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What is going to happen is most likely they will relax shelter-in-place orders, some businesses will gradually reopen back up,

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FIFY

KidDoc said:

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culdeus said:

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cone said:

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is South Korea going to be a closed system into perpetuity?

as far as the virus is concerned, they are still virgin timber

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So is Vietnam. And to an extent India.

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This is why A&M is studying BCG vaccine as a preventative for COVID. India should have been over run with deaths but it was not. Is universal BCG the answer?

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We had a discussion about BCG on here, I want to say maybe two months ago now, because it was pointed out that not only was BCG being looked at as a preventative, but South Korea was one of the few remaining countries that had mandatory inoculations of BCG in recent years which might explain part of their low infection and fatality rate.

swintie said:

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KidDoc said:

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culdeus said:

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cone said:

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is South Korea going to be a closed system into perpetuity?

as far as the virus is concerned, they are still virgin timber

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So is Vietnam. And to an extent India.

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This is why A&M is studying BCG vaccine as a preventative for COVID. India should have been over run with deaths but it was not. Is universal BCG the answer?

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Am I the only one chuckling about "what does Coach Gillispie have to do with this?" I guess I need to use the "googles" and figure out what BCG stands for LOL.

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It is a vaccine to prevent Tuberculosis. We don't have an issue with TB in the US so it isn't one of the standard courses. Other countries (SK, India, etc) still routinely give the vaccine. It is approved for Bladder cancer in the US because it also has the effect of generally boosting the immune system.

Since it isn't specific for COVID, it would not prevent the disease and stop the spread, but it is theorized that the immune enhancing effect would reduce the severity. A person who would have needed to be hospitalized would instead be a mild case and a patient who would have died just needed hospitalization. The hope is it helps now until a covid specific vaccine is available.

Since it is already approved in the US and clearly safe, they can jump straight to the larger scale trial to show efficacy. And since the end goal isn't immunity but reduced severity, it might be faster to show sufficient effectiveness for approval.

I hope this happens.

Fairly technical discussion of how BCG might interact with the Immune and Metabolic systems.

https://www.cell.com/cell-reports/pdfExtended/S2211-1247(16)31552-2
Immunometabolic Pathways in BCG-Induced Trained Immunity

The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such as monocytes, a process termed trained immunity. Here, we show that BCG induction of trained immunity in monocytes is accompanied by a strong increase in glycolysis and, to a lesser extent, glutamine metabolism, both in an in-vitro model and after vaccination of mice and humans. Pharmacological and genetic modulation of rate-limiting glycolysis enzymes inhibits trained immunity, changes that are reflected by the effects on the histone marks (H3K4me3 and H3K9me3) underlying BCG-induced trained immunity. These data demonstrate that a shift of the glucose metabolism toward glycolysis is crucial for the induction of the histone modifications and functional changes underlying BCG-induced trained immunity. The identification of these pathways may be a first step toward vaccines that combine immunological and metabolic stimulation.

BiochemAg97,

A video on Medcram a while back was the first I heard about the notion of adaptation in the innate immune system. These are pretty fascinating ideas linking metabolism, immunity and pathologies in both. Is this Trained Immunity a legitimate thing?



"Insulin Signaling and Insulin Resistance Facilitate Trained Immunity in Macro****es Through Metabolic and Epigenetic Changes"
https://www.frontiersin.org/articles/10.3389/fimmu.2019.01330/full

Obesity induces metabolic inflammation, a chronic low-grade inflammation characterized by systemic increased levels of pro-inflammatory factors and insulin resistance. Energy storage organs like adipose tissue, liver and muscle exceed their capacity to preserve homeostasis, leading to metabolic stress. this condition is capable of altering responses mediated by innate immune cells. Macro****es are central mediators of inflammatory responses and are causally linked to obesity-related pathologic conditions, including Type 2 diabetes (T2D) and cardiovascular disease (1).

During recent years, the dogma that only adaptive immunity is responsible for immune memory has been challenged and the concept of innate immune training has emerged. In plants, invertebrates and mammals, cells of innate immunity have been shown to possess a form of memory, also termed "Trained Immunity." Trained immunity is defined as persistent alteration of innate immune responses, which depends on prior exposure to a signal. For example, exposure to -glucan, infection or vaccination, results in elevated pro-inflammatory cytokines after a secondary infection. Exposure to insulin or Saturated Fatty Acids (SFAs) also results in altered TLR responses (2, 3) Trained immunity also describes altered responses to pathogens occuring after severe inflammation, such as endotoxin tolerance or Compensatory Anti-inflammatory Response Syndrome (CARS) (4). Innate immune cells shown to be part of "trained immunity" are monocytes, NK cells and dendritic cells (5, 6). This review will focus on macro****e trained immunity, which includes bone marrow-derived monocytes/macro****es and tissue resident macro****es that are self-renewing embryo-derived (710). Innate immune training is not only associated with infectious stimuli but also to non-infections conditions, such as obesity and insulin resistance (3, 11, 12).

The BCG vaccination connection merits more study. However, a new study from Israel finds no evidence of BCG vaccination protecting against SARS-CoV-2 infections. Apparently, since 1982 only immigrants to Israel from countries with high levels of TB have been regularly immunized with BCG. So, within Israel they can look for an effect of the vaccination. They found no significant effect of BCG vaccination: https://jamanetwork.com/journals/jama/fullarticle/2766182

Pumpkinhead said:

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A year from now, in your daily routine, whether if it having to stand on a little dot in some line to stay 6 feet apart, have to wear a mask somewhere, there is protective thing between you and a cashier so can't breath in their face, capacity limits, whatever...there will probably be something in your 'new normal' that reminds you of COVID.

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things i feel confident predicting at this point.

1. a year from now, in the vast majority of the country, life will largely be as it was pre-February. the virulence and actual death rate for the broad population is simply too low to justify the sort of long-term social disruption you are predicting. Most businesses cannot maintain profitability in the scenarios you describe, and government cannot bail out those businesses indefinitely. rational behavior will dictate far greater protective effort and restrictions for at-risk categories, and normalcy for the rest. States/regions that attempt to stick to the sort of 'everybody is at risk' strategies as you describe are going to be economically decimated and face rapid declines in financially well-off population - which will force them to relax those one-size-fits-all restrictions.

2. elderly will continue to be at risk, especially in nursing home environments where many elderly are densely packed. this will drive a reversion to elders living out life with family instead of being in elder care facilities. home health care service businesses are a great investment in anticipation of this inevitable trend.

3. obesity as a 'normal' condition to be embraced (Lizzo etc) will fade as a social justice trend.

4. there will be no vaccine for COVID 19. I really hope i'm wrong about this, but see no reason for the broad statements of faith that these viruses that have long confounded scientists are suddenly going to be overcome by massive amounts of money and effort. nature has her way and her day, whether we like her or not.

just my view.

CompEvoBio94 said:

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The BCG vaccination connection merits more study. However, a new study from Israel finds no evidence of BCG vaccination protecting against SARS-CoV-2 infections. Apparently, since 1982 only immigrants to Israel from countries with high levels of TB have been regularly immunized with BCG. So, within Israel they can look for an effect of the vaccination. They found no significant effect of BCG vaccination: https://jamanetwork.com/journals/jama/fullarticle/2766182

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Those results don't really surprise me. It isn't expected to prevent infection since it isn't going to create any covid specific antibodies. And the study is too small to really see an effect on severity with only 1 severe case in each group. Also they are only looking at people who have COVID symptoms.

We shall see the results of the controlled study eventually. I'm just not sure it is going to be a big enough effect or early enough to make a difference. The Oxford Jenner Group has their vaccine in their massive phase 2/3 trial with hopes of getting approval in 6 months. Having the BCG vaccine showing reduced severity and having an effective vaccine at about the same time... I think the choice to go with the COVID specific vaccine would be obvious.

I'm going to disagree with your reasoning for 4, but not really with your sentiment. One of the big reasons we don't have an existing vaccine against a corona virus for humans is we haven't been motivated for long enough to get one approved. We do however have a corona virus vaccine for cattle, so we know it can be done. And I think an Israeli group has one for pigs or is close. Obviously not the same virus as the one causing COVID19, but same family.

Human CoVs that cause a cold aren't really worth the effort to develop a vaccine. Even if you stop HuCoV based colds, there are still other virus families that cause colds so you would see minimal benefit.

SARS and MERS we controlled well enough and fast enough without a vaccine that further development was put on ice. It is impossible to do a phase2/3 study to show the vaccine protects you if no one is going to be exposed to the virus. And injecting people with live virus to test the vaccine is not really an option. However, they have all been shown to work in monkeys where we can vaccinate and then inject with a high dose of live virus.

Now, do we have one next May... timing is the bigger complication. If the Jenner Group is successful, then yes. If we are waiting for Fauci's NAIAD sponsored RNA vaccine, then we are going to be waiting into 2022, unless they decide to speed it up. Hard to say on the many many other vaccines in various stages of testing.

BiochemAg97 said:

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I'm going to disagree with your reasoning for 4, but not really with your sentiment.

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hope you are right.

Those articles always blindly paint Sweden as some death factory. Their numbers are markedly better than Massachusetts despite a 40%+ larger population.

fig96 said:

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NASAg03 said:

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They also say that Georgia isn't a success story because they fake their numbers or don't sequence them properly (hard to do based on differences between date reported and actual dates).

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I'd be very hesitant to call Georgia a success story at this point.

They did seem to put out some creatively manipulated graphs last week and got rightly called out for it, and their case numbers seem a bit suspect. The graph of cases there per reported data follows no logical curve or pattern which would seem to indicate inaccurate data at some point in the process.

It's really too early to tell what's going to happen anywhere in the US at this point with quarantine restrictions being lifted very recently, we'll know a lot more in a few weeks.

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For reference, this is the Georgia plot being referenced. I'm not sure what they were going for by arranging the dates out of order.

fig96 said:

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dragmagpuff said:

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fig96 said:

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NASAg03 said:

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They also say that Georgia isn't a success story because they fake their numbers or don't sequence them properly (hard to do based on differences between date reported and actual dates).

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I'd be very hesitant to call Georgia a success story at this point.

They did seem to put out some creatively manipulated graphs last week and got rightly called out for it, and their case numbers seem a bit suspect. The graph of cases there per reported data follows no logical curve or pattern which would seem to indicate inaccurate data at some point in the process.

It's really too early to tell what's going to happen anywhere in the US at this point with quarantine restrictions being lifted very recently, we'll know a lot more in a few weeks.

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For reference, this is the Georgia plot being referenced. I'm not sure what they were going for by arranging the dates out of order.

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It sure seems like being out of order creates a downward trend that doesn't actually exist.

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https://thisistrue.com/fixing-georgia/

The author of this one took the GA image and used photoshop to rearrange to the right date order. He assumes the last two days which are way down are incomplete data and ignores the suggestion of a drastic drop the last two days. From his modified graph, it looks like a jump on May 3 and all but the yellow county (Fulton) basically flat or slightly down afterwards. Fulton looks to be still going up if we assume the last two days is incomplete data.

I chose Massachusetts because Boston and Stockholm have similar population sizes and densities of 13k per square mile.

There just aren't many American cities that dense.

Keegan99 said:

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I chose Massachusetts because Boston and Stockholm have similar population sizes and densities of 13k per square mile.

There just aren't many American cities that dense.

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I didn't see Stockholm mentioned in the post I quoted, only Sweden and Massachusetts. Since Sweden has 40% larger population that Mass, that seemed to be what you were comparing.

THe Boston MSA is 3.5 times larger, in population, then Stockholms.

Pointless discussion anyway.

Can't explain why, but every time I read about Sweden the mental image is Toronto, even though it's basically the population of Georgia.

Herd immunity is a nice goal for smaller countries, but I don't think the US has the stomach to get there sans vaccine. The math isn't kind.

Fitch

I hear you but IMHO, the virus is here and if your hospitals have plenty of capacity locking down your economy does nothing but kill more in the long run and ruin your country. The deaths are coming whether we can stomach them or not. Texas hospitals are not even close to having issues, actually the opposite. Without patients people are getting furloughed and no one is getting treated. How many deaths are we going to see now from a multitude of other conditions not getting treated? It will dwarf covid before long. Someone posted early the suicide hotline calls have increase like 8,000% alone. I haven't read that study myself so don't quote that.

Open being safe, not stupid. Americans can do anything they put their minds to. I think people are taking safety serious now and want to get back to work and living.

https://www.worldometers.info/coronavirus/country/sweden/

Sweden looking like they are coming out the other side now. All trends are looking good.

Fitch said:

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Can't explain why, but every time I read about Sweden the mental image is Toronto, even though it's basically the population of Georgia.

Herd immunity is a nice goal for smaller countries, but I don't think the US has the stomach to get there sans vaccine. The math isn't kind.

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Have you heard anything from any leader in America about actually trying to protect the elderly and nursing homes in any reopening plan? The answer is no. America does not apparently have the will to tell certain people they are more at risk than someone else and include it in the plan.

If we actually planned around the risk areas, we can cut down the mortality rate drastically and get to where we need to be. I'd argue we could have done it from the beginning, at least with age groups, based on corroborating data from SK, Italy, and other more reliable countries.

Beat40 said:

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Fitch said:

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Can't explain why, but every time I read about Sweden the mental image is Toronto, even though it's basically the population of Georgia.

Herd immunity is a nice goal for smaller countries, but I don't think the US has the stomach to get there sans vaccine. The math isn't kind.

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Have you heard anything from any leader in America about actually trying to protect the elderly and nursing homes in any reopening plan? The answer is no. America does not apparently have the will to tell certain people they are more at risk than someone else and include it in the plan.

If we actually planned around the risk areas, we can cut down the mortality rate drastically and get to where we need to be. I'd argue we could have done it from the beginning, at least with age groups, based on corroborating data from SK, Italy, and other more reliable countries.

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I could be wrong, but I don't think you've heard anything because the announcements have been focused, almost exclusively, on aspects of life where there is to be a change in status. I think nursing homes are still on lockdown in most states, denying visitors, ramping up testing for staff, and making sure that staff has PPE. I haven't heard of any state easing restrictions on nursing homes, but, I could have missed that.

seroprevalence in Sweden is like 7%

they are no where near herd

good news is that even mild social distancing works to drop R0, but their economy is still going to be relatively in the toilet

DadHammer said:

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Fitch

I hear you but IMHO, the virus is here and if your hospitals have plenty of capacity locking down your economy does nothing but kill more in the long run and ruin your country. The deaths are coming whether we can stomach them or not. Texas hospitals are not even close to having issues, actually the opposite. Without patients people are getting furloughed and no one is getting treated. How many deaths are we going to see now from a multitude of other conditions not getting treated? It will dwarf covid before long. Someone posted early the suicide hotline calls have increase like 8,000% alone. I haven't read that study myself so don't quote that.

Open being safe, not stupid. Americans can do anything they put their minds to. I think people are taking safety serious now and want to get back to work and living.

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To clarify, I'm in the pro-reopening camp. I'm also hopeful we'll approach this thoughtfully and seriously.

I'd argue the deaths aren't necessarily coming regardless -- but there is a higher chance of more loss of life if as a society we let frustration overtake reason and "go back" to normal practices, come what may. In that same vein, a disconcerting pattern I've seen here on TexAgs is some posters ruminating on herd immunity as a goal to achieve without apparently acknowledging that even with a lower (and apparently falling) IFR of 0.5-1.0%, that's a crap ton of people when multiplied by the US population.

I'll quit flogging the horse on this one, though.

it would be nice to define what success looks like moving forward

all frustration comes from us not knowing what we're doing this for and whether or not we're succeeding

and of course the goal post moving

first it was hospital capacity, then it was % positives as a share of overall region testing, now what is it?

Beat40 said:

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Fitch said:

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Can't explain why, but every time I read about Sweden the mental image is Toronto, even though it's basically the population of Georgia.

Herd immunity is a nice goal for smaller countries, but I don't think the US has the stomach to get there sans vaccine. The math isn't kind.

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Have you heard anything from any leader in America about actually trying to protect the elderly and nursing homes in any reopening plan? The answer is no. America does not apparently have the will to tell certain people they are more at risk than someone else and include it in the plan.

If we actually planned around the risk areas, we can cut down the mortality rate drastically and get to where we need to be. I'd argue we could have done it from the beginning, at least with age groups, based on corroborating data from SK, Italy, and other more reliable countries.

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Yes, and I disagree with the bolded part. Texas is halfway through a two week period testing every nursing home resident and staff member in the state. It's a focus, but we seem to be figuring out it's practically impossible to indefinitely put up a fire wall around vulnerable populations. People are imperfect at maintaining the rigor required to keep the bug out.

Fair thoughts and I tend to agree.

The "goal post moving" dynamic doesn't bother me, though. Evolving situations should have evolving goals.