SARS-CoV-2 - Credit NIAID
#15,471
Five months ago, in COVID-19 & The `M' Word, we looked at the inevitability of seeing multiple mutations in the SARS-CoV-2 virus over time, as it is a single-stranded RNA virus and is therefore subject to `duplication errors' during replication (see Mechanisms of Viral Mutation).
All viruses mutate, some very slowly, and others - like HIV or Influenza - very rapidly. Most mutations convey no biological advantage to the virus, and many are actually detrimental. Only a few are apt to `improve' the fitness of the virus.
But, when viruses make trillions of copies of themselves, every once in awhile a more biologically `fit' virus will emerge; one that can compete with its parental strain, and sometimes even supplant it.
In early May of this year, in More COVID-19 (SARS-CoV-2) Mutation Reports, we looked at a pre-print paper from researchers at the Los Alamos National Laboratory that described a new and increasingly dominant `European' strain of COVID-19 which they believed had enhanced transmissibility.
The gist of this report was a new strain (G clade) of SARS-CoV-2 emerged in Europe in February carrying the D614G mutation (among others), and has since overtaken the original Asian strain in many regions of the world due to its enhanced transmissibility.
The paper was subsequently published in the journal Cell:
Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID19 Virus
In Brief Korber et al. present evidence that there are now more SARS-CoV-2 viruses circulating in the human population globally that have the G614 form of the Spike protein versus the D614 form that was originally identified from the first human cases in Wuhan, China. Follow-up studies show that patients infected with G614 shed more viral nucleic acid compared with those with D614, and G614-bearing viruses show significantly higher infectious titers in vitro than their D614 counterparts.
Although many researchers cautioned that the pronouncement of a more transmissible `G' clade may be premature, over the summer we've seen several other studies that seem to support the theory that the D614G mutation enhances transmissibility.
In June, in Scripps Research Institute: SARS-CoV-2 and the D614G Mutation, we looked at one such study:
The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity
Lizhou Zhang1#, Cody B Jackson1#, Huihui Mou1#, Amrita Ojha1, Erumbi S Rangarajan2, Tina Izard2, Michael Farzan1*, Hyeryun Choe1*
Mutated coronavirus shows significant boost in infectivity
COVID-19-causing viral variant taking over in the United States and Europe now carries more functional, cell-binding spikes.
June 12, 2020
Yesterday a new study was published on the medRxiv pre-print server, which appears to add more weight to the idea that the D614G mutation increases the transmissibility of the SARS-CoV-2 virus.
Scott Wesley Long, Randall J Olsen, Paul A. Christensen, David W Bernard, James J. Davis, Maulik Shukla, Marcus Nguyen, Matthew Ojeda Saavedra, Prasanti Yerramilli, Layne Pruitt, Sishir Subedi, Hung-Che Kuo, Heather Hendrickson, Ghazaleh Eskandari, Hoang A.T. Nguyen, James Hunter Long, Muthiah Kumaraswami, Jule Goike, Daniel Boutz, Jimmy Gollihar, Jason S. McLellan, Chia-Wei Chou, Kamyab Javanmardi, Ilya J. Finkelstein, James Musser
doi: https://doi.org/10.1101/2020.09.22.20199125
This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
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.
Continue . . . )
A press release from Houston Methodist hospital provides additional background. I'll have a brief postscript when you return.
HOUSTON METHODIST COVID-19 STUDY SHOWS RAPID SPREAD AND POTENTIAL FOR MUTANT VIRUSES
Infectious disease pathologists sequence more than 5,000 strains of SARS-CoV-2 gene
HOUSTON - September 23, 2020
Media Contact:
Lisa Merkl, 832.667.5916
Molecular analysis of COVID-19’s powerful second wave in Houston – from May 12 to July 7 – shows a mutated virus strain linked to higher transmission and infection rates than the coronavirus strains that caused Houston’s first wave. Gene sequencing results from 5,085 COVID-positive patients tested at Houston Methodist since early March show a virus capable of adapting, surviving and thriving – making it more important than ever for physician scientists to understand its evolution as they work to discover effective vaccines and therapies.
In the second major gene sequencing study conducted by James M. Musser, M.D., Ph.D., chair of the Department of Pathology and Genomic Medicine at Houston Methodist, and his team of infectious disease pathologists, they found that the two waves affected different types of patients. The study, preprinted under the title “Molecular architecture of early dissemination and massive second wave of the SARS-CoV-2 virus in a major metropolitan area,” provides the first molecular characterization of SARS-CoV-2 strains causing two distinct COVID-19 disease waves, a problem now occurring extensively in many European countries.
Houston’s second wave hit significantly younger patients who had fewer underlying conditions and were more likely to be Hispanic/Latino living in lower income neighborhoods. In addition, virtually all COVID-19 strains studied during the second wave displayed a Gly614 amino acid replacement in spike protein – the part of the virus that mediates invasion into human cells, gives the coronavirus its telltale crown-like appearance and is the major focus of vaccine efforts worldwide. While this mutation has been linked with increased transmission and infectivity, as well as a higher virus load in the nasopharynx, which connects the nasal cavity with the throat, the mutation did not increase disease severity, researchers said.
The findings reinforce researchers’ concerns of the virus gaining momentum through naturally occurring mutations capable of producing mutant viruses that can escape vaccines – dubbed ‘escapians’ – or mutants that can resist drugs and other therapies.
“This extensive virus genome data gathered from Houston’s earliest cases to date, coupled with the growing database we are building at Houston Methodist, will help us identify the origins of new infection spikes and waves,” said Musser, who is corresponding author on the study. “This information can be an especially helpful community resource as schools and colleges re-open and public health constraints are further relaxed.”
Given the urgency of finding effective treatments for COVID-19, the preliminary report is posted to the preprint server medRxiv, and a manuscript is under peer-review at a prominent scientific journal. This preprint is not the final version of the article.
At this point in time, it is important to note that researchers have not found any evidence that this `mutated' SARS-CoV-2 strain is any deadlier than the older Asian strain, only that it appears more transmissible.
This mutation may help explain why Europe and North America - where this new strain is dominant - have had a much harder time controlling transmission than have China, Taiwan, Hong Kong and Japan.
Presumably, if this `G' clade gets introduced into Asian countries often enough, it will present similar challenges there.
Viruses survive, and thrive, based on their ability to mutate and adapt. That is how this (presumably) bat-origin virus jumped species, and sparked COVID pandemic, and that is how this virus will ensure its survival going forward.
We should expect this virus will continue to evolve, and that it will continue to surprise us along the way.
