Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1

Mutations in the genome of SARS-CoV-2 can affect the performance of molecular diagnostic assays. In some cases, such as S-gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here, we describe partial ORF1ab gene target failure (pOGTF) on the cobas SARS-CoV-2 assays, defined by a $2-thermocycle delay in detection of the ORF1ab gene compared to that of the E-gene. We demonstrate that pOGTF is 98.6% sensitive and 99.9% specific for SARS-CoV-2 lineage BA.2.12.1, an emerging variant in the United States with spike L452Q and S704L mutations that may affect transmission, infectivity, and/ or immune evasion. Increasing rates of pOGTF closely mirrored rates of BA.2.12.1 sequences uploaded to public databases, and, importantly, increasing local rates of pOGTF also mirrored increasing overall test positivity. Use of pOGTF as a proxy for BA.2.12.1 provides faster tracking of the variant than whole-genome sequencing and can benefit laboratories without sequencing capabilities

SARS-CoV-2 variants, spike mutations and immune escape.

Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of 'variants of concern', that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets

SARS‐CoV‐2 worldwide replication drives rapid rise and selection of mutations across the viral genome: a time‐course study – potential challenge for vaccines and therapies

Abstract Scientists and the public were alarmed at the first large viral variant of SARS‐CoV‐2 reported in December 2020. We have followed the time course of emerging viral mutants and variants during the SARS‐CoV‐2 pandemic in ten countries on four continents. We examined > 383,500 complete SARS‐CoV‐2 nucleotide sequences in GISAID (Global Initiative of Sharing All Influenza Data) with sampling dates extending until April 05, 2021. These sequences originated from ten different countries: United Kingdom, South Africa, Brazil, United States, India, Russia, France, Spain, Germany, and China. Among the 77 to 100 novel mutations, some previously reported mutations waned and some of them increased in prevalence over time. VUI2012/01 (B.1.1.7) and 501Y.V2 (B.1.351), the so‐called UK and South Africa variants, respectively, and two variants from Brazil, 484K.V2, now called P.1 and P.2, increased in prevalence. Despite lockdowns, worldwide active replication in genetically and socio‐economically diverse populations facilitated selection of new mutations. The data on mutant and variant SARS‐CoV‐2 strains provided here comprise a global resource for easy access to the myriad mutations and variants detected to date globally. Rapidly evolving new variant and mutant strains might give rise to escape variants, capable of limiting the efficacy of vaccines, therapies, and diagnostic tests

Expressive Analysis of Gut Microbiota in Pre- and Post- Solid Organ Transplantation Using Bayesian Topic Models

There is a growing evidence that variation in gut microbial communities has important associations with overall host health, and that the diversity and the richness of such communities is helpful in distinguishing patients at high risk of life-threatening post-transplantation conditions. The aim of our paper is to provide an expressive and highly interpretable characterization of microbiome alterations, with the goal of achieving more effective transplantations characterized by a rejection rate as low as possible, and to avoid more severe complications by treating patients at risk in a timely and effective way. For this purpose, we propose using topic models to identify those bacterial species that have the most important weight under the two different experimental conditions (healthy and transplanted patients, or patients whose fecal microbiota has been sampled both in pre- and post-transplantation phases). Topic models are Bayesian statistical models that are not affected by data scarcity, because conclusions we can draw borrow strength across sparse gut microbiome samples. By exploiting this property, we show that topic models are expressive methods for dimensionality reduction which can help analyze variation and diversity in gut microbial communities. With topic models the analysis can be carried out at a level close to natural language, as the output can be easily interpreted by clinicians, since most abundant species are automatically selected and the microbial dynamics can be tracked and followed over time