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Cell Studies on SARS-CoV-2 Spike Variant, Host Transcriptomes, Glioma-Infiltrating T Cells

An international team considers fitness patterns for SARS-CoV-2 isolates containing the N439K mutation in the receptor-binding motif of the coronavirus spike protein. By bringing together genome sequence, clinical, structural, and epidemiological data for N439K-containing isolates identified in dozens of countries, the researchers saw signs that the same mutation has independently arisen in more than on SARS-CoV-2 lineage, leading to enhanced affinity for the ACE2 receptor in human hosts and a slight uptick in viral loads without a clear shift in in vitro viral replication fitness. "N439K provides a sentinel example of immune escape, indicating that [receptor-binding motif] variants must be evaluated when considering vaccines and the therapeutic or prophylactic use of [monoclonal antibodies]," they report. "Long-term control of the pandemic with vaccines will require systematic monitoring of immune escape variants and may require new vaccine preparations that address the variants circulating globally."

Investigators at Peking University and elsewhere share findings from a single-cell transcriptomic analysis of immune features found in individuals infected with SARS-CoV-2. Based on single-cell RNA sequencing data for nearly 1.5 million individual cells in hundreds of samples from 196 individuals with or without SARS-CoV-2 infections, for example, the team uncovered peripheral immune subtype profiles that varied depending on everything from COVID-19 disease stage and severity to host age and biological sex. Along with new details to the epithelial and immune cells involved in SARS-CoV-2 infections, the data offered a look at immune cell types that appear to contribute to so-called "cytokine storms" in some individuals with severe forms of COVID-19. Together, the authors write, the new data "provide a rich resource for understanding the pathogenesis and developing effective therapeutic strategies for COVID-19." 

A team led by investigators at Dana-Farber Cancer Institute, Harvard Medical School, and the Broad Institute presents findings from a single-cell RNA-seq analysis of immune T cells infiltrating tumor samples from dozens of individuals with diffuse glioma. Focusing on samples from 31 individuals with isocitrate dehydrogenase (IDH)-mutant or IDH-wild type forms of diffuse glioma, the researchers got a look at gene expression in related infiltrating T cells, along with insights into the clonally expanded T cell populations identified in the tumors. Their results hint that it may be possible to boost anti-glioma T cell activity using antibodies that interfere with the natural killer (NK) cell receptor CD161 or by inactivating the KLRB1 gene that codes for the receptor. "Our work provides an atlas of T cells in gliomas," the authors write, "and highlights CD161 and other NK cell receptors as immunotherapy targets."

The Scan

US Booster Eligibility Decision

The US CDC director recommends that people at high risk of developing COVID-19 due to their jobs also be eligible for COVID-19 boosters, in addition to those 65 years old and older or with underlying medical conditions.

Arizona Bill Before Judge

The Arizona Daily Star reports that a judge weighing whether a new Arizona law restricting abortion due to genetic conditions is a ban or a restriction.

Additional Genes

Wales is rolling out new genetic testing service for cancer patients, according to BBC News.

Science Papers Examine State of Human Genomic Research, Single-Cell Protein Quantification

In Science this week: a number of editorials and policy reports discuss advances in human genomic research, and more.