Reply
 
Thread Tools Display Modes
  #1  
Old 05-11-2020, 02:50 PM
AK84 is online now
Guest
 
Join Date: Apr 2008
Posts: 17,019

Second COVID19 wave questions.


There has been a lot of talk that the COVID19 is likely to peak again in the autumn and winter and much like the Spanish flu of 1918, this is likely to be much worse, I have read stuff like that a similar result to the NYC and Lombardy experience in this first wave would be seen a having dodged a bullet in the second wave.

It appears that second waves are almost always worse than first ones (besides the Spanish flu, the 1957 Asian flu, and the 2009 Swine flu pandemic's second waves were also worse, with the 1968 Hong Kong flu being an exception).
Why is this case? Surely by the time a second wave hits, the population is no longer virgin as it was in the first wave, there should be some resistance.
  #2  
Old 05-11-2020, 03:56 PM
VOW is online now
Member
 
Join Date: Apr 2002
Location: NE AZ
Posts: 4,286
You'll always have pockets of people who miss exposure the first time around.

The whole "flattening the curve" tactic proposed by Dr Fauci and the experts was to move the bulk of the population away from exposure. So the US has a huge number of people who are vulnerable to COVID-19.

With the stay-at-home restrictions lifted, you've got all these unexposed people out and about, mingling. And in many places, the infection is still spreading. Much much more slowly, but it is still in existence.

And remember that there are asymptomatic carriers.

The second wave can easily surpass the numbers created by the first wave. The fatalities aren't always in the portion of the population "just waiting to die." The greatest number of fatalities came from the 18-44 age group.

And now there is a rare form of COVID-19 infecting children. It attacks their hearts.

This second wave is due to hit around the start of the regular flu season. Some people might end up infected with both simultaneously.


~VOW
__________________
Klaatu Barada Nikto
  #3  
Old 05-11-2020, 04:31 PM
DSeid's Avatar
DSeid is online now
Guest
 
Join Date: Sep 2001
Location: Chicago, IL
Posts: 23,964
Quote:
Originally Posted by AK84 View Post
There has been a lot of talk that the COVID19 is likely to peak again in the autumn and winter and much like the Spanish flu of 1918, this is likely to be much worse, I have read stuff like that a similar result to the NYC and Lombardy experience in this first wave would be seen a having dodged a bullet in the second wave.

It appears that second waves are almost always worse than first ones (besides the Spanish flu, the 1957 Asian flu, and the 2009 Swine flu pandemic's second waves were also worse, with the 1968 Hong Kong flu being an exception).
Why is this case? Surely by the time a second wave hits, the population is no longer virgin as it was in the first wave, there should be some resistance.
As I understand it the reason to explain such in past influenza pandemics is seasonal forcing: transmissibility of influenza (and the common cold coronaviruses) are decreased during summer months. The first wave in those influenza pandemic cases began later in the season and were able to spread it around but then seasonality of spread suppressed it to lower levels. Increased transmissibility with season change to Fall/Winter then picked up with scattered seeds early in the next season favoring its faster spread.

In this particular (COVID-19) case it is not known if there is decreased transmissibility during summer but it is suspected that there may be to some degree. The concerns for a much worse Fall peak then include suppression of the first peak by season and mitigation, with both brakes potentially being released to some degrees in the Fall, still with the vast overwhelming majority of the population susceptible, and overlapping with influenza demands upon the system.

Here's how it's explained as one possible potential pattern in a recent model published in Science.
Quote:
High seasonal variation in transmission leads to smaller peak incidence during the initial pandemic wave but larger recurrent wintertime outbreaks
The amount of seasonal variation in SARS-CoV-2 transmission could differ between geographic locations, as for influenza (12). The R0 for influenza in New York declines in the summer by about 40%, while in Florida the decline is closer to 20%, which aligns with the estimated decline in R0 for HCoV-OC43 and HCoV-HKU1 (table S8). A 40% summertime decline in R0 would reduce the unmitigated peak incidence of the initial SARS-CoV-2 pandemic wave. However, stronger seasonal forcing leads to a greater accumulation of susceptible individuals during periods of low transmission in the summer, leading to recurrent outbreaks with higher peaks in the post-pandemic period (Fig. 3C).
Even the the 1968 pandemic followed that pattern everywhere else but in North America.
  #4  
Old 05-11-2020, 04:35 PM
DSeid's Avatar
DSeid is online now
Guest
 
Join Date: Sep 2001
Location: Chicago, IL
Posts: 23,964
Quote:
Originally Posted by VOW View Post

... And now there is a rare form of COVID-19 infecting children. It attacks their hearts. ...
Accuracy is important in these discussion. Experts are not yet sure that COVID-19 is causing that syndrome (it is rare enough that they cannot be so sure) but the consensus opinion of the experts is that if it is caused by COVID-19 it is not the virus attacking the hearts, but an over response by the immune system that is doing it.
  #5  
Old 05-11-2020, 05:16 PM
Stranger On A Train is offline
Guest
 
Join Date: May 2003
Location: Manor Farm
Posts: 19,840
Quote:
Originally Posted by VOW View Post
And now there is a rare form of COVID-19 infecting children. It attacks their hearts.
There is no indication that there is a separate strain of SARS-CoV-2 (the virus that causes the COVID-19 disease); it appears that a small proportion of children who have been infected and show antibodies may also have some kind of susceptibility to post-infection immune response that produces a Kawasaki disease-like sequela which causes inflammation and necrosis of endothelial tissue (not just the heart).

Quote:
Originally Posted by VOW View Post
This second wave is due to hit around the start of the regular flu season. Some people might end up infected with both simultaneously.
While this may happen and is a real concern, the reason that second waves of infection are sometimes larger than the first is primarily that the disease has had time to spread geographically. This is especially true if there are a significant number of asymptomatic carriers or a suppression due to seasonal effects. When the virus reemerges it has a wide spread of infection clusters that are very difficult to control. The particular 1918 H1N1 strain that caused the Spanish Flu is unknown but was uniquely virulent and infectious compared to other Type A H1N1 influenza viruses, causing cytokine response syndrome (a “cytokine storm” that results in the immune system attacking healthy cells of the body) that has not been seen since.

The number of people infected in a “first wave” of any novel virus strain is generally not that high because people who are infectious also tend to not circulate because they feel unwell, and thus, an outbreak is self-limiting. However, as the virus establishes itself in a population and/or finds an reservoir like domestic animals, it tends to winnow out non-viable mutations and becomes better adapted to its host, such that when it reenters a population or gets transferred to a previously unaffected population it can spread rapidly, hence why smallpox ravaged Eurasian populations over and over again for hundreds of years, and then when introduced to the Americas was catastrophic in its mortality.

In the case of SARS-CoV-2, we’ve collectively been very effective in squashing its spread even in countries that took less-than-comprehensive steps or were dilatory in their response, but even with that most populations likely have less than double digit percentage of exposure, and with what is an often poorly measured lifting of isolation measures and hygiene practices we can expect the second wave—which is going to come well before influenza season starts in October—will almost certainly grow to have a greater daily mortality rate than the first wave of the pandemic.

And we’re going to see successive waves of greater or lesser mortality and morbidity until there is enough exposure in the population to achieve a herd immunity threshold, which we currently don’t have enough information to evaluate and it is possible will not even exist of the virus can remain persistent in its spread or find a reservoir in domestic animals. We never achieved a herd immunity with respect to chicken pox until a vaccine was available despite the fact that nearly every person on the planet was exposed to it in childhood and developed significant lifelong immunity from the main presentation.

Stranger
  #6  
Old 05-11-2020, 05:38 PM
nelliebly is offline
Guest
 
Join Date: Jul 2017
Location: Washington
Posts: 3,052
Stranger, thanks for the excellent and well-informed reply. Why don't we achieve herd immunity with certain viruses without a vaccine? Are they less contagious? My mom had me play with every pox-y kid on the block and finally concluded I was immune. I got chicken pox as an adult and was very ill.

I've read speculation we may not get a COVID vaccine, but I hadn't considered that without a vaccine, we'd never achieve herd immunity.
  #7  
Old 05-11-2020, 05:45 PM
AK84 is online now
Guest
 
Join Date: Apr 2008
Posts: 17,019
So,
1. It's going to comeback in autumn in a big way
2. As nearly everyone went into someform of lockdown, far fewer people actually got exposed.
3. Which means that we have managed to wreck hue economy **and** ensure that the second wave KS much worse?
4. We better hope Covid is not seasonal, since that will ensure a steady low burn, rather than a huge Spike?
5. Maybe the herd immunity proposals back in March weren't totally cray cray?
  #8  
Old 05-11-2020, 06:21 PM
Velocity is offline
Guest
 
Join Date: Jun 2014
Posts: 17,465
Quote:
Originally Posted by AK84 View Post
So,
1. It's going to comeback in autumn in a big way
2. As nearly everyone went into someform of lockdown, far fewer people actually got exposed.
3. Which means that we have managed to wreck hue economy **and** ensure that the second wave KS much worse?
4. We better hope Covid is not seasonal, since that will ensure a steady low burn, rather than a huge Spike?
5. Maybe the herd immunity proposals back in March weren't totally cray cray?
My totally non-scientific, non-expert, proposal: We just have to race that Covid-19 vaccine out much faster than usual. Yes, there will be dangers of a vaccine that hasn't gone through the normal, slow, drawn-out-over-years regulatory process that vaccines normally go through. But if this fall/winter second wave is going to claim 500,000 lives and cause organ damage to 4 million other people, it's worth the risky gamble.
  #9  
Old 05-11-2020, 06:33 PM
DSeid's Avatar
DSeid is online now
Guest
 
Join Date: Sep 2001
Location: Chicago, IL
Posts: 23,964
It might come back in Autumn in a big way. It is one possible outcome. Not the only one. One to want to avoid to be sure.

Unknown how many got exposed so far and definitely regional variation. More in NYC say than in Minnesota. Data still incomplete at best.

Uncontrolled would clearly have overwhelmed many systems. Flattening the curve was required. The debate now is between those who think of flattening the curve as keeping within system capacity while capacity is built up, while more become resolved, yes slowly approaching herd immunity, and those who believe the curve can be flattened to near zero and maintained there ad infinitum and are wanting to do that at any cost or risk. And in both camps how to structure easing off the brakes.

Strong seasonal suppression facilitates a bigger Fall spike but allows quicker release of the brake now. The risk of that though is the need to reapply the brakes hard in the Fall ... which as a practical matter would be hard to accomplish once eased off.

It is cray cray to explicitly go for herd immunity in a short period of time as the goal when there is not enough known to model with any confidence. Step one has had to be to first get it cooled down, under control, and to not let it get back out of control. Still not enough to have more solid inputs into the models? Then proceed slowly and cautiously. It is harder in many ways to successfully reapply brakes than to release them with caution. How much caution, what to measure? Discussions ongoing!

It is not cray cray to have an understanding that depending on a vaccine as the only way out is reckless planning, and to have a slow path that keeps the disease within some controlled level while opening up, and understanding that if a vaccine never arrives that path will, at some unknown right now point, lead to herd immunity and some level of the disease that is lived with as normal moving forward.

Racing a vaccine out would be reckless as well, and unsuccessful. Too few would agree to take it to reach herd immunity and they would be right to refuse.
  #10  
Old 05-11-2020, 06:51 PM
Stranger On A Train is offline
Guest
 
Join Date: May 2003
Location: Manor Farm
Posts: 19,840
Quote:
Originally Posted by nelliebly View Post
Why don't we achieve herd immunity with certain viruses without a vaccine? Are they less contagious? My mom had me play with every pox-y kid on the block and finally concluded I was immune. I got chicken pox as an adult and was very ill.

I've read speculation we may not get a COVID vaccine, but I hadn't considered that without a vaccine, we'd never achieve herd immunity.
To be clear, I'm just stating that this is a potentiality, not a likelihood. The vast majority of viruses either achieve a level of infection that results in a degree of herd immunity and the virus becomes endemic in the population, or they disappear entirely or become much less virulent such that they are no longer a serious threat. Chickenpox in particular became a seasonal epidemic because of a combination of its extreme infectiousness, low morbidity and almost no mortality in children, and because exposed humans are actually a reservoir for the varicella zoster virus which resides in the dorsal ganglion of sensory nerves.

There has been a lot of handwringing about the notion that SARS-CoV-2 could mutate like seasonal influenza and negate any attempt at a vaccine. Now, it is true the virus, like all RNA viruses, will mutate frequently. However, the reason influenza strains mutate so aggressively into more virulent strains is because of recombination where two viruses will infect a host and swap genomic material. We've seen no evidence of this so far, and the amount of variation seen in viable SARS-CoV-2 subgroups has been very small with no variation seen in the aggregate in regard to the pathogenesis, morbidity, and mortality. There may be some evidence that some subgroups are more or less infectious due to changes in the receptor binding domain of the spike protein but the test data is so scattered I doubt any real epidemiological conclusions can be gathered at this point. The big concern is whether the genes that produces the spike protein mutates and an antibody will no longer recognize the virus, which is what happens with the unrelated coronaviruses. However, even alterations to the spike protein will probably not completely negate antibody response from a prior exposure.

Quote:
Originally Posted by AK84 View Post
So,
1. It's going to comeback in autumn in a big way
2. As nearly everyone went into someform of lockdown, far fewer people actually got exposed.
3. Which means that we have managed to wreck hue economy **and** ensure that the second wave KS much worse?
4. We better hope Covid is not seasonal, since that will ensure a steady low burn, rather than a huge Spike?
5. Maybe the herd immunity proposals back in March weren't totally cray cray?
We don't know that it will peak again in fall; in fact, in the United States at least I expect it start swinging up again by June, and depending on how states react or fail, we could see a peaking in July or August. The point of the 'lockdown', e.g. distancing and self-isolation measures was never to stop the virus; it was to get enough time to assess what data we had, develop better testing, allow health systems to better prepare, and figure out how to enable crucial systems like education, medicine, courts, and essential businesses to function while preventing the spread from achieving epidemic levels.

The notion of herd immunity needs to be addressed in a definitional fashion; that is, achieving herd immunity isn't a strategy; it is (hopefully) the end result regardless of what approach we take. That is, the virus will no longer be able to outbreak at epidemic levels once a threshold percentage of the population is exposed. Vulnerable people will still be vulnerable (and that isn't just the elderly and immunocompromised, which should be readily apparent now) and the virus will almost certainly not go away, but if it can only infect every second or third person that cuts its effective basic infection number to half or a third, and if that brings it down close to unity, we can track and trace individual infections versus just having to look at community spread in the aggregate. Just shooting for maximum infection rate to achieve herd immunity as quickly as possible is like trying to surf into a wave; it doesn't work, you look stupid trying, and there is a good chance you're going to break something.

Barring a vaccine that, frankly, is not going to be available by the end of the year (and I would not bet the mortgage on the end of 2021 either) a large portion of the population is going to be exposed, which is how we managed infectious pathogens prior to vaccines. As long as we can care for those people who experience serious presentation but can be saved by medical treatments (and hopefully find interventions that prevent people from being put on intrusive ventilation) we can minimize mortality to the degree possible but people are going to die regardless of when and how we chose to reopen. However, if we just open everything at once and encourage people to mingle without regard for distancing guidelines we will maximize the mortality by overwhelming the health system. And this doesn't just affect the people who die; it affects their families, the businesses they work for or patronize, the institutions they support, and perhaps most poignantly, the medical personnel and first responders trying in vain to save them and becoming infected in the process. And if for no other reason, we need to minimize mortality to protect our health care workers and health systems for everyones' benefit.

As for "we have managed to wreck hue economy": this virus is a love tap compared to what a truly virulent influenza pandemic could be like; instead of a case fatality rate of ~1%, we could be looking at a pandemic of 20% or greater, and nobody would argue that we should just operate like normal if one in five people were dying. And we'd better figure that out, because that pandemic is out there somewhere in the future. The history of civilization--ever since we've lived in large concentrated populations--has been one of repeated epidemic disease which devastated entire empires and laid waste to civilizations. Unlike those pre-industrial civilizations with no good notion of the infectious model of disease or the ability to stockpile perishable goods and manage supply chains, we can actually take effective measures to prevent disease spread and protect critical food production and distribution systems. But doing so clearly requires a more measured and thoughtful approach than simply assuming that an invisible hand will take care of it via market forces. The damage this has wrought on our economy is a wakeup call that we need more robust systems for the future.

Stranger
  #11  
Old 05-11-2020, 06:57 PM
Stranger On A Train is offline
Guest
 
Join Date: May 2003
Location: Manor Farm
Posts: 19,840
Quote:
Originally Posted by Velocity View Post
My totally non-scientific, non-expert, proposal: We just have to race that Covid-19 vaccine out much faster than usual. Yes, there will be dangers of a vaccine that hasn't gone through the normal, slow, drawn-out-over-years regulatory process that vaccines normally go through. But if this fall/winter second wave is going to claim 500,000 lives and cause organ damage to 4 million other people, it's worth the risky gamble.
One of those "dangers of a vaccine that hasn't gone through the normal, slow, drawn-out-over-years regulatory process that vaccines normally go through" is antibody-dependent enhancement (ADE):
Abstract

In general, virus-specific antibodies are considered antiviral and play an important role in the control of virus infections in a number of ways. However, in some instances, the presence of specific antibodies can be beneficial to the virus. This activity is known as antibody-dependent enhancement (ADE) of virus infection. The ADE of virus infection is a phenomenon in which virus-specific antibodies enhance the entry of virus, and in some cases the replication of virus, into monocytes/macrophages and granulocytic cells through interaction with Fc and/or complement receptors. This phenomenon has been reported in vitro and in vivo for viruses representing numerous families and genera of public health and veterinary importance. These viruses share some common features such as preferential replication in macrophages, ability to establish persistence, and antigenic diversity. For some viruses, ADE of infection has become a great concern to disease control by vaccination. Consequently, numerous approaches have been made to the development of vaccines with minimum or no risk for ADE. Identification of viral epitopes associated with ADE or neutralization is important for this purpose. In addition, clear understanding of the cellular events after virus entry through ADE has become crucial for developing efficient intervention. However, the mechanisms of ADE still remain to be better understood.
So, a bad vaccine could have the effect of making a virus more infectious, more virulent, and capable of reproducing and mutating faster.

Still sound like a good bet to you?

Stranger

Last edited by Stranger On A Train; 05-11-2020 at 06:59 PM.
  #12  
Old 05-11-2020, 08:22 PM
echoreply's Avatar
echoreply is offline
Guest
 
Join Date: Dec 2003
Location: Boulder, CO
Posts: 1,096
Quote:
Originally Posted by Velocity View Post
My totally non-scientific, non-expert, proposal: We just have to race that Covid-19 vaccine out much faster than usual. Yes, there will be dangers of a vaccine that hasn't gone through the normal, slow, drawn-out-over-years regulatory process that vaccines normally go through. But if this fall/winter second wave is going to claim 500,000 lives and cause organ damage to 4 million other people, it's worth the risky gamble.
That is exactly what is happening. The big catch is that there are tests and other steps which can't be skipped, and those take time. A vaccine that doesn't work, or is even harmful, doesn't do anybody any good.
  #13  
Old 05-11-2020, 09:02 PM
Jaguars! is offline
Guest
 
Join Date: Nov 2010
Location: NZ
Posts: 316
Quote:
Originally Posted by AK84 View Post
So,
3. Which means that we have managed to wreck hue economy **and** ensure that the second wave KS much worse?
I won't speak to the medical side of things, but in this respect, the first part of your statement is rather hollow. There never was a real choice between public health or economic health. The economy was always going get wrecked, it's just a matter of degree. Consider the best and worst cases.

In places where the virus spread out of control such as New York or Italy, economic activity pretty much just ground to a halt. Society simply couldn't handle normal activity with a severe disease spreading and a. Governments hands wree forced, they locked down and b. People stopped going out of their own accord.

However, in countries where effective lockdowns take place, economic activity reduces hugely too as many workers can't do their jobs and many businesses go under or lay off workers. In my country of New Zealand, we appear to have stopped community transmission (touch wood!) but no one currently knows what the future will hold as the massive tourism sector is dead as well as half a dozen specialized export sectors. Unemployment has skyrocketed.

So essentially there was never a case that any economy in an interconnected world would escape unscathed from the moment things got out of control in Wuhan.
  #14  
Old 05-11-2020, 09:45 PM
PastTense is online now
Guest
 
Join Date: Jan 2013
Posts: 8,442
Quote:
Originally Posted by DSeid View Post
It is cray cray to explicitly go for herd immunity in a short period of time as the goal when there is not enough known to model with any confidence. ...

It is not cray cray to have an understanding that depending on a vaccine as the only way out is reckless planning
Cray Cray??
  #15  
Old 05-11-2020, 10:32 PM
squeegee's Avatar
squeegee is offline
Member
 
Join Date: Dec 2000
Location: Aptos CA
Posts: 9,338
Quote:
Originally Posted by PastTense View Post
Cray Cray??
Chrissakes, it's in the Oxford dictionary.
Along with "chrissakes" I'm sure.

Last edited by squeegee; 05-11-2020 at 10:33 PM.
  #16  
Old 05-11-2020, 10:49 PM
DSeid's Avatar
DSeid is online now
Guest
 
Join Date: Sep 2001
Location: Chicago, IL
Posts: 23,964
Quote:
Originally Posted by PastTense View Post
Cray Cray??
See AK84’s item #5 it was referencing.

__________________
Oy.

Last edited by DSeid; 05-11-2020 at 10:50 PM.
  #17  
Old 05-12-2020, 12:00 AM
Gestalt is offline
Guest
 
Join Date: Apr 2003
Posts: 1,657
I just want to thank Stranger for such a thoughtful, evidence-based analysis.

Do you have any thoughts on the likelihood of a 20% morality rate influenza pandemic? I do just wonder if there is some phenomenon where increased mortality correlates with decreased transmission rate, such as with SARS and MERS. Or did we just get lucky with those? My understanding is that viruses with fast-onset of symptoms tend to "burn out" more quickly, and of course one of the tricky elements of COVID-19 is the long latency period. But I don't see a reason why a virus couldn't have a long latency period and a high morality rate.
  #18  
Old 05-12-2020, 12:51 AM
Stranger On A Train is offline
Guest
 
Join Date: May 2003
Location: Manor Farm
Posts: 19,840
Quote:
Originally Posted by Gestalt View Post
Do you have any thoughts on the likelihood of a 20% morality rate influenza pandemic? I do just wonder if there is some phenomenon where increased mortality correlates with decreased transmission rate, such as with SARS and MERS. Or did we just get lucky with those? My understanding is that viruses with fast-onset of symptoms tend to "burn out" more quickly, and of course one of the tricky elements of COVID-19 is the long latency period. But I don't see a reason why a virus couldn't have a long latency period and a high morality rate.
So, I picked 20% mortality as an extreme worst case for a virulent influenza (smallpox ran upwards of 30%, and some strains of Ebola virus are around 90% mortality) but even 5% would be horrific if combined with an R0>4. In such a case, with, say, a week-long infection cycle at 5% mortality you'd be looking at over 800K deaths in three months and as many as 200M deaths a month after that; essentially, it would just run until it burnt itself out unless we were able to respond affirmatively and effectively to completely lockdown the population and drive down the effective replication number. Most viruses that are really infectious tend to be fairly mild (even influenza generally has an R0<2) and most really virulent pathogens like those that cause viral hemorrhagic fevers tend to be not much greater than 1 because of how quickly the virus disables the host.

But a just-so pathogen could have the right combination of infectiousness and virulence, and if it had a long enough latency period or caused hosts to start shedding very quickly after infection we might not be able to track it quickly enough to forestall outbreaks. That was the case with the 1918 H1N1 strain, which if it reappeared today would likely have similar mortality (which is why epidemiologists were so paranoid about the predicted 2009 A(H1N1)pdm09 pandemic even though it ended up having a CFR that was no worse than typical seasonal influenza strains. With SARS we were lucky that patients didn't really start to be infectious until they were already presenting signs & symptoms, and with MERS it just really wasn't all that infectious for person-to-person contact; most infections were due to either direct interactions with the zoologic host (dromedary camels) or intimate contact (direct contact with bodily fluids) between people. SARS-CoV-2 has all the criteria to be that kind of just-so pathogen except it seems very limited about the people it can severely affect although it presents mild symptoms in a large proportion of people. Some alteration in the viral genome that would make it more virulent would turn this from a 'love tap' to a serious threat to modern civilization, and I don't mean crashing the stock market or putting people out of work. And the virus that can do that is hypothetically out there in the virosphere of countless billions of different strains of viruses, and even if it doesn't exist now, viruses mutate and recombine so easily that it will come eventually just as plagues have ravaged and destroyed civilizations that have come before us despite not being as dependent on a fragile network of global manufacturing and distribution.

We really need to put some serious work into preparing for this, because no amount of blue-shirted security guards or advanced fighter aircraft is going to stop a viral pandemic.

Stranger

Last edited by Stranger On A Train; 05-12-2020 at 12:51 AM.
  #19  
Old 05-12-2020, 01:44 AM
Gestalt is offline
Guest
 
Join Date: Apr 2003
Posts: 1,657
Quote:
Originally Posted by Stranger On A Train View Post

We don't know that it will peak again in fall; in fact, in the United States at least I expect it start swinging up again by June, and depending on how states react or fail, we could see a peaking in July or August. The point of the 'lockdown', e.g. distancing and self-isolation measures was never to stop the virus; it was to get enough time to assess what data we had, develop better testing, allow health systems to better prepare, and figure out how to enable crucial systems like education, medicine, courts, and essential businesses to function while preventing the spread from achieving epidemic levels.
I had another question--when you suggest a late summer peak, are you thinking that's when we will achieve herd immunity, and therefore do not anticipate another upswing in the fall/winter (assuming low mutagenicity and persistent immunity)? Do you think the warm weather and increased sunlight will not have a noticeable attenuating effect on the virus?
  #20  
Old 05-12-2020, 02:13 AM
AK84 is online now
Guest
 
Join Date: Apr 2008
Posts: 17,019
Quote:
Originally Posted by Jaguars! View Post
I won't speak to the medical side of things, but in this respect, the first part of your statement is rather hollow. There never was a real choice between public health or economic health. The economy was always going get wrecked, it's just a matter of degree. Consider the best and worst cases.

In places where the virus spread out of control such as New York or Italy, economic activity pretty much just ground to a halt. Society simply couldn't handle normal activity with a severe disease spreading and a. Governments hands wree forced, they locked down and b. People stopped going out of their own accord.

However, in countries where effective lockdowns take place, economic activity reduces hugely too as many workers can't do their jobs and many businesses go under or lay off workers. In my country of New Zealand, we appear to have stopped community transmission (touch wood!) but no one currently knows what the future will hold as the massive tourism sector is dead as well as half a dozen specialized export sectors. Unemployment has skyrocketed.

So essentially there was never a case that any economy in an interconnected world would escape unscathed from the moment things got out of control in Wuhan.
The economy was probably unsavable by the time most of the planet began to enter lockdown, mid March 2020.
And entering lockdown was the right call, no question about it. The bloody thing was spreading like wildfire and as DSeid has said, the brakes needed to be applied and fast.
The point I was making was that if a second wave is likely a lockdown might have made it guaranteed to be worse and continuing with one right now might be a bad idea.
  #21  
Old 05-12-2020, 04:02 AM
septimus's Avatar
septimus is offline
Guest
 
Join Date: Dec 2009
Location: the Land of Smiles
Posts: 21,501
Speeding up a vaccine by even one month might save 100,000 lives. The U.S. once dropped bombs killing a hundred thousand innocents to curtail a war; challenge trials conducted on healthy young human volunteers entail only tiny risk compared with the potential savings of lives.
Quote:
Originally Posted by Miami Herald
On Tuesday, U.S. Reps. Bill Foster of Illinois and Donna Shalala of Florida [former Secretary of Health&HS] requested that the FDA and U.S. Department of Health and Human Services approve human-challenge trials for COVID-19, if the risk is scientifically rational.

“The enormous human cost of the COVID-19 epidemic alters the optimization of the risk/benefit analysis in favor of more rapid approval and deployment,” the letter said. “Every week of delay in the deployment of a vaccine to the seven billion humans on Earth will cost thousands of lives.”
Quote:
Originally Posted by Financial Times
Around 100 Covid-19 vaccines are currently in development worldwide, with several in the early stages of clinical trials.

Volunteers are unlikely to be in short supply — more than 14,000 have already signed up on an online register run by the US-based vaccine advocacy group 1DaySooner.
  #22  
Old 05-12-2020, 07:39 AM
VOW is online now
Member
 
Join Date: Apr 2002
Location: NE AZ
Posts: 4,286
I just remember the Seventies, when it seemed like every newscaster seemed to be warning the population of impending doom via Swine Flu. It was going to be the biggest baddest worstest of all flu. The laboratories worked like crazy to develop and distribute the vaccine, and it was free. People lined up in droves to get their shots with an air gun, (OWWW!)

I can't even remember how bad the flu season ended up being.

Years later, some people had trouble functioning, unable to perform even their own care. Nobody knew what was going on. The strange new illness was Epstein-Barr, and was apparently triggered by the Swine Flu shot.


~VOW
__________________
Klaatu Barada Nikto
  #23  
Old 05-12-2020, 07:51 AM
Stranger On A Train is offline
Guest
 
Join Date: May 2003
Location: Manor Farm
Posts: 19,840
Quote:
Originally Posted by Gestalt View Post
I had another question--when you suggest a late summer peak, are you thinking that's when we will achieve herd immunity, and therefore do not anticipate another upswing in the fall/winter (assuming low mutagenicity and persistent immunity)? Do you think the warm weather and increased sunlight will not have a noticeable attenuating effect on the virus?
No, we will definitely not achieve herd immunity levels by late summer; given the infectiousness of this disease and the asymptomatic spread, I think a significant herd immunity threshold is going to be at least 60% and likely exceeding 80% to really push it down below epidemic levels. I based that guestimate on the premise that we're going see greater infections as states open up that will start becoming apparent in June, and then a bunch of states will try locking things back down with a similar lag period to what we saw before (or perhaps a little faster as people in states that were previously less affected take it more seriously.) There is no particular reason to believe that spread of SARS-CoV-2 will be attenuated by ambient heat in the way seasonal influenza is, and while sunlight definitely does destroy exposed virus there are plenty of areas that are shadowed (on the underside of a door handle or any place inside without good ventilation) where virions can accumulate. SARS-CoV-2 is spreading just fine in subtropical and tropical countries like Brazil.

Quote:
Originally Posted by septimus View Post
Speeding up a vaccine by even one month might save 100,000 lives. The U.S. once dropped bombs killing a hundred thousand innocents to curtail a war; challenge trials conducted on healthy young human volunteers entail only tiny risk compared with the potential savings of lives.
An unsafe vaccine could cost millions of lives and undermine efforts to later deploy a proven vaccine. Challenge trials (where patients are inoculated and then exposed to live virus) are ethically suspect, particularly if the virus has not first been through safety trials. The suggestion has been made here and elsewhere that volunteers from medical and front-line workers who are likely to be exposed anyway could be used in a pseudo-"challenge trial" but again a 'bad' vaccine could literally make this virus an order of magnitude more lethal. Let's permit the actual experts in immunology and virology follow the decades of immunology research processes and safety protocols developed by the experience of trying and seeing what works and what doesn't instead of trying to do an end run around sound science. And instead of depending on the "Hail Mary pass" of a quick vaccine, let's work to find therapeutics and ways of reopening parts of our economy and society in absence of a vaccine that may not come for years or at all.

Stranger
  #24  
Old 05-12-2020, 08:05 AM
AK84 is online now
Guest
 
Join Date: Apr 2008
Posts: 17,019
Just want to point out that Brazil's worst outbreak is in Sao Paulo, whose climate includes a relatively cold winter season (its autumn there right now), with the temperatures falling to below freezing somewhat regularly.

Although I have read that Manaus is also suffering and that's equatorial.
Wuhan is about 30'N, the same latitude as Cairo, Houston, and New Orleans. It's actually south of Baghdad, Atlanta and Islamabad. Traditionally 30N is considered the start of the temperate zone. It is the first northern latitude where seasonality becomes noticeable (as in needing heating in the winter).

Last edited by AK84; 05-12-2020 at 08:09 AM.
  #25  
Old 05-12-2020, 08:05 AM
septimus's Avatar
septimus is offline
Guest
 
Join Date: Dec 2009
Location: the Land of Smiles
Posts: 21,501
Quote:
Originally Posted by Stranger On A Train View Post
An unsafe vaccine could cost millions of lives ...
You try the vaccine on some dozens of volunteers, then expose them to the virus. If the vaccine is ineffective then 1 or 2 of the volunteers may die — after all, they're young healthy volunteers not in a high-risk group. How do you get from "1 or 2" to "millions"?

OF COURSE, you proceed in a manner condoned by policy and medical experts -- you're just changing risk priorities, as Secretary Shalala suggests.

Last edited by septimus; 05-12-2020 at 08:08 AM.
  #26  
Old 05-12-2020, 08:08 AM
Jasmine's Avatar
Jasmine is online now
Member
 
Join Date: Jul 1999
Location: Chicagoland
Posts: 2,705
COVID-19 arrived here in earnest in late March. The concern is that, in the Fall, it will resurface at the same time other flu and cold viruses normally resurface, so the impact will be greater because of that alone. In a few short months, all these questions will be answered.

As my dad used to say, "We shall see what we shall see."
__________________
"The greatest obstacle to discovery is not ignorance -- it is the illusion of knowledge."
--Daniel J Boorstin
  #27  
Old 05-12-2020, 08:16 AM
Jay Z is online now
Guest
 
Join Date: Dec 2017
Posts: 93
Quote:
Originally Posted by AK84 View Post
Just want to point out that Brazil's worst outbreak is in Sao Paulo, whose climate includes a relatively cold winter season (its autumn there right now), with the temperatures falling to below freezing somewhat regularly.

Although I have read that Manaus is also suffering and that's equatorial.
Wuhan is about 30'N, the same latitude as Cairo, Houston, and New Orleans. It's actually south of Baghdad, Atlanta and Islamabad. Traditionally 30N is considered the start of the temperate zone. It is the first northern latitude where seasonality becomes noticeable (as in needing heating in the winter).
Sao Paulo's coldest month is July, with an average low of 56 degrees. It's not as cold as you're implying.
  #28  
Old 05-12-2020, 08:30 AM
Andy L is online now
Member
 
Join Date: Oct 2000
Posts: 7,555
Quote:
Originally Posted by VOW View Post

Years later, some people had trouble functioning, unable to perform even their own care. Nobody knew what was going on. The strange new illness was Epstein-Barr, and was apparently triggered by the Swine Flu shot.


~VOW
Guillain–Barré, not Epstein-Barr. Epstein-Barr virus causes mononucleosis

Last edited by Andy L; 05-12-2020 at 08:30 AM.
  #29  
Old 05-12-2020, 09:11 AM
Stranger On A Train is offline
Guest
 
Join Date: May 2003
Location: Manor Farm
Posts: 19,840
Quote:
Originally Posted by septimus View Post
You try the vaccine on some dozens of volunteers, then expose them to the virus. If the vaccine is ineffective then 1 or 2 of the volunteers may die — after all, they're young healthy volunteers not in a high-risk group. How do you get from "1 or 2" to "millions"?
Antibody-Dependent Enhancement. A vaccine that is rushed through a single limited phase of testing may not be well vetted for safety in the genral population, particularly considering that hypothetical challenge trials would likely select the “young healthy volunteers” as you note but it is older people, many of whom have underlying conditions that may aggravate their response, who are disproportionately affected. Given how poorly we understand the pathogenesis of this virus even in otherwise healthy people with very mild symptoms, rushing to deploy a virus “as fast as possible” without the kind of safeguards that immunologists have learned—sometimes by grievous error such as the 1976 H1N1 vaccine previously mentioned—could have catastrophic consequences. Even if it doesn’t result in ADE, an ineffectual vaccine may discourage compliance in future vaccination campaigns. Again, we have these testing protocols for very good reasons, not just bureaucratic ‘red tape’ to employ functionaries.

Quote:
Originally Posted by septimus View Post
OF COURSE, you proceed in a manner condoned by policy and medical experts -- you're just changing risk priorities, as Secretary Shalala suggests.
As a former Secretary of Health and Human Services, Donna Shalala has some authority in public health policy. However, her education and professional experience are in political science and law, not virology or immunology. In the question of whether the risk of challenge trials and other ethically problematic measures are necessary we should consult with the people with technical expertise in the field.

Stranger
  #30  
Old 05-12-2020, 09:17 AM
septimus's Avatar
septimus is offline
Guest
 
Join Date: Dec 2009
Location: the Land of Smiles
Posts: 21,501
Quote:
Originally Posted by Stranger On A Train View Post
In the question of whether the risk of challenge trials and other ethically problematic measures are necessary we should consult with the people with technical expertise in the field.
Obviously. The point is that policy-makers need to provide inputs regarding risk assessment; medical experts may be constrained by literal adherence to the Hippocratic Oath.
  #31  
Old 05-12-2020, 09:42 AM
VOW is online now
Member
 
Join Date: Apr 2002
Location: NE AZ
Posts: 4,286
Quote:
Originally Posted by Andy L View Post
Guillain–Barré, not Epstein-Barr. Epstein-Barr virus causes mononucleosis

Whups, sorry!

That's what happens when I post after only one cup of coffee!


~VOW
__________________
Klaatu Barada Nikto
  #32  
Old 05-12-2020, 09:24 PM
DSeid's Avatar
DSeid is online now
Guest
 
Join Date: Sep 2001
Location: Chicago, IL
Posts: 23,964
Quote:
Originally Posted by septimus View Post
You try the vaccine on some dozens of volunteers, then expose them to the virus. If the vaccine is ineffective then 1 or 2 of the volunteers may die — after all, they're young healthy volunteers not in a high-risk group. How do you get from "1 or 2" to "millions"?

OF COURSE, you proceed in a manner condoned by policy and medical experts -- you're just changing risk priorities, as Secretary Shalala suggests.
"Some dozens" really is a bit of an understatement ... but neither here nor there.

If all you who are talking about with the urge to speed it up or race it through is to approve human challenge trial with lower risk populations, well personally I think that is a fine ethical way to proceed. But realistically that bit is just one of the many steps to prove a vaccine product safe and effective across all demographics. Speedy it still likely will not be. Shave some time off maybe.

From the Financial Times Article quoted is some interesting stuff. One bit is this:
Quote:
Then there is the question of what virus to use. The NIH group suggests developing a special “challenge strain” with reduced virulence to administer in challenge trials.
FWIW ... one option for influenza immunization has been a live attenuated influenza vaccine administered as a nasal spray, brand name FluMist. It faded off in use when in one season it was not a great match against H1N1 but is approved for use again both last year and in the current season with a modified H1N1 component.

One wonders if development of a reduced virulence SARS-CoV-2 to use in a challenge would spin off a Live Attenuated SARS-CoV-2 Vaccine ... although the fact that FluMist had disappointed against H1N1 may leave a developers a bit hesitant to go there. But theoretically a live attenuated vaccine is more likely to provoke a T-cell response than most of the other approaches proposed, so the temptation may still be there, given the reduced virulence bug may be half way to product.
  #33  
Old 05-12-2020, 09:29 PM
DSeid's Avatar
DSeid is online now
Guest
 
Join Date: Sep 2001
Location: Chicago, IL
Posts: 23,964
Huh. Googling a bit comes up with this proposed approach. Interesting.
Quote:
Valo Tx will use its PeptiCRAd technology to coat an (undisclosed) adenovirus vaccine vector, engineered to express coronavirus associated spike proteins, with HLA-matched peptides optimized to further boost CD8+ T-cell immune responses.

Both components of the proposed vaccine have been tested individually. Non-replicating adenoviruses have been through clinical safety-testing and adenoviral vectors in general have been used safely in thousands of people across a wide range of ages. It is much faster to manufacture the clinical grade peptides necessary for coating the adenovirus, than re-engineering and manufacturing a new virus, making this approach more flexible and enabling clinical testing to progress quickly in the event that a new coronavirus strain emerges.

Most vaccines focus on boosting the antibody B cells response, but a T-cell immune response is important given that the infection targets the respiratory tract. COVID-19 replicates particularly fast and it appears that, by the time neutralizing antibodies are produced, many cells in the lungs have already become infected and require cell-mediated clearance. Adenoviral vectors are particularly strong at inducing T-cell mediated immune responses, and it is hoped that the SARS-COV-2 spike proteins will be processed to induce both T-cell and antibody mediated immunity to COVID-19. Additionally coating the adenovirus with peptides specifically selected for driving CD-8+ T-cells is expected to further enhance the cell mediated immune response; with the added capacity to broaden the immune targets.
  #34  
Old 05-12-2020, 10:11 PM
nearwildheaven is offline
Guest
 
Join Date: Apr 2013
Posts: 14,204
COVID isn't the 1918 influenza virus, and I personally think we are in the "second wave" right now, due to all the people, myself included, who quite likely had it before it was officially identified.

I just hope that there's no third wave, fourth wave, etc.
  #35  
Old 05-12-2020, 11:03 PM
RickJay is offline
Charter Jays Fan
Moderator
 
Join Date: Jun 2000
Location: Oakville, Canada
Posts: 43,037
Quote:
Originally Posted by septimus View Post
You try the vaccine on some dozens of volunteers, then expose them to the virus. If the vaccine is ineffective then 1 or 2 of the volunteers may die — after all, they're young healthy volunteers not in a high-risk group. How do you get from "1 or 2" to "millions"?
Dozens? That may do for a Phase 1 trial. It's not close to enough to ascertain if the vaccine actually WORKS. You need a substantial clinical trial.
__________________
Providing useless posts since 1999!
  #36  
Old 05-13-2020, 07:49 AM
asahi's Avatar
asahi is online now
Guest
 
Join Date: Aug 2015
Location: On your computer screen
Posts: 13,205
Quote:
Originally Posted by AK84 View Post
There has been a lot of talk that the COVID19 is likely to peak again in the autumn and winter and much like the Spanish flu of 1918, this is likely to be much worse, I have read stuff like that a similar result to the NYC and Lombardy experience in this first wave would be seen a having dodged a bullet in the second wave.

It appears that second waves are almost always worse than first ones (besides the Spanish flu, the 1957 Asian flu, and the 2009 Swine flu pandemic's second waves were also worse, with the 1968 Hong Kong flu being an exception).
Why is this case? Surely by the time a second wave hits, the population is no longer virgin as it was in the first wave, there should be some resistance.
There's no resistance if it has only hit 5-10% of the population. A major outbreak will easily infect two to three times that amount. Even if it's a widespread pandemic, perhaps only a third of the global population might be exposed to it within the first year. There's the potential to infect more. Viruses can also mutate from year to year.

The 1918 flu's second wave was arguably the first true wave, as the initial outbreak in spring of that year was geographically confined. It didn't become a pandemic until soldiers from the US brought it to Europe, and then brought it back to the US in the fall of that year. The spring 1919 was bad, but it accounted for only 20-30% of the entire fatalities during the entire pandemic.

The fear that people have now - in the US anyway - is that a failed public health response will allow COVID-19 to hang around until fall, which is when the flu season begins. If that happens, reopening the country would be an absolute nightmare, as would holding a regular presidential election.
  #37  
Old 05-13-2020, 07:51 AM
asahi's Avatar
asahi is online now
Guest
 
Join Date: Aug 2015
Location: On your computer screen
Posts: 13,205
Quote:
Originally Posted by nearwildheaven View Post
COVID isn't the 1918 influenza virus, and I personally think we are in the "second wave" right now, due to all the people, myself included, who quite likely had it before it was officially identified.

I just hope that there's no third wave, fourth wave, etc.
Nope. Right now is the first wave - the second inning of a 9-inning baseball game. We're a long way from being done with this, and contrary to what you may believe, the reality is that a very small percentage of the world's population has been exposed. Probably 92-97% of the US population has not been exposed. We're nowhere near being done with this.
  #38  
Old 05-13-2020, 06:10 PM
septimus's Avatar
septimus is offline
Guest
 
Join Date: Dec 2009
Location: the Land of Smiles
Posts: 21,501
Quote:
Originally Posted by RickJay View Post
Dozens? That may do for a Phase 1 trial. It's not close to enough to ascertain if the vaccine actually WORKS. You need a substantial clinical trial.
If successful, it would give the confidence to proceed with bigger trials and speed up vaccine availability.

Look, you guys may be qualified to debate the details of vaccine trials, but that's a topic on which I know nothing. I am just arguing that the usual Hippocratic Oath proscription against challenge trials should be weakened given the speed with which this virus may spread. Experts would still guide the details, but "ethical standards" — unrelated to either science or utilitarian goals — need to be reviewed if they would otherwise be likely to (hugely!) increase human suffering.
  #39  
Old 05-13-2020, 06:49 PM
Stranger On A Train is offline
Guest
 
Join Date: May 2003
Location: Manor Farm
Posts: 19,840
Quote:
Originally Posted by septimus View Post
Look, you guys may be qualified to debate the details of vaccine trials, but that's a topic on which I know nothing. I am just arguing that the usual Hippocratic Oath proscription against challenge trials should be weakened given the speed with which this virus may spread. Experts would still guide the details, but "ethical standards" — unrelated to either science or utilitarian goals — need to be reviewed if they would otherwise be likely to (hugely!) increase human suffering.
There is nothing in the modern “Lasagna version” of the Hippocratic oath that specifically proscribes or limits the ability of physicians to conduct challenge trials. I suppose you could interpret “I will prevent disease whenever I can,” as an explicit prohibition but the development of a vaccine that physicians have good confidence in is fulfilling that dictum.

The problem with rushing to challenge trials—aside from the possibility that a bad vaccine could cause the virus pathogenesis to become more virulent—is that the ethical framework for minimizing unintended mortality would drive you to select only young and healthy participants. But while COVID-19 is not only seen in the elderly and those with underlying conditions, the most severe cases are disproportionately presented in that population. A challenge trial that is successful in only a population of young and healthy individuals can really only be assured to demonstrate safety and efficacy in those populations. In the normal Phase I/II/III trials, safety is demonstrated first phase, basic efficacy and confirmation of safety in the second phase, and then efficacy in the broad spectrum of population demographics in the third phase.

And quite frankly if we had a vaccine candidate in the next few months there really isn’t any need to run a challenge trial; the infectiousness of the SARS-CoV-2 virus is such that you just need to identify uninfected candidates who are in an exposed occupation and enroll them in the study because there is a statistical likelihood of infections for medical personnel, first responders, and other public-facing workers. And if we get to the point that the population pool is saturated with previously-exposed people who are seropositive then you’ve probably achieved a certain threshold of herd immunity anyway and should now be focusing on determining how long immunity will last.

There was some discussion back when the MERS outbreak occurred about running a vaccine candidate through challenge trials specifically because of how quickly the virus burns out in person-to-person spread leaving little potential for unforced infection, and the consensus was that the risk of future outbreak achieving uncontrollable epidemic proportions was low enough that more potential harm could be done via the challenge trials than by the wild virus itself. Now, you could make the reverse argument for SARS-CoV-2–that spread is guaranteed and a working vaccine will potentially save millions of lives versus the few hundred you make risk in a well-structured challenge trial—but then that goes back to the point that if this disease is so infectious and there are so many uninfected or non-immune people out there, then you don’t actually need to run a challenge trial; you can just run a normal three phase safety and efficacy trial. Running a challenge trial provides very little if any benefit in speeding up the process.

There is another potential alternative; it would be possible to run a trial using a coronavirus with a similar enough structure—particularly in the S protein—that the vaccine would also protect from but that lacks the lethal pathogenesis of SARS-CoV-2. If such a virus existed, you could use it as a trial mechanism to test for efficacy (although obviously it wouldn’t give you safety). However, if such a virus existed, it would likely also convey some level of immunity and would be a candidate for a vaccine, provided you have enough confidence that it woudn’t be able to recombine with the real SARS-CoV-2 or a live attenuated virus vaccine (if that is what you are testing) to produce another novel pathogen.

So, pretty much any testing of vaccines (and virtually any other drug that affects the immune system or other organ functions) has ethical concerns because with any new drug there is always some potential for unforeseen harms. But the particular case in which challenge trials are really both ethically justifiable and are really necessary to significantly speed up approval are very narrow; it would essentially have to be a virus that is contagious enough to be a serious threat of epidemic spread, but not in an epidemic phase such that it is unlikely that your study population will be naturally exposed to the virus in a statistically significant quantity; or else the harms of infection are not serious enough to be of concern should the vaccine not work (in which case it is unlikely anyone would develop a vaccine).

Stranger
Reply

Bookmarks

Thread Tools
Display Modes

Posting Rules
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts

BB code is On
Smilies are On
[IMG] code is Off
HTML code is Off

Forum Jump


All times are GMT -5. The time now is 08:21 AM.

Powered by vBulletin® Version 3.8.7
Copyright ©2000 - 2020, vBulletin Solutions, Inc.

Send questions for Cecil Adams to: cecil@straightdope.com

Send comments about this website to: webmaster@straightdope.com

Terms of Use / Privacy Policy

Advertise on the Straight Dope!
(Your direct line to thousands of the smartest, hippest people on the planet, plus a few total dipsticks.)

Copyright © 2019 STM Reader, LLC.

 
Copyright © 2017