489 symptom-free healthcare workers for SARS-CoV-2 and found no positive results, strongly suggesting that the prevalence of SARS-CoV-2 was <1%.
View Article and Find Full Text PDFBackground: Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is possible among symptom-free individuals and some patients are avoiding medically necessary healthcare visits for fear of becoming infected in the healthcare setting. Limited data are available on the point prevalence of SARS-CoV-2 infection in symptom-free U.S.
View Article and Find Full Text PDFExosome cargoes are highly varied and include proteins, small RNAs, and genomic DNA (gDNA). The presence of gDNA suggests that different intracellular compartments contribute to exosome loading, resulting in distinct exosome subpopulations. However, the loading of gDNA and other nuclear contents into exosomes (nExo) remains poorly understood.
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