What if there is no cure?

CelticRambler

That's the one, though the fact that it's French is coincidental. That is work carried out by a Parisian group; where I work [Alsace], there's a lot more cross-border cooperation with Switzerland and Germany. The reassuring aspect of that study isn't so much the drug but the treatment outcome they defined as their test: ventilation/death or not death. Other trials (Hydroxchlor/Azith, Remdesivir) are more about an "improvement" of one kind or another in the patient's response, which is a bit too easy to fudge. We already know that the American Remdesivir trial was fudged by changing the parameters part way through, so it'll be interesting to see exactly what they did and why. At the moment, I'm more inclined to think the Chinese study will be the more realistic.

There are a couple of other promising trials/treatments I'm keeping an eye on, one Chinese (monoclonal antibodies, underway) and one pan-European (immunomodulation, only just greenlighted, so probably won't report till the end of the year).

In the meantime, there's quite a lot of innovation taking place on the delivery of oxygen without using/needing ventilators - again, frontline staff applying all their creativity to fix the problem now with equipment and techniques that are already available, instead of waiting for government sponsored reactionary programmes to deliver the wrong thing too late (it's beginning to look like traditional ventilation isn't appropriate for most Covid-19 patients, and may in fact have contributed to the high death rate in some intensive care facilities/countries).

What Username Guidelines

CelticRambler wrote: »

That's the one, though the fact that it's French is coincidental. That is work carried out by a Parisian group; where I work [Alsace], there's a lot more cross-border cooperation with Switzerland and Germany. The reassuring aspect of that study isn't so much the drug but the treatment outcome they defined as their test: ventilation/death or not death. Other trials (Hydroxchlor/Azith, Remdesivir) are more about an "improvement" of one kind or another in the patient's response, which is a bit too easy to fudge. We already know that the American Remdesivir trial was fudged by changing the parameters part way through, so it'll be interesting to see exactly what they did and why. At the moment, I'm more inclined to think the Chinese study will be the more realistic.

There are a couple of other promising trials/treatments I'm keeping an eye on, one Chinese (monoclonal antibodies, underway) and one pan-European (immunomodulation, only just greenlighted, so probably won't report till the end of the year).

In the meantime, there's quite a lot of innovation taking place on the delivery of oxygen without using/needing ventilators - again, frontline staff applying all their creativity to fix the problem now with equipment and techniques that are already available, instead of waiting for government sponsored reactionary programmes to deliver the wrong thing too late (it's beginning to look like traditional ventilation isn't appropriate for most Covid-19 patients, and may in fact have contributed to the high death rate in some intensive care facilities/countries).

Is that with the device usually used for sleep apnoea? And is that similar to what the doc in NY was saying about hypoxia?

CelticRambler

What Username Guidelines wrote: »

Is that with the device usually used for sleep apnoea? And is that similar to what the doc in NY was saying about hypoxia?

Not sure what NY doc was saying what, but "probably yes" to both questions. One NY hospital has been successfully using simple plastic "bubbles" and low pressure, high concentration oxygen, following collaboration with a unit that handles scuba diving accidents (specifically divers suffering "the bends").

Sorry for the lack of links. I've been flitting through info on various devices these last few days while trying to wrap up several garden projects between thunderstorms!

ShineOn7

Gynoid wrote: »

What if you don't have a willy to wave? Do you have to wave the closest willy to you?

Sounds like Boards in the mid 2000s when everyone was riding each other on here. The best Boards era ;-)

Xertz

ShineOn7 wrote: »

Sounds like Boards in the mid 2000s when everyone was riding each other on here. The best Boards era ;-)

There’ll be none of that this year, at least not without full spacesuits and a lot of hand washing!

ek motor

CelticRambler wrote: »

That's the one, though the fact that it's French is coincidental. That is work carried out by a Parisian group; where I work [Alsace], there's a lot more cross-border cooperation with Switzerland and Germany. The reassuring aspect of that study isn't so much the drug but the treatment outcome they defined as their test: ventilation/death or not death. Other trials (Hydroxchlor/Azith, Remdesivir) are more about an "improvement" of one kind or another in the patient's response, which is a bit too easy to fudge. We already know that the American Remdesivir trial was fudged by changing the parameters part way through, so it'll be interesting to see exactly what they did and why. At the moment, I'm more inclined to think the Chinese study will be the more realistic.

There are a couple of other promising trials/treatments I'm keeping an eye on, one Chinese (monoclonal antibodies, underway) and one pan-European (immunomodulation, only just greenlighted, so probably won't report till the end of the year).

In the meantime, there's quite a lot of innovation taking place on the delivery of oxygen without using/needing ventilators - again, frontline staff applying all their creativity to fix the problem now with equipment and techniques that are already available, instead of waiting for government sponsored reactionary programmes to deliver the wrong thing too late (it's beginning to look like traditional ventilation isn't appropriate for most Covid-19 patients, and may in fact have contributed to the high death rate in some intensive care facilities/countries).

What do you think are the chances of antibody-dependent enhancement being a reality with SARS-CoV-2 ? Is it a realistic possibility in the event of re-infection (if that was possible) ? What would the implications of this be ?

https://www.nature.com/articles/s41577-020-0323-4

DeVore

Just about that Selenium thing... theres a thing with statistical analysis that people need to understand: Its not a game you can play backwards.

Let me explain,
Say I'm, looking to see if, lets say, Copper has an effect on this. I set up a test, I look at results based on data which gives geographic prevalence of various metals and minerals. I am looking for something statistically significant that shows the presence of copper strongly predicts some outcome in the virus. Sounds good right? And it is good... for Copper.

Lets say that I dont find any meaningful "statistically significant" link between Copper and positive/negative viral outcomes.
By "statistically significant" what we usually mean is "its 95% likely this isnt just a fluke". 95% is just a threshold thats been accepted for a long time so lets run with that. Its a measure of how "unlikely this result is a freak of random chance".


So, we didnt find a link for Copper.... buuuuut, its a BIG list full of lots of metals and minerals and all sorts of stuff. What if we just look down the list and find one that IS statistically significant! I mean, whats wrong with that?
Well its like buying a million lotto tickets and then declaring you know how to win the lotto. Or rolling a bag of d100 dice and finding one that rolled a 1 and declaring you have a dice that rolls 1s!

In short, you cant play this game backwards. If you want to do that then the "95%" threshold for "statistical significance" has to be a hellova lot higher (something closer to 99.99995% )

Hmmzis

ek motor wrote: »

What do you think are the chances of antibody-dependent enhancement being a reality with SARS-CoV-2 ? Is it a realistic possibility in the event of re-infection (if that was possible) ? What would the implications of this be ?

https://www.nature.com/articles/s41577-020-0323-4

That's a concern for any vaccine development. The issue is that, if the vaccine causes ineffective antibodies to be produced, while still reacting to the infection as if they were effective, then the virus simply gains free reign while the body thinks it's fighting it. That is worse than without a vaccine as the body would have developed effective antibodies on its own.

For SARS-cov-2 all vaccine developers are very aware of that effect from the early SARS-cov attempts where some of the candidates caused lung and liver damage in animals due to this effect.


Btw. the reinfection thing got clarified and refuted:

https://www.businessinsider.com/coronavirus-south-korean-reactivated-cases-not-reinfected-experts-2020-4?r=US&IR=T

(among other sources)

ek motor

Hmmzis wrote: »

That's a concern for any vaccine development. The issue is that, if the vaccine causes ineffective antibodies to be produced, while still reacting to the infection as if they were effective, then the virus simply gains free reign while the body thinks it's fighting it. That is worse than without a vaccine as the body would have developed effective antibodies on its own.

For SARS-cov-2 all vaccine developers are very aware of that effect from the early SARS-cov attempts where some of the candidates caused lung and liver damage in animals due to this effect.


Btw. the reinfection thing got clarified and refuted:

https://www.businessinsider.com/coronavirus-south-korean-reactivated-cases-not-reinfected-experts-2020-4?r=US&IR=T

(among other sources)

Did it get refuted though ? That article just shows the probability of at least short term immunity, which was never really in doubt. What about a longer-term timescale ?

It would make sense that people would develop relatively short-term immunity similar to other coronaviruses. The question is what happens say two years down the line - immunity has probably waned and so the possibility or a re-infection is the reality. What then happens to the person who has picked it up a second time ? We already know SARS-1 had a mechanism for ADE, and given the similarities it would be reasonable to assume the possibilty of ADE in the event of re-infection in SARS-CoV-2 (obviously probably wouldn't occur for a couple of years).

CelticRambler

ek motor wrote: »

What do you think are the chances of antibody-dependent enhancement being a reality with SARS-CoV-2 ? Is it a realistic possibility in the event of re-infection (if that was possible) ? What would the implications of this be ?

Not quite sure what you're asking in the first sentence. ADE is a reality with SARS-CoV-2. That's what put Boris Johnson (and many others) in hospital, and it occurs at around 7-10 days after the first signs of infection. So if it's a feature of the illness, then yes, any effective vaccine carries that risk also. Hence the conclusion of the author of that article:

preclinical testing in laboratory animal virus challenge models finds that experimental vaccines in virus vectors can cause immunopathology owing to mononuclear cell and eosinophil infiltration of the lung.

Now they go on to say they've potentially found a way to limit this risk: using alum as an adjuvant. Well, that's going to melt the heads of the tinfoil-hat-wearers! :pac: WTF? The government is going to inject aluminium into everyone??? So they can better control us with their 5G antennae? :mad: When you see the debate about the contact-tracing apps, can you imagine the fireworks over an obligatory "aluminium-based" vaccine?

As to the question of whether one can expect an ADE response to subsequent infections, it's not so much SARS-CoV-2 (and/or it's vaccine) that's the problem - it's SARS-CoV-3, -4, -5 ... One thing that we do know is that this virus (in both its original and -2 versions) makes use of a receptor known as ACE, which is implicated in heart disease and high blood pressure. Both of these are now considered "manageable" diseases of older age - frequently by using ACE-inhibitors. It's entirely possible that we are quite simply, if inadvertently, preparing a cohort of older people to be perfect targets for Covid illness.

And here's the potential torpedo waiting for every vaccine currently in development: in clinical trials, they'll be given to healthy 18-50 year-olds and (probably) show no adverse side effects. They might even provoke a protective antibody response. Great ... and then they're given to older people with high blood pressure, and suddenly you've got thousands of vaccine-induced Covid cases. That's where pre-clinical animal testing comes in (lots of it, in lots of different animal species) but it looks like all around the world exceptions are going to be made in the rush to "reopen the economy". I won't be buying shares in any vaccine manufacturers just yet.

Hmmzis wrote: »

Btw. the reinfection thing got clarified and refuted

Clarified, yes; refuted, no. The updated info highlights the tests' inaccuracy with respect to false positives. It does not prove that recovered patients can't be reinfected, only that these cases were false positives. It leaves open the possibility that there are undiagnosed real repeat infections, and also leads to the question: how many of the country's other positive results were non-active infections?

Hmmzis

Here is one in Cell where they check the IgG and IgM antibodies in recovered patients. Looks like in most they are protective, except patient #9. That patient is a curious case. Lots of T-cell activity, so might have cleared the infection that way? I'm just a layman in this, so would appreciate a layman's version of that case, if someone could provide one.

https://www.cell.com/action/showPdf?pii=S1074-7613%2820%2930181-3


And getting the Common Cold is good for you (in terms of SARS-cov-2)?

https://www.medrxiv.org/content/10.1101/2020.04.17.20061440v1

CelticRambler

Hmmzis wrote: »

Here is one in Cell where they check the IgG and IgM antibodies in recovered patients. Looks like in most they are protective,

Hmmm ... yeah ... maybe ... but that's not what the study says. It demonstrates that people who recovered from Covid-19 have signs in their blood that show they've recovered from Covid-19. It does not demonstrate that having these antibodies protects the person from subsequent infection, because they didn't try to re-infect the patients.

One must always bear in mind that in vitro studies do not replicate the real world circumstances that lead to infection and disease, and when it comes to respiratory infections, in vitro studies are about as far from the real world as you can get.

As an aside - look at the ages of the patients in that study - all relatively young. So however useful the results might be (statistically insignificant, given the tiny number of patients), they still don't help explain why old people are so vulnerable and/or whether any antibody will help those patients.

Hmmzis wrote: »

And getting the Common Cold is good for you (in terms of SARS-cov-2)?

This one is interesting, but a bit "chicken or egg?" Were the healthy donors less susceptible because they already had useful antibodies as a result of previous exposure to common cold coronaviruses, or do they have immune systems that are less discriminatory than the others and just lob any old T-cell at an incoming virus?

If, in the fullness of time, it's shown that exposure to the common cold coronavirus confers a degree of protection against SARS-CoV-n, then all the advice about hand washing, wearing masks and gloves, social distancing, etc, will have been counterproductive.

Hmmzis

Could this put a spanner in the works for some of the more targeted RBD based vaccines?

https://www.pnas.org/content/early/2020/05/05/2003138117

Since before activation the RBD is in the down position, some of the antibody types might not find the right place to bind?

Looks a good bit different to SARS1, RBD might not be the best strategy for attack after all. Whole spike or inactivated virus might be better since no current vaccine efforts have found AED effects with SARS-cov-2 and the thing is mutating even slower that its predecessor.

Gen 2 vaccines would have to look at ways how to make the body recognize the folded RBD and attack it that way. Maybe a combo of both folded and upright RBD expression in cells to train the immune system to recognize both?

ChAdOx (the Oxford one) uses the whole spike and the early Chinese one uses inactivated virus. None have shown AED in animal models and also shown protecting abilities in animal models. Hopefully that will translate to humans as well.

The whole spike should allow antibodies to be created for the S above the RBD, preventing full binding to the ACE2 receptor. As per the above study, the S is already a bit crap at binding, so hopefully even a crappy antibody on the spike could prevent proper cell entry. Sure the RBD will bind to the receptor, but if the spike is redndered useless further up, cell entry could be compromised or disabled completely.
So some of the 1st gen vaccines might not provide full protection if going after just the RBD or the S induced antibodies don't render the spike inert.

PhilOssophy

All the talk is of when will a vaccine be found.
What if one isn't?
1984 was when HIV vaccine was first touted - Margaret Heckler said in 2 years there would be one, 36 years on we still have no vaccine.
What if Covid-19 is the same?

Beasty

Threads merged

owlbethere

https://www.sciencedaily.com/releases/2020/04/200422132600.htm

This is about a MERS vaccine. It looks promising for this covid19

Hmmzis

PhilOssophy wrote: »

All the talk is of when will a vaccine be found.
What if one isn't?
1984 was when HIV vaccine was first touted - Margaret Heckler said in 2 years there would be one, 36 years on we still have no vaccine.
What if Covid-19 is the same?

The fact that the vast majority of SARS-cov-2 victims survive and clear the virus would suggest it's nothing like HIV.

There are vaccine candidates for HIV btw.:

https://www.sciencedaily.com/releases/2018/07/180707090650.htm

Very few people, if any, have cleared HIV without medical treatment. Even with medical treatments it's hard to manage. HIV is one of the if not the most difficult viruses to deal with. It hides all its identifying machinery, mutates like mad within the body, so the immune system can't keep up with all the new viral versions floating around, can persist in the body for years without causing any symptoms. It's not even doing the dirty job of killing the host, that it leaves to other pathogens (due to AIDS).

SARS-cov-2 on the other hand is like fast, loud hooligan that has stumbled into an all-you-can-eat buffet. It's trump card is speed, it spreads easily and quickly. The immune system has not much trouble clearing it though, the mess it leaves behind is not pretty, unfortunately.

Even for HIV there are limts to what it can mutate in order to preserve viability. Hence, a vaccine is possible, the trick is to use the right proteins to trick the immune system into producing the right antibodies against the parts of the pathogen it can't do without.

owlbethere

Hmmzis wrote: »

The fact that the vast majority of SARS-cov-2 victims survive and clear the virus would suggest it's nothing like HIV.

There are vaccine candidates for HIV btw.:

https://www.sciencedaily.com/releases/2018/07/180707090650.htm

Very few people, if any, have cleared HIV without medical treatment. Even with medical treatments it's hard to manage. HIV is one of the if not the most difficult viruses to deal with. It hides all its identifying machinery, mutates like mad within the body, so the immune system can't keep up with all the new viral versions floating around, can persist in the body for years without causing any symptoms. It's not even doing the dirty job of killing the host, that it leaves to other pathogens (due to AIDS).

SARS-cov-2 on the other hand is like fast, loud hooligan that has stumbled into an all-you-can-eat buffet. It's trump card is speed, it spreads easily and quickly. The immune system has not much trouble clearing it though, the mess it leaves behind is not pretty, unfortunately.

Even for HIV there are limts to what it can mutate in order to preserve viability. Hence, a vaccine is possible, the trick is to use the right proteins to trick the immune system into producing the right antibodies against the parts of the pathogen it can't do without.

I love your post and I love your choice of words

Montage of Feck

The chances of getting an effective vaccine in any reasonable time frame are miniscule.
So is it time we face up to the fact that this thing is eventually going to kill approximately 15% of the population and plan for this eventually?

More like 1% of the population, most over 80 with underlying conditions, if we don't isolate them.

However the 2nd wave could attack mainly young people like the Spanish flu did.

threeball

[Deleted User] wrote: »

More like 1% of the population, most over 80 with underlying conditions, if we don't isolate them.

However the 2nd wave could attack mainly young people like the Spanish flu did.

And how do you reckon thats going to happen? Are we by some amazing coincidence going to see this virus combine with another virus just like 1918. If the stars align we might even be lucky enough that it becomes a corona-ebola hybrid.

Wibbs

Deleted User wrote: »

However the 2nd wave could attack mainly young people like the Spanish flu did.

Why do people keep dragging this old story out? It almost certainly won't, nay can't happen. The second wave in the 1918 pandemic came about because of a very particular set of circumstances with a very different type of virus, circumstances that aren't in play now. The tendency is for viruses to get less fatal over time. Less fatal means more infected, which means more virus survival. The "best" virus would be one that was highly infectious and showed no symptoms or fatalities in the host. It would reproduce like wildfire and never die out unless the host did.

threeball wrote: »

And how do you reckon thats going to happen? Are we by some amazing coincidence going to see this virus combine with another virus just like 1918.

This did not happen in 1918. Viruses can't "combine".

ShineOn7

Montage of Feck wrote: »

The chances of getting an effective vaccine in any reasonable time frame are miniscule.
So is it time we face up to the fact that this thing is eventually going to kill approximately 15% of the population and plan for this eventually?

Deleted User wrote: »

More like 1% of the population, most over 80 with underlying conditions, if we don't isolate them.

However the 2nd wave could attack mainly young people like the Spanish flu did.

Ah yes. Nothing like some Boards Gloom Porn over your first morning coffee