COVID-19 becoming more contagious but not deadlier — Houston genome analysis

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The first study to analyse the structure of the novel coronavirus from two waves of infection in a major city found that a more contagious strain dominates recent samples, researchers led by James Musser from Houston Methodist Hospital are quoted in a Reuters Health report as saying.

They examined more than 5,000 genomes from viruses recovered in the earliest phase of the pandemic in Houston, an ethnically diverse city of 7m, and from an ongoing more recent wave of infections.

The study, which has not yet been reviewed by outside experts, found that nearly all strains in the second wave had a mutation, known as D614G, which has been shown to increase the number of “spikes” on the crown-shaped virus.

The spikes are what allow the virus to bind to and infect cells, increasing the ability of the mutated virus to infect cells.

The Houston researchers said patients infected with the variant strain had significantly higher amounts of the virus on initial diagnosis. But they found little evidence that mutations in the virus have made it deadlier, noting that severity of COVID-19, the disease caused by the virus, was more strongly linked to patients’ underlying medical conditions and genetics.

They also said some regions of the spike protein – the primary target of coronavirus vaccines now in development – showed several mutations, possibly indicating that the virus is changing in order to evade the body’s immune response.

Previous studies have shown that the coronavirus is mutating and evolving as it adapts to its human hosts.

Abstract
We sequenced the genomes of 5,085 SARS-CoV-2 strains causing two COVID-19 disease waves in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. The genomes were from viruses recovered in the earliest recognized phase of the pandemic in Houston, and an ongoing massive second wave of infections. The virus was originally introduced into Houston many times independently. Virtually all strains in the second wave have a Gly614 amino acid replacement in the spike protein, a polymorphism that has been linked to increased transmission and infectivity. Patients infected with the Gly614 variant strains had significantly higher virus loads in the nasopharynx on initial diagnosis. We found little evidence of a significant relationship between virus genotypes and altered virulence, stressing the linkage between disease severity, underlying medical conditions, and host genetics. Some regions of the spike protein – the primary target of global vaccine efforts – are replete with amino acid replacements, perhaps indicating the action of selection. We exploited the genomic data to generate defined single amino acid replacements in the receptor binding domain of spike protein that, importantly, produced decreased recognition by the neutralizing monoclonal antibody CR30022. Our study is the first analysis of the molecular architecture of SARS-CoV-2 in two infection waves in a major metropolitan region. The findings will help us to understand the origin, composition, and trajectory of future infection waves, and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution.

Authors
Scott Wesley Long, Randall J Olsen, Paul A. Christensen, David W Bernard, James J Davis, Maulik Shukla, Marcus Nguyen, Matthew Ojeda Saavedra, Prasanti Yerramilli, LaynePruitt, Sishir Subedi, Hung-Che Kuo, Heather Hendrickson, Ghazaleh Eskandari, Hoang AT Nguyen, James Hunter Long, Muthiah Kumaraswami, Jule Goike, Daniel Boutz, Jimmy Gollihar, Jason S McLellan, Chia-Wei Chou, Kamyab Jayanmardi, Ilya J Finkelstein, James Musser

 

Reuters Health report

 

medRxiv abstract (not peer reviewed)

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