New Variants

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trader32176
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Re: New Variants

Post by trader32176 »

Study reveals possible SARS-CoV-2 escape mutant that may re-infect immune individuals

1/17/21


https://www.news-medical.net/news/20210 ... duals.aspx


A recent study by US researchers shows how the 501Y.V2 variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), characterized by several mutations, is able to escape neutralization by present first-wave anti-SARS-CoV-2 antibodies and potentially re-infect COVID-19 convalescent individuals. The paper is currently available on the bioRxiv* preprint server.

As many variants of SARS-CoV-2 emerge and subsequently displace first-wave viruses, it is pivotal not only to appraise their relative transmissibility and virulence in causing coronavirus disease (COVID-19), but also their propensity to escape antibody neutralization.

Of utmost interest are variants harboring mutations that can affect the interaction of the viral spike receptor-binding domain (S RBD) with the viral receptor on host cells, angiotensin-converting enzyme 2 (ACE2), which provides an entry point for the coronavirus.

Variants with a greater binding affinity for ACE2 are likely to spread more. Furthermore, transmissibility is linked to mortality, as an inevitable increase in infection rates caused by the novel variants will result in higher disease and death toll.

However, these dire repercussions of more rapid and widespread infections can also be compounded by a loss of efficacy of currently available antibody-based treatments and vaccines and a decrease of protective immunity in individuals previously infected with a 'first wave' virus.

In order to improve our understanding of the risks posed by an individual or combined mutations in these 'second wave' variants, a research group from ImmunityBio company in California conducted a computational analysis of interactions of the S RBD with human ACE2.

In silico simulation methods

In this study, the researchers have utilized millisecond-scale MD simulation methods to investigate mutations (E484K, K417N, and N501Y) at the S RBD-ACE2 interface in the rapidly spreading South African variant 501Y.V2 – and their effects on RBD binding affinity and spike glycoprotein conformation.

The wild-type ACE2/RBD complex was built from the cryo-electron microscopy structure. Moreover, ten copies of each RBD mutant were minimized, equilibrated and simulated, and the minimization processed occurred in two phases.

Finally, principal component analysis (PCA) was pursued by using the full set of simulations of the triple mutant, E484K and N501Y systems. Simulation structures were extrapolated onto the eigenvectors for every mutation system.

The great escape from neutralization

The study revealed greater affinity of K484 S RBD for ACE2 in comparison to E484, as well as the greater probability of modified conformation when compared to the original structure. This may actually represent mechanisms by which the new 501Y.V2 viral variant was able to replace original SARS-CoV-2 strains.

More specifically, both E484K and N501Y mutations were shown an increase affinity of S RBD for human ACE2 receptor, while E484K was able to switch the charge on the flexible loop region of RBD, resulting in the formation of novel favorable contacts.

The aforementioned improved affinity is a likely culprit for more rapid spread of this variant due to greater transmissibility, which is a prime reason why it is important to track these mutations and act in a timely manner.

Furthermore, the induction of conformational changes is responsible for the escape of the 501Y.V2 variant (distinguished from the B.1.1.7 UK variant by the presence of E484K mutation) from neutralization by existing anti-SARS-CoV-2 antibodies and re-infect COVID-19 convalescent individuals.

Implications for further vaccine design

"We believe the MD simulation approach used here similarly represents a tool to be used in the arsenal against the continuing pandemic, as it provides insight into the likelihood mutations alone or in combination may have effects that lessen the efficacy of existing therapies or vaccines", say the authors of this study.

"We suggest vaccines whose efficacies are largely dependent upon humoral responses to the S antigen only are inherently limited by the emergence of novel strains and dependent upon frequent re-design," they add.

On the other hand, a vaccine that evokes a vigorous T-cell response is much less subject to changes due to accruing mutations and, thus, provides a better and more efficient approach to protection against this disease.

Finally, the ideal vaccine would also incorporate a second, conserved antigen (such as the SARS-CoV-2 nucleocapsid protein), which would likely elicit an effective humoral and cell-mediated immune response - even when confronted with a rapidly changing virus.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

Nelson, G. et al. (2020). Molecular dynamic simulation reveals E484K mutation enhances spike RBD-ACE2 affinity and the combination of E484K, K417N and N501Y mutations (501Y.V2 variant) induces conformational change greater than N501Y mutant alone, potentially resulting in an escape mutant. bioRxiv. https://doi.org/10.1101/2021.01.13.426558, https://www.biorxiv.org/content/10.1101 ... 3.426558v1
trader32176
Posts: 1779
Joined: Fri Jun 26, 2020 5:22 am

Re: New Variants

Post by trader32176 »

New SARS-CoV-2 variant emerges in the U.S.

1/18/21


https://www.news-medical.net/news/20210 ... he-US.aspx


Even as the rollout of vaccines all over the world brings a glimmer of hope that the current coronavirus disease 2019 (COVID-19) pandemic may end in the near future, new variants continue to emerge, some with the potential to escape vaccine-induced or therapeutic antibodies. Now, a new preprint research paper published on the bioRxiv* server describes a new American variant that may have become the dominant strain in the USA.

New regional variants arise over the course of a pandemic in part due to lockdowns, which restrict the population movement over a period of time. Another factor is the occurrence of multiple mutations at the same time. Epidemiologic surveillance of an infectious outbreak may involve genomic sequencing, which can allow new variants to be identified early in the course of the disease.

This method allowed the detection of a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, which arose early last year, but has now become very common in the USA. Called 20C-US by the researchers in the current study, it is part of the B.1.2 lineage.

Finding the new variant

The first isolation of this variant was towards the end of May 2020. Early on, it showed the presence of five mutations, which led to five changes in amino acid sequence. The affected genes are involved in virion maturation and release, viral protein processing, conservation of the RNA genome, and translation of viral proteins. It later acquired a pair of new mutations. One of these is the Q677H mutation in the spike protein adjacent to the spike cleavage site.

The researchers sequenced viral samples from Illinois and traced the emergence of a dominant strain within the 20C clade. The five defining mutations were then identified, namely, N1653D and R2613C in ORF (open reading frame) 1b, G172V in ORF3a, and P67S and P199L in the nucleocapsid (N) gene. The N gene mutation simultaneously introduced a stop codon mutation into ORF14.

Random samples were then sequenced from the national pool, showing that this variant made up a large proportion of genomes for most U.S. states, increasing over time, especially since July 2020. In the two months of November and December 2020, this strain makes up half of all sequenced isolates from the U.S.. However, it makes up only a minute proportion of sequences from other countries, including those as near the U.S. as Mexico and as far away as Australia and Poland.

Emergence of 20C-US

The researchers now searched for all genomes from the Global Initiative for Sharing All Influenza Data (GISAID) database, which had the five defining mutations of the 20C-US variant. Two additional mutations were needed for this lineage, namely, ORF8:S24L and ORF1a:L3352F. The latter pair were first seen in March and April 2020 from Minnesota and Louisiana. This then gave way to five new sequences containing the first defining 20C-US mutation, namely, ORF3a:G172V, early in April.

Subsequently, several sequences from late May-early June showed the remaining four defining mutations, which seem to have either occurred simultaneously or in very rapid succession. These genomes were mostly from Texas. Following this, the new isolate appears to grow in prevalence across the country.

Strangely, however, the earliest isolate containing all five mutations was from Spain, having been obtained from a 90-year-old woman in Spain. This sequence has another mutation at all. It is very rare for mutations to reverse over time and improbable that all four mutations would arise in two different places in the same virus. The only other place where the same combination has been found was Australia, on June 24, 2020. Thus, either the Spanish or the Texan genomes could be the earliest acquisition of the four novel mutations.

Recently acquired mutations

The researchers then searched GISAID for more recent mutations in this variant, using as a stem the three defining mutations N1653D in ORF1b, G172V in ORF3a, and P67S in the N gene, along with either N:P199L or any mutations at position 2613 in ORF1b. They found over 4,600 sequences, which were phylogenetically arranged to yield a clear branch beginning at two new mutations appearing together. One was 1C4805T, a synonymous nucleotide-level mutation, and a non-synonymous ORF1a: M2606I, which first occurred together in late June 2020, in Wisconsin and Illinois. It is then observed extensively over the eastern and Midwestern USA. About half the U.S. sequences now contain the ORF1a:M2606I mutation.

In mid-August, the ORF1a:M2606I branch produced another branch containing the mutation Q677H in the spike gene, which rapidly expanded to 10% of the parent branch's genomes. While this mutation has often been observed in multiple viral lineages, it has never been part of an expanding or established branch until it was seen in this branch, perhaps because of other compensating mutations or amino acid residues in the rest of the protein. Thus, it is found in only 0.27% of global genomes, but it makes up almost 4.8% of genomes within the 20C-US lineage, indicating an 18-fold increase in prevalence. It is mainly found in the upper Midwest, namely, Minnesota, Wisconsin, and Michigan.

Further, close temporal tracking of the ORF1a:M2606I vs. the whole 20C-US genome number shows that the former shows a slowing in growth, perhaps because it has somewhat lower fitness than the latter. However, the S:Q677H mutation may have compensatory effects. While this cannot be authoritatively established at this time due to the paucity of data, further sequencing will help uncover how these two mutations interact and their effect on viral survival.

Impact of mutations

The ORF1b:N1653D and ORF1b:R2613C both affect proteins that are essential for RNA genome and transcript integrity, nsp14 and nsp16, respectively. These could alter the mutation rates and efficiency of translation as well.

The parental ORF1a:L3352F mutation in 20C-US is in nsp5 could perhaps improve protein stability, while the relatively new ORF1a:M2606I mutation affects nsp3. This is within the C-terminal domain and is involved in anchoring the viral replication transcription complex (RTC) to the endoplasmic reticulum membrane so that nsp3 can interact with other cytosolic proteins.

ORF3a: G172V is within a protein that is involved in multiple aspects of the viral life cycle at the membrane surface, as well as modulating the host cell's innate immune response and apoptosis. This mutation is within a domain that transports materials to the cell membrane and modulates interactions with viral or cellular factors.

The Q677H mutation in the spike protein, next in position to the furin cleavage site, is thought to increase the infectivity of SARS-CoV-2. This enzyme promotes the cleavage of the spike protein, which is essential for efficient viral entry into cells. The mutated residue is in a similar site to D614G, the globally dominant genome sequence.

What are the implications?

The researchers plotted the prevalence of 20C-US genomes in the USA up to December, arriving at the prediction that this would be the most common variant in the country by this point. However, it continues to make up a much larger proportion of the total infections in central and Midwest USA compared to the Northeast and Western seaboard states.

Interestingly, the increase in this strain's dominance is synchronous with the start of the second wave of COVID-19. This cannot be explained by a large-scale increase or change in population mobility patterns, whether for shopping, recreation, pharmacy, or transit station use. In fact, workplace visits increased only a little. Without these explanations to account for this variant's expansion, it seems that this trend will continue.

Further study is required to follow up on the fate of the Q677H mutation, which may be involved in viral entry. Tracing this mutation with the M2606I would help understand how this virus is evolving and how its phylogeny affects real-time outcomes of the pandemic.

On the available (admittedly scanty) evidence, it is possible that the 20C-US may be more transmissible but less virulent, a fitness advantage that could allow extensive but quiet spread.

The 20C-US variant is one of several that have rapidly acquired multiple mutations, such as the U.K. 501Y.V1 and South African 501Y.V2 strains. The researchers say this event may have caused a sudden increase in fitness, allowing it to outcompete circulating strains, just as with the D614G mutation earlier.

"The ongoing evolution of 20C-US, as well as other dominant region-specific variants emerging around the world, should continue to be monitored with genomic, epidemiologic, and experimental studies to understand viral evolution and predict future outcomes of the pandemic," said the researchers.


They caution, "Unless successful vaccination efforts can be greatly accelerated, we predict the emergence of dominant novel variants in parts of the world that are relatively isolated from other global regions, possibly including Brazil, New Zealand, the African west coast, and Japan."

Surveillance will help update vaccine development and predict major potentially dangerous shifts in viral fitness, hopefully in time to take successful countermeasures.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

Pater, A. A. et al. (2021). Emergence and Evolution of a Prevalent New SARS-CoV-2 Variant in the United States. bioRxiv doi: https://doi.org/10.1101/2021.01.11.426287. https://www.biorxiv.org/content/10.1101 ... 1.426287v1
curncman
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More contagious COVID-19 variants bring new uncertainties to California

Post by curncman »

More contagious COVID-19 variants bring new uncertainties to California
Coronavirus patients are housed in a makeshift ER unit at Arrowhead Regional Medical Center last month.(Irfan Khan / Los Angeles Times)

By RONG-GONG LIN II, LUKE MONEY
JAN. 20, 20215 AM


SAN FRANCISCO — Confirmed coronavirus cases in California surged past the 3 million mark Tuesday at a moment of growing optimism that the outbreak might finally be leveling off, even as officials noted some alarming factors that could complicate projections.
Cases continued to flatten across California — including in hard-hit Los Angeles County — after two months of record-setting surges. COVID-19 hospitalizations have also flattened and started to decline slightly, giving some desperately needed breathing room to medical facilities still overwhelmed by COVID-19 patients.

After a slow start, California is beginning to ramp up distribution of the coronavirus vaccine, which officials see as the best hope of bending the curve and bringing back the battered economy. Limited supply of the vaccine will likely mean many will still have to wait weeks if not months to get their shots, but there is growing hope the incoming Biden administration can accelerate vaccination efforts.

But despite these positive developments, officials are expressing growing concerns about new and potentially more contagious variants of the coronavirus that have been detected in California and beyond. One of the new variants is believed to be 50% more transmissible than the conventional variety of the coronavirus, which if it became widespread, would lead to more infections, hospitalizations and deaths.


It’s possible that one of the new mutant variants may become the dominant version of the coronavirus spreading in the state in the coming months — at the same time many Californians hope to see the economy reopen significantly if conditions continue to improve. Much of the state has been on a stay-at-home order for six weeks, leaving many owners of small businesses, including restaurants, hair salons and gyms on the brink of financial ruin.


The Sacramento region had its stay-at-home order lifted last week, giving counties there the option of allowing hair salons to reopen in a limited capacity and outdoor restaurant dining to resume. Continued improvement in the pandemic elsewhere will probably put new pressure on government officials to allow additional businesses to reopen, although projected available ICU capacity remains critically limited in Southern California, the San Joaquin Valley and the Bay Area.

State officials say stay-at-home orders in a region will be lifted once available ICU capacity is forecast to be 15% or greater over the next four weeks.


Health experts said they’d like to see significant decreases in both cases and hospitalizations before becoming comfortable that California is heading out of the surge. Decreases in daily coronavirus cases in recent days could have been affected by the delays in reporting over the three-day Martin Luther King Jr. Day weekend.

“Cautious optimism may be in order,” said Dr. Robert Kim-Farley, medical epidemiologist and infectious diseases expert at the UCLA Fielding School of Public Health. “Yet even if we are flattening at this stage, this is way too high of a level to be satisfied with merely flattening the curve. We have to make substantial decreases in the number of cases, hospitalizations and deaths.”

The 3-million case mark, confirmed through an independent Times survey of county and city health departments, demonstrates how widely the coronavirus has spread throughout the nation’s most-populous state.

Clearing that threshold means roughly 1 out of every 13 Californians have tested positive at some point during the pandemic. But officials have long believed that testing captures only a certain percentage of those who are infected, because many with the virus have mild symptoms or none at all.

Even so, the growth in the documented case count has been meteoric. It took roughly 10 months for the state to reach 1 million confirmed cases, which happened in mid-November. California went on to hit 2 million cumulative infections shortly before Christmas.

Now, only about four weeks later, the state has added another million cases to its total.

California has recorded more than 34,400 cumulative coronavirus deaths, and daily death tolls are still high. A Times tally found 696 deaths reported Tuesday, the second highest single-day tally of the entire pandemic. An average of roughly 500 Californians have died from COVID-19 daily recently. So many people are dying in L.A. County a day that air quality officials have lifted limits on cremations.


Dr. Tomás Aragón, the state public health officer and director of the California Department of Public Health, called the case number “a serious reminder that COVID-19 is prevalent throughout” the state. He added: “We all need to do our part by staying home; wearing a mask; avoiding gathering, especially indoors; frequent hand washing and getting vaccinated when eligible and available.

“While we are seeing some encouraging signs as hospitalizations and case rates are decreasing, California remains relentless in its commitment in the battle against COVID-19,” Aragón said. “We cannot become complacent because a vaccine is now available.”

California has also seen a flattening, and even a slight decline, in the number of people requiring hospitalization for COVID-19. State hospitalizations reached a peak about two weeks ago, on Jan. 6, at 21,936; by Monday, there were 20,062 coronavirus-positive Californians in the state’s hospitals.


COVID-19 hospitalizations have dropped in 10 out of the last 12 days.

The number of people ill enough to require intensive care has also dipped from a high of 4,868 on Jan. 10 to to 4,693 as of Monday. The number of people with COVID-19 in California’s ICUs have dropped in seven of the last eight days.

Though slight, any declines come as welcome news to California’s beleaguered hospitals and healthcare workers, who have had to contend with sharp and sustained increases in the number of COVID-19 patients since early November.

“These are rays of hope shining through,” said Dr. Mark Ghaly, California’s health and human services secretary.

Many ICUs throughout the state remain stressed, however — particularly in Southern California and the San Joaquin Valley, which have both reported 0% availability in their intensive care units for weeks. That has forced critically ill patients to wait for ICU beds while in the emergency room, which then has kept sick patients waiting for hours in ambulances just outside the hospital’s doors.

Declines in the daily case rate, as well as in the percentage of people being tested who are found to be infected, hopefully foreshadow a corresponding dip in the number of COVID-19 patients needing to go to the hospital, Ghaly said Tuesday. Another promising data point, he added, is that the modeled statewide rate of transmission, or R-effective, has now dipped below 1 — meaning those who test positive are, on average, going on to infect fewer than one other person.

When the R-effective is below 1, case counts will gradually decrease.

“The good news is that ... the spread of COVID is not growing in the state, but decreasing — just a little more slowly than we would like,” Ghaly said.

The variant that has attracted the most attention recently has been the one known as B.1.1.7 — a mutated variant first identified in Britain in September and has since been identified in L.A., San Diego and San Bernardino counties. It is not one of the most dominant variants in California, but that could change soon.

But the new mutant variants pose new threats.

Research suggests B.1.1.7 is about 50% more transmissible than the standard variety of the coronavirus, and the U.S. Centers for Disease Control and Prevention has warned that variant could be predominant by March. A more transmissible virus means that people are even more likely to get infected with the virus if they’re exposed to it and are not wearing masks and practicing physical distancing.

Scientists do think that the existing coronavirus vaccines are effective against the B.1.1.7 variant. But the fact that it’s believed to be more contagious means the variant, by virtue of it potentially infecting more people, would then result in an increase in hospitalizations and deaths.
trader32176
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Joined: Fri Jun 26, 2020 5:22 am

Re: New Variants

Post by trader32176 »

Scientists call for strict control measures to reduce the spread of new COVID-19 variants

1/25/21


https://www.news-medical.net/news/20210 ... iants.aspx


A group of scientists is calling on governments to consider the continued use of strict control measures as the only way to reduce the evolution and spread of new COVID-19 variants.

The experts in evolution, virology, infectious disease and genomics - at the University of East Anglia (UEA), Earlham Institute and University of Minnesota - warn that while governments are negotiating a "precarious balance" between saving the economy and preventing COVID-19 fatalities, stronger action now is the best way to mitigate against more serious outcomes from such virulent strains later.

While COVID-19 vaccine deployment is now underway, a threat to vaccine effectiveness comes from other emerging strains, both existing - such as the UK, South Africa and Brazil variants - and those yet to come.

In an editorial for the journal Virulence, Professors Cock van Oosterhout, Neil Hall, Hinh Ly, and its editor-in-chief Prof Kevin Tyler say:


" Continuing public health efforts to encourage vaccination as well as continued use of proper personal protective equipment (PPE), such as proper masking and maintaining safe social interactions, is of utmost importance.

Humanity is faced with a new reality. The faster we adapt, the better our long-term prospects. We must stop the evolution and spread of more virulent virus strains now. We, therefore, support public health policies with strict control measures in order to protect our public health system, our individual wellbeing, and our future."

The researchers look back at what has happened and how best to respond now, highlighting that the roll-out of economic stimulus packages and related activities in many countries appears to have fueled the rate of person-to-person transmission.

As a result, they say at the start of winter the population number of the virus continued from a much higher base than would otherwise have been the case, adding: "By not absolutely minimizing the R number when we had the chance, we extended the pathogen transmission chains, providing more opportunity for it to mutate and evolve into more virulent variants."

Additionally, they highlight that an increased virulence - or higher R value - can also result from the virus evolving the ability to infect people for longer. The authors warn that continued virus evolution in animal hosts, such as cats and mink, followed by transmission into susceptible human hosts, poses a significant long-term risk to public health, suggesting that the vaccination of certain domesticated animals might be important to halt further virus evolution and "spillback" events.

"Vaccination against a viral pathogen with such high prevalence globally is without precedent and we, therefore, have found ourselves in unchartered waters. However, what we can be certain about is that, as long as the vaccine stays effective, a higher uptake of the vaccines will: reduce the number of COVID-19-related deaths, stem the spread of the transmissible strain of the virus, and reduce risk of the evolution of other, even more, virulent strains in the future.

"Furthermore, it is not unthinkable that vaccination of some domesticated animal species might also be necessary to curb the spread of the infection."

Source:

University of East Anglia
trader32176
Posts: 1779
Joined: Fri Jun 26, 2020 5:22 am

Re: New Variants

Post by trader32176 »

B.1.1.7 variant and healthcare workers’ travel worry

1/25/21


https://www.news-medical.net/news/20210 ... worry.aspx


The emergence of the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to a global pandemic in 2020. The RNA virus mutated over time, and multiple variants of SARS-CoV-2 are now circulating globally. So far, several thousands of people have been reportedly infected with the B.1.1.7 variant globally. One of the most significant mutations in this variant is the N501Y gene coding for the spike S protein, which helps the virus attach to angiotensin-converting enzyme 2 (ACE2) receptors on the host cell surface.

The COVID-19 Genomics UK consortium, which performs random sequencing of positive COVID-19 samples in the UK, was the first to identify the B.1.1.7 lineage. This new variant is said to have first emerged in September 2020 in the UK. Over 3,000 cases of the new variant have been reported in the UK as of December 26, 2020. This new mutant has been reported to have a higher transmission rate than the original virus and has become one of the main circulating variants in many parts of the UK.

The new variant has since spread to many other countries globally, including Canada and the United States. According to the European Centre for Disease Prevention and Control (ECDC) recommendations, residents in the affected areas should restrict movement and all kinds of travel, including international travel. The UK and several countries have imposed travel restrictions to limit the spread of the new variant.

Assessing travel-related anxiety in healthcare workers associated with new SARS-CoV-2 variants

Recently a team of researchers from Saudi Arabia, the United Arab Emirates, and the United States assessed travel-related anxiety in healthcare workers (HCWs) considering the emergence of new variants caused by SARS-CoV-2 mutations. The study is published on the preprint server, medRxiv*.

As part of the study, an online, cross-sectional questionnaire was sent to HCWs between December 21, 2020, and January 7, 2021. The knowledge and awareness of HCWs about the SARS-CoV-2 B.1.1.7 lineage, their associated travel-related anxiety, and the generalized anxiety disorder (GAD-7) score were the outcome variables assessed.

Most HCWs were aware of the emergence of the new variant and that it is more infectious


Out of the 1,058 HCWs who completed the online survey, 66.5% were female, and 59.0% were nurses. 9.0% of these HCWs indicated that they had previously contracted COVID-19 themselves. Most of the HCWs (97.3%) were aware of the emergence of the new B.1.1.7 variant and 73.8% of the HCWs were aware that the B.1.1.7 lineage is more infectious. However, 78.0% of HCWs thought the new variant causes more severe disease, and only 50.0% of the HCWs knew that currently available COVID-19 vaccines effectively prevent it.

Around 66.7% of HCWs had not registered to receive the current COVID-19 vaccine. The most common information source about the new variant for HCWs was social media platforms (67%), and this subgroup was considerably more worried about traveling.

Nurses were more worried about travel than physicians (P=0.001) and those who had not traveled in the past three months and those who had not registered for or received the COVID-19 vaccine were also more worried (P = 0.037 and P < 0.001, respectively).

Utilization of official social media platforms and targeted vaccine campaigns may help reduce travel-related anxiety among HCWs

To summarize, based on the findings, most HCWs were aware of the emergence of the new SARS-CoV-2 variant B.1.1.7 and had substantial travel-related anxiety. Increased worry was found among HCWs whose primary source of information was social media, those who have not received the COVID-19 vaccine, and those with greater GAD-7 scores.

The authors believe that the utilization of official social media platforms may improve the dissemination of accurate information among HCWs about the evolving mutations and new variants of SARS-CoV-2. According to the authors, more targeted vaccine campaigns will assure HCWs about the efficacy of the current COVID-19 vaccines toward new variants of SARS-CoV-2.

“HCWs should abstain from international travel for leisure to decrease the risk of introducing new variants to their health care facilities when they return.”

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

SARS-CoV-2 B.1.1.7 lineage-related perceptions and travel worry among healthcare workers Mohamad-Hani Temsah, Mazin Barry, Fadi Aljamaan, Abdullah N Alhuzaimi, Ayman Al-Eyadhy, Basema Saddik, Fahad Alsohime, Ali Alhaboob, Khalid Alhasan, Ali Alaraj, Rabih Halwani, Amr Jamal, Nurah Alamro, Reem Temsah, Shuliweeh Alenezi, Fahad Alzamil, Ali Alsomaily, Jaffar A. Al-Tawfiq, medRxiv, 2021.01.19.21250111; doi: https://doi.org/10.1101/2021.01.19.21250111, https://www.medrxiv.org/content/10.1101 ... 21250111v1
trader32176
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Re: New Variants

Post by trader32176 »

New COVID-19 variant identified in Brazilian Amazon spreads faster

2/1/21


https://www.news-medical.net/news/20210 ... aster.aspx


A new variant of the virus that causes COVID-19, identified in Brazil, is likely more transmissible than its parent strain because of mutations in the spike protein, according to researchers.

The P1 variant of the SARS-CoV-2 virus, found in the city of Manaus, has a number of mutations compared to the B.1.1.28 lineage, especially in the spike protein region, says Esther Sabino, one of the researchers involved in its genetic characterization.

This would lead to an increase in its transmissibility, although it is not known currently whether it would also lead to an increased risk of severe infections, researchers say.

The health system in Manaus, capital of the northern Brazilian state of Amazonas, has collapsed for a second time amid a surge in COVID-19 cases, medical charity Doctors Without Borders (MSF) reported this month, with insufficient oxygen supplies leaving some hospitals unable to ventilate patients.

" This spike protein is found on the surface of the virus and binds to receptors in human cells. Mutations in this region in general can alter the behavior of viruses, increasing their transmissibility."

- Esther Sabino, Researcher

The researcher added that the 'spike' is the most important protein in the development of vaccines because the virus uses it as a gateway to infect human cells.

Sabino leads the Brazilian research team of the Brazil-UK Centre for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE), that between 15 and 23 December tested 31 COVID-19 positive samples from Manaus.

Thirteen of those samples exhibited the P1 variant, which had not been detected in previous surveillance samples in the city between March and November 2020, the study found. The variant has also been detected in Japan in people arriving from Brazil.

The study, which is still in the preprint phase and has not yet been peer-reviewed, has been published on Virological.org, a website showing the most recent findings about the evolution and epidemiology of the virus.

The CADDE team has shared samples of the virus with other laboratories for in vitro research and is developing tools for faster detection of the variant in COVID-19 tests.

Evolving strains

According to the authors, the variant found in Manaus is different from others identified around the world, such as B.1.1.7 in the United Kingdom and B.1.351 in South Africa, and even elsewhere in Brazil, like the P2 in Rio de Janeiro and another in Rio Grande do Sul.

“These variants have different origins, but share similar mutations,” said Fernando Spilki, a virology professor at Feevale University and coordinator of Brazil’s science ministry Corona-omics Network, who did not take part in the study.

Although all of them share mutations, researchers do not know whether the variants evolved independently from each other or if they are related.

What is known is that the variant found in Manaus has alterations of its own and is adapting to the local population to increase its adaptive advantage and survive longer.

Co-author and genetics expert Renato Aguiar, a professor at the Federal University of Minas Gerais, explains that viruses are only able to thrive because of the speed with which they mutate and evolve by copying parts of the genetic code of their hosts. “This is how they manage to jump from a bat to a pangolin, then to a macaque or a human, for example,” he said.

While the new variant may increase the number of re-infections, there’s no evidence that it causes new infections to be more severe, says Aguiar.

“The severity of and mortality [rate] from COVID-19 has no direct connection with mutations – it has much more to do with characteristics of hosts,” in this case, humans, he noted.

The behavior of the P1 strain will depend on how humans behave, he warned: “More gatherings will stimulate the virus to spread faster. It’s a cascade: the more gatherings, the more the virus replicates. The more it replicates, the more it mutates. The more it mutates, the more abundant it becomes.”

This in turn leads to more severe cases and deaths, as is the case in Manaus, the only city with ICU beds in the Amazonas state, with more than 4.2 million inhabitants.

More than 7,000 people have died of COVID-19 in Amazonas since the pandemic began in early 2020, with more than 47,500 confirmed cases this January alone.

Sabino says the group does not yet have data to predict how the immune system of vaccinated people will behave in contact with the P1 strain.

However, Spilki emphasized that the most important and effective measure to avoid new coronavirus strains from evolving resistance to vaccines is effective vaccination. “Ideally, we would need vaccination as fast and as wide as possible to stop the virus from mutating and to avoid trouble with new variants in the future,” he added.

Source:


SciDev.Net
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Re: New Variants

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What's Going On With All These Coronavirus Variants? An Illustrated Guide

2/2/21



https://www.npr.org/sections/goatsandso ... ated-guide
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Re: New Variants

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Researchers report a new SARS-CoV-2 variant of concern in Uganda

2/15/21


https://www.news-medical.net/news/20210 ... ganda.aspx


The etiological agent of the coronavirus disease 2019 (COVID-19) – severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – was first identified in Wuhan, China, in December 2019. Since then, the virus has infected more than 107 million people worldwide and caused over 2.4 million deaths. Due to its high transmissibility, it has been difficult to contain the virus in an epidemic region.

Towards the latter part of 2020, a new variant of SARS-CoV-2 (lineage B.1.1.7) emerged in England and another one, (B.1.351), also known as 501Y.V2, in South Africa. Both of which are observed to have heightened transmissibility, with some early studies even suggesting an increase in virulence in these mutations.

In a concerning new development, an interdisciplinary research team from Uganda and the UK report the emergence and spread of a new SARS-CoV-2 variant of the A lineage with multiple protein changes throughout the viral genome. The researchers recently released their findings in a preprint on the medRxiv* server.


The researchers report the emerging A sub-lineages, A.23 and A.23.1 of the SARS-COV-2.

The research team reports the A.23.1 sub-lineage to be the major virus lineage now observed in the Kampala region in Uganda. This sub-lineage is reported to encode multiple spike proteins, nsp6 (nonstructural protein), ORF8 and ORF9 (open reading frames 8 and 9) protein changes. Some of these replacements are predicted to be functionally similar to those observed in lineage B variants of concern (VOCs).

The Kampala region has become an epicenter of viral transmission in the country; 60-80% of the country’s new cases daily have been identified there, from June 2020 to January 2021. The researchers generated the SARS-CoV-2 genomic sequence data to monitor virus movement and changes thereof.

The researchers also report that across the entire region’s epidemic, 39% of the strains can be classified as the major B lineage, whereas 61% are within the A lineage. Interestingly, when the transportation was characterized by land travel (primarily truck drivers’ movements) and no flights, the lineage B.1 strains predominated. Over the course of their study, however, the researchers unexpectedly found that, almost exclusively, the A lineage viruses are found in the Kampala region up to late January 2021.

Because the researchers identify the lineage A strain as originating from a truck driver (strain UG053) as basal to the newly emergent A.23 variant, they recommend continuous monitoring of all truck drivers transiting into and out of Uganda. This will help to better understand the inland cross-country entry and exit, and circulation of the strains in this region, where (large scale) genomic surveillance is still not exhaustive.


Notably, the genome sequences from 6 lethal Ugandan cases belonged to two lineages A.25 and B.1.393. While the SARS-CoV-2 lineage A is less prevalent than lineage B in Europe, the UK and the USA, the presence of lineage A viruses from lethal community cases throughout Uganda indicates that this lineage is circulating in the country and is capable of severe infection.

To monitor the epidemic in more detail, the researchers generated the full genome SARS-CoV-2 sequences from SARS-CoV-2 positive samples in Uganda. From this analysis, the researchers present a maximum-likelihood phylogenetic tree comparing all available complete and high-coverage Uganda sequences.

Several variant lineages were observed at low frequencies and only briefly and may have undergone apparent extinction, similar to patterns observed in the UK and Scotland, the researchers write.

The researchers also found that the SARS-CoV-2 outbreaks in and around the prisons to be the lineage A.23, with three amino acid (aa) changes encoded in the exposed S1 domain of the spike protein (F157L, V367F, and Q613H).

Whereas the A.23.1 virus’s sequence encoded 4 or 5 amino acid changes in the spike protein plus additional protein changes in nsp3, nsp6, ORF8, and the ORF9.

A plot of nucleotide changes over time for Ugandan lineage A viruses showed a consistent evolutionary rate of roughly 2 nucleotide change per month that has been observed for SARS-CoV-2 throughout the pandemic.”

All organisms mutate. Viruses are found to have the highest per base pair per generation mutation rates. This study reports the emergence and spread of a new SARS-CoV-2 variant of the A lineage (A.23.1) with multiple protein changes throughout the viral genome.

The spread of a new variant with heightened transmissibility and/or virulence can place more pressure on the healthcare system – and ultimately result in a higher mortality rate. There is also a risk that new variants may undermine current vaccines and therapies, aimed at preventing or mitigating COVID-19, based on earlier strains.

From a screening of the SARS-CoV-2 genomic data from GISAID, the researchers observed that the A.23 and A.23.1 sub-lineages are now circulating in 12 countries outside of Uganda (from Africa, Asia, Europe, North America and Oceania); this indicates the global movement of the newly emerging variants.

This study also highlights the importance of rapid genomic surveillance of infectious pathogens and also the need to closely monitor the virus’s movements. Significant changes observed in the spike protein – that may impact the transmission, infection, and immune selection – are crucial to understanding the evolution of the virus and warrant additional studies on the functional consequences.

Although the clinical impact of the A.23.1 variant is not yet clear it is essential to continue careful monitoring of this variant, as well as a rapid assessment of the consequences of the spike protein changes for vaccine efficacy.”

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

Daniel Lule Bugembe et al. (2021) A SARS-CoV-2 lineage A variant (A.23.1) with altered spike has emerged and is dominating the current Uganda epidemic. medRxiv 2021.02.08.21251393; doi: https://doi.org/10.1101/2021.02.08.21251393, https://www.medrxiv.org/content/10.1101 ... 21251393v1
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Re: New Variants

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Detection of emerging SARS-CoV-2 variant in New York

2/16/21


https://www.news-medical.net/news/20210 ... -York.aspx


Researchers at the California Institute of Technology in Pasadena have developed a software tool called "Variant Database" that has detected an emerging lineage of severe acute respiratory coronavirus 2 (SARS-CoV-2) isolates in New York.

The novel SARS-CoV-2 virus is the agent responsible for the coronavirus disease 2019 (COVID-19) pandemic that continues to sweep the globe and has now caused more than 2.41 million deaths.

The Variant Database (VBD) tool can be used to quickly assess the rapidly changing mutational landscape of the viral spike protein that SARS-CoV-2 uses to bind to and infect host cells.

The team says the pattern of mutations in the emerging lineage (now designated B.1.526) suggests that it arose partly in response to selective pressure from antibodies.

"This lineage appeared in late November 2020, and isolates from this lineage account for around 5% of coronavirus genomes sequenced and deposited from New York during late January 2021," writes the team.

Anthony West and colleagues say that based on the collection dates of isolates from this lineage, it appears that they are now increasing in frequency.

A pre-print version of the research paper is available on the bioRxiv* server, while the article undergoes peer review.

The variants that have emerged since early stages of the pandemic

Following the early months of the COVID-19 pandemic, the vast majority of SARS-CoV-2 isolates were found to contain the spike mutation D614G.

Several other variants emerged during the fall of 2020, containing numerous mutations that seemed to be focused on the spike protein.

"Multiple lines of evidence support escape from antibody selective pressure as a driving force for the development of these variants," says West and colleagues.

As concerns grow about the effects these mutations could have on the efficacy of antibody therapies and vaccines developed to protect against COVID-19, wide-scale genomic surveillance has been implemented to help researchers monitor and understand the evolution of SARS-CoV-2.

However, "analysis of this wealth of genomic sequences requires a variety of bioinformatics techniques," say the researchers.

The VDB software tool

The VDB software tool created by West and colleagues enables rapid analysis of the changing mutational landscape within the SARS-CoV-2 spike protein.

The tool consists of one program that examines the pattern of spike mutation in a collection of sequenced isolates and another program that generates a list of spike mutations from a multiple sequence alignment. The tool implements a mutation pattern query language that generates a collection of isolates (a "cluster") and a group of spike mutations (a "pattern").


"Generally, clusters can be obtained from searches for patterns, and patterns can be found by examining a given cluster," says West and colleagues.

Clusters can be filtered by variables such as geographical location, collection date, the number of mutations or the presence or absence of a mutation pattern.

What did the authors find?


The team detected an emerging lineage of viral isolates in the New York region that shares mutations with previously reported variants. Several clusters of isolates were detected that had mutations at sites in the spike protein known to be associated with resistance to antibodies against SARS-CoV-2.

The lineage (now designated as B.1.526) comprises two main branches: one including the mutation E484K and another including the mutation S477N, both of which are located within the receptor-binding domain of the spike protein.

What is known so far about these mutations?


Research has previously shown that E484K disrupts the neutralization of numerous anti-SARS-CoV-2 antibodies. The mutation has been identified in variant B.1.351 that recently emerged in South Africa and in the B.1.1.248 variant recently identified in Brazil.

The S477N mutation, which has been identified in several earlier variants, lies near the binding site of multiple antibodies. It has been shown to increase viral infectivity by enhancing the binding of the spike protein to its host cell receptor angiotensin-converting enzyme 2 (ACE2).

"The overall pattern of mutations in this cluster suggests that it arose in part in response to selective pressure from antibodies," writes the researchers.

This B.1.526 variant emerged in late November 2020 and based on the collection dates of isolates from this lineage, it appears that they are now increasing in frequency, concludes West and the team.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

West AP, et al. SARS-CoV-2 lineage B.1.526 emerging in the New York region detected by software utility created to query the spike mutational landscape. bioRxiv, 2021. doi: https://doi.org/10.1101/2021.02.14.431043, https://www.biorxiv.org/content/10.1101 ... 4.431043v1
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Re: New Variants

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Two coronavirus variants have merged – here's what you need to know

2/17/21


https://www.newscientist.com/article/22 ... d-to-know/


Two variants of the coronavirus first identified in the UK and in California appear to have combined into a heavily mutated hybrid. This could signal a new phase of the covid-19 pandemic, as more hybrid variants may emerge.

What exactly has been discovered?

So far, a single genome sequence of the SARS-CoV-2 coronavirus deposited in a database of thousands from the US. The sequence has tell-tale signs of being a hybrid virus created by a recombination event between two different lineages of SARS-CoV-2.

What is a recombination event?

Coronaviruses such as SARS-CoV-2 have an evolutionary superpower called “recombination” which allows two closely related viruses to mix-and-match their genomes into novel combinations. Unlike regular mutation, which proceeds slowly one change at a time, recombination can produce wholesale changes in a coronavirus genome in one single swoop.

Has the hybrid been detected among actual viruses circulating in people?

No, although the sequence is from a virus taken from an infected person, so it is a plausible hypothesis that the recombinant virus is in the community. However, it could have already fizzled out after failing to transmit to other people. The US has relatively low rates of viral sequencing, so it is hard to say either way.

There is another possibility: the recombination event may have occurred within the sample after it was taken from the infected person, not while it was inside their body. In which case it is an accidental laboratory artefact, not a wild virus.

Could it somehow leak out from the lab?

That would be very unlikely. The sample itself, and hence the virus, has almost certainly been destroyed by now, in line with usual safety procedures. If so, all that remains is a sequence of letters in a database.

Do we know where and when the sample was taken?

No, but southern California in the past month or so is a good guess. It was discovered during an investigation of a recent surge of covid-19 cases in Los Angeles apparently caused by a new SARS-CoV-2 variant called B.1.429.

How did New Scientist find out about it?

It was reported on 2 February at a virtual scientific conference organised by the New York Academy of Sciences. In a presentation about the outbreak in Los Angeles, Bette Korber of Los Alamos National Laboratory in New Mexico said: “We found at least a single recombinant.” She went on to add further details. For example, she showed a graphical representation of the viral genome showing clearly that it is a mosaic of sequences from two different lineages, which is hard to explain any other way than recombination.

The discovery has yet to be published in a scientific journal or posted on a preprint server and Korber declined to comment further.

Do we know which lineages recombined?

Yes. The hybrid is a mash-up of the B.1.1.7 variant first detected in Kent, UK, late last year, and the lesser-known B.1.429, which appears to have originated in southern California. Both are known to be circulating in the Los Angeles area.

Both of these variants carry mutations on their spike proteins that appear to confer an advantage. B.1.1.7 has one called Δ69/70, which makes the virus more transmissible. B.1.429 has a different one called L452R, which can confer resistance to antibodies. Perhaps worryingly, the hybrid virus carries both.

“This kind of event could actually allow the virus to have coupled a more infections virus with a more resistant virus,” Korber said at the conference.

How worried should we be?

Right now, not very. There is no evidence that the recombinant is being transmitted from person to person, though Korber said it couldn’t be ruled out and that it would be necessary to watch for “expansion” – meaning that the recombinant could appear in the population and then increase in frequency, suggesting it is out-competing existing viruses.

But looking forward, we need to add this sort of event to our list of worries. As more genetically distinct variants of SARS-CoV-2 emerge and begin circulating in the same geographical areas, the chances of nasty recombinants increase. This particular recombinant may go nowhere, but it may herald a new phase of the pandemic with recombinants emerging all over the place.

Is this a surprise?

Not really. Even before SARS-CoV-2 emerged, recombination was recognised as an important agent of evolutionary change in coronaviruses. It is possible that recombination led to SARS-CoV-2 emerging in the first place.

Virologists warned about recombination quite early on in the covid-19 pandemic, and have been on the lookout for it since. Two analyses published in December and January independently reported that it hadn’t yet been detected, though that may be because up until then all circulating viruses were so genetically similar that it was impossible to tease out ongoing recombination events from the background noise of normal mutation.

However, recently emerged variants, including B.1.1.7 and B.1.429, may be genetically distinct enough that recombination leaves a detectable trace in the genome.

How can two different viruses meet up to recombine?


In a word, co-infection. In places such as California where two distinct variants are in circulation, individual people can be infected with both at the same time. If individual host cells end up harbouring the two variants, the scene is set for recombination.

How exactly does recombination happen?

It occurs because the coronavirus enzyme that replicates its genome is prone to slipping off the RNA strand it is copying and then rejoining where it left off. If a host cell contains two different coronavirus genomes, the enzyme can repeatedly jump from one to the other, stitching together a mosaic genome. This is more likely to occur where the two viruses are closely related, but has been documented between quite distantly related coronaviruses. So it isn’t impossible that SARS-CoV-2 could recombine with a common-cold-causing coronavirus, with unknown consequences. As yet that hasn’t been seen.

The flu virus also recombines to create new and potentially deadly viral strains. Is it the same process?

Not exactly. The influenza genome is carried on eight separate pieces of RNA, rather than the single one in coronaviruses. If a human or animal is co-infected with two different strains of flu, the RNA pieces can be rearranged into new combinations which may go on to become a novel pandemic strain.
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