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Why Delta variant is able to spread so well

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redsturgeon
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Why Delta variant is able to spread so well

#430215

Postby redsturgeon » July 25th, 2021, 9:01 am

https://www.nature.com/articles/d41586-021-01986-w

Viral load is roughly 1,000 times higher in people infected with the Delta variant than those infected with the original coronavirus strain, according to a study in China.


John

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Re: Why Delta variant is able to spread so well

#430216

Postby GrahamPlatt » July 25th, 2021, 9:17 am

So is this still entirely down to the changes in the spike protein, enabling more efficient cell penetration, or is there something about it that speeds up its ability to replicate within cells?

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Re: Why Delta variant is able to spread so well

#430217

Postby Nimrod103 » July 25th, 2021, 9:19 am

GrahamPlatt wrote:So is this still entirely down to the changes in the spike protein, enabling more efficient cell penetration, or is there something about it that speeds up its ability to replicate within cells?


Can't find it now, but I think John Campbell said it replicates in the cell much more rapidly, and it released in abundance.

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Re: Why Delta variant is able to spread so well

#430230

Postby onthemove » July 25th, 2021, 10:46 am

redsturgeon wrote:https://www.nature.com/articles/d41586-021-01986-w

Viral load is roughly 1,000 times higher in people infected with the Delta variant than those infected with the original coronavirus strain, according to a study in China.


John


More of it in the blood doesn't really seem a satisfactory answer as to how or why the delta variant is "able" to spread so well (title of thread).

It's a bit like saying Usain Bolt is "able" to win his races because he runs faster. It's not incorrect, it just doesn't really seem to be all that enlightening with regards explaining his ability.

Surely to understand 'ability' in this context for the virus, as the other posters have now eluded to, surely we'd need to understand what it is about the delta variant that achieves that higher viral load, which the article doesn't really consider at all.

I must admit, I do find it puzzling... if there's a 1000x higher viral load, how is it that this isn't doing significantly more damage to organs, etc, and isn't meaning infection is far more serious. The article states "A number of other questions about the Delta variant remain unanswered. It’s still unclear, for instance, whether it is more likely to cause severe disease than the original strain"... how can you have 1000x more virus particles in the blood, and not have (an unambiguously) more severe disease as a result? Surely that's going to require a much more massive immune response, etc, and doing more simultaneous damage?

Caveat - the study only compared 62 patients with the original vs 63 with delta strain, and it does say "She and Cowling both suspect that estimates of the exact difference in viral load between Delta and the original strain are likely to shift as more scientists study the virus in various populations.".

I've just tried to lookup a little more on PCR tests, as the research above used PCR tests to measure viral load, and aren't PCR tests what the test and trace are using to confirm cases(?). Which lead me to wonder, if PCR tests are measuring viral load, how has this not been picked up much earlier from the PCR testing being done for test and trace. 1000x higher viral load is surely quite significant that the test and trace PCR testing would have noticed it?

I'm not sure I've found an answer to that yet, but I did come across this... "False negatives can occur up to 30% of the time with different PCR tests, meaning they’re more useful for confirming the presence of an infection than giving a patient the all-clear. They can also provide false positive results, as they’re so sensitive they can potentially signal a positive result upon detecting dead, deactivated virus still present in the body of someone who has recovered from Covid-19." https://www.medicaldevice-network.com/f ... r-antigen/

And also this... "Viral load and how it is measured Viral load tests measure the quantity of genetic material, commonly RNA, of a virus present in the blood. Several tests are typically done over an extended period, with initial measurements serving as the baseline and subsequent measurements compared to this. Viral load measurements can differ daily, and therefore long-term trends are used to evaluate disease progression." https://www.news-medical.net/health/Wha ... -Load.aspx

Which, I dunno... if these tests can give 30% false negative, and also give false positives, and measurements can fluctuate daily.... how much confidence can we have in research on just 62 / 63 people?

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Re: Why Delta variant is able to spread so well

#430233

Postby redsturgeon » July 25th, 2021, 11:23 am

onthemove wrote:
redsturgeon wrote:https://www.nature.com/articles/d41586-021-01986-w

Viral load is roughly 1,000 times higher in people infected with the Delta variant than those infected with the original coronavirus strain, according to a study in China.


John


More of it in the blood doesn't really seem a satisfactory answer as to how or why the delta variant is "able" to spread so well (title of thread).



Who mentioned more of it in the blood?

John

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Re: Why Delta variant is able to spread so well

#430234

Postby Lootman » July 25th, 2021, 11:24 am

redsturgeon wrote:https://www.nature.com/articles/d41586-021-01986-w

Viral load is roughly 1,000 times higher in people infected with the Delta variant than those infected with the original coronavirus strain, according to a study in China.

It makes me wonder what if Delta had been the original variant? It clearly would have spread faster and further than happened in early 2020, perhaps to the point that containment measures would have been inadequate.

In which case we would have tested the government's original "herd immunity" theory without any conscious effort.

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Re: Why Delta variant is able to spread so well

#430235

Postby scrumpyjack » July 25th, 2021, 11:27 am

redsturgeon wrote:https://www.nature.com/articles/d41586-021-01986-w

Viral load is roughly 1,000 times higher in people infected with the Delta variant than those infected with the original coronavirus strain, according to a study in China.


John


The Wuhan lab must have been working very hard to improve the effectiveness of their virus so much!

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Re: Why Delta variant is able to spread so well

#430236

Postby onthemove » July 25th, 2021, 11:36 am

redsturgeon wrote:
Who mentioned more of it in the blood?

John


You did - at least in what you quoted (which was the substance of your post).

Here's what you quoted (my bold)... "Viral load is roughly 1,000 times higher in people infected with the Delta variant than those infected with the original coronavirus strain, ..."

Here's what viral load is...

"What is Viral Load?
Viral load refers to the amount of virus in an infected person’s blood." https://www.news-medical.net/health/Wha ... -Load.aspx

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Re: Why Delta variant is able to spread so well

#430237

Postby redsturgeon » July 25th, 2021, 11:45 am

onthemove wrote:
redsturgeon wrote:
Who mentioned more of it in the blood?

John


You did - at least in what you quoted (which was the substance of your post).

Here's what you quoted (my bold)... "Viral load is roughly 1,000 times higher in people infected with the Delta variant than those infected with the original coronavirus strain, ..."

Here's what viral load is...

"What is Viral Load?
Viral load refers to the amount of virus in an infected person’s blood." https://www.news-medical.net/health/Wha ... -Load.aspx



Interesting. The papers only mention the use of PCR testing and not whether blood samples or nose/throat swabs were used. I assumed they would be using swabs.

John

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Re: Why Delta variant is able to spread so well

#430264

Postby onthemove » July 25th, 2021, 1:26 pm

redsturgeon wrote:Interesting. The papers only mention the use of PCR testing and not whether blood samples or nose/throat swabs were used. I assumed they would be using swabs.

John


I wasn't sure what to assume, because I wasn't sure if sticking a swab up your nose or back of throat could provide a suitable viral load measurement, (vs just being useful for detecting if the virus is there or not, with the risk of 30% false negatives, etc).

That's why I first googled viral load to try to understand what it specifically refers to and came across that link that I provided that said it was in relation to blood. I've also come across a few other links from seemingly reputable sources that also say viral load is usually measured in relation to blood or plasma.

Which I can understand, because a volume of blood is easily measurable, so it's easy to see how you could get a parts-per-volume measurement.

I'm less clear how you can get a parts-per-volume measurement from a swab... I mean, how do you know how much volume you have in the swab?

But further googling does suggest that nose and throat swabs are used for measuring viral load, albeit, they each tend to give significantly different results. Though it's not clear whether that's because of the nature of how they work, or whether that's because there are genuinely different viral loads in those place - or a mix of the two.

I've gone to the original paper that the Nature article seems to be based upon, and they do mention - buried away in the details - they were using throat swabs...

"Virus amplification and sequencing
245 Total RNAs were extracted from oropharyngeal swab samples by using QIAamp Viral
246 RNA Mini Kit (Qiagen, Cat. No. 52904). Virus genomes were generated by two
247 different approaches, (i) using commercial sequencing kit of BGI (ATOPlex
248 1000021625) and sequencing on the BGI MGISEQ-2000 (n=25), and (ii) using
249 version 3 of the ARTIC COVID-19 multiplex PCR primers
250 (https://artic.network/ncov-2019) for genome amplification, followed by library
251 construction with Illumina Nextera XT DNA Library Preparation Kit and sequencing
252 with PE150 (n=63) or SE100 (n=38) on Illumina Miniseq. We report only
253 high-quality genome sequences for which we were able to generate >95% genome
254 coverage. " https://www.medrxiv.org/content/10.1101 ... 2.full.pdf


I must admit, I'm surprised that they can get a 'measurable' - as in being able to quantify - the viral load from a swab in a reliable and comparable way, rather than just looking at a rough and ready threshold to establish a 'positive' test result.

After a bit of googling to try to understand a little more about how viral load can be established from such swabs, I've not yet got a definitive understanding (specifically how they quantify the volume in the sample in the swab so that they can then relate the number of viral particles to that volume), but have come across this article in my search...

"Conclusions: NPS [nasopharyngeal swabs] had significantly higher SARS-CoV-2 detection rate, sensitivity, and viral load than OPS [oropharyngeal swabs].(...) NPS should be recommended for (...) and monitoring SARS-CoV-2 load. " https://www.frontiersin.org/articles/10 ... 00334/full


But then, perhaps that research reported in the Nature article was specifically looking at throat swabs on the presumption (?) that this would be the most relevant to transmission(coughing/breathing?)

Or perhaps this new paper is saying that the load with the delta variant is now higher in the throat(?) compared to previous variants.

It does feel a bit poor that they haven't been much clearer about what viral load it is they are referring to and how they measured it.

I mean, there's quite a difference in how I would read...

- 'viral load is 1000x higher with the delta variant'
vs
- 'viral load in the throat is 1000x higher with the delta variant'

After spending much more time now looking into this than I ever intended to, I'm now more inclined to read the nature article as saying the latter, not the former.

Which puts it in quite a different perspective, as (iirc) I've already seen plenty of papers referenced reporting that the different variants can result in different quantities of the virus being present in different areas of the anatomy.

Like I mentioned in an earlier post, I did question how a 1000x viral load wouldn't result in a much more serious outcome for the infected patient.

And this probably provides the answer... if that 1000x viral load is just in the throat, and not the blood, etc, then potentially it's a little more 'out of the way' and less of a problem for the infected patient and could perhaps therefore explain why it doesn't automatically mean you'd expect the patient to be sicker.

If only the paper and article had been clearer about that up front!

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Re: Why Delta variant is able to spread so well

#430269

Postby redsturgeon » July 25th, 2021, 1:45 pm

onthemove wrote:
redsturgeon wrote:Interesting. The papers only mention the use of PCR testing and not whether blood samples or nose/throat swabs were used. I assumed they would be using swabs.

John


I wasn't sure what to assume, because I wasn't sure if sticking a swab up your nose or back of throat could provide a suitable viral load measurement, (vs just being useful for detecting if the virus is there or not, with the risk of 30% false negatives, etc).

That's why I first googled viral load to try to understand what it specifically refers to and came across that link that I provided that said it was in relation to blood. I've also come across a few other links from seemingly reputable sources that also say viral load is usually measured in relation to blood or plasma.

Which I can understand, because a volume of blood is easily measurable, so it's easy to see how you could get a parts-per-volume measurement.

I'm less clear how you can get a parts-per-volume measurement from a swab... I mean, how do you know how much volume you have in the swab?

But further googling does suggest that nose and throat swabs are used for measuring viral load, albeit, they each tend to give significantly different results. Though it's not clear whether that's because of the nature of how they work, or whether that's because there are genuinely different viral loads in those place - or a mix of the two.

I've gone to the original paper that the Nature article seems to be based upon, and they do mention - buried away in the details - they were using throat swabs...

"Virus amplification and sequencing
245 Total RNAs were extracted from oropharyngeal swab samples by using QIAamp Viral
246 RNA Mini Kit (Qiagen, Cat. No. 52904). Virus genomes were generated by two
247 different approaches, (i) using commercial sequencing kit of BGI (ATOPlex
248 1000021625) and sequencing on the BGI MGISEQ-2000 (n=25), and (ii) using
249 version 3 of the ARTIC COVID-19 multiplex PCR primers
250 (https://artic.network/ncov-2019) for genome amplification, followed by library
251 construction with Illumina Nextera XT DNA Library Preparation Kit and sequencing
252 with PE150 (n=63) or SE100 (n=38) on Illumina Miniseq. We report only
253 high-quality genome sequences for which we were able to generate >95% genome
254 coverage. " https://www.medrxiv.org/content/10.1101 ... 2.full.pdf


I must admit, I'm surprised that they can get a 'measurable' - as in being able to quantify - the viral load from a swab in a reliable and comparable way, rather than just looking at a rough and ready threshold to establish a 'positive' test result.

After a bit of googling to try to understand a little more about how viral load can be established from such swabs, I've not yet got a definitive understanding (specifically how they quantify the volume in the sample in the swab so that they can then relate the number of viral particles to that volume), but have come across this article in my search...

"Conclusions: NPS [nasopharyngeal swabs] had significantly higher SARS-CoV-2 detection rate, sensitivity, and viral load than OPS [oropharyngeal swabs].(...) NPS should be recommended for (...) and monitoring SARS-CoV-2 load. " https://www.frontiersin.org/articles/10 ... 00334/full


But then, perhaps that research reported in the Nature article was specifically looking at throat swabs on the presumption (?) that this would be the most relevant to transmission(coughing/breathing?)

Or perhaps this new paper is saying that the load with the delta variant is now higher in the throat(?) compared to previous variants.

It does feel a bit poor that they haven't been much clearer about what viral load it is they are referring to and how they measured it.

I mean, there's quite a difference in how I would read...

- 'viral load is 1000x higher with the delta variant'
vs
- 'viral load in the throat is 1000x higher with the delta variant'

After spending much more time now looking into this than I ever intended to, I'm now more inclined to read the nature article as saying the latter, not the former.

Which puts it in quite a different perspective, as (iirc) I've already seen plenty of papers referenced reporting that the different variants can result in different quantities of the virus being present in different areas of the anatomy.

Like I mentioned in an earlier post, I did question how a 1000x viral load wouldn't result in a much more serious outcome for the infected patient.

And this probably provides the answer... if that 1000x viral load is just in the throat, and not the blood, etc, then potentially it's a little more 'out of the way' and less of a problem for the infected patient and could perhaps therefore explain why it doesn't automatically mean you'd expect the patient to be sicker.

If only the paper and article had been clearer about that up front!


I guess my assumption was based on the fact that the thousands of coronavirus PCR tests we have personally been involved with have all been throat and/or nasal swabs.

Assumptions are of course not recommended but appear to be correct in the instance.

John

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Re: Why Delta variant is able to spread so well

#430278

Postby Mike4 » July 25th, 2021, 2:05 pm

redsturgeon wrote:
I guess my assumption was based on the fact that the thousands of coronavirus PCR tests we have personally been involved with have all been throat and/or nasal swabs.

Assumptions are of course not recommended but appear to be correct in the instance.

John




Dr John published a video last night on this, where he seems to be saying the size of the viral load is indicated by the number of cycle thresholds used to detect the virus in a swab sample. 34 cycles for the original strain of the virus, 24 cycle thresholds for Delta.

https://www.youtube.com/watch?v=JccyYEW ... hnCampbell

Oops forgot to spell it out, I think Dr John either implies or says that this reduction in the number of cycles necessary from 34 to 24 equates to a 1,000-fold difference in the concentration of viral particles in the samples.

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Re: Why Delta variant is able to spread so well

#430287

Postby GrahamPlatt » July 25th, 2021, 3:03 pm

Yes, that I already understood (PCR cycles), but what I want to know is how it comes about that it’s so prolific. If it’s just better at penetrating cells, then OK, that’s the spike protein at work. But if it’s replicating faster within cells, then some other genetic change has occurred, which I’ve not heard about.

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Re: Why Delta variant is able to spread so well

#430290

Postby Julian » July 25th, 2021, 3:55 pm

GrahamPlatt wrote:Yes, that I already understood (PCR cycles), but what I want to know is how it comes about that it’s so prolific. If it’s just better at penetrating cells, then OK, that’s the spike protein at work. But if it’s replicating faster within cells, then some other genetic change has occurred, which I’ve not heard about.

You might find this video interesting starting at time index 9:35 up to about time index 13:08 - https://youtu.be/K4PRJNeWCkw - which seems to address exactly your question.

- Julian

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Re: Why Delta variant is able to spread so well

#430301

Postby GrahamPlatt » July 25th, 2021, 4:49 pm

Thank you Julian. However, having watched it I don’t feel the q. has been answered. Prof. Barclay describes why delta is more transmissible (it’s “stickier”, and evades our interferons by (to pinch a well-known phrase) being “oven ready” at the point of impaction). However, she does not really address (admits there is little known) about it’s other properties. As to how it produces higher viral loads then, one might imagine that because this stickiness will operate not just in the nose and throat, but also in the rest of the body, viral particles circulating in the blood stream are more likely to go on to infect the next cell in the chain, and so on. BUT, if that’s so, given that infected cells die (bursting as they release their viral parasites), a higher viral load would seem then to imply a lot more dead host cells, so why is it that these patients aren’t a whole lot sicker? Is each cell producing more virus before it burts? More virus but less cell death?

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Re: Why Delta variant is able to spread so well

#430319

Postby Julian » July 25th, 2021, 6:33 pm

GrahamPlatt wrote:Thank you Julian. However, having watched it I don’t feel the q. has been answered. Prof. Barclay describes why delta is more transmissible (it’s “stickier”, and evades our interferons by (to pinch a well-known phrase) being “oven ready” at the point of impaction). However, she does not really address (admits there is little known) about it’s other properties. As to how it produces higher viral loads then, one might imagine that because this stickiness will operate not just in the nose and throat, but also in the rest of the body, viral particles circulating in the blood stream are more likely to go on to infect the next cell in the chain, and so on. BUT, if that’s so, given that infected cells die (bursting as they release their viral parasites), a higher viral load would seem then to imply a lot more dead host cells, so why is it that these patients aren’t a whole lot sicker? Is each cell producing more virus before it burts? More virus but less cell death?

Interesting thought about cell death but one observation I will make is - are you thinking too much in terms of the infected person’s body being a closed system? Of this massively increased viral load being detected, from I think we have determined swabbing, how much of it would have been destined to infect other cells within the infected host and how much of it would have been shed (breathed out) to potentially form aerosols that find other passers by? Might there be something in the infection patterns of a host infected with Delta vs earlier variants that means replication is higher in the early stages (upper respiratory tract) and that the explosion of virus “up top” means that a much higher percentage is shed into the external environment vs Alpha for instance? Maybe if/when the remaining-in-the-host virus fails to be defeated by the host’s immune system in its early stages the virus’s progress deeper into the host is not as alarmingly accelerated as these 1,000-fold increases seen from swabbing?

All well beyond my pay grade so I’m only throwing out a few random thoughts to keep the discussion going rather than claiming I have any answers.

- Julian

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Re: Why Delta variant is able to spread so well

#431045

Postby ursaminortaur » July 28th, 2021, 8:46 pm

In the US the CDC is advising that fully vaccinated individuals should wear masks in cetain indoor spaces as there is evidence that fully vaccinated individuals can spread the Delta variant.


https://www.theguardian.com/world/2021/jul/28/cdc-director-new-mask-guidance-vaccinated-spreading-delta-variant

The director of the Centers for Disease Control and Protection spoke on Wednesday about evidence that vaccinated people can spread the Covid-19 Delta variant to others, after the nation’s top health agency expanded on its new guidance that fully vaccinated Americans wear masks indoors in certain places.

Rochelle Walensky said “new science” observed in recent days demonstrated that new variants of the coronavirus were transmissible by people who have been fully vaccinated in some cases.

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Re: Why Delta variant is able to spread so well

#431061

Postby Bouleversee » July 28th, 2021, 10:20 pm

There has always been the suggestion that even vaccinated people might pick up and pass on the virus, especially in the case of variants.

All the more reason why I was surprised and somewhat annoyed to find that the driver who had been sent to pick me up to view a couple of apartments in a retirement village (far too small for me) was not wearing a facemask and when I called out after locking the door that I had forgotten to get mine out of another handbag and would quickly get it, said it didn't matter. Well, it does matter so far as I am concerned since apart from being somewhat long in the tooth I have IPF and I don't feel inclined to take unnecessary risks. I asked whether he had been double jabbed and he said he hadn't had any jabs as he thought the vaccine poisoned the system. After further discussion, during which he said he took a lateral flow test every other day, he said he would wear a mask if I wished (yes please!) but by then we were almost at our destination. I find it extraordinary that a chauffeur is allowed to have such a cavalier attitude to his passengers, especially given the destination. I opened my window wide but he didn't open his at all.

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Re: Why Delta variant is able to spread so well

#431065

Postby 9873210 » July 28th, 2021, 10:36 pm

Bouleversee wrote: I opened my window wide but he didn't open his at all.

I believe the best procedure is to sit in the opposite back seat and open the other two windows. In most vehicles this will create an airflow that tends to separate the two occupants.

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Re: Why Delta variant is able to spread so well

#431093

Postby GrahamPlatt » July 29th, 2021, 7:37 am

Julian wrote:heads up


A lot of detail here. Not for the squeamish.

https://www.nature.com/articles/d41586- ... -mIUbJPGI8


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