SARS-CoV-2 Antiviral Prescribing Gaps Among Non-Hospitalized High-Risk Adults.

Within a multi-state clinical cohort, SARS-CoV-2 antiviral prescribing patterns were evaluated from April 2022-June 2023 among non-hospitalized SARS-CoV-2-infected patients with risk factors for severe COVID-19. Among 3,247 adults, only 31.9% were prescribed an antiviral agent (87.6% nirmatrelvir/ritonavir, 11.9% molnupiravir, 0.5% remdesivir), highlighting the need to identify and address treatment barriers.

El sicariato: una mirada al fenómeno desde la perspectiva criminológica / Contract assasination: a criminological perspective on the phenomenon / Sicariato: uma perspectiva criminológica sobre o fenômeno

Antecedentes: el sicariato es un fenómeno de violencia que afecta a la sociedad contemporánea, en medio de valores relativos al respeto de la vida y la integridad humana. En Colombia, los datos y cifras de los homicidios evidencian que durante los años 2017-2020 se presentaron aproximadamente 26 161 casos en la modalidad sicariato; las motivaciones se asocian fundamentalmente al narcotráfico, economías ilegales, disputas territoriales y factores sociales. Objetivo: identificar la etimología de la palabra "sicario", características, investigaciones y algunas tendencias generacionales sobre el sicariato. Método: este estudio se realizó desde un enfoque cualitativo, diseño documental mediante la revisión de algunas teorías sobre subculturas criminales (Cohen, 1955), el aprendizaje de la conducta delictiva (Sutherland, 1974), aprendizaje social (Bandura, 1987; Becker, 1974), crimen y castigo (Bourdieu, 1997), el entorno social que lo rodea y economía criminal, otros autores y revisión bases de datos: Mendeley, Proquest, Redalyc, base, BBC learning english, entre otros. Resultados: este trabajo permitió recoger conceptos, características, tendencias delictivas y análisis criminológicos del fenómeno; se establecen algunas tipologías, por modus operandi y capacidad del perpetrador del hecho punible, surgimiento del sicariato en Colombia y algunas características de los códigos de conducta de las dos últimas generaciones de sicarios. Finalmente, se plantean las conclusiones.

Background: hired assassination is a phenomenon of violence that affects contemporary society, amidst values related to respect for life and human integrity. In Colombia, homicide data and figures show that during the years 2017-2020 there were approximately 26 161 cases in the form of hired killings; the motivations mainly associated with drug trafficking, illegal economies, territorial disputes and social factors. Objective: to identify the etymology of the word "sicario", characteristics, research and some generational trends regarding contract killing. Method: this study was conducted based on a qualitative approach, documentary design by reviewing several theories on criminal subcultures (Cohen, 1955), learning about criminal behaviour (Sutherland, 1974), social learning (Bandura, 1987; Becker, 1974), crime and punishment (Bourdieu, 1997) and the surrounding social environment and criminal economy, studying other authors and reviewing the databases: Mendeley, Proquest, Redalyc, base, BBC learning English, among others. Results: this work allowed the collection of concepts, characteristics, criminal trends and criminological analysis of the phenomenon; some typologies are established, by modus operandi and capacity of the perpetrator of the punishable act, the emergence of assasination by contract in Colombia and some characteristics of the codes of conduct of the last two generations of hitmen. Finally, conclusions are drawn.

Antecedentes: o sicariato ou o assassinato contratado é um fenômeno de violência que afeta a sociedade contemporânea, em meio a valores relacionados ao respeito à vida e à integridade humana. Na Colômbia, os dados e números de homicídios mostram que, durante 2017 e 2020, houve aproximadamente 26 161 casos na forma de sicariato ou assassinatocontratado; as motivações estão associadas principalmente ao tráfico de drogas, economias ilegais, disputas territoriais e fatores sociais. Objetivo: identificar a etimologia da palavra "sicário", características, pesquisas e algumas tendências geracionais sobre o sicariato. Método: este estudo foi realizado a partir de uma abordagem qualitativa, com desenho documental, por meio da revisão de algumas teorias sobre subculturas criminais (Cohen, 1955), aprendizagem do comportamento criminoso (Sutherland, 1974), aprendizagem social (Bandura, 1987; Becker, 1974), crime e castigo (Bourdieu, 1997), ambiente social circundante e economia criminal, outros autores e bancos de dados de revisão: Mendeley, Proquest, Redalyc, base, BBC learning english, entre outros. Resultados: este trabalho permitiu a coleta de conceitos, características, tendências criminais e análise criminológica do fenômeno; são estabelecidas algumas tipologias, por modus operandi e capacidade do autor do ato punível, o surgimento do sicariato na Colômbia e algumas características dos códigos de conduta das duas últimas gerações de sicários. Por fim, são apresentadas as conclusões.

Evidence for SARS-CoV-2 Delta and Omicron co-infections and recombination.

BACKGROUND: Between November 2021 and February 2022, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants co-circulated in the United States, allowing for co-infections and possible recombination events. METHODS: We sequenced 29,719 positive samples during this period and analyzed the presence and fraction of reads supporting mutations specific to either the Delta or Omicron variant. FINDINGS: We identified 18 co-infections, one of which displayed evidence of a low Delta-Omicron recombinant viral population. We also identified two independent cases of infection by a Delta-Omicron recombinant virus, where 100% of the viral RNA came from one clonal recombinant. In the three cases, the 5' end of the viral genome was from the Delta genome and the 3' end from Omicron, including the majority of the spike protein gene, though the breakpoints were different. CONCLUSIONS: Delta-Omicron recombinant viruses were rare, and there is currently no evidence that Delta-Omicron recombinant viruses are more transmissible between hosts compared with the circulating Omicron lineages. FUNDING: This research was supported by the NIH RADx initiative and by the Centers for Disease Control Contract 75D30121C12730 (Helix).

A Method for Variant Agnostic Detection of SARS-CoV-2, Rapid Monitoring of Circulating Variants, and Early Detection of Emergent Variants Such as Omicron.

The rapid emergence of SARS-CoV-2 variants raised public health questions concerning the capability of diagnostic tests to detect new strains, the efficacy of vaccines, and how to map the geographical distribution of variants to understand transmission patterns and loads on healthcare resources. Next-generation sequencing (NGS) is the primary method for detecting and tracing new variants, but it is expensive, and it can take weeks before sequence data are available in public repositories. This article describes a customizable reverse transcription PCR (RT-PCR)-based genotyping approach which is significantly less expensive, accelerates reporting, and can be implemented in any lab that performs RT-PCR. Specific single-nucleotide polymorphisms (SNPs) and indels were identified which had high positive-percent agreement (PPA) and negative-percent agreement (NPA) compared to NGS for the major genotypes that circulated through September 11, 2021. Using a 48-marker panel, testing on 1,031 retrospective SARS-CoV-2 positive samples yielded a PPA and NPA ranging from 96.3 to 100% and 99.2 to 100%, respectively, for the top 10 most prevalent World Health Organization (WHO) lineages during that time. The effect of reducing the quantity of panel markers was explored, and a 16-marker panel was determined to be nearly as effective as the 48-marker panel at lineage assignment. Responding to the emergence of Omicron, a genotyping panel was developed which distinguishes Delta and Omicron using four highly specific SNPs. The results demonstrate the utility of the condensed panel to rapidly track the growing prevalence of Omicron across the US in December 2021 and January 2022.

SARS-CoV-2 variant Delta rapidly displaced variant Alpha in the United States and led to higher viral loads.

We report on the sequencing of 74,348 SARS-CoV-2 positive samples collected across the United States and show that the Delta variant, first detected in the United States in March 2021, made up the majority of SARS-CoV-2 infections by July 1, 2021 and accounted for >99.9% of the infections by September 2021. Not only did Delta displace variant Alpha, which was the dominant variant at the time, it also displaced the Gamma, Iota, and Mu variants. Through an analysis of quantification cycle (Cq) values, we demonstrate that Delta infections tend to have a 1.7× higher viral load compared to Alpha infections (a decrease of 0.8 Cq) on average. Our results are consistent with the hypothesis that the increased transmissibility of the Delta variant could be due to the ability of the Delta variant to establish a higher viral load earlier in the infection as compared to the Alpha variant.

Using symptom-based case predictions to identify host genetic factors that contribute to COVID-19 susceptibility.

Epidemiological and genetic studies on COVID-19 are currently hindered by inconsistent and limited testing policies to confirm SARS-CoV-2 infection. Recently, it was shown that it is possible to predict COVID-19 cases using cross-sectional self-reported disease-related symptoms. Here, we demonstrate that this COVID-19 prediction model has reasonable and consistent performance across multiple independent cohorts and that our attempt to improve upon this model did not result in improved predictions. Using the existing COVID-19 prediction model, we then conducted a GWAS on the predicted phenotype using a total of 1,865 predicted cases and 29,174 controls. While we did not find any common, large-effect variants that reached genome-wide significance, we do observe suggestive genetic associations at two SNPs (rs11844522, p = 1.9x10-7; rs5798227, p = 2.2x10-7). Explorative analyses furthermore suggest that genetic variants associated with other viral infectious diseases do not overlap with COVID-19 susceptibility and that severity of COVID-19 may have a different genetic architecture compared to COVID-19 susceptibility. This study represents a first effort that uses a symptom-based predicted phenotype as a proxy for COVID-19 in our pursuit of understanding the genetic susceptibility of the disease. We conclude that the inclusion of symptom-based predicted cases could be a useful strategy in a scenario of limited testing, either during the current COVID-19 pandemic or any future viral outbreak.

Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

The highly transmissible B.1.1.7 variant of SARS-CoV-2, first identified in the United Kingdom, has gained a foothold across the world. Using S gene target failure (SGTF) and SARS-CoV-2 genomic sequencing, we investigated the prevalence and dynamics of this variant in the United States (US), tracking it back to its early emergence. We found that, while the fraction of B.1.1.7 varied by state, the variant increased at a logistic rate with a roughly weekly doubling rate and an increased transmission of 40%-50%. We revealed several independent introductions of B.1.1.7 into the US as early as late November 2020, with community transmission spreading it to most states within months. We show that the US is on a similar trajectory as other countries where B.1.1.7 became dominant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

As of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated the prevalence and growth dynamics of this variant in the United States (U.S.), tracking it back to its early emergence and onward local transmission. We found that the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K., was a reliable proxy for B.1.1.7 detection. We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, detection of the variant increased at a logistic rate similar to those observed elsewhere, with a doubling rate of a little over a week and an increased transmission rate of 35-45%. By performing time-aware Bayesian phylodynamic analyses, we revealed several independent introductions of B.1.1.7 into the U.S. as early as late November 2020, with onward community transmission enabling the variant to spread to at least 30 states as of January 2021. Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.