Wastewater sequencing reveals early cryptic SARS-CoV-2 variant transmission.

As 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 and/or sequencing capacity, which can also introduce biases1-3. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing4,5. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We developed and deployed improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detected emerging variants of concern up to 14 days earlier in wastewater samples, and identified multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.

SGLT2 Inhibitors, Malnutrition, Cachexia, and Survival in Heart Failure Patients with a History of Anthracycline Treatment.

Patients undergoing anthracycline-based cancer treatments have an increased risk of heart failure (HF) and adverse metabolic outcomes such as malnutrition and cachexia. This retrospective study explored the impact of sodium-glucose co-transporter 2 inhibitors (SGLT2i) on these outcomes in HF patients previously treated with anthracyclines. Using the TriNetx research network, we identified 1,545 patients with a history of SGLT2i use and 17,681 without. We then performed 1:1 propensity score matching resulting in 1,323 patients within each cohort. Patients were analyzed over a 5-year period. SGLT2i use was associated with significantly reduced risks of cachexia (HR 0.453, 95% CI [0.286-0.718]), malnutrition (HR 0.702, 95% CI [0.547-0.900]), adult failure to thrive (HR 0.489, 95% CI [0.345-0.693]), and all-cause mortality (HR 0.490, 95% CI [0.423-0.568]). These findings call for additional research to determine whether SGLT2i may indeed improve nutritional status and survival in patients receiving anthracycline therapy.

Coarse-to-Fine Localization of Underwater Acoustic Communication Receivers.

For underwater acoustic (UWA) communication in sensor networks, the sensing information can only be interpreted meaningfully when the location of the sensor node is known. However, node localization is a challenging problem. Global Navigation Satellite Systems (GNSS) used in terrestrial applications do not work underwater. In this paper, we propose and investigate techniques based on matched field processing for localization of a single-antenna UWA communication receiver relative to one or more transmit antennas. Firstly, we demonstrate that a non-coherent ambiguity function (AF) allows significant improvement in the localization performance compared to the coherent AF previously used for this purpose, especially at high frequencies typically used in communication systems. Secondly, we propose a two-step (coarse-to-fine) localization technique. The second step provides a refined spatial sampling of the AF in the vicinity of its maximum found on the coarse space grid covering an area of interest (in range and depth), computed at the first step. This technique allows high localization accuracy and reduction in complexity and memory storage, compared to single step localization. Thirdly, we propose a joint refinement of the AF around several maxima to reduce outliers. Numerical experiments are run for validation of the proposed techniques.

Multi-omic QTL mapping in early developmental tissues reveals phenotypic and temporal complexity of regulatory variants underlying GWAS loci.

Most GWAS loci are presumed to affect gene regulation, however, only ∼43% colocalize with expression quantitative trait loci (eQTLs). To address this colocalization gap, we identify eQTLs, chromatin accessibility QTLs (caQTLs), and histone acetylation QTLs (haQTLs) using molecular samples from three early developmental (EDev) tissues. Through colocalization, we annotate 586 GWAS loci for 17 traits by QTL complexity, QTL phenotype, and QTL temporal specificity. We show that GWAS loci are highly enriched for colocalization with complex QTL modules that affect multiple elements (genes and/or peaks). We also demonstrate that caQTLs and haQTLs capture regulatory variations not associated with eQTLs and explain ∼49% of the functionally annotated GWAS loci. Additionally, we show that EDev-unique QTLs are strongly depleted for colocalizing with GWAS loci. By conducting one of the largest multi-omic QTL studies to date, we demonstrate that many GWAS loci exhibit phenotypic complexity and therefore, are missed by traditional eQTL analyses.

Safer at school early alert: an observational study of wastewater and surface monitoring to detect COVID-19 in elementary schools.

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. Methods: The objective of this study was to determine the effectiveness and accuracy of community-based passive wastewater and surface (environmental) surveillance to detect SARS-CoV-2 infection in neighborhood schools compared to weekly diagnostic (PCR) testing. We implemented an environmental surveillance system in nine elementary schools with 1700 regularly present staff and students in southern California. The system was validated from November 2020 to March 2021. Findings: In 447 data collection days across the nine sites 89 individuals tested positive for COVID-19, and SARS-CoV-2 was detected in 374 surface samples and 133 wastewater samples. Ninety-three percent of identified cases were associated with an environmental sample (95% CI: 88%-98%); 67% were associated with a positive wastewater sample (95% CI: 57%-77%), and 40% were associated with a positive surface sample (95% CI: 29%-52%). The techniques we utilized allowed for near-complete genomic sequencing of wastewater and surface samples. Interpretation: Passive environmental surveillance can detect the presence of COVID-19 cases in non-residential community school settings with a high degree of accuracy. Funding: County of San Diego, Health and Human Services Agency, National Institutes of Health, National Science Foundation, Centers for Disease Control.

Wastewater and surface monitoring to detect COVID-19 in elementary school settings: The Safer at School Early Alert project.

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. Methods: The objective of this study was to determine the effectiveness and accuracy of community-based passive wastewater and surface (environmental) surveillance to detect SARS-CoV-2 infection in neighborhood schools compared to weekly diagnostic (PCR) testing. We implemented an environmental surveillance system in nine elementary schools with 1700 regularly present staff and students in southern California. The system was validated from November 2020 - March 2021. Findings: In 447 data collection days across the nine sites 89 individuals tested positive for COVID-19, and SARS-CoV-2 was detected in 374 surface samples and 133 wastewater samples. Ninety-three percent of identified cases were associated with an environmental sample (95% CI: 88% - 98%); 67% were associated with a positive wastewater sample (95% CI: 57% - 77%), and 40% were associated with a positive surface sample (95% CI: 29% - 52%). The techniques we utilized allowed for near-complete genomic sequencing of wastewater and surface samples. Interpretation: Passive environmental surveillance can detect the presence of COVID-19 cases in non-residential community school settings with a high degree of accuracy. Funding: County of San Diego, Health and Human Services Agency, National Institutes of Health, National Science Foundation, Centers for Disease Control.

Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission.

As 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. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.