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Most SARS-CoV-2 virus strains feature a specific mutation that makes them more transmissible, to the point that these strains now predominate globally, new evidence shows.
In contrast to a greater variety of strains early in the pandemic, now 99.9% of circulating SARS-CoV-2 strains in the study feature the D614G mutation on the spike protein. In addition, people infected with a D614G strain have higher nasopharynx viral loads at diagnosis.
It’s not all bad news. This single-point mutation was not associated with worse clinical COVID-19 severity. Also, the mutation isn’t expected to interfere with the efficacy any of the antibody cocktails, small molecule therapies or vaccines in development.
Dr Ilya Finkelstein
Furthermore, “as bad as SARS-CoV-2 is, we may have dodged a bullet in terms of how quickly it mutates,” study author Ilya Finkelstein, PhD, told Medscape Medical News. This virus mutates much slower than HIV, for example, giving researchers a greater chance to stay one step ahead, he said.
The study was published online October 30 in the journal mBio.
Molecular Sleuthing
The research was possible because colleagues at the Houston Methodist Hospital system sequenced the genome of 5085 SARS-CoV-2 strains early in the outbreak and during a second wave of infection over the summer, Finkelstein said.
The unique data source also includes information from plasma, convalescent plasma, and patient outcomes. Studying a large and diverse population in a major metropolitan area like Houston helps create a “molecular fingerprint” for the virus that will continue to be very useful, said Finkelstein, a researcher and director of the Finkelstein Lab at the University of Texas Austin.
D614G was the most common genetic substitution the researchers found, appearing in 82% of SARS-CoV-2 strains during the first wave from March 5 to May 11. The proportion with this mutation jumped to 99.9% by the second wave, defined as May 12 to July 7 in the study.
The jump in mutation frequency “occurred very rapidly, in a matter of just a few months,” the researchers note.
The presence of the mutation during the first wave was independently associated with mechanical ventilation days, overall length of stay, and ICU length of stay. However, it was not associated with any significant differences in patient outcomes.
The D614G mutation is now so common worldwide that these viruses are considered reference strains. Researchers believe D614G predominates because it increases the spike protein’s ability to open cells for the virus to enter.
Despite the large number of virus strains evaluated, the samples only represent about 10% of COVID-19 cases in Houston during the study, a potential limitation. Also, some collected samples could not be used for high-quality genome analysis because of limited virus nucleic acid.
Also, it remains unclear if host-virus immune interactions play a significant role. However, the researchers note in the paper that “available data suggest that in the aggregate, host genetics does not play an overwhelming role in determining outcome in the great majority of adult patients, once virus infection is established.”
Surveillance Ongoing
“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,” the researchers add.
Going forward, the ongoing molecular surveillance of SARS-CoV-2 “may provide critical insights into the origin of the new infection spikes and waves that are occurring as public health constraints are further relaxed, schools and colleges reopen, holidays occur, commercial air travel increases and individuals change their behavior because of COVID-19 ‘fatigue,’ ” the researchers note.
They add that the genome data will also be useful in assessing ongoing molecular evolution in spike and other proteins “as baseline herd immunity is generated, either by natural exposure to SARS-CoV-2 or by vaccination.”
Further Validation Warranted
“The study is very interesting and well performed,” Professor Noam Shomron, PhD, a member of the faculty of medicine at Tel Aviv University, Israel, told Medscape Medical News.
Analyzing the “SARS-CoV-2 molecular evolution in a specific region in the USA…could be viewed as a microcosm of what occurs in other large cities in the USA,” he said.
However, “before jumping to conclusions, this should be further validated,” added Shomron, who authored a study suggesting differences in genetic alleles could partially explain variations across countries in the infection rates, severity, and mortality associated with SARS-CoV-2.
“We know that many other features and contributors might affect the results — even social constraints could generate a bias in the observations,” he said.
Finkelstein and Shomron have disclosed no relevant financial relationships.
mBio. Published online October 30, 2020. Full text
Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology and rheumatology. Follow Damian on Twitter: @MedReporter.