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Cell Studies on Early SARS-CoV-2 Spread, Severe COVID-19, TB Targets

A team from the Scripps Research Institute, Tulane University, and elsewhere describes SARS-CoV-2 movement in Louisiana during the early stages of the COVID-19 pandemic. For their journal pre-proof article, researchers sequenced 235 SARS-CoV-2 isolates collected in Louisiana during the spring of 2020 and analyzed them alongside sequences for almost 1,300 isolates collected in other parts of the world early last year. Combined with flight data and other epidemiological clues, the sequences suggest travelers from other parts of the US brought SARS-CoV-2 to Louisiana in one main introduction event, where it circulated under the radar until March, despite an uptick in spread at Mardi Gras celebrations in New Orleans in February. "Our findings suggest that large-scale events in the beginning of 2020 may have contributed significantly to SARS-CoV-2 transmission early in the COVID-19 epidemic in the US, which is in contrast to epidemic waves later in the epidemic that were also fueled by inherently more transmissible lineages," the authors suggest. "Without widespread availability of vaccination and testing, large gatherings of people without strict control efforts will continue to amplify the COVID-19 pandemic."

With single-cell RNA sequencing on nasopharyngeal swab samples from dozens of individuals with or without COVID-19 who were tested at the University of Mississippi Medical Center from April to September of last year, investigators from Harvard Medical School, the Broad Institute, and other centers in the US explore host responses to SARS-CoV-2 infection. From scRNA-seq data on nearly 32,500 individual cells, they saw SARS-CoV-2-related effects ranging from ciliated cell loss to lower-than-usual local immune responses in the nose, which coincided with more severe disease. "In mild and moderate COVID-19, epithelial cells express anti-viral/interferon-responsive genes, while cells in severe COVID-19 have muted anti-viral responses despite equivalent viral loads," the team writes, noting that "failed nasal epithelial anti-viral immunity may underlie and precede severe COVID-19."

Finally, a team led by investigators at Cornell and Rockefeller universities reports on results from a CRISPR interference (CRISPRi)-based screen for potential targets in the tuberculosis (TB)-causing pathogen Mycobacterium tuberculosis. Based on the gene expression shifts and fitness effects found in M. tuberculosis with CRISPRi, coupled with whole-genome sequencing, the researchers distinguished between genes that appeared more or less vulnerable to treatment targeting in a reference strain called H37Rv and in a hypervirulent M. tuberculosis clone known as HN878.­ "Our results quantitatively redefine essential bacterial processes and identify high-value targets for drug development."

The Scan

Could Mix It Up

The US Food and Drug Administration is considering a plan that would allow for the mixing-and-matching of SARS-CoV-2 vaccines and boosters, the New York Times says.

Closest to the Dog

New Scientist reports that extinct Japanese wolf appears to be the closest known wild relative of dogs.

Offer to Come Back

The Knoxville News Sentinel reports that the University of Tennessee is offering Anming Hu, a professor who was acquitted of charges that he hid ties to China, his position back.

PNAS Papers on Myeloid Differentiation MicroRNAs, Urinary Exosomes, Maize Domestication

In PNAS this week: role of microRNAs in myeloid differentiation, exosomes in urine, and more.