Hopeful good news from Italy: virus weakening?

10,966 Views | 59 Replies | Last: 5 yr ago by eidetic78
BiochemAg97
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DTP02 said:

My curiosity is piqued by the idea of a quantitatively smaller viral load. The Italian doc is quoted as saying they are seeing infinitesimally smaller viral loads the last 10 days than during their peak. This isn't some random doc but is the head of one of the largest research hospitals in Europe, so I think we can assume he's not talking out his rear.

The topic of "viral load" and how it impacts spread, and especially severity, has been discussed over the last few months but I don't know that there has really been much clarity let alone anything approaching a consensus.

This raises a lot of questions which aren't necessarily about the virus possibly mutating, but more about how this virus actually works in its "original" state.

Why are they seeing such a huge difference in viral load?

How much does viral load impact symptomatic vs asymptomatic infection?

How much does it impact severity of symptoms?

If a patient has "infinitesimally smaller" viral load, is that enough to trigger antibodies/immunity or is there a threshold which must be met to trigger immune response?

You can see how critical some of these questions and answers are:

If a tiny viral load leads to asymptomatic patients but yields immunity, then we already have a poor man's vaccine.

Even if we can't go that far, it's still important in determining ongoing mitigation strategies.

1) smaller dose during infection should lead to overall smaller viral load as it would take time for the smaller dose to catch up to larger dose. Also a mutation that slowed down the viral replication or slowed down how quickly it entered a cell could lead to lower doses.

2 and 3) the immune system takes time to respond. With a smaller viral load, the immune system can respond when less damage is done, which could lead to better clinical outcomes (reduced or no symptoms).

4) if there is a small enough amount and it is handled easily by it may not create a strong immune response. This is one of the things they test for in vaccines. You need a sufficient response to get immunity, and that may require a larger dose or additional doses of vaccine.

Infinitesimally smaller viral load doesn't sound like much of a difference.

jenn96
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Equinsu Ocha said:

That might have been the best 3 post exchange in the history of TexAgs.

Seriously, thank you guys. I needed that today.
Ranger222
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Quotes from a group of scientists on this matter:
Quote:

The comments, which received widespread attention following a Reuters report, prompted vigorous pushback from Michael Ryan, a top official with the World Health Organization, who said Monday during an online news conference that "we need to be exceptionally careful not to create a sense that all of a sudden the virus by its own volition has now decided to be less pathogenic. That is not the case at all."

The consensus among other experts interviewed Monday is that the clinical findings in Italy likely do not reflect any change in the virus itself.

Zangrillo's clinical observations are more likely a reflection of the fact that with the peak of the outbreak long past, there is less virus in circulation, and people may be less likely to be exposed to high doses of it. In addition, only severely sick people were likely to be tested early on, compared with the situation now when even those with mild symptoms are more likely to get swabbed, experts said.

Vaughn Cooper, an infectious-disease expert at the University of Pittsburgh School of Medicine, said the new coronavirus mutates slowly compared with influenza and other microbes, and its genetic changes appear to be "mostly inconsequential."

"I believe it's safe to say that the differences that doctors are reporting in Italy are entirely due to changes to medical treatment and in human behavior, which limit transmission and numbers of new infections initiated by large inocula a larger dose of virus appears to be worse rather than changes in the virus itself," he said.

All viruses evolve over time, and many infectious-disease experts think the novel coronavirus will eventually become less lethal to human beings, joining four other coronaviruses in causing common colds. But there is no solid evidence so far that it has changed significantly in the five months since it was first recognized among patients in Wuhan, China.

"The virus hasn't lost function on the time scale of two months," said Andrew Noymer, an epidemiologist at the University of California at Irvine. "Loss of function is something I expect over a time scale of years."

Researchers Harm van Bakel, Emilia Sordillo and Viviana Simon at the Icahn School of Medicine at Mount Sinai, who have been focusing on the genetics of the novel coronavirus, said in an interview that they had not seen a dip in viral load among patients in that hospital system since March, nor have they detected any major genetic changes in the virus in New York City.


https://www.washingtonpost.com/health/experts-dispute-reports-coronavirus-is-becoming-less-lethal/2020/06/01/8f8ace7c-a432-11ea-b619-3f9133bbb482_story.html
cone
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Quote:

people may be less likely to be exposed to high doses of it


it'd be nice if they expanded on this, since it seems pretty critical
HotardAg07
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Keegan99
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Or the small portion of people with the physiology to shed massive amounts of virus have largely already been infected (maybe shedding correlates to susceptibility to infection? That is, both are signs that you're a really, really good host?) and have been taken out of play thanks to immunity?
CardiffGiant
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Yeah I'm not a DR or epidemiologist but this virus spreads so easily which means it's replicating itself at a rapid rate. I would think this continual replication is part of the reason why the mutations take place hence you're seeing the mutations happen quicker than other viruses. If I'm way off on this, one of the Dr's please correct me.
BiochemAg97
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CardiffGiant said:

Yeah I'm not a DR or epidemiologist but this virus spreads so easily which means it's replicating itself at a rapid rate. I would think this continual replication is part of the reason why the mutations take place hence you're seeing the mutations happen quicker than other viruses. If I'm way off on this, one of the Dr's please correct me.
It is actually fairly slow compared to other respiratory RNA viruses like the flu.

DNA viruses generally mutate more slowly because the proteins that replicate DNA are more accurate than the proteins that replicate RNA.
DTP02
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BiochemAg97 said:

DTP02 said:

My curiosity is piqued by the idea of a quantitatively smaller viral load. The Italian doc is quoted as saying they are seeing infinitesimally smaller viral loads the last 10 days than during their peak. This isn't some random doc but is the head of one of the largest research hospitals in Europe, so I think we can assume he's not talking out his rear.

The topic of "viral load" and how it impacts spread, and especially severity, has been discussed over the last few months but I don't know that there has really been much clarity let alone anything approaching a consensus.

This raises a lot of questions which aren't necessarily about the virus possibly mutating, but more about how this virus actually works in its "original" state.

Why are they seeing such a huge difference in viral load?

How much does viral load impact symptomatic vs asymptomatic infection?

How much does it impact severity of symptoms?

If a patient has "infinitesimally smaller" viral load, is that enough to trigger antibodies/immunity or is there a threshold which must be met to trigger immune response?

You can see how critical some of these questions and answers are:

If a tiny viral load leads to asymptomatic patients but yields immunity, then we already have a poor man's vaccine.

Even if we can't go that far, it's still important in determining ongoing mitigation strategies.

1) smaller dose during infection should lead to overall smaller viral load as it would take time for the smaller dose to catch up to larger dose. Also a mutation that slowed down the viral replication or slowed down how quickly it entered a cell could lead to lower doses.

2 and 3) the immune system takes time to respond. With a smaller viral load, the immune system can respond when less damage is done, which could lead to better clinical outcomes (reduced or no symptoms).

4) if there is a small enough amount and it is handled easily by it may not create a strong immune response. This is one of the things they test for in vaccines. You need a sufficient response to get immunity, and that may require a larger dose or additional doses of vaccine.

Infinitesimally smaller viral load doesn't sound like much of a difference.




To clarify, I said "infinitesimally smaller" which put you on the wrong track because it negates the meaning if interpreted literally. The Italian doc actually said the viral load was infinitesimal in comparison, which means it's incredibly smaller.
CardiffGiant
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Thanks for the response. Very educational! Had no idea.
DadHammer
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No matter for what reason Italy looks to be just about over covid.

https://www.worldometers.info/coronavirus/country/italy/
PlaneCrashGuy
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Ranger222 said:

I have a PhD in Microbiology/Immunology and I currently am working on a SARS-CoV-2 project.
Get the "Verified Doctor" tag from TexAgs.
I'm not sure if people genuinely believe someone is going to say, "Wow, if some people say I'm a moron for not believing this, it clearly must be true."

It's not much a persuasive argument. It really just sounds like a bunch of miniature dachshunds barking because the first one one barked when it thought it heard something.
KlinkerAg11
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How far behind Italy are we on the timeline of a major outbreak?

A month?
Windy City Ag
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Bloomberg had a pretty good article summarizing a lot of what was said and reinforcing Ranger's point.

https://www.bloomberg.com/opinion/articles/2020-06-04/coronavirus-post-peak-lull-in-cases-doesn-t-mean-weaker-virus

Quote:

There's an enormous difference between a lull caused by a persistent shift in the virus, and one caused by other dynamics. The first means that the virus has a real chance of petering out as a major threat over time. The second scenario means that the virus could return with a vengeance if countries and individuals put their guard down. At the moment, there just doesn't seem to be enough evidence to support the idea of a shift.

Coronaviruses are slow to mutate compared to influenza, and Covid-19 doesn't appear to be different. Most mutations don't result in any kind of meaningful change to how a virus acts. Early Studies of SARS-CoV2 genomes have found genetic changes but not a lineage that meets the definition of a new strain, a branch of the virus that's functionally different from others.

One pre-print at over 15,000 genomes from the University College of London's Genetics Institute examined the possible emergence of a more transmissible strain. The mutations it found appeared to be either neutral or slightly harmful to Covid's spread, and a less infectious version is less likely to stick around. The researchers didn't look at the possibility of a mutation that makes the virus less deadly, but said most recurrent genetic changes they'd seen so far don't seem like evolutionary adaptations.

If the virus isn't shifting into a milder form, what else can explain why it doesn't seem as bad in some places? The fact is, many other things could be at work. The virus may well appear weaker in areas on the other side of a peak because expanded testing and surveillance are catching people earlier in the course of their illness, as opposed to months ago when most were only tested if they got sick enough to brave a packed hospital. Clinicians also know more about how to treat people, and are no longer as overwhelmed.
A solid portion of those most vulnerable due to a weakened immune system or other factors have likely already been infected, especially in hard-hit areas in Italy. Those that haven't are better protected by public health measures, a lower level of community spread, possible temporary seasonal effects, and at least some degree of acquired immunity in the population.

Given all that, the most prudent path for a long time to come is to treat Covid-19 as the deadly threat it was in Italy a short few weeks ago and continues to be around the world.
eidetic78
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They won't give it to scientists. Even virologists like myself. I suggested maybe a flask icon or something.
PlaneCrashGuy
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eidetic78 said:

They won't give it to scientists. Even virologists like myself. I suggested maybe a flask icon or something.
Leave it to TexAgs to come up with something so smart and botch the execution.
I'm not sure if people genuinely believe someone is going to say, "Wow, if some people say I'm a moron for not believing this, it clearly must be true."

It's not much a persuasive argument. It really just sounds like a bunch of miniature dachshunds barking because the first one one barked when it thought it heard something.
Patentmike
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Ranger222 said:

The virus is not mutating fast enough to weaken substantially in this amount of time.

Will it eventually weaken? Yes, it is expected that it will. However, this will be expected over many years and decades.

The idea that infections today are not as serious as infections in February or March probably has more to do with other factors than the genetics of the virus.
SARS had a less virulent variant pop up in less than 6 months. It happens.
PatentMike, J.D.
BS Biochem
MS Molecular Virology


Patentmike
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eidetic78 said:

They won't give it to scientists. Even virologists like myself. I suggested maybe a flask icon or something.
What do you study?
PatentMike, J.D.
BS Biochem
MS Molecular Virology


eidetic78
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my training is in molecular virology and microbiology. Did my Ph.D. at Baylor College of Medicine studying the human microbiome and viral metagenomics. Basically the populations of microbes (viruses, bacteria, fungi, etc..) that live on/in us all the time, how those populations impact different aspects of our lives, and developing the molecular techniques needed to perform those kinds of studies.

We know those microbial populations can produce many vitamins/metabolites that we need but cannot make ourselves, digest plant fibers that we cannot, prevent colonization by pathogens, impact our mood, impact our appetite, on and on.

Currently I'm the lab technical director of a service center in the Texas Medical Center. So, I don't study any specific thing right now. As director of the service center, I help plan and execute experiments involving microbiome related topics with other labs and pharma companies from all over. Typically, they do the recruiting and sample collecting, send it to us, and we do the rest (extraction, sequencing, analysis, and help write it up).

The topics are vast. Some examples are a potential viral etiology of Type 1 diabetes. The TEDDY study if you want to look it up. Stands for The Environmental Determinants of Diabetes in the Young in collaboration with the University of South Florida. Many pharma groups are putting their own special probiotic cocktails through clinical trials and we process those samples for them. Many having to do with GI diseases and treatment thereof. My lab is also processing samples for the Texas Medical Center Genomic Center for Infectious Disease which you can check out here https://gcid.research.bcm.edu/ They have all kinds of different human pathogen related projects.

So, to answer but not answer your question, I mostly consult on the technical aspects of all of the above. Feasibility of different techniques and protocols, budgets, timelines, blah blah.

Right now, we've turned our lab into a sars-cov-2 testing facility. So we're pushing up to 1000 tests a day (RTqPCR tests) through for the city of Houston, Harris County, local medical center personnel, etc..
Patentmike
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eidetic78 said:

my training is in molecular virology and microbiology. Did my Ph.D. at Baylor College of Medicine studying the human microbiome and viral metagenomics. Basically the populations of microbes (viruses, bacteria, fungi, etc..) that live on/in us all the time, how those populations impact different aspects of our lives, and developing the molecular techniques needed to perform those kinds of studies.

We know those microbial populations can produce many vitamins/metabolites that we need but cannot make ourselves, digest plant fibers that we cannot, prevent colonization by pathogens, impact our mood, impact our appetite, on and on.

Currently I'm the lab technical director of a service center in the Texas Medical Center. So, I don't study any specific thing right now. As director of the service center, I help plan and execute experiments involving microbiome related topics with other labs and pharma companies from all over. Typically, they do the recruiting and sample collecting, send it to us, and we do the rest (extraction, sequencing, analysis, and help write it up).

The topics are vast. Some examples are a potential viral etiology of Type 1 diabetes. The TEDDY study if you want to look it up. Stands for The Environmental Determinants of Diabetes in the Young in collaboration with the University of South Florida. Many pharma groups are putting their own special probiotic cocktails through clinical trials and we process those samples for them. Many having to do with GI diseases and treatment thereof. My lab is also processing samples for the Texas Medical Center Genomic Center for Infectious Disease which you can check out here https://gcid.research.bcm.edu/ They have all kinds of different human pathogen related projects.

So, to answer but not answer your question, I mostly consult on the technical aspects of all of the above. Feasibility of different techniques and protocols, budgets, timelines, blah blah.

Right now, we've turned our lab into a sars-cov-2 testing facility. So we're pushing up to 1000 tests a day (RTqPCR tests) through for the city of Houston, Harris County, local medical center personnel, etc..
that's pretty cool. I was a PhD candidate in Molecular Virology at BCM, but took a terminal Masters to go to Law School. Other life issues contributed to that decision, but I'm much happier doing legal work than I was in the lab.
PatentMike, J.D.
BS Biochem
MS Molecular Virology


Gordo14
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Patentmike said:

Ranger222 said:

The virus is not mutating fast enough to weaken substantially in this amount of time.

Will it eventually weaken? Yes, it is expected that it will. However, this will be expected over many years and decades.

The idea that infections today are not as serious as infections in February or March probably has more to do with other factors than the genetics of the virus.
SARS had a less virulent variant pop up in less than 6 months. It happens.


Sure. And what are the odds that it's now the dominant strain of the virus. For the virus to be less virulent in general it has to be the dominant strain. Eventually this will happen, yes, over years... But what about all of the other strains of the virus that are more virulent? The point is it's really not possible for a less virulent strain to have taken over the global COVID-19 population over the past month.

I know people are getting tired of this subject and want to move on with their lives and so everybody is grasping at whatever they can to just end it. But the truth is we are always on the virus' timeline. We've kicked the can down the road with our actions in March and April. But hospitalizations in Texas have a pretty clear upward trend - so increasing cases is not just a function of testing. And furthermore, hospitalizations are a lagging indicator. I was optimistic we could maybe make it without going backwards until October/November... But we really should mentally prepare for this thing going out of control again - potentially in a month or so. And if the virus is prevelant enough societal structure will break down whether you want it to or not.
Keegan99
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Quote:

But hospitalizations in Texas have a pretty clear upward trend...

No.



Hospitalizations are effectively flat over the past month.


Quote:

But we really should mentally prepare for this thing going out of control again...

When was it ever "out of control" in Texas?!
BowSowy
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Keegan99 said:

Quote:

But hospitalizations in Texas have a pretty clear upward trend...

No.



Hospitalizations are effectively flat over the past month.


Quote:

But we really should mentally prepare for this thing going out of control again...

When was it ever "out of control" in Texas?!
Yes. Thank you. It's not surprising that we see an uptick in cases (as expected).
DadHammer
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With the massive increase in Testing over the last weeks we should see an increase of positives anyway. Luckily it seems the percentage of positive tests is going down. It seems to be stabilizing in the community and that is a great thing. Let's Not over react and and try to make this thing worse than it is. The data just doesn't support over reaction.

If you review the impact in heavy hit countries like Spain and Italy after about 12-14 weeks the virus seems to have run its course and is dying out pretty quickly. We will get through this pretty soon.

Stay positive and safe and start to live again.
cone
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the difference being Texas was never hit hard whereas Spain and Italy were
eidetic78
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That's awesome.

I took the LSAT prior to the GRE thinking I wanted to go to law school as well. In the end, grad school was "cheaper" since BCM pays for everything and includes a stipend. I considered ending with a terminal masters and going to law school multiple times throughout the latter part of my ph.d. Just never did...
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