Quantifying the immunological distinctiveness of emerging SARS-CoV-2 variants in the context of prior regional herd exposure.

The COVID-19 pandemic has seen the persistent emergence of immune-evasive SARS-CoV-2 variants under the selection pressure of natural and vaccination-acquired immunity. However, it is currently challenging to quantify how immunologically distinct a new variant is compared to all the prior variants to which a population has been exposed. Here, we define "Distinctiveness" of SARS-CoV-2 sequences based on a proteome-wide comparison with all prior sequences from the same geographical region. We observe a correlation between Distinctiveness relative to contemporary sequences and future change in prevalence of a newly circulating lineage (Pearson r = 0.75), suggesting that the Distinctiveness of emergent SARS-CoV-2 lineages is associated with their epidemiological fitness. We further show that the average Distinctiveness of sequences belonging to a lineage, relative to the Distinctiveness of other sequences that occur at the same place and time (n = 944 location/time data points), is predictive of future increases in prevalence (Area Under the Curve, AUC = 0.88 [95% confidence interval 0.86 to 0.90]). By assessing the Delta variant in India versus Brazil, we show that the same lineage can have different Distinctiveness-contributing positions in different geographical regions depending on the other variants that previously circulated in those regions. Finally, we find that positions that constitute epitopes contribute disproportionately (20-fold higher than the average position) to Distinctiveness. Overall, this study suggests that real-time assessment of new SARS-CoV-2 variants in the context of prior regional herd exposure via Distinctiveness can augment genomic surveillance efforts.

Differences in Emergency Department Sepsis Care: Do Race, Sex, and Language Matter?

Study Objectives: Sepsis accounts for half of hospital deaths and is a priority area of quality measurement and improvement by the Centers for Medicare and Medicaid Services (CMS). Social determinants of health have been associated with sepsis outcomes, with racial and ethnically minoritized patients experiencing higher mortality rates and worse outcomes. Standardization of emergency department (ED) sepsis-care protocols and quality measurement have improved sepsis outcomes and are closely tracked. However, it is unknown whether there are differences in ED sepsis care protocol adherence or outcomes by race, sex, or primary language spoken. The Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure is a CMS quality measure used to bundle and track multiple elements of sepsis care that are shown to improve sepsis outcomes. This measure includes obtaining blood cultures and serum lactate measurements and timely administration of intravenous fluid and antibiotics, if indicated. In this study, we hypothesized there would be a difference in 3- hour bundle compliance based on differences in race, sex, and/or language spoken. Method(s): We conducted a retrospective chart review of adult ED patients who met SEP-1 reporting guidelines for severe sepsis, septic shock, or sepsis with organ failure, from April 8, 2019 to January 21, 2022 at a large health system in Rhode Island with over 150,000 annual ED visits. We included patients who had 3-hour bundle compliance reported to CMS. Statistical analysis was completed using univariate descriptive analyses and bivariate analyses with a chi-square test of independence. We conducted logistic regression to identify factors associated with 3-hour sepsis bundle compliance and differences in sepsis treatment by race, ethnicity, sex, primary language spoken, and use of an interpreter, adjusting for emergency severity index (ESI), disposition, inpatient department, and COVID test results. Result(s): The study population included 3,182 patients of which 44.6% (1418/3182) were female, 78.4% (2495/3182) white, and 11.3 % (360/3182) were Hispanic or Latino. The majority (85.5%, 2722/3182) spoke English. Among people who spoke a language other than English, over two-thirds (66.3%, 305/460) received an interpreter. Less than a quarter 23.5% (749/3182) had severe sepsis, over a third (35.5%, 1131/3182) had septic shock, and 40.9% (1302/3182) had sepsis with organ failure. Overall compliance with the SEP-1 bundle was low at 44.9% (1430/3182). There were no significant differences in sepsis bundle compliance by patient sex, race, ethnicity, or language spoken. Logistic regression showed a lower likelihood of compliance with the sepsis bundle among patients with severe sepsis compared to sepsis patients with organ failure (aOR 0.77 [95% CI: 0.65-0.90]). Conclusion(s): Our study did not identify a disparity in SEP-1 bundle compliance by sex, race, ethnicity, or language spoken. These findings support the hypothesis that using standardized ED sepsis protocols and measures are important tools to mitigate and/or prevent disparities in ED sepsis care. We also found low compliance with the SEP-1 bundle, with higher compliance noted among individuals with more severe disease, potentially diluting differences that may exist between demographic groups. Future studies are needed in populations with higher SEP-1 compliance to determine whether there are differences by sex, race, or language spoken. No, authors do not have interests to disclose Copyright © 2022

The Sequence Read Archive: a decade more of explosive growth.

The Sequence Read Archive (SRA, https://www.ncbi.nlm.nih.gov/sra/) stores raw sequencing data and alignment information to enhance reproducibility and facilitate new discoveries through data analysis. Here we note changes in storage designed to increase access and highlight analyses that augment metadata with taxonomic insight to help users select data. In addition, we present three unanticipated applications of taxonomic analysis.

VADR: validation and annotation of virus sequence submissions to GenBank.

BACKGROUND: GenBank contains over 3 million viral sequences. The National Center for Biotechnology Information (NCBI) previously made available a tool for validating and annotating influenza virus sequences that is used to check submissions to GenBank. Before this project, there was no analogous tool in use for non-influenza viral sequence submissions. RESULTS: We developed a system called VADR (Viral Annotation DefineR) that validates and annotates viral sequences in GenBank submissions. The annotation system is based on the analysis of the input nucleotide sequence using models built from curated RefSeqs. Hidden Markov models are used to classify sequences by determining the RefSeq they are most similar to, and feature annotation from the RefSeq is mapped based on a nucleotide alignment of the full sequence to a covariance model. Predicted proteins encoded by the sequence are validated with nucleotide-to-protein alignments using BLAST. The system identifies 43 types of "alerts" that (unlike the previous BLAST-based system) provide deterministic and rigorous feedback to researchers who submit sequences with unexpected characteristics. VADR has been integrated into GenBank's submission processing pipeline allowing for viral submissions passing all tests to be accepted and annotated automatically, without the need for any human (GenBank indexer) intervention. Unlike the previous submission-checking system, VADR is freely available (https://github.com/nawrockie/vadr) for local installation and use. VADR has been used for Norovirus submissions since May 2018 and for Dengue virus submissions since January 2019. Since March 2020, VADR has also been used to check SARS-CoV-2 sequence submissions. Other viruses with high numbers of submissions will be added incrementally. CONCLUSION: VADR improves the speed with which non-flu virus submissions to GenBank can be checked and improves the content and quality of the GenBank annotations. The availability and portability of the software allow researchers to run the GenBank checks prior to submitting their viral sequences, and thereby gain confidence that their submissions will be accepted immediately without the need to correspond with GenBank staff. Reciprocally, the adoption of VADR frees GenBank staff to spend more time on services other than checking routine viral sequence submissions.