# Tracing COVID19 Genome Evolution: 3 Major Genotypes A, B and C



## xkm1948 (Apr 10, 2020)

Brand new paper coming out from PNAS, This is from a quite several relative big shot in the field of genome evolution. The authors utilized high quality genome sequenced across the world for accurate viral ancestry prediction.


Link to paper:








						Phylogenetic network analysis of SARS-CoV-2 genomes
					

This is a phylogenetic network of SARS-CoV-2 genomes sampled from across the world. These genomes are closely related and under evolutionary selection in their human hosts, sometimes with parallel evolution events, that is, the same virus mutation emerges in two different human hosts. This makes...




					www.pnas.org
				




PDF version:


			https://www.pnas.org/content/pnas/early/2020/04/07/2004999117.full.pdf
		


Original Abstract:
In a phylogenetic network analysis of 160 complete human severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) genomes, we find three central variants distinguished by amino acid changes, which we have named A, B, and C, with A being the ancestral type according to the bat outgroup coronavirus. The A and C types are found in significant proportions outside East Asia, that is, in Europeans and Americans. In contrast, the B type is the most common type in East Asia, and its ancestral genome appears not to have spread outside East Asia without first mutating into derived B types, pointing to founder effects or immunological or environmental resistance against this type outside Asia. The network faithfully traces routes of infections for documented coronavirus disease 2019 (COVID-19) cases, indicating that phylogenetic networks can likewise be successfully used to help trace undocumented COVID-19 infection sources, which can then be quarantined to prevent recurrent spread of the disease worldwide.


Some key talk away from this paper:

1. *Type A* COVID19 is the ancestor to all the other genotypes
2. Most United States cases are *type A*, so is Australia.
3. *Type B* overwhelmingly dominates China as well as other East Asian countries
4. *Type C *is mostly found in European countries and it has little linkage with *type B*.
5. *Type B* almost seems super well adapted to human of East Asian genomic lineage due to immunological difference compared to either African or European lineage. Terrifying to be honest as the virus is well adapted to target only a sub population of homo sapiens.

Now this is becoming really puzzling. Previously most researchers hypothesized that COVID19 originated from Wuhan China. From the genomic data so far, it seems to be not the case.

I will say this publications has generated quite a lot of discussion in scientific field. The "really bad flu season" experienced by the United States from 2019 to 2020 may need to be re-investigated to accurately trace the origin COVID19. Good thing is most medical clinics have samples swabs stored in liquid nitrogen for sequencing analysis. Just need to access them and we will know whether it was a bad flu season or it was something else.

As more and more genomic information becomes available, researchers across the world will eventually get to the bottom of the origin.

Finding and understanding the origin is crucial. Because whatever the original host for these corona-virus is, there will definitely be new varients of this virus ready to jump onto human. Finding the viral reservoir can give us precious time in predicting future coronavirus outbreaks. @the54thvoid

It is not a question of "IF" another wave of coronavirus will hit, it is a matter of "How soon"


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## HTC (Apr 10, 2020)

xkm1948 said:


> *Now this is becoming really puzzling. Previously most researchers hypothesized that COVID19 originated from Wuhan China. From the genomic data so far, it seems to be not the case.*


Seriously???


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## xkm1948 (Apr 10, 2020)

HTC said:


> Seriously???



Which is why it is super puzzling. On top of that, there does not seem to be a lot of Type A found in Chinese or Korean or Japanese population. You would think as the source of the viral outbreak, Wuhan should have the highest proportion of the ancestral genotype Type A.

Nobody knows why. We need to sequence more current paitients as well as older samples.


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## Ferrum Master (Apr 10, 2020)

xkm1948 said:


> From the genomic data so far, it seems to be not the case.



I think everyone already knows that. TBH I think I did have it also during early January.

For example this years Dakar Rally. This year in Saudi Arabia. Team mechanics got ill out the blue, including our teams. The official versions was some sort of tropical virus. Even Carlos Sainz said it was BS, and stated it was definetly COVID-19 there already on full scale in Dec/Jan.


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## xkm1948 (Apr 10, 2020)

Ferrum Master said:


> *I think everyone already knows that.* TBH I think I did have it also during early January.
> 
> For example this years Dakar Rally. This year in Saudi Arabia. Team mechanics got ill out the blue, including our teams. The official versions was some sort of tropical virus. Even Carlos Sainz said it was BS, and stated it was definetly COVID-19 there already on full scale in Dec/Jan.




Well I don't know that.

There are efforts pushing to access and sequence previously stored clincal swabs of paitients died from 2H 2019 flu related complications. Getting data from these samples will probably make the whole picture clearer in terms of viral origins.

So far there are quite a lot of resistence doing that as most labs are closed. On top of that all available DNA/RNA sequencing capacity has been diverted to helping current patients. So hopefully the older samples are still good a few month from now.


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## neatfeatguy (Apr 10, 2020)

xkm1948 said:


> Well I don't know that.
> 
> There are efforts pushing to access and sequence previously stored clincal swabs of paitients died from 2H 2019 flu related complications. Getting data from these samples will probably make the whole picture clearer in terms of viral origins.
> 
> So far there are quite a lot of resistence doing that as most labs are closed. On top of that all available DNA/RNA sequencing capacity has been diverted to helping current patients. So hopefully the older samples are still good a few month from now.



A guy I know and a friend of his have been trying to tell the hospital that took blood from them back in late November, early December, to have it tested. He had all the symptoms of what they say covid-19 gives and his friend was hospitalized for 4 days due to severe respiratory issues that came with all the other symptoms they say covid-19 has.

I'm not sure if they still have samples or if they're even listening....or as you say, just not able to get it done due to reasons beyond their control.

Based on people I know, symptoms they've had since they've been sick over the past 6 months, I believe that the covid-19 virus has been floating among us a lot longer than they tell us.


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## Ferrum Master (Apr 10, 2020)

xkm1948 said:


> Well I don't know that.
> 
> There are efforts pushing to access and sequence previously stored clincal swabs of paitients died from 2H 2019 flu related complications. Getting data from these samples will probably make the whole picture clearer in terms of viral origins.
> 
> So far there are quite a lot of resistence doing that as most labs are closed. On top of that all available DNA/RNA sequencing capacity has been diverted to helping current patients. So hopefully the older samples are still good a few month from now.



Well, that's sports news... maybe tech people are not into it often, despite having a Madrid Real chair eyesore in the review section for some unknown reasons.

Objectively... 3-5 years till we get something against it that's trialed and effective. I am not very optimistic really... there will no fast solutions, despite the calculation power... it still will end up to the professional virologist team talent.



neatfeatguy said:


> Based on people I know, symptoms they've had since they've been sick over the past 6 months, I believe that the covid-19 virus has been floating among us a lot longer than they tell us.



Exactly... I can say it even for myself.


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## xkm1948 (Apr 10, 2020)

neatfeatguy said:


> A guy I know and a friend of his have been trying to tell the hospital that took blood from them back in late November, early December, to have it tested. He had all the symptoms of what they say covid-19 gives and his friend was hospitalized for 4 days due to severe respiratory issues that came with all the other symptoms they say covid-19 has.
> 
> I'm not sure if they still have samples or if they're even listening....or as you say, just not able to get it done due to reasons beyond their control.
> 
> Based on people I know, symptoms they've had since they've been sick over the past 6 months, I believe that the covid-19 virus has been floating among us a lot longer than they tell us.




Blood MUST be liquid nitrogen flash frozen to preserve the RNA genome of the virus. At the very least it would require high salt "Viral Transportation Medium"

Not sure how many hospitals are doing this as a good practice to preserve the sensitive genomic material. Not keeping my hope high TBH 



Ferrum Master said:


> Well, that's sports news... maybe tech people are not into it often, despite having a Madrid Real chair eyesore in the review section for some unknown reasons.
> 
> Objectively... 3-5 years till we get something against it that's trialed and effective. I am not very optimistic really... there will no fast solutions, despite the calculation power... it still will end up to the professional virologist team talent.
> 
> ...




We have stuff that can combat it relatively safe: plasma from recovered patients. But yeah, good luck getting a shit ton of them to treat every single infected individuals.

Besides that, you can pray to Darwin that this virus does not mutate too fast for our vaccine R&D cycles. If the viral mutation out runs our vaccine R&D plus clinical trails, we will be f*ucked big time. By that time we will probably have to loosen up the regulation of vaccine clinical trails.


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## the54thvoid (Apr 10, 2020)

The genetic sequencing has been helpful for so many aspects of lineage, whether it be human or viral. To hear Covid has a branch that suggests it pre-existed Wuhan is pretty amazing.







That's an abnormal peak in 2017-2018 - over 50% more deaths than the previous years. Makes you wonder about what made that season so bad? And I hate to say it - did the CDC miss something?


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## Space Lynx (Apr 10, 2020)

Mother nature has a way of balancing herself out. That is the beauty of physics, the hubris of humans knows no bounds.


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## xkm1948 (Apr 10, 2020)

lynx29 said:


> Mother nature has a way of balancing herself out. That is the beauty of physics, the hubris of humans knows no bounds.




Our population is quite a bit overblown TBH. But yeah, nature is truly scary. So much unknown from the microscopic world of bacteria and virus.



the54thvoid said:


> The genetic sequencing has been helpful for so many aspects of lineage, whether it be human or viral. To hear Covid has a branch that suggests it pre-existed Wuhan is pretty amazing.
> 
> 
> 
> ...




Yeah, quite a lot of stuff got swapped underneath the "flu" carpet that is for sure. 

Then again. It costs a lot of money to diagnoise every single flu symptom. So yeah I can definitely see it being an oversight of the health care systems.


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## Ferrum Master (Apr 10, 2020)

xkm1948 said:


> Besides that, you can pray to Darwin that this virus does not mutate too fast for our vaccine R&D cycles.



We don't have mass measures to check which strain - A,B,C we gathered... what vaccine... Year 2020 is cancelled for sure.


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## the54thvoid (Apr 10, 2020)

Yet without bacteria we would die, such is our symbiotic relationship.


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## xkm1948 (Apr 10, 2020)

the54thvoid said:


> Yet without bacteria we would die, such is our symbiotic relationship.




Exactly.

Which brings me to my point of view: governments MUST FUND basic science research! Not just the directly human applicable biomedical research, but general understanding of all major science.

OK I am off topic myself.


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## the54thvoid (Apr 10, 2020)

xkm1948 said:


> Exactly.
> 
> Which brings me to my point of view: governments MUST FUND basic science research! Not just the directly human applicable biomedical research, but general understanding of all major science.
> 
> OK I am off topic myself.



Meh - Happy Easter, have an off-topic hall pass.


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## FordGT90Concept (Apr 10, 2020)

But how is it suddenly lethal everywhere?  If COVID-19 already went around the USA a year ago without killing very many people, why is it killing 5.5% that test positive now?


I was sick at the end of February, was tested positive for influenza-A.  Lab confirmed to not be COVID-19.  I had a bacterial-induced cough a year ago, Z-Pak fixed that.  Z-Pak doesn't work on COVID-19.  Yeah, no, I didn't have COVID-19 in the last five years unless I had no symptoms with it.


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## HTC (Apr 10, 2020)

FordGT90Concept said:


> But how is it suddenly lethal everywhere?  If COVID-19 already went around the USA a year ago without killing very many people, why is it killing 5.5% that test positive now?


A "bad" mutation?


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## Ferrum Master (Apr 10, 2020)

Well... at least the air quality is really shapen up better... That's really not a bad thing...

On long term cancer death risk toll for respiratory illnesses actually might kick back.


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## FordGT90Concept (Apr 10, 2020)

HTC said:


> A "bad" mutation?


Happening everywhere at the same time?  There should be a fourth genotype of the lethal variety then.


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## xkm1948 (Apr 10, 2020)

FordGT90Concept said:


> But how is it suddenly lethal everywhere?  If COVID-19 already went around the USA a year ago without killing very many people, why is it killing 5.5% that test positive now?




There were quite a lot of death that were categorized as flu related complications. It was well reported that 2019 later half had one of the worst flu year.

2019 is definitey when COVID19 made the jump to human.


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## the54thvoid (Apr 10, 2020)

FordGT90Concept said:


> But how is it suddenly lethal everywhere?  If COVID-19 already went around the USA a year ago without killing very many people, why is it killing 5.5% that test positive now?



This is a curve ball but stay with me....

In doping in sports, there was a scientific consensus that blood testing wasn't required. A statistician with an interest in sports worked with sport scientists to come up with an equation that could be used to demonstrate that, for example, where 99% of elite athletes achieve a performance within 'x%' of each other, if an athlete is '2x%' it's a marker for drugs - because at the top 1%, huge increases in performance are 'virtually' impossible.

So, take a known average (the flu) and then look at a huge outlier - it's a marker for something else. I'm not saying Covid-19, but such a massive jump is unlikey to be standard flu.


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## HTC (Apr 10, 2020)

FordGT90Concept said:


> Happening everywhere at the same time?  *There should be a fourth genotype of the lethal variety then.*


You *may* have that backwards: there should be a 4th genotype of the "much less" lethal variety (by comparison with the current virus), which *MAY explain how "it was missed"* in 2019 since, most likely, it was thought of as "a mere flu".


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## Space Lynx (Apr 10, 2020)

xkm1948 said:


> Exactly.
> 
> Which brings me to my point of view: governments MUST FUND basic science research! Not just the directly human applicable biomedical research, but general understanding of all major science.
> 
> OK I am off topic myself.



You have a stronger probability of getting that funding with the left wing political spectrum if we look at historical budget proposals for vast majority of nation states. 



HTC said:


> You *may* have that backwards: there should be a 4th genotype of the "much less" lethal variety (by comparison with the current virus), which *MAY explain how "it was missed"* in 2019 since, most likely, it was thought of as "a mere flu".



That chart is very very interesting. I really do think maybe COVID 19 was here last year, I mean let's face it, the medical community never actually tests to see if people have the flu or not, I have never heard of anyone being tested actually. If you have the symptoms they just diagnose you with it, a bad cough and fever, we will mark that as flu. I went to urgent care 3x in January-February this year with a deep lung cough that had me on my knees seeing silver stars, never coughed like that my entire life. It turns out I am allergic to Penicillin, so they gave me Azithromycin (this was before ZPAC might be an answer to COVID 19 was even a thing), and on day 4 or so of taking this antibiotic I was fully cured, but since there are no tests it was just touted up as some kind of bug or flu is what I was told in urgent care. Never been that sick my entire life though.

Would be nice if they stockpile tests or figure out a way to ramp up production for testing. Ventilators are nice and all, but last I heard they only have like 30-40% survival rate with ventilators, maybe it's time to ramp up production on tests, and isolate those people that test positive, and eventually over time we will get a vaccine and herd immunity will form. This is really the only path forward I think, even if it mutates like the cold or flu each year, the vaccine will still work a little possibly preventing deaths even if it only limits the newly developed form of it by 30% of it, etc. The data shows even in years when the flu vaccine does not match the current virus, the ability of people who got the vaccine to fight it off quick was better than those who did not get the vaccine.

So there is hope at least.


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## FordGT90Concept (Apr 11, 2020)

the54thvoid said:


> So, take a known average (the flu) and then look at a huge outlier - it's a marker for something else. I'm not saying Covid-19, but such a massive jump is unlikey to be standard flu.


But it wasn't a "massive jump."  COVID spreads so fast and ~5% of those that get hospitalized for it wind up dead.  Influenza doesn't do that.  The COVID strains that are global now stands out like a sore thumb: just look at ICUs.


I think my point is this paper needs peer review.  It implies things that don't align with observed patterns.  There's something missing.


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## xkm1948 (Apr 11, 2020)

FordGT90Concept said:


> But it wasn't a "massive jump."  COVID spreads so fast and ~5% of those that get hospitalized for it wind up dead.  Influenza doesn't do that.  The COVID strains that are global now stands out like a sore thumb: just look at ICUs.
> 
> 
> I think my point is this paper needs peer review.  It implies things that don't align with observed patterns.  There's something missing.



This is published, peer-reviewed. This is NOT biorxiv. And PNAS has some of the most rigorous peer review process.


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## FordGT90Concept (Apr 11, 2020)

Let me rephrase, your commentary in the OP about 2019 flu season was your own.  It's not in the article.  So I mistakenly questioned the article...


Finally read the paper a bit and...the virus is thought to have originated from a bat.  From a bat, it diverged: one prominent strain was found exclusively in China; the other prominent strain was found 3/4 in USA and 1/4 in China.  Each mutation apparently coalesced into genotype A which is in China, Australia, Europe, and East Asia.  One of A's mutations was B which is the type that swept through China and, to a lesser extent, East Asia.  Type B seems to only be effective against Asians because everyone not Asian caught a mutated version of it...including type C which is found in Australia.

Isolation is the only way to fight this thing.  The more people it infects, the more it mutates.  The authors of the paper literally tracked some of these genotypes to a specific carrier that traveled around the world.  I'll just quote it because it's a lot of information and tells some stories of the virus (extra line breaks are mine to split cases):


> On 25 February 2020, the first Brazilian was reported to have been infected following a visit to Italy, and the network algorithm reflects this with a mutational link between an Italian and his Brazilian viral genome in cluster C (SI Appendix, Fig. S1).
> 
> In another case, a man from Ontario had traveled from Wuhan in central China to Guangdong in southern China and then returned to Canada, where he fell ill and was conclusively diagnosed with coronavirus disease 2019 (COVID-19) on 27 January 2020. In the phylogenetic network (SI Appendix, Fig. S2), his virus genome branches from a reconstructed ancestral node, with derived virus variants in Foshan and Shenzhen (both in Guangdong province), in agreement with his travel history. His virus genome now coexists with those of other infected North Americans (one Canadian and two Californians) who evidently share a common viral genealogy.
> 
> The case of the single Mexican viral genome in the network is a documented infection diagnosed on 28 February 2020 in a Mexican traveler to Italy. Not only does the network confirm the Italian origin of the Mexican virus (SI Appendix, Fig. S3), but it also implies that this Italian virus derives from the first documented German infection on 27 January 2020 in an employee working for the Webasto company in Munich, who, in turn, had contracted the infection from a Chinese colleague in Shanghai who had received a visit by her parents from Wuhan. This viral journey from Wuhan to Mexico, lasting a month, is documented by 10 mutations in the phylogenetic network.


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## xkm1948 (Apr 11, 2020)

Isolation will slow it not beat it. To beat it we need specialized anti-viral drug, soon.

29000bp is not a small genome size for a virus. The more complex a virus gets the harder for it to get more successful mutations.

ACE2 receptor entry utilization by COVID19 is already pretty much maxed out its transmission rate. The only way for it to be more successful is going the retroviral way: inserting itself into our genome, like HIV. That would be extremely nasty.


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## HTC (Apr 11, 2020)

xkm1948 said:


> *Isolation will slow it not beat it.* To beat it we need specialized anti-viral drug, soon.
> 
> 29000bp is not a small genome size for a virus. The more complex a virus gets the harder for it to get more successful mutations.
> 
> ACE2 receptor entry utilization by COVID19 is already pretty much maxed out its transmission rate. The only way for it to be more successful is going the retroviral way: inserting itself into our genome, like HIV. That would be extremely nasty.



But it will help hospitals cope with "the rush" of patients @ the same time that require hospitalization and especially those with severe symptoms, which is the whole point of lockdowns.

Like seen in Italy and Spain, the number of new cases does indeed come down and *it seems* the ICU cases are alleviating in these countries. Unfortunately, both Italian and Spanish medical communities were hit hard so they have a lot fewer "combat units" with which to face this "battle", so the death toll is *still* in "dark numbers" but it's coming down, albeit slowly.


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## Space Lynx (Apr 11, 2020)

HTC said:


> But it will help hospitals cope with "the rush" of patients @ the same time that require hospitalization and especially those with severe symptoms, which is the whole point of lockdowns.
> 
> Like seen in Italy and Spain, the number of new cases does indeed come down and *it seems* the ICU cases are alleviating in these countries. Unfortunately, both Italian and Spanish medical communities were hit hard so they have a lot fewer "combat units" with which to face this "battle", so the death toll is *still* in "dark numbers" but it's coming down, albeit slowly.



Until we stop social distancing and isolating, which has to happen some time cause economy and all that. Then there will be a bigger second wave because we won't be able to afford another shut down. Hospitals will still be overwhelmed, but hopefully by then we will have a more clear cut answer on a new medicine. I had luck with ZPAC myself, hopefully the studies show I was not the only one.


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## FordGT90Concept (Apr 11, 2020)

xkm1948 said:


> To beat it we need specialized anti-viral drug, soon.


Seems doubtful to catch all the genotypes.  Isolation prevents the formation and spread of more genotypes.

Antiviral drugs in general are few and far between with limited effectiveness.



xkm1948 said:


> ACE2 receptor entry utilization by COVID19 is already pretty much maxed out its transmission rate.   The only way for it to be more successful is going the retroviral way: inserting itself into our genome, like HIV.


It is extremely transmissible hence all of the social measures necessary to slow it down.  It's already way too "successful."


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## HTC (Apr 11, 2020)

lynx29 said:


> Until we stop social distancing and isolating, which has to happen some time cause economy and all that. Then there will be a bigger second wave because we won't be able to afford another shut down. Hospitals will still be overwhelmed, but hopefully by then we will have a more clear cut answer on a new medicine. I had luck with ZPAC myself, hopefully the studies show I was not the only one.


But we've already learned steps that work and steps that don't, so we can avoid unnecessary measures, not need a harder stance and, most especially, we can take steps RIGHT AWAY, instead of the "wait and see approach" most countries took: the faster steps are taken, the faster "normalcy" returns, if we still remember what "normal" feels like after this ends for good.


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