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Increased Virulence In SARS CoV2 Italian Lineage


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The Italian lineage has the D614G mutation in the Spike Protein.  A recent pre-print notes increased virulence.

Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2

The mutation Spike D614G is of urgent concern; after beginning to spread in Europe in early February, when introduced to new regions it repeatedly and rapidly becomes the dominant form. 

https://www.biorxiv.org/content/10.1101/2020.04.29.069054v1.full.pdf+html

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Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2

Korber B1, Fischer WM1, Gnanakaran S1, Yoon H1, Theiler J1, Abfalterer W1, Foley B1, Giorgi EE1, Bhattacharya T1, Parker MD3, Partridge DG4, Evans CM4, de Silva TI4,5, on behalf of the Sheffield COVID-19 Genomics Group#, LaBranche CC2, and Montefiori DC2 1T6:

Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545 USA

2Duke Human Vaccine Institute & Department of Surgery, Durham, North Carolina, 27710 USA

3Sheffield Biomedical Research Centre & Sheffield Bioinformatics Core, University of Sheffield, Sheffield, UK.

4Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.

5Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, UK. #Members of Sheffield COVID-19 Genomics Group: Adrienne Angyal, Rebecca L. Brown, Laura Carrilero, Luke R. Green, Danielle C. Groves, Katie J Johnson, Alexander J Keeley, Benjamin B Lindsey, Paul J Parsons, Mohammad Raza, Sarah Rowland-Jones, Rachel M. Tucker, Dennis Wang, Matthew D. Wyles Corresponding Author and Lead Contact: Bette Korber, [email protected]

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Abstract

We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike (S) protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. To date we have identified fourteen mutations in Spike that are accumulating. Mutations are considered in a broader phylogenetic context, geographically, and over time, to provide an early warning system to reveal mutations that may confer selective advantages in transmission or resistance to interventions. Each one is evaluated for evidence of positive selection, and the implications of the mutation are explored through structural modeling. The mutation Spike D614G is of urgent concern; after beginning to spread in Europe in early February, when introduced to new regions it repeatedly and rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections. These finding have important implications for SARS-CoV-2 transmission, pathogenesis and immune interventions.

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Preliminary research identifies mutation that may put people at risk for a second COVID-19 infection

By 
5Researchers have identified 14 mutations of the so-called Spike protein on the coronavirus, and they say that one mutation may put people at risk for a second infection with another mutated version of the virus, according to a preprint shared by the Los Alamos National Laboratory. A preprint is a type of preliminary report that has not been peer-reviewed and is not considered factual. The D614 mutation, which may be replacing the original Wuhan version of the virus, may also heighten the risk of a second infection and may be associated with higher rates of transmissibility. "Increased infectivity would be consistent with rapid spread," the researchers wrote. In the early weeks of the pandemic, the D614 mutation was the most common form of the virus, with exceptions in Italy and Switzerland; however, throughout March, a form of the virus with the G614 mutation began to dominate. The mutations followed a similar path in the U.S., Canada, and some other countries, starting with the D614 form and then a rapid rise of the G614 mutation, which carries a higher viral load in patients. "The D614 form was the dominant local form early in the epidemic. Wherever G614 entered a population, a rapid rise in its frequency followed, and in many cases G614 became the dominant local form in a matter of only a few weeks," they wrote. The researchers also said it's unclear why the D614 version of the virus is replacing the original virus. "We do not know what is driving this selective sweep," they concluded.

https://www.marketwatch.com/story/preliminary-research-identifies-mutation-that-may-put-people-at-risk-for-a-second-covid-19-infection-2020-05-05

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Scientists say COVID-19 mutation more contagious than original strain is increasing at ‘alarming rate’

By Austin Williams
Published 
Updated 20 mins ago
 

LOS ANGELES - Researchers at Los Alamos National Laboratory say they have identified 14 new mutations of the novel coronavirus that first originated in Wuhan, China in hopes of creating an early warning system to reveal new strains that may render future vaccines ineffective.

One mutation that is of urgent concern to researchers is called “mutation spike D614G” which scientists say first appeared in February in Europe and became dominant strain across the world by mid-March.

The study notes that by the time the new strain was being tracked by the Global Initiative for Sharing All Influenza Data (GISAID), a German public-private organization aimed at sharing data related to influenza and the coronavirus, it was found in 29 percent of the global samples, but almost exclusively in Europe.

The spike refers to COVID-19’s commonly observed exterior spike structure that allows the virus to attach itself to host cells. After analyzing data from over 6,000 novel coronavirus sequences from around the world, researchers believe the virus’ spikes have mutated, adding to the efficiency in which the virus spreads. 

“D614G is increasing in frequency at an alarming rate, indicating a fitness advantage relative to the original Wuhan strain that enables more rapid spread,” researchers write. 

The adaptation of the virus’ spikes presents a challenge for a possible vaccine which may not be effective on these new mutations.

One of the main concerns researchers have is not knowing whether or not COVID-19 cases would decrease seasonally with warmer weather as summer approaches, allowing the virus leeway to continue to develop new strains over time.

According to the Los Angeles Times, one of the study’s lead authors, Bette Korber, wrote about the research on her Facebook page, saying, “The story is worrying, as we see a mutated form of the virus very rapidly emerging, and over the month of March becoming the dominant pandemic form.”

“When viruses with this mutation enter a population, they rapidly begin to take over the local epidemic, thus they are more transmissible,” Korber added.

https://www.fox32chicago.com/news/scientists-say-covid-19-mutation-more-contagious-than-original-strain-is-increasing-at-alarming-rate

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Researchers hypothesize that a highly contagious strain of the coronavirus is spreading, but other experts remain skeptical

People wear face masks and observe social distancing as they wait at an open-air market in Turin, Italy, which reopened Monday after two months of closure because of the coronavirus.
People wear face masks and observe social distancing as they wait at an open-air market in Turin, Italy, which reopened Monday after two months of closure because of the coronavirus. (Marco Alpozzi/AP)
May 5, 2020 at 7:46 p.m. EDT

A research paper from scientists at Los Alamos National Laboratory, not yet peer-reviewed, reports that one strain of the novel coronavirus has emerged in Europe and become dominant around the planet, leading the researchers to believe the virus has mutated to become more contagious.

The bold hypothesis, however, was immediately met with skepticism by many infectious-disease experts, and there is no scientific consensus that any of the innumerable mutations in the virus so far have changed the general contagiousness or lethality of covid-19, the disease caused by the coronavirus.

The Los Alamos scientists, led by computational biologist Bette Korber and working in conjunction with researchers at Duke University and the University of Sheffield in England, examined a global database of strains of SARS-CoV-2, the virus that causes the disease. According to their analysis, one strain featuring a mutation dubbed Spike D614G quickly out-competed other strains after it appeared in Europe.

The mutation affects the structure of a protein, called the spike protein, that is critical to the virus’s ability to infect human cells. The researchers believe this structural change enhances infectivity.

“The mutation Spike D614G is of urgent concern; it began spreading in Europe in early February, and when introduced to new regions it rapidly becomes the dominant form,” the authors write. They describe the mutation “increasing in frequency at an alarming rate, indicating a fitness advantage relative to the original Wuhan strain that enables more rapid spread.”

The paper will now have to survive the intense scrutiny of a research community trying to deliver urgently needed information while remaining scientifically rigorous.

 

Francis Collins, director the National Institutes of Health, said in a brief email that officials there are aware of the paper, and that it “draws rather sweeping conclusions” about the mutant strain.

 
The novel coronavirus is a master of disguise: Here's how it works
 
 
The novel coronavirus uses a number of tools to infect our cells and replicate. What we've learned from SARS and MERS can help fight covid-19. (Video: Brian Monroe/Photo: Brian Monroe/The Washington Post)

The consensus has been that strains of the coronavirus are functionally the same, even if they look genetically different. The fact that the coronavirus is mutating is unsurprising, because all viruses mutate as they replicate. So far, this virus appears relatively stable, according to virologists, but the vast extent of the spread of the coronavirus has given it ample opportunity to evolve.

 

When the Los Alamos research team examined thousands of genome sequences uploaded to the Global Initiative on Sharing of All Influenza Data database, they identified several mutations that distinguished the version of the virus circulating in Europe from the version that originated in Wuhan; the Spike D614G mutation was among them.

But Hanage, like many other outside researchers, was not convinced this mutation actually affects the virus’ ability to infect people. Though the mutated form has become the dominant strain, that could be a consequence of a “founder effect,” Hanage said.

 

When the mutated version arrived in northern Italy, an older and more susceptible population was unable to contain it. “It’s the fox that got into the henhouse,” Hanage said.

Hanage pointed to Washington state, where the virus was recognized relatively early and public health measures have proved effective at reducing cases. Both strains were circulating in the state by mid-March — and now, cases of both strains appear to be falling at the same rate. If the European strain really were more transmissible, he would expect it to crowd out all other versions.

 

One prominent scientist, Stanley Perlman, a virologist at the University of Iowa who played a role in naming the coronavirus, said Tuesday that the Los Alamos study looks credible.

“It certainly looks like it is more readily transmissible. Viruses mutate to become more transmissible, but not generally to become more virulent (unless this enhances transmissibility),” Perlman said in an email.

The research community is far from embracing any of the studies that haven’t gone through the rigorous peer-review process before publication in a journal. Hanage said people should view these pre-print papers skeptically, because the findings have not been reviewed and potentially challenged by other researchers.

“This is science in an extraordinarily difficult and intense time,” Hanage said.

David O’Connor, a virologist at the University of Wisconsin, said the most interesting feature of the Los Alamos research is that the same pattern was seen in multiple locations. But he said “significant caution is warranted” because the data was not collected randomly. The vast majority of SARS-CoV-2 genomes in online databases come from Europe and North America, meaning strains from these regions are overrepresented in research.

The Los Alamos scientists did not find evidence that patients with the mutant strain of the virus were more likely to be hospitalized. An increase in contagiousness does not necessarily correlate with greater lethality. The opposite is actually more common as viruses mutate, and some experts speculate that covid-19 could become a milder disease over the course of many years as the virus circulates through the human population.

Since the early days of the outbreak in China, scientists have known that SARS-CoV-2 is unusually contagious — more so than influenza or a typical cold virus. Scientific estimates of the reproduction number — the R0, which is the number of new infections that each infected person generates on average — have varied among different communities and different points but have generally been between 2 and 4. That is significantly higher than seasonal influenza.

One criticism of the Los Alamos hypothesis is that there could be other explanations for why one strain of a virus becomes dominant. University of Wisconsin virologist Thomas Friedrich, who has spent years studying the evolution and transmission of the Zika virus, said a virus that makes its way into a highly susceptible population — for example, Europe in January — will spread like wildfire, quickly becoming the dominant strain in the region.

That doesn’t necessarily mean it picked up a mutation that boosts its ability to infect people. It could mean the virus just got lucky — and humans got caught off-guard.

When the Zika virus migrated across the Pacific to the Americas and began to cause birth defects, scientists thought it may have picked up some kind of “microcephaly mutation” right when the outbreak in the Americas began, Friedrich said.

Experiments showed the virus strain did carry a mutation, and was able to cause nerve tissue damage when it was injected into mouse brains. But when scientists were able to study other variants, they found many of them also had the ability to harm fetuses. What made the virus strain in the Americas so dangerous wasn’t the mutation, but that people on this side of the Pacific had no immunity.

https://www.washingtonpost.com/health/researchers-hypothesize-that-a-highly-contagious-strain-of-the-coronavirus-is-spreading-but-other-experts-remain-skeptical/2020/05/05/db90d790-8ee7-11ea-9e23-6914ee410a5f_story.html?pwapi_token=eyJ0eXAiOiJKV1QiLCJhbGciOiJIUzI1NiJ9.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.zcupIEgZT-6XK-F1hIjod0F5aCJ2DTdFbd4qOB_jAOs&utm_campaign=wp_to_your_health&utm_medium=email&utm_source=newsletter&wpisrc=nl_tyh&wpmk=1

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