COVID SARS-CoV-2 Mutations: B.1.1.7, B.1.351 & D614G Research

[pinball1970]

I really wonder how does this calculated. Regarding an effective R the rate of immunity within the population has really remarkable effect: so a slightly immunity-bypassing variant with an actually lower (!) R0 might spread with higher R in a population which had a bad wave previously - or was thoroughly vaccinated.

Probably a lot of factors, how viable the virus is on fomites, how long, in droplets/air how effective it is at entering cells, how many copies, where in the respiratory system, antibody evasion...

 

[atyy]

I really wonder how does this calculated. Regarding an effective R the rate of immunity within the population has really remarkable effect: so a slightly immunity-bypassing variant with an actually lower (!) R0 might spread with higher R in a population which had a bad wave previously - or was thoroughly vaccinated.

Tweet by Jeffery Barrett
"It's clear that B.1.617.2 has been growing faster than B.1.1.7 in UK for a few weeks. Key question for policy, not yet fully answered, is how much due to:
1. vaccine efficacy
2. intrinsic transmissibility
3. human epidemiological factors"

He has follow up posts discussing data from many sources, but not yet giving a clear picture.

 

[Ygggdrasil]

The WHO has announced new nomenclature for some of the variants of concern:

Each variant will be given a name from the Greek alphabet, in a bid to both simplify the public discussion and to strip some of the stigma from the emergence of new variants. A country may be more willing to report it has found a new variant if it knows the new version of the virus will be identified as Rho or Sigma rather than with the country’s name, Maria Van Kerkhove, the WHO’s Coronavirus lead, told STAT in an interview.

Under the new scheme, B.1.1.7, the variant first identified in Britain, will be known as Alpha and B.1.351, the variant first spotted in South Africa, will be Beta. P.1, the variant first detected in Brazil, will be Gamma and B.1.671.2, the so-called Indian variant, is Delta.

https://www.statnews.com/2021/05/31/the-name-game-for-coronavirus-variants-just-got-a-little-easier/

Here's the WHO's official page on variants of concern/variants of interest:
https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/

 

[Ygggdrasil]

Cases slowly increasing again in the UK, it's not quite a spike but we went over 4000 cases in 24 hours first time since early April.
Several days over 3000 before that when we had been bubbling along for weeks at 2500.
Approx 60% of the population first jab, a third both
https://coronavirus.data.gov.uk/details/vaccinations

The Indian is 60% more transmissible and the vaccines are also a lot less effective. As low as 33%.
https://www.bmj.com/content/373/bmj.n1346

@PeroK has a handle on UK @Ygggdrasil and Atty

Tweet by Jeffery Barrett
"It's clear that B.1.617.2 has been growing faster than B.1.1.7 in UK for a few weeks. Key question for policy, not yet fully answered, is how much due to:
1. vaccine efficacy
2. intrinsic transmissibility
3. human epidemiological factors"

He has follow up posts discussing data from many sources, but not yet giving a clear picture.

It's worth noting the current COVID-19 outbreak in India (presumably driven by the delta variant, B.1.617) has been occurring in some areas that were estimated to have high (~50%) exposure rates earlier in the pandemic:

Studies that tested for SARS-CoV-2 antibodies — an indicator of past infection — in December and January estimated that more than 50% of the population in some areas of India’s large cities had already been exposed to the virus, which should have conferred some immunity, says Manoj Murhekar, an epidemiologist at the National Institute of Epidemiology in Chennai, who led the work. The studies also suggested that, nationally, some 271 million people had been infected1 — about one-fifth of India’s population of 1.4 billion.

These figures made some researchers optimistic that the next stage of the pandemic would be less severe, says Ramanan Laxminarayan, an epidemiologist in Princeton University, New Jersey, who is based in New Delhi. But the latest eruption of COVID-19 is forcing them to rethink.

One explanation might be that the first wave primarily hit the urban poor. Antibody studies might not have been representative of the entire population and potentially overestimated exposure in other groups, he says.

https://www.nature.com/articles/d41586-021-01059-y

Similarly, Manaus and other regions of Brazil were estimated to have very high rates of exposure to the virus earlier in the pandemic yet also suffered major new waves in Jan 2021, likely driven by the gamma variant P.1 (https://www.thelancet.com/article/S0140-6736(21)00183-5/fulltext). Like the delta variant B.1.617 from India, the gamma variant also has a mutation at position E484 of the spike protein, which is thought to help the variant evade antibody-based immunity.

Of course, there are other non-mutually exclusive factors that could potentially explain some of these resurgences, including overestimation of prior immunity. For example, research has shown that the epsilon variants (B.1.427/B.1.429) from California are more transmissible than the original SARS-CoV-2 strain (Deng et al 2021 and Peng et al 2021), and the delta variant from India shares the L452R spike protein mutation with the epsilon variant, so increased transmissibility is also likely an issue.

Given that it seems like the vaccines protect against severe disease from the variants (even if they are less effective at preventing symptomatic disease and transmission), it will be interesting to see if the current resurgence of COVID-19 in the UK continues, will we still see large new waves of hospitalizations and deaths associated with the new wave of infections.

 

[Ygggdrasil]

This is probably the most relevant thread for this article?

https://www.sciencealert.com/we-hav...-sars-cov-2-can-insert-itself-into-our-genome

Paper here

https://www.pnas.org/content/118/21/e2105968118

A part of our genome is already ERV remnants, about 5%?

Transposons 17%

I have read about these (on a pretty pop level) for Evolution links with other primates

These sequences can do nothing, make copies of themselves, code for “something” or be involved in a regulatory role.

https://www.frontiersin.org/articles/10.3389/fchem.2016.00021/full (or do this)

COVID is not retrovirus and I do not know what consequences this could have if the findings hold up.

ERV sequences are ancient this is be new
Is something our genome just coped with in the past? Without much ado?
Do we know when the last big event was? In terms of this sort of viral insertion?

Some general stuff on ancient ERVs, transposons and epigenetics but it would be nice to get a view from the cell biology guys if they have time

It's worth noting that the PNAS paper used a somewhat artificial system in which they boosted the expression of some of the ERV elements to get SARS-CoV-2 to integrate into the genome. Whether this happens under more normal cellular conditions is still not clear.

A recent pre-print paper argues that integration of the SARS-CoV-2 genome is likely to be rare in the absence of the artificial system used in the PNAS paper:

Human genome integration of SARS-CoV-2 contradicted by long-read sequencing
Smits et al. bioRxiv 2021
https://www.biorxiv.org/content/10.1101/2021.05.28.446065v1

Abstract:

A recent study proposed severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we applied deep (>50x) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2, and did not find any evidence of the virus existing as DNA. By examining ONT data from separate HEK293T cultivars, we resolved the complete sequences of 78 L1 insertions arising in vitro in the absence of L1 overexpression systems. ONT sequencing applied to hepatitis B virus (HBV) positive liver cancer tissues located a single HBV insertion. These experiments demonstrate reliable resolution of retrotransposon and exogenous virus insertions via ONT sequencing. That we found no evidence of SARS-CoV-2 integration suggests such events in vivo are highly unlikely to drive later oncogenesis or explain post-recovery detection of the virus.

 

[Astronuc]

The B.1.1.7 is now being called 'Alpha' coronavirus, or Alpha SARS-Cov-2?

According to an article in NY Times,

Alpha has 23 mutations that set it apart from other coronaviruses. When the variant started to surge in Britain, researchers began inspecting these genetic tweaks to look for explanations as to why it was spreading faster than other variants.

To investigate how Alpha achieved this invisibility, the researchers looked at how the Coronavirus replicated inside of infected cells. They found that Alpha-infected cells make a lot of extra copies — some 80 times more than other versions of the virus — of a gene called Orf9b.

https://www.nytimes.com/2021/06/07/health/covid-alpha-uk-variant.html

 

[pinball1970]

The B.1.1.7 is now being called 'Alpha' coronavirus, or Alpha SARS-Cov-2?

According to an article in NY Times,

https://www.nytimes.com/2021/06/07/health/covid-alpha-uk-variant.html

Yeah they have been given Greek letters. Indian is Delta

 

[Ygggdrasil]

The B.1.1.7 is now being called 'Alpha' coronavirus, or Alpha SARS-Cov-2?

Yes, see post #53 from last week for more information: https://www.physicsforums.com/threads/sars-cov-2-mutations.998345/post-6498262

 

[Phil Core]

While not a scientific journal or peer reviewed I found this article on the B.1.1.7 variant to be well done -

Inside the B.1.1.7 Coronavirus Variant​

https://www.nytimes.com/interactive/2021/health/coronavirus-mutations-B117-variant.html

1. It mentions that this variant contains more mutations than would be expected.
2. It reports on the increased bonding affinity of this variant. This article, as well as ever other article I have seen, does not report a measure for the binding strength of B.1.1.7
3. Prior articles on the increased binding strength of the original SARS-CoV-2 offer an increase in the positive charge of the surface area where the spike interfaces with the ACE2. This article stress changes in the shape of the B.1.1.7 variant. No mention is made of surface charge.

4. What I found to be the most interesting is this statement - "A number of researchers suspect that People with weakened immune systems can remain infected with replicating coronaviruses for several months, allowing the virus to accumulate many extra mutations."

Here is an example of the claim - https://jamanetwork.com/journals/jama/fullarticle/2779850 -

Researchers Tie Severe Immunosuppression to Chronic COVID-19 and Virus Variants​

 

[Astronuc]

Co-infection with two variants of SARS-Cov-2
https://www.independent.co.uk/news/health/covid-variant-cases-infection-mutation-b1881309.html

A 90-year-old woman in Belgium was infected with Alpha and Beta variants of the Covid-19 virus at the same time.

The unvaccinated woman was admitted to hospital in the Belgian city of Aalst on 3 March of this year following a number of falls and was confirmed as being Covid positive on the same day.

Despite showing no initial signs of respiratory distress, she soon deteriorated and died five days after her admission.

When the patient’s respiratory sample was processed for genomic sequencing, researchers discovered that she had been infected by the Alpha and Beta variants, which first emerged in the UK and South Africa respectively.

“This is one of the first documented cases of co-infection with two Sars-CoV-2 variants of concern,” said molecular biologist Dr Anne Vankeerberghen, who helped write a study on the woman.

Since both Alpha and Beta variants were circulating in Belgium at the time, it is expected that the lady was co-infected with different viruses from two different people. How the woman was infected, i.e., from what contacts, is unknown.

The Independent reports that in January 2021, scientists in Brazil reported that two people had been simultaneously infected with two different coronavirus variants, though research into these cases has yet to be published in a scientific journal.

Do superspreader events typically involve a single variant?

 

[atyy]

Co-infection with two variants of SARS-Cov-2
https://www.independent.co.uk/news/health/covid-variant-cases-infection-mutation-b1881309.html

Not quite the same, but about mutations arising in one person.
https://www.scientificamerican.com/...se-in-people-with-compromised-immune-systems/

 

[Laroxe]

Co-infection with two variants of SARS-Cov-2
https://www.independent.co.uk/news/health/covid-variant-cases-infection-mutation-b1881309.html

A 90-year-old woman in Belgium was infected with Alpha and Beta variants of the Covid-19 virus at the same time.Since both Alpha and Beta variants were circulating in Belgium at the time, it is expected that the lady was co-infected with different viruses from two different people. How the woman was infected, i.e., from what contacts, is unknown.

The Independent reports that in January 2021, scientists in Brazil reported that two people had been simultaneously infected with two different coronavirus variants, though research into these cases has yet to be published in a scientific journal.

Do superspreader events typically involve a single variant?

I imagine this should be quite rare, an infection with one virus puts the immune system on alert and makes infection with a new virus less likely. Activation of the immune system is metabolically quite costly, it can also be risky, so it isn't the normal state. This is suggested as an explanation as to why epidemics of viral diseases, "do the rounds," one at a time. This is a general response of the innate immune system to virus attacks rather than anything specific to Covid 19. Presumably, if exposure to both was around the same time, or if the infection was so advanced as to inhibit immunity, something Covid is quite good at, this effect would be less likely. Selective pressure tends to mean that, eventually, one variant will come to predominate in any given population.
Genomic analysis suggests that superspreading evens can usually be traced back to a single individual, they tend to occur in specific environments that limit the number of possible sources of infection, like cruise ships or institutions. They are referred to as "events" in order to avoid demonising specific individuals and attributions of blame. Identification of the source is only possible because the virus adapts to its host, this means that every individual has some changes to its genome, in effect a personal variant, though one only really of "concern" to the infected individual. It may be that certain individuals shed more virus particles than others, so are more infectious. It's thought that the majority of people who act as the source are asymptomatic or in the prodromal phase of infection. This means that these events almost inevitably involve a specific variant of concern but in theory a single event, at which there are several sources of infection, might lead to several clusters of infection. The effect on immune surveillance, combined with the probability of multiple exposure to different variants, would work against the likelihood of dual infections These events are particularly important early in an epidemic and make predictions about how the disease will spread, very difficult.

 

[Astronuc]

A new variant of SARS-Cov-2, B.1.621, evolved in Colombia and is now in Florida, US. This is why wearing a mask on a plane and in public is important.

Characterization of the emerging B.1.621 variant of interest of SARS-CoV-2
https://www.medrxiv.org/content/10.1101/2021.05.08.21256619v1.full.pdf

Abstract

SARS-CoV-2 genetic diversity has the potential to impact the virus transmissibility and the escape from natural infection- or vaccine-elicited neutralizing antibodies. Here, we report the emergence of the B.1.621 lineage, considered a variant of interest (VOI) with the accumulation of several mutations affecting the Spike protein, including the amino acid changes I95I, Y144T, Y145S and the insertion 146N in the N-terminal domain, R346K, E484K and N501Y in the Receptor Binding Domain and P681H in the S1/S2 cleavage site of the Spike protein. The rapid increase in frequency and fixation in a relatively short time in some cities that were near the theoretical herd immunity suggests an epidemiologic impact. Further studies will be required to assess the biological and epidemiologic roles of the substitution pattern found in the B.1.621 lineage.

It doesn't have a greek letter yet.

In Colombia, the National Genomic Characterization Program led by the Instituto Nacional de Salud has carried out real-time monitoring of the SARS-CoV-2 lineages since the beginning of the pandemic (7,8).Until December 2020, over thirty lineages were circulating inside the country without evidence of VOC and VOI importation. However, a lineage turnover accompanied the third epidemic peak during March and April 2021, involving the emergence of B.1 lineage descendants with high mutation accumulation (B.1.621 and the provisionally assigned B.1+L249S+E484K) (9), as well as the introduction of the B.1.1.7, P.1 and VOI in some cities.

In this study, we reported the emergence and spread of the novel B.1.621 lineage of SARS-CoV-2, a new VOI with the insertion 146N and several amino acid substitutions in the Spike protein (Y144T, Y145S, R346K, E484K, N501Y and P681H).

 

[Ygggdrasil]

Here's a nice graph from nextstrain.org showing the emergence of delta:

https://nextstrain.org/ncov/gisaid/global

At its peak in April 2021, Alpha made up ~ 46% of sequences submitted to GISAID. Delta now makes up ~73% of sequences submitted to GISAID.

 

[Astronuc]

I was talking with a family member and doctor, who mentioned they are dealing with Delta, Delta-plus, Epsilon and Lambda.

At the end of June, Delta was not as dominant in the US, and Delta-plus was just taking off in India. I hadn't heard much about Epsilon or Lambda then either.

I think we covered Delta very well, but now Delta Plus is surging in parts of the US and world.

The Delta Plus variant – also known as B.1.617.2.1 or AY.1 – contains a new mutation in the spike protein the virus uses to enter human cells, called K417N. As it’s still closely linked to Delta, it’s been called Delta Plus rather than another letter in the Greek alphabet, according to WHO’s naming system for COVID-19 variants. So far, Delta Plus has been found in relatively low numbers.

https://www.gavi.org/vaccineswork/theres-now-delta-plus-variant-covid-19-what-does-mean

Both Epsilon (B.1.427/B.1.429) and Lambda variants may have some immunity to vaccines, but it's not clear which vaccines.
https://science.sciencemag.org/content/373/6555/648 (I noticed a type in B1.1.427, so there may be others)

A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429), which was originally detected in California, carries spike glycoprotein mutations S13I in the signal peptide, W152C in the N-terminal domain (NTD), and L452R in the receptor-binding domain (RBD).

https://en.wikipedia.org/wiki/SARS-CoV-2_Epsilon_variant
https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html
https://gvn.org/covid-19/epsilon-b-1-427-b-1-429/https://en.wikipedia.org/wiki/SARS-CoV-2_Lambda_variant

The Lambda genome has the following amino acid mutations, all of which are in the virus's spike protein code: G75V, T76I, Δ246-252, L452Q, F490S, D614G and T859N.

https://www.news-medical.net/news/2...s-potential-to-become-variant-of-concern.aspx

Then there is the Colombia variant (B.1.621), considered a variant of interest (VOI), which . . .

. . . has the accumulation of several substitutions affecting the Spike protein, including the amino acid changes T95I, Y144T, Y145S and the insertion 146N in the N-terminal domain, R346K, E484K and N501Y in the Receptor-binding Domain (RBD) and P681H1 in the S1/S2 cleavage site of the Spike protein. The rapid increase in frequency and fixation in a relatively short time in Magdalena, Atlántico, Bolivar, Bogotá D.C, and Santander that were near the theoretical herd immunity suggests an epidemiologic impact.

https://www.newsweek.com/colombian-covid-variant-spreading-areas-florida-1613503

The B.1.621 variant, which is being commonly referred to as the Colombian Variant, is responsible for 10 percent of COVID patients at one Miami hospital, according to a health official's report on Monday.

August 2 - https://coronavirus.nautil.us/colombian-covid-variant/

A variant of COVID-19 that first originated in Colombia is now spreading in south Florida, and one health official said the Colombian strain has accounted for about 10% of the positive cases being sequenced at the University of Miami’s pathology lab.

Edit/update - related discussion
https://www.physicsforums.com/threa...coronavirus-different-from-the-others.985500/

 

[Ygggdrasil]

I was talking with a family member and doctor, who mentioned they are dealing with Delta, Delta-plus, Epsilon and Lambda.

Here's a nice figure from the CDC showing the prevalence of the different variants in the US:

https://covid.cdc.gov/covid-data-tracker/#variant-proportions

Currently, the Delta variants make up a huge proportion of cases in the US, with other variants contributing only a few percent of cases at most. Lambda has not yet shown up in the US, so it's not known how well that would spread in the US yet.

However, Epsilon, which the WHO no longer classifies as a variant of interest, shows a different story. This variant was first detected in California, and researchers found that the variant spread much faster than the original strain of SARS-CoV-2. During the Winter surge in California, Epsilon went from ~3% of cases in October 2020 to ~60% of cases in Feb 2021 (CDPH data). However, since then, the prevalence of Epsilon has steadily decreased down to 0.1% of cases in July 2021. This decrease likely suggests that the Epsilon variant was outcompeted by more transmissible variants, first Alpha and later Delta.

 

[Astronuc]

A month later (almost), the Delta variant dominates

Parts of Texas have no ICU beds, and I heard reports that Alabama has no ICU beds left, and apparently similar shortages are occurring in Louisiana and Mississippi.

 

[Astronuc]

I heard a presentation (unpublished) the other day on the sequencing of a group of SARS-Cov-2 specimens taken from a select population, with 2 Alpha variant and the rest Delta variant as I recall. Each sample had a unique set of mutations, which made me wonder with the Delta virus spread, it seems a new subvariant is available from each person who becomes infected. A term used was non-synonomous mutations, and there were about 16 (+/-) mutations in each specimen.

From last year, Investigating the genomic landscape of novel Coronavirus (2019-nCoV) to identify non-synonymous mutations for use in diagnosis and drug design - Journal of Clinical Virology, July 2020
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227581/

 

[atyy]

A term used was non-synonomous mutations, and there were about 16 (+/-) mutations in each specimen.

A synonymous mutation is a mutation in the RNA sequence that does not affect the amino acid sequence of a protein (because more than one RNA sequence can correspond to a particular amino acid). Since the amino acid sequence (not the RNA sequence) determines how the virus interacts with cells, synonymous mutations have no effect on whether the virus will more easily evade the vaccine or become more transmissible.

A non-synonymous mutation is a changes the protein, so these can affect immune escape and transmissibility.

 

[Laroxe]

Yes, I heard that discussed on TWiV. The virus adapts to each new host, very specifically apparently, so we all get our own version, given a little time. I expect these changes will be less likely to involve the parts of the virus that get them the label of variants of concern, as the selective pressures will be different and will respond to the intra organism variations. Many of these changes will be lost as the virus makes its way through the population and are replaced, but some will persist, and are still transmissible. This has been suggested as the explanation for the observation that the effects of convalescent plasma is only significant when it's collected from the local population of the recipient's. However, the logistics of the donor plasma schemes, the rather unimpressive results and the development of synthetic monoclonals, means that this was never really tested.

There will of course continue to be mutations that occur that have nothing to do with the host's individual differences, but might still affect the viruses inter-organism behaviours, the risk of these changes is related to the amount of virus circulating in the population.

 

[Evo]

And now we can add MU.

The World Health Organization said a strain of the Coronavirus that causes COVID-19 and that was first detected in Colombia in January has become a “variant of interest” and will be closely monitored for signs it is resistant to the vaccines that have been authorized for use so far.

In its weekly epidemiological update, the agency said the variant, B.1.621, to which it has assigned the Greek letter mu, has “a constellation of mutations that indicate potential properties of immune escape.”

https://www.abcactionnews.com/news/...-organization-monitoring-new-covid-19-variant

 

[Ygggdrasil]

Another new variant C.1.2 has been detected in South Africa:

South African scientists have detected a new Coronavirus variant with multiple mutations but are yet to establish whether it is more contagious or able to overcome the immunity provided by vaccines or prior infection.

The new variant, known as C.1.2, was first detected in May and has now spread to most South African provinces and to seven other countries in Africa, Europe, Asia and Oceania, according to research which is yet to be peer-reviewed.

It contains many mutations associated in other variants with increased transmissibility and reduced sensitivity to neutralising antibodies, but they occur in a different mix and scientists are not yet sure how they affect the behaviour of the virus. Laboratory tests are underway to establish how well the variant is neutralised by antibodies.

https://www.reuters.com/world/afric...iant-still-studying-its-mutations-2021-08-30/

Here's the non-peer-reviewed pre-print describing the variant:

The continuous evolution of SARS-CoV-2 in South Africa: a new lineage with rapid accumulation of mutations of concern and global detection
https://www.medrxiv.org/content/10.1101/2021.08.20.21262342v2

SARS-CoV-2 variants of interest have been associated with increased transmissibility, neutralization resistance and disease severity. Ongoing SARS-CoV-2 genomic surveillance world-wide has improved our ability to rapidly identify such variants. Here we report the identification of a potential variant of interest assigned to the PANGO lineage C.1.2. This lineage was first identified in May 2021 and evolved from C.1, one of the lineages that dominated the first wave of SARS-CoV-2 infections in South Africa and was last detected in January 2021. C.1.2 has since been detected across the majority of the provinces in South Africa and in seven other countries spanning Africa, Europe, Asia and Oceania. The emergence of C.1.2 was associated with an increased substitution rate, as was previously observed with the emergence of the Alpha, Beta and Gamma variants of concern (VOCs). C.1.2 contains multiple substitutions (R190S, D215G, E484K, N501Y, H655Y and T859N) and deletions (Y144del, L242-A243del) within the spike protein, which have been observed in other VOCs and are associated with increased transmissibility and reduced neutralization sensitivity. Of greater concern is the accumulation of additional mutations (C136F, Y449H and N679K) which are also likely to impact neutralization sensitivity or furin cleavage and therefore replicative fitness. While the phenotypic characteristics and epidemiology of C.1.2 are being defined, it is important to highlight this lineage given its concerning constellations of mutations.

Yesterday (9/1), the WHO designated the C.1.2 variant as an alert for further monitoring: https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/

 

[Astronuc]

Another new variant C.1.2 has been detected in South Africa:

Jan 28 - https://www.cdc.gov/coronavirus/201...riefs/scientific-brief-emerging-variants.html
From the CDC, "In South Africa, another variant of SARS-CoV-2 (known as 20H/501Y.V2 or B.1.351) emerged independently of B.1.1.7. This variant shares some mutations with B.1.1.7. Cases attributed to this variant have been detected in multiple countries outside of South Africa. This variant was reported in the US at the end of January 2021."

Is C.1.2 related to the other earlier variants?

 

[Ygggdrasil]

Jan 28 - https://www.cdc.gov/coronavirus/201...riefs/scientific-brief-emerging-variants.html
From the CDC, "In South Africa, another variant of SARS-CoV-2 (known as 20H/501Y.V2 or B.1.351) emerged independently of B.1.1.7. This variant shares some mutations with B.1.1.7. Cases attributed to this variant have been detected in multiple countries outside of South Africa. This variant was reported in the US at the end of January 2021."

Is C.1.2 related to the other earlier variants?

In the paper linked above, genetic analysis shows that C.1.2 does not appear to be closely related to or directly descended from the Beta variant (B.1.351) (in fact, the aforementioned Mu variant, colored red and labeled 21H in the figure, is closer to Beta) :

https://www.medrxiv.org/content/10.1101/2021.08.20.21262342v2

The C.1.2 variant arose from the C.1 variant, a variant that was present in the first wave of COVID-19 in South Africa, but had seemed to disappear by Jan 2021. C.1.2 began rising in prevalence in May 2021. Of the major VOCs/VOIs, C.1.2 seems most closely related to Lambda (C.37).

Shows how global viral evolution is where a new variant from Colombia (Mu) is closely related to an older variant from South Africa (Beta), whereas the newer variant from South Africa (C.1.2) is more closely related from a different variant from South America (Lambda, which was first detected in Peru).

 

[Sagittarius A-Star]

And now we can add MU.
https://www.abcactionnews.com/news/...-organization-monitoring-new-covid-19-variant

A new COVID-19 variant called Mu that might be able to evade immunity from vaccines has been detected in almost every US state

Source:
https://www.businessinsider.com/covid-19-mu-variant-detected-in-47-us-states-and-dc-2021-9

Here, we demonstrate that the Mu variant is highly resistant to sera from COVID-19 convalescent and BNT162b2-vaccinated individuals. Direct comparison of different SARS-CoV-2 spike proteins revealed that Mu spike is more resistant to serum-mediated neutralization than all other currently recognized variants of interest (VOI) and concern (VOC).

Source:
https://www.biorxiv.org/content/10.1101/2021.09.06.459005v1

 

[Astronuc]

So, as far as I can tell, C.1.2 is still a VOI and doesn't yet have a Greek letter assigned. Back in July, the B.1.621 variant, which was "being commonly referred to as the Colombian Variant, was responsible for 10 percent of COVID patients at one Miami hospital," according to a health official's report at the time (last week in July). Now it's detected in nearly every US state.

https://www.cbc.ca/news/health/latest-coronavirus-variants-mu-c12-1.6161194
According to the article by CBC.ca dated September 02, . . .

The [Mu] variant was first detected in Colombia back in January, and since then, the country has experienced hundreds of cases and the variant has also been reported in 39 other countries around the world.

Here in Canada, it's barely making a splash: Mu cases have been reported for weeks, but so far, the variant hasn't made up more than three per cent of cases in any given week and recently totalled just 0.3 per cent — though federal data since mid-July is still accumulating and could change.

with respect to C.1.2

A team of scientists from South Africa detected the new variant, which was first observed in May and has since spread to seven other countries in Africa, Europe, Asia and Oceania, according to a preprint study that hasn't yet been peer-reviewed.

"It's still not clear where this came from," noted Dr. Zain Chagla, an infectious diseases specialist with McMaster University in Hamilton. "It was first identified in South Africa but people need to know that South Africa has actually quite good sequencing networks and so it may not be the origin."

 

[Ygggdrasil]

So, as far as I can tell, C.1.2 is still a VOI and doesn't yet have a Greek letter assigned.Back in July, the B.1.621 variant, which was "being commonly referred to as the Colombian Variant, was responsible for 10 percent of COVID patients at one Miami hospital," according to a health official's report at the time (last week in July). Now it's detected in nearly every US state.

https://www.cbc.ca/news/health/latest-coronavirus-variants-mu-c12-1.6161194
According to the article by CBC.ca dated September 02, . . .

with respect to C.1.2

The WHO maintains three levels of concern regarding novel variants: variants of concern (VOC), variants of interest (VOI) and alerts for further monitoring. See the WHO page on variants for more information on the definitions: https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/

Currently, C.1.2 is classified as an alert for further monitoring (date of designation 1-Sep-2021). Only VOC and VOI are assigned Greek letters. We await further research/epidemiology on C.1.2 to see if it warrants classification as a VOI.

Currently, >99% of infections in the US are due to Delta:

https://covid.cdc.gov/covid-data-tracker/#variant-proportions

Mu currently accounts for only 0.1% of infections in the US. It will be important to track this number over the next few months to see if Mu infections continue to rise even as Delta infections (hopefully) begin to fall.

Here's data from Nextstrain showing the prevalence of mutations at position 145 of the spike protein (the Y145S mutation appears to be fairly specific for Mu):

https://nextstrain.org/ncov/gisaid/global?c=gt-S_145

The global prevalence of this mutation has remained fairly low low since it first appeared ~ March 2021, which suggests that it probably is not more transmissible than Delta.

 

[Astronuc]

One point I was trying to make, but perhaps not clearly, is that back in July, the B.1.621 variant, which was then commonly referred to as the Colombian Variant, did not have a Greek letter. Then in less than 5 weeks based on Evo's post, it received a letter, and went from Florida to ~47 other states.

And now we can add MU.

I'm curious about the statement in the CBC.ca article, "It was first identified in South Africa but people need to know that South Africa has actually quite good sequencing networks and so it may not be the origin." I'm wondering if the travel of people between South America and Africa, or South Africa, is being monitored, partly based on Ygggdrasil comment: "the newer variant from South Africa (C.1.2) is more closely related from a different variant from South America (Lambda, which was first detected in Peru)." Could asymptomatic, infected people be carrying variants across borders?

Clearly, the variant from Colombia made it to Miami, Florida.

 

[Astronuc]

And now we can add MU.

https://www.abcactionnews.com/news/...-organization-monitoring-new-covid-19-variant

Mu variant outbreak in Florida with hundreds of cases!
https://www.newsweek.com/mu-covid-variant-outbreak-florida-hundreds-detected-cases-1627068

https://www.baynews9.com/fl/tampa/news/2021/09/09/mu-variant-in-florida

Mu appears to be very rare right now. According to the online database outbreak.info, mu makes up less than half a percent of global COVID cases. CDC data shows it made up just .1% of US cases last week. Florida does have more cases of the mu variant than any state except California. Outbreak.info shows 305 cases have been reported here. Teng said direct flights from Colombia to Florida are one possible reason that number is higher than other states. Iovine said it's important to keep that total in perspective. "If you look at the overall number of cases that we're having in Florida...305 is very little, relatively speaking," she said.

 

[Ygggdrasil]

From the CDC's Sep 10 COVID Data Tracker Weekly Review:

On August 30, 2021, the Mu (B.1.621) variant of the virus that causes COVID-19 was classified as a Variant of Interest (VOI) by the World Health Organization (WHO). CDC has not escalated this variant to a VOI in the United States, where the Mu variant reached its peak in late June (<5% of circulating variants) and has steadily decreased since.

https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html

The fact that it's prevalence has been decreasing in the past few months (as Delta has risen) suggests that it is less transmissible than Delta (consistent with some of the other data I've posted above). Mu is still definitely capable of causing outbreaks, but those outbreaks are likely less of a concern than the hundreds of thousands of cases of Delta currently out there.

 

[Astronuc]

A review of Coronavirus specimens collected in Los Angeles County shows the mu and lambda variants were circulating earlier this summer, but the delta variant remains dominant, officials said Friday.

The highly contagious delta has “crowded out all of the other previously circulating strains,” now accounting for 100% of all strains sequenced in L.A. County, said Barbara Ferrer, the county’s public health director.

But when the lab that sequences the cases re-analyzed samples with an updated version of the genetic library used to identify variants, it reclassified many older specimens as mu or lambda variants.

The county is now reporting a total of 232 cases linked to the mu variant so far, while last week it had said 167 cases were identified to date. Another 28 cases were linked to the lambda variant.

https://ktla.com/news/local-news/mu...lier-than-thought-but-delta-crowded-them-out/

So how did Mu get there? Direct flights from Colombia, or flights from Miami.

On September 6, LA Times reported only 167 cases attributed to Mu variant.
https://www.latimes.com/california/...-variant-recorded-in-167-people-in-l-a-county

https://www.forbes.com/sites/brucel...les-county-reports-167-cases/?sh=41693bd13032

While it sounds a bit like how a cat would say “new variant,” the Mu variant of the Covid-19 Coronavirus is far from a catastrophe. There's nothing yet to suggest that the current Covid-19 vaccines won’t work against the newly-named Mu variant. However, not enough is really known about this latest addition to the World Health Organization (WHO) “Variants of Interest” list to draw any strong conclusions. Nonetheless, it has already made its way to nearly every state in the U.S. And that includes California.

Yes, according to an announcement from the Los Angeles County Department of Public Health on Friday, the Mu variant of the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has been in Los Angeles County since at least mid-June. From June 19 through Augusts 21, the Department has found the Mu variant in 167 samples. Although the variant only accounts for less than one percent of all Covid-19 Coronavirus samples that have been sequenced in California and the U.S., it’s clear that the Mu variant had entered the U.S. by the start of Summer.

Mu variant found in every US state bar Nebraska​

https://www.independent.co.uk/news/...ant-nebraska-florida-california-b1915826.html

Is Nebraska even looking? I have seen maps where Nebraska isn't reporting Covid infections.

 

[Astronuc]

The fact that it's prevalence has been decreasing in the past few months (as Delta has risen) suggests that it is less transmissible than Delta (consistent with some of the other data I've posted above). Mu is still definitely capable of causing outbreaks, but those outbreaks are likely less of a concern than the hundreds of thousands of cases of Delta currently out there.

The Delta variant was first identified in India in December 2020. Did it first infect people within 50 to 100 miles of an international airport?

WHO profile of Delta
First sample documented - India, Oct-2020, VOI: 4-Apr-2021, VOC: 11-May-2021
https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/

https://cov-lineages.org/lineage.html?lineage=B.1.617.2 First date 2020-08-21, which is earlier than Oct-2020

https://cov-lineages.org/lineage_list.html

I think Mu is just getting started in the US.

From WHO page, VOI Table: Mu (B.1.621); Earliest documented sample, Colombia, Jan-2021; VOI: 30-Aug-2021

B.1.621
United States of America 45.0%, Colombia 14.0%, Mexico 10.0%, Spain 9.0%, Chile 4.0%
First date identified: 2021-01-11

B.1.621.1
United States of America 63.0%, Spain 12.0%, Austria 5.0%, Dominican_Republic 5.0%, Switzerland 3.0% First date identified: 2021-04-14

https://cov-lineages.org/index.html#global_reports

 

[atyy]

Chise on Twitter: "Mu (B.1.621) is NOT vaccine resistant. Stop the misinformation. Fold-reduction in LIVE VIRUS studies is less that than of Beta, Gamma and Delta."

 

[Astronuc]

Welcome R.1 variant.

A new variant has been detected in a Kentucky nursing home, infecting 45 residents and health care personnel. Many of these infections arose in fully vaccinated individuals. The variant, which originated in Japan, has over 10,000 entries in the GISAID SARS-CoV-2 database. The variant contains five mutations previously noted in variants of concern or interest, two of which are in the Spike protein (Figure 1). It also contains many unique mutations. Here we describe the potential effects of each mutation on replication, immune evasion, and pathogenesis.

https://www.forbes.com/sites/willia...new-usjapan-variant-to-watch/?sh=626ab6b35097

The R.1 variant shares a common origin with all variants of interest or concern. They are marked by what I call the Triad, three mutations, one the 5’ untranslated region: C241U, a second in the viral polymerase NSP12: P323L, and the third D614G in the exterior S1 domain of the spike protein. The D614G mutation increases the infectivity. The contribution of the other two members of the Triad remains a mystery. Together these three mutations characterize the first major variant first observed in early 2020. That virus soon displaced almost all of the original Wuhan isolates. The Triad virus is the parent of all variants of concern or, interest including Alpha, Beta, Gamma, Delta, Lambda, and Mu. Only two currently circulating variants, A.30 and A.23.1, both of East Africa origin, lack the Triad and are most likely independent descendants of the original Wuhan virus.

I'm guessing each country with an infected population is going to develop a unique variant. Interesting comment: "The contribution of the other two members of the Triad remains a mystery."COVID-19 Outbreak Associated with a SARS-CoV-2 R.1 Lineage Variant in a Skilled Nursing Facility After Vaccination Program — Kentucky, March 2021
https://www.cdc.gov/mmwr/volumes/70/wr/mm7017e2.htm

Detection of R.1 lineage severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) with spike protein W152L/E484K/G769V mutations in Japan​

https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009619

We aimed to investigate novel emerging severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) lineages in Japan that harbor variants in the spike protein receptor-binding domain (RBD). The total nucleic acid contents of samples from 159 patients with Coronavirus disease 2019 (COVID-19) were subjected to whole genome sequencing. The SARS-CoV-2 genome sequences from these patients were examined for variants in spike protein RBD. In January 2021, three family members (one aged in their 40s and two aged under 10 years old) were found to be infected with SARS-CoV-2 harboring W152L/E484K/G769V mutations. These three patients were living in Japan and had no history of traveling abroad.

. . .
As of April 22, 2021, R.1 lineage SARS-CoV-2 has been identified in 2,388 SARS-CoV-2 entries in the GISAID database, many of which were from Japan (38.2%; 913/2,388) and the United States (47.1%; 1,125/2,388). Compared with that in the United States, the percentage of SARS-CoV-2 isolates belonging to the R.1 lineage in Japan increased more rapidly over the period from October 24, 2020 to April 18, 2021. R.1 lineage SARS-CoV-2 has potential escape mutations in the spike protein RBD (E484K) and N-terminal domain (W152L); therefore, it will be necessary to continue to monitor the R.1 lineage as it spreads around the world.

 

[pinball1970]

The Delta variant was first identified in India in December 2020. Did it first infect people within 50 to 100 miles of an international airport?

WHO profile of Delta
First sample documented - India, Oct-2020, VOI: 4-Apr-2021, VOC: 11-May-2021
https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/

https://cov-lineages.org/lineage.html?lineage=B.1.617.2 First date 2020-08-21, which is earlier than Oct-2020

https://cov-lineages.org/lineage_list.html

I think Mu is just getting started in the US.

From WHO page, VOI Table: Mu (B.1.621); Earliest documented sample, Colombia, Jan-2021; VOI: 30-Aug-2021

I checked previous PHE and there was no Mu mentioned
Checking today there are 47 cases, no deaths as yet but some of those did end up in hospital. P19

https://assets.publishing.service.g...le/1014926/Technical_Briefing_22_21_09_02.pdfDELTA deaths since Feb 1st to Aug 30th page 22

Every month the unvaccinated group gets smaller but the uptake has stagnated at less that 15,000 per day on some days.
Following the roll out to kids this should accelerate again soon.

https://www.theguardian.com/world/2...for-children-aged-12-15-what-you-need-to-know

Lastly it was reported in the METRO UK today 21.9.21 that we have a surplus of 100M vaccines that could go beyond their use by date and get wasted.
Checking just now it looks like we will try and get these out to other countries.

https://www.bbc.co.uk/news/uk-57436535

 

[Astronuc]

According to the Manchester Evening News, COVID-19 was the third leading cause of death August in England, up from 9th leading cause in July.

 

[pinball1970]

Good catch @Astronuc My local news-paper, it does a quite good break downs of the boroughs in terms of numbers and initiatives, mobile vaccine centres targeting low uptake areas and such.

July was a good month, months of lock down followed by a staggered lifting of measures.

Outside venues opened middle of May, then inside venues but with masks and other restrictions middle of June.

So it took a while for cases to start go up again before restrictions lifted middle of July. 30-50 deaths per day.

Fast forward a couple of months and we are at 200 deaths per day which is over twice that of rate for lung cancer deaths in 2018.

However that is still only 1/10th of the death rate when ALPHA was at its peak in Jan, with few double vaccinated proportionally.

I would like to think the rate will not go up too much more now.

On the plus side we high vaccine levels with 3 million kids lined up for jabs, the numbers seem to have plateaued.

On the down side (in terms of spread) kids back at school and the summer festivals went ahead including Park life held in Manchester, 76,000 attendance.

The events are out side granted but there is an awful lot of mingling at these events, especially getting in and out, communal toilets bars etc.

Also the kids have got to get to from A B

So buses, trams & trains packed full of teenagers (I had to walk through them) the most mobile mixers with low vaccination rates…. mixing.

We may get a blip from that and others like it.

Statistically though, those youngsters will not need hospital treatment.

 

[Astronuc]

Looking back to the beginning, late 2019, and how SARS-Cov-2 mutated and spread, I was curious about the earliest strains/variants.

An evolutionary portrait of the progenitor SARS-CoV-2 and its dominant offshoots in COVID-19 pandemic​

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523107/

Abstract: We report the likely most recent common ancestor of SARS-CoV-2 – the Coronavirus that causes COVID-19. This progenitor SARS-CoV-2 genome was recovered through a novel application and advancement of computational methods initially developed to reconstruct the mutational history of tumor cells in a patient. The progenitor differs from the earliest coronaviruses sampled in China by three variants, implying that none of the earliest patients represent the index case or gave rise to all the human infections. However, multiple Coronavirus infections in China and the USA harbored the progenitor genetic fingerprint in January 2020 and later, suggesting that the progenitor was spreading worldwide as soon as weeks after the first reported cases of COVID-19. Mutations of the progenitor and its offshoots have produced many dominant Coronavirus strains, which have spread episodically over time. Fingerprinting based on common mutations reveals that the same Coronavirus lineage has dominated North America for most of the pandemic. There have been multiple replacements of predominant Coronavirus strains in Europe and Asia and the continued presence of multiple high-frequency strains in Asia and North America. We provide a continually updating dashboard of global evolution and spatiotemporal trends of SARS-CoV-2 spread.

In Molecular Biology and Evolution
https://academic.oup.com/mbe/article/38/8/3046/6257226

 

[Astronuc]

Newsweek - Delta Sub-Variant AY.4.2, Possibly More Contagious Than Delta, Spreads to More States
https://www.msn.com/en-us/health/me...-than-delta-spreads-to-more-states/ar-AAPQ5GI

According to Outbreak.Info, which uses virus sequencing data from the GISAID database, AY.4.2 has now been identified in four states—North Carolina, Massachusetts, Washington and California—in addition to the District of Columbia, as of October 21.

Just two days ago, AY.4.2 had only been detected in California, North Carolina and DC.

. . .

The new AY.4.2 sub-lineage is one of more than three dozen evolutions of the original Delta variant that have been identified globally.

According to the Centers for Disease Control and Prevention, the Delta variant (first identified in the U.K. and has since become the dominant form of the SARS-CoV-2 virus) is highly contagious—scientists think it is more than twice as infectious as previous variants.

The AY.4.2 sub-lineage of Delta contains two characteristic mutations—called Y145H and A222V—on the spike protein of the SARS-CoV-2 virus, which it uses to bind and enter human cells.

 

[pinball1970]

Newsweek - Delta Sub-Variant AY.4.2, Possibly More Contagious Than Delta, Spreads to More States
https://www.msn.com/en-us/health/me...-than-delta-spreads-to-more-states/ar-AAPQ5GI

This from UKHSA

https://assets.publishing.service.g...t_data/file/1029715/technical-briefing-27.pdf

Delta AY.4.2* VUI-21OCT-01 VUI very steep curve page 14 and actual number pg 13

 

[Astronuc]

A potentially faster-spreading "sub-lineage" of the coronavirus Delta variant named AY.4.2 has been spotted by labs in at least 8 states, and health authorities in the United Kingdom say they are investigating a growing share of cases from this strain of the virus.

Labs in California, Florida, Maryland, Massachusetts, Nevada, North Carolina, Rhode Island and Washington state, plus the District of Columbia, have so far spotted at least one case of AY.4.2.

https://www.cbsnews.com/news/covid-delta-plus-variant-ay-4-2-states/

There are variants of the Covid-19 Coronavirus like the Delta variant. Then there are subvariants, which are variants of the variants. And AY.4.2 is a Delta subvariant that has now spread to at least 42 different countries, including the U.S., according to the latest World Health Organization (WHO) Weekly epidemiological update on Covid-19. This AY.4.2 takes the Delta variant and raises it three additional mutations, including two that affect the oh-so-important spike proteins that studs the surface of the virus. These mutations are called A222V and Y145H, . . .

https://www.forbes.com/sites/brucel...avirus-subvariant-has-spread-to-42-countries/

https://gvn.org/covid-19/delta-b-1-617-2/

https://www.bbc.com/news/health-58965650

https://www.cnbc.com/2021/10/21/the-delta-variant-has-a-mutation-what-we-know-so-far.html

I can't find any statement from WHO.int yet.

Repeating myself: What doesn't kill you, mutates and tries again, and again, . . .

 

[Ygggdrasil]

Regarding AY.4.2, data from England do suggest that AY.4.2 infections (purple on the graph below) continued to rise as delta infections (B.1.617.2, green on graph below) leveled off in Sep-Oct, which does suggest potential increased transmissibility of AY.4.2 over B.1.617.2:

https://covid19.sanger.ac.uk/lineages/raw

Unfortunately, it does not look like the US CDC variant tracking site tracks AY.4.2, as all of the delta lineages (except AY.1 and AY.2) are aggregated with B.1.617.2.

 

[Astronuc]

Some recent numbers on variants in California.

https://www.cdph.ca.gov/Programs/CID/DCDC/Pages/COVID-19/COVID-Variants.aspx
low proportion of AY.1 and AY.2 in the State

 

[Ygggdrasil]

While most studies of COVID-19 variants have focused on mutations in the spike protein (which are important for determining the strength with which the virus binds to the ACE2 receptor in the cells it infects as well as binding to antibodies), here's a paper studying mutations to other proteins encoded by the SARS-CoV-2 virus. In particular, they find some mutations help to enhance the activity of Orf9b in helping the virus to evade the innate immune system.

Evolution of enhanced innate immune evasion by SARS-CoV-2
https://www.nature.com/articles/s41586-021-04352-y

Abstract:

Emergence of SARS-CoV-2 variants of concern (VOCs) suggests viral adaptation to enhance human-to-human transmission1,2. Although much effort has focused on characterisation of spike changes in VOCs, mutations outside spike likely contribute to adaptation. Here we used unbiased abundance proteomics, phosphoproteomics, RNAseq and viral replication assays to show that isolates of the Alpha (B.1.1.7) variant3 more effectively suppress innate immune responses in airway epithelial cells, compared to first wave isolates. We found that Alpha has dramatically increased subgenomic RNA and protein levels of N, Orf9b and Orf6, all known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein required for RNA sensing adaptor MAVS activation. Moreover, the activity of Orf9b and its association with TOM70 was regulated by phosphorylation. We propose that more effective innate immune suppression, through enhanced expression of specific viral antagonist proteins, increases the likelihood of successful Alpha transmission, and may increase in vivo replication and duration of infection4. The importance of mutations outside Spike in adaptation of SARS-CoV-2 to humans is underscored by the observation that similar mutations exist in the Delta and Omicron N/Orf9b regulatory regions.