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COVID-19 medical discussion


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2 hours ago, Brisketexan said:

Man, I gotta say....nobody can turn a bare hypothesis into a hard conclusion like you can.  It's your gift.

I like the hypothesis.  I hope that, after it has been exposed to rigorous examination pursuant to the scientific method, it will become a proven theory.  But right now, it's a hypothesis with enough smoke around it that it merits real analysis.  That's it.

We MIGHT be seeing evidence of herd immunity via T-cell immunity taking hold.....but we don't have nearly enough evidence to say that it's likely.

To clarify, evidence of herd immunity being attained in certain major cities, and certain regions and nations is one thing, why it is happening apparently without 60-70% of the respective populations being infected is another.  Just looking at the graphs of those places it looks likely that herd immunity is emerging.  "Likely" is not making a "hard conclusion."  Looking at the graphs, "likely" reaching herd immunity is not wild-assed conjecture.  Is is certain?  No, of course not.  But it's not a blip.  These sustained trends have been emerging for a few weeks now.  

What could explain herd immunity being achieved around 20% instead of 60-70% for a "novel" pathogen?  T cell immunity is the best explanation I've seen.  Moreover, it's why I posted the well thought out twit thread last page for everyone to digest.  It contains math, and numbers and science stuff.

To get from theorized 60%+ required population exposure for herd immunity to a "novel" pathogen down to 20%+ for HI, you have to account for about an additional 40% of the population being neutral to spreading infection.  Look at the math and science stuff above re T cell immunity and non-antibody mediated cross-reactivity.  It computes.  But no, the knee-jerk is to respond with a ginned-up caricature of some reich wing friendly clown-doctor spreading the vile unholy word that Plaquenil could be even remotely safe, you know, for actual human ingestion.  *gasp*

If HI is emerging in various areas, the outstanding question is "does it change management"?  My initial thought is no.  You don't stop distancing, hand washing, and mask wearing.  All of those things help accelerate R0 being less than 1 and the viral run stalling out.  But it also means that places where only 5% of the population has been exposed due to effective curve flattening from distancing, masking up, and hand hygiene still stand to have new cases persist at higher levels than places like NY, MA, CT, NJ etc where they got burned hot and fast but where hell has passed.  While that sounds like a mixed-news scenario, the 5% places that have coordinated state govt and a willing population is where you can eliminate it through continued mitigation behaviors, contact tracing, and EARLY targeted use with cheap generic repurposed drugs like Ivermectin and the Quinine derivatives to safely help EARLY to limit hospitalizations, illness severity, and risk of death.

food for thought: if a pandemic is a war, big pharma is the military industrial complex.  chew on that for a sec.

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5 hours ago, Rip76 said:

https://bgr.com/2020/08/10/coronavirus-update-effect-of-ordinary-water-on-covid-19/
 

Scientists from Russia’s VECTOR State Research Center of Virology and Biotechnology have shared a coronavirus update that purports to include a shockingly easy way to kill particles associated with the COVID-19 virus. Are you ready for this? These scientists say the coronavirus has a newly identified weakness, and it’s … water. Just ordinary, room-temperature water, though boiling water works even better.

So . . . drown the patient?  Or for a more effective solution, drown them in boiling water?

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1 hour ago, triplehorn said:

To clarify, evidence of herd immunity being attained in certain major cities, and certain regions and nations is one thing, why it is happening apparently without 60-70% of the respective populations being infected is another.  Just looking at the graphs of those places it looks likely that herd immunity is emerging.  "Likely" is not making a "hard conclusion."  Looking at the graphs, "likely" reaching herd immunity is not wild-assed conjecture.  Is is certain?  No, of course not.  But it's not a blip.  These sustained trends have been emerging for a few weeks now.  

What could explain herd immunity being achieved around 20% instead of 60-70% for a "novel" pathogen?  T cell immunity is the best explanation I've seen.  Moreover, it's why I posted the well thought out twit thread last page for everyone to digest.  It contains math, and numbers and science stuff.

To get from theorized 60%+ required population exposure for herd immunity to a "novel" pathogen down to 20%+ for HI, you have to account for about an additional 40% of the population being neutral to spreading infection.  Look at the math and science stuff above re T cell immunity and non-antibody mediated cross-reactivity.  It computes.  But no, the knee-jerk is to respond with a ginned-up caricature of some reich wing friendly clown-doctor spreading the vile unholy word that Plaquenil could be even remotely safe, you know, for actual human ingestion.  *gasp*

If HI is emerging in various areas, the outstanding question is "does it change management"?  My initial thought is no.  You don't stop distancing, hand washing, and mask wearing.  All of those things help accelerate R0 being less than 1 and the viral run stalling out.  But it also means that places where only 5% of the population has been exposed due to effective curve flattening from distancing, masking up, and hand hygiene still stand to have new cases persist at higher levels than places like NY, MA, CT, NJ etc where they got burned hot and fast but where hell has passed.  While that sounds like a mixed-news scenario, the 5% places that have coordinated state govt and a willing population is where you can eliminate it through continued mitigation behaviors, contact tracing, and EARLY targeted use with cheap generic repurposed drugs like Ivermectin and the Quinine derivatives to safely help EARLY to limit hospitalizations, illness severity, and risk of death.

food for thought: if a pandemic is a war, big pharma is the military industrial complex.  chew on that for a sec.

I'm hopeful that we're seeing positive news, that will result in positive outcomes.

But other things we must consider-- many of the places that you're citing that have very positive downward trends that are remaining low, also haven't opened up the riskiest indoor spaces like bars and inside restaurant dining capacity.  An example of a place that looked to have strong downward trends, and then opened up bars, and then saw subsequent large increases in cases, is Spain.

So there are plenty of independent variables here, that warrant close analysis.

I'm not as down on your ideas as some others, but if we want to analyze this with rigor and intent, then we have to understand all of the variables.

 

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1 hour ago, utee94 said:

So there are plenty of independent variables here, that warrant close analysis.

Exactly, my concern is that Triplehorn’s Dr. Twitter doesn’t remember confounding variables. You cannot responsibly take that big of a leap with the infection and second wave data.  I have hypothesized that T cell functions have played a role in cross and herd immunity but I sure wouldn’t want to make public health policy on it yet. 

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1 hour ago, utee94 said:

I'm hopeful that we're seeing positive news, that will result in positive outcomes.

But other things we must consider-- many of the places that you're citing that have very positive downward trends that are remaining low, also haven't opened up the riskiest indoor spaces like bars and inside restaurant dining capacity.  An example of a place that looked to have strong downward trends, and then opened up bars, and then saw subsequent large increases in cases, is Spain.

So there are plenty of independent variables here, that warrant close analysis.

I'm not as down on your ideas as some others, but if we want to analyze this with rigor and intent, then we have to understand all of the variables.

 

I haven't been keeping up lately as I've been too busy at work. What happened in Iran after they opened up the bars?

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Exactly, my concern is that Triplehorn’s Dr. Twitter doesn’t remember confounding variables. You cannot responsibly take that big of a leap with the infection and second wave data.  I have hypothesized that T cell functions have played a role in cross and herd immunity but I sure wouldn’t want to make public health policy on it yet. 

Yea but yolo.
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1 hour ago, StruggleBus said:

If this T cell thing is legit then I’m good. My kids have gotten me sick at least 30 times. A few of those had to be coronaviruses 

Seriously. My wife and I have joked about being immune because our toddler has brought home every virus/bug/plague known to man from daycare to us. Would be cool if it was actually a thing.

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54 minutes ago, Newdoc said:

Exactly, my concern is that Triplehorn’s Dr. Twitter doesn’t remember confounding variables. You cannot responsibly take that big of a leap with the infection and second wave data.  I have hypothesized that T cell functions have played a role in cross and herd immunity but I sure wouldn’t want to make public health policy on it yet. 

Yeah, I've wondered about this. I didn't read triple's link but I've read some other folks speculating along similar lines.

Do we have any sort of group that we can use as a control? Where their behavior has remained largely unchanged over time? If we did, it would be really interesting to see what happened after the first spike. Problem is that's mostly going to be third world places like Brazil, Africa, or Arkansas, and those places are definitely not going to have reliable data.

It's interesting and would be pretty fantastic if there's validity to it. I'm skeptical. Not because I don't believe it, but just because that's my default state.

Edited by BradInATX
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Well, this isn’t great.  Final piece in the puzzle on aerosol vs droplets and aerosol pulls out the win. It seems to indicate you can get infected through the air at 16 feet. 
 

https://www.nytimes.com/2020/08/11/health/coronavirus-aerosols-indoors.html?campaign_id=9&emc=edit_nn_20200812&instance_id=21197&nl=the-morning&regi_id=115763618&segment_id=35842&te=1&user_id=52582b04c3b92afd841aaf462e715115

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I got a pre-screening call today about being involved in the vaccine trial.  Both my wife and I signed up so we may be getting some follow up calls for the screening process.  Is there any reason why I shouldn't go ahead and participate with the trial?  Are there any medical posters here that can give me a really good reason that we shouldn't participate if chosen? 

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5 hours ago, kevwun said:

How soon after the trial do they let you know if you got the vaccine or not?

I haven't made it that far in the process yet.  I'd be pissed to join this study only to find out that I got the placebo.  That alone may make me not participate. 

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This guy makes sense to me, anyway:

https://www.washingtonexaminer.com/opinion/hydroxychloroquine-works-in-high-risk-patients-and-saying-otherwise-is-dangerous

This company's penny stock up 10x due to good results in seriously ill patients:

RADNOR, Pa. and GENEVA, Aug. 2, 2020 /PRNewswire/ -- NeuroRx, Inc. and Relief Therapeutics Holdings AG (SIX:RLF, OTC:RLFTF) "Relief" today announced that RLF-100 (aviptadil) showed rapid recovery from respiratory failure in the most critically ill patients with COVID-19. At the same time, independent researchers have reported that aviptadil blocked replication of the SARS coronavirus in human lung cells and monocytes.

RLF-100 has been granted Fast Track designation by FDA and is being developed as a Material Threat Medical Countermeasure in cooperation with the National Institutes of Health and other federal agencies. Further research will be conducted.

The first report of rapid clinical recovery under emergency use IND was posted by doctors from Houston Methodist Hospital. The report describes a 54-year-old man who developed COVID-19 while being treated for rejection of a double lung transplant and who came off a ventilator within four days.1 Similar results were subsequently seen in more than 15 patients treated under emergency use IND and an FDA expanded access protocol which is open to patients too ill to be admitted to the ongoing Phase 2/3 FDA trial.

https://seekingalpha.com/pr/17955298-rlfminus-100-aviptadil-clinical-trial-showed-rapid-recovery-from-respiratory-failure-and

 

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43 minutes ago, JohnLocke said:

This guy makes sense to me, anyway:

https://www.washingtonexaminer.com/opinion/hydroxychloroquine-works-in-high-risk-patients-and-saying-otherwise-is-dangerous

This company's penny stock up 10x due to good results in seriously ill patients:

RADNOR, Pa. and GENEVA, Aug. 2, 2020 /PRNewswire/ -- NeuroRx, Inc. and Relief Therapeutics Holdings AG (SIX:RLF, OTC:RLFTF) "Relief" today announced that RLF-100 (aviptadil) showed rapid recovery from respiratory failure in the most critically ill patients with COVID-19. At the same time, independent researchers have reported that aviptadil blocked replication of the SARS coronavirus in human lung cells and monocytes.

RLF-100 has been granted Fast Track designation by FDA and is being developed as a Material Threat Medical Countermeasure in cooperation with the National Institutes of Health and other federal agencies. Further research will be conducted.

The first report of rapid clinical recovery under emergency use IND was posted by doctors from Houston Methodist Hospital. The report describes a 54-year-old man who developed COVID-19 while being treated for rejection of a double lung transplant and who came off a ventilator within four days.1 Similar results were subsequently seen in more than 15 patients treated under emergency use IND and an FDA expanded access protocol which is open to patients too ill to be admitted to the ongoing Phase 2/3 FDA trial.

https://seekingalpha.com/pr/17955298-rlfminus-100-aviptadil-clinical-trial-showed-rapid-recovery-from-respiratory-failure-and

 

Hell, that result alone may be enough to convince me this is the cure.  Double lung transplant recovered??  That's amazing. 

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7 hours ago, JohnLocke said:

This guy makes sense to me, anyway:

https://www.washingtonexaminer.com/opinion/hydroxychloroquine-works-in-high-risk-patients-and-saying-otherwise-is-dangerous

This company's penny stock up 10x due to good results in seriously ill patients:

RADNOR, Pa. and GENEVA, Aug. 2, 2020 /PRNewswire/ -- NeuroRx, Inc. and Relief Therapeutics Holdings AG (SIX:RLF, OTC:RLFTF) "Relief" today announced that RLF-100 (aviptadil) showed rapid recovery from respiratory failure in the most critically ill patients with COVID-19. At the same time, independent researchers have reported that aviptadil blocked replication of the SARS coronavirus in human lung cells and monocytes.

RLF-100 has been granted Fast Track designation by FDA and is being developed as a Material Threat Medical Countermeasure in cooperation with the National Institutes of Health and other federal agencies. Further research will be conducted.

The first report of rapid clinical recovery under emergency use IND was posted by doctors from Houston Methodist Hospital. The report describes a 54-year-old man who developed COVID-19 while being treated for rejection of a double lung transplant and who came off a ventilator within four days.1 Similar results were subsequently seen in more than 15 patients treated under emergency use IND and an FDA expanded access protocol which is open to patients too ill to be admitted to the ongoing Phase 2/3 FDA trial.

https://seekingalpha.com/pr/17955298-rlfminus-100-aviptadil-clinical-trial-showed-rapid-recovery-from-respiratory-failure-and

 

 Take it to the #stonks thread. 

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33 minutes ago, Anastasis said:

 Take it to the #stonks thread. 

I'm not interested in it as an investment.  Just pointing out the treatment is generating some buzz, and people are putting money on it.  It hasn't been tested in many patients, but so far the treatment has had remarkable success.

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20 hours ago, Hate said:

I got a pre-screening call today about being involved in the vaccine trial.  Both my wife and I signed up so we may be getting some follow up calls for the screening process.  Is there any reason why I shouldn't go ahead and participate with the trial?  Are there any medical posters here that can give me a really good reason that we shouldn't participate if chosen? 

I got my second call back from one of the research centers here in Austin that is testing the Moderna vaccine.  I go in on Tuesday to get blood work done.  If I make it past that round, I would either get a placebo or the actual vaccine, not sure if they will tell me which one I'm getting.  

My sister, who is a nurse, knows a few Doctors that are participating in a Covid-19 vaccine trial. I think a lot of participants are high risk and probably in the medical field.  

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They won't tell you.  Best indication would probably be if you pop a fever after the shots. 

 

Interesting article from Wired, aligns with the thread I linked earlier regarding the use of monkey kidney cells in early bench studies of covid, and why it gave us a headfake on HCQ. 

 

https://www.wired.com/story/scientists-may-be-using-the-wrong-cells-to-study-covid-19/

BY NOW THERE’S little doubt about hydroxychloroquine: It doesn’t work for treating Covid-19. But there’s a bigger, more important lesson hidden in the story of its failure—a rarely mentioned, but altogether crucial, error baked into the early research. The scientists who ran the first, promising laboratory experiments on the drug had used the wrong kind of cells. Instead of testing its effects on human lung cells, they relied on a supply of mass-produced, standardized cells made from a monkey’s kidney. In the end, that poor decision made their findings more or less irrelevant to human health. Worse, it’s possible that further research into novel Covid-19 cures will end up being compromised by the same mistake. 

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On 8/11/2020 at 6:59 PM, Newdoc said:

Exactly, my concern is that Triplehorn’s Dr. Twitter doesn’t remember confounding variables. You cannot responsibly take that big of a leap with the infection and second wave data.  I have hypothesized that T cell functions have played a role in cross and herd immunity but I sure wouldn’t want to make public health policy on it yet. 

The variables are undoubtedly multifactorial and manifest as a mosaic across the world population.  Some variables are larger contributors and some are small.  T cell cross reactivity would appear to be a substantial one, given the eye opening data around the prevalence of T cell immune cross-reactivity to a supposed 'novel' pathogen.  A smaller variable might be something like people who may share a genetic mutation that prevents Covid from infecting their cells - as is the case for HIV.  In HIV, the CCR5 receptor mutation confers this advantage and is thought to have appeared and propagated in the human population a couple thousand years ago.  An estimated 10% of people carry this innate genetic resistance to being infected with HIV.  But that 10% affects the math and helps lower the threshold for herd immunity.  Shutting down along with distancing and masks affects the curves - the rate to burnout - but not the percent infected needed for actual herd immunity.  With deadly outbreaks, the goal should still be for eradication without enduring the carnage before bottoming out at herd immunity.

In the end, you just look at the curves.  The second waves appear to have occurred in various cities and regions when opening up happened prematurely with a relatively small percentage of infected population.  If a default to herd immunity ends up being around 20% of population exposed, we should feel very, very fortunate compared to early worst case predictions.

 

Quote

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excess mortality in Europe has totally collapsed VVV

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On 8/11/2020 at 5:30 PM, utee94 said:

I'm hopeful that we're seeing positive news, that will result in positive outcomes.

But other things we must consider-- many of the places that you're citing that have very positive downward trends that are remaining low, also haven't opened up the riskiest indoor spaces like bars and inside restaurant dining capacity.  An example of a place that looked to have strong downward trends, and then opened up bars, and then saw subsequent large increases in cases, is Spain.

So there are plenty of independent variables here, that warrant close analysis.

I'm not as down on your ideas as some others, but if we want to analyze this with rigor and intent, then we have to understand all of the variables.

 

Out here in OR, given relative size of state population, infections suggest we're still over-performing on shutdowns, masks, and distancing.  If we open up too fast, we're taking a ride on the Kingda Ka.  My question is, for how much longer do we have to smolder to reach herd immunity than those states that spiked hard?  If it results in delayed major openings past December for Oregon, letting the heat turn up on local spread might not be the worst thing.  The folks OR is working with for modeling (the WA folks I believe) are calculating this to inform the risk/benefit of timed phased openings.  Could be getting ahead of eventual reality, but today I'm still leaning towards the worst being behind us and relative normality returning by mid-Oct into Nov in the US without a bumper Spanish Flu fall/winter reprise.  The US missed the window to nip this one at inception, and I expect we'll do better next time around.

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Oh surprise.  Ivermectin is now being targeted with the same playbook as hcq was:

What is ivermectin, and should we be using it to treat Covid-19?

Scaremongering about safety with a safe drug.  Daktari images of injecting pig medicine.  Imprecise language followed by mixed associations that distort perception and meaning.  Pitching the exclusivity of needing large randomized controlled trials to ever "know."  This article features a greatest hits of big pharma media tropes targeting a fearful public. There are several others I could highlight.  It should all start to sound familiar by now.  

There's a usurpation, a theft,  of the doctor-patient relationship underway that I've never witnessed.  I understand the need for heightened precaution and vigilance for a new and lethal pathogen.  But we're past that now as it relates to basic safety with concurrent use during coronavirus infection, and with early treatment in particular where the initial disease course is no different than a common cold.  Not only have they been proven safe since January, a large preponderance of evidence shows they can help - a lot - when applied optimally. 

Research is only as useful as the questions being being asked.  There's a naked pattern of asking the wrong questions, narrowly and exclusively pointing to those subsequent negative answers, and speaking with imprecise umbrella generalities that ignore vital distinctions.  It's all about control and profit.  The business and marketing front of big pharma is due some serious comeuppance after this.

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12 minutes ago, triplehorn said:

Oh surprise.  Ivermectin is now being targeted with the same playbook as hcq was:

The clinical trials that involve random assignment playbook?  Nefarious shit indeed. 

  

12 minutes ago, triplehorn said:

Imprecise language followed by mixed associations that distort perception and meaning.

 

giphy-downsized.gif

 

Edited by Anastasis
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Don't have a link to it yet, but seeing in the morning news that we (the US) are starting to produce a strain of COVID-19 for use in challenge trials. Meaning intentionally infecting folks to test vaccine efficacy

Med and pharma folks - what the fuck, over?

Edit for source: https://www.reuters.com/article/us-health-coronavirus-vaccine-challenge/exclusive-u-s-to-make-coronavirus-strain-for-possible-human-challenge-trials-idUSKCN25A1EL

Edited by Captainant
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1 hour ago, Captainant said:

Don't have a link to it yet, but seeing in the morning news that we (the US) are starting to produce a strain of COVID-19 for use in challenge trials. Meaning intentionally infecting folks to test vaccine efficacy

Med and pharma folks - what the fuck, over?

Edit for source: https://www.reuters.com/article/us-health-coronavirus-vaccine-challenge/exclusive-u-s-to-make-coronavirus-strain-for-possible-human-challenge-trials-idUSKCN25A1EL

There was some discussion on challenge trials in the early pages of this thread.  I think it's too late to make a difference at this point, as the phase III trials are already in the field.

But hey, what's the worst that could happen...

CHICAGO (Reuters) - U.S. government scientists have begun efforts to manufacture a strain of the novel coronavirus that could be used in human challenge trials of vaccines 

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23 minutes ago, Anastasis said:

But hey, what's the worst that could happen...

CHICAGO (Reuters) - U.S. government scientists have begun efforts to manufacture a strain of the novel coronavirus that could be used in human challenge trials of vaccines 

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2 hours ago, triplehorn said:

I hope you're right, but there is a lot of correlation vs. causation going on with the numbers going down. We will see if the numbers skyrocket again once schools open up. That's my fear. 

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41 minutes ago, Mitch Cumsteen said:

I hope you're right, but there is a lot of correlation vs. causation going on with the numbers going down. We will see if the numbers skyrocket again once schools open up. That's my fear. 

Regarding the path to herd immunity, restrictive measures alter the shapes of the curves, but the the area under the curves are the same unless definitive interventions like vaccines are available before herd immunity occurs.  Other available meds like HCQ and Ivermectin could conceivably help approach the end game of herd immunity more safely and with a lot less mortality.

Regarding HCQ as an early intervention to reduce need for hospitalization and death take note of this:

Over 3 Cr N95 masks, 1.28 Cr PPEs, 10 Cr HCQ tablets given to states, UTs by Centre for free

Quote

New Delhi, Aug 13 (PTI) The government has distributed more than 3.04 crore N95 masks and over 1.28 crore personal protection equipment (PPE) kits among the states, Union territories and central institutions for free since March 11, the health ministry said on Thursday.

Also, more than 10.83 crore hydroxychloroquine (HCQ) tablets have been distributed among them, it added.

That is 108 Million doses of HCQ that have been distributed to India's population so far, provided by the Indian govt for free.

With 2.5M Covid cases, India ranks 3rd in the world behind the US and Brazil.  India's CFR is at about 1.9 to 2 while the US is at about 3 to 3.1.  If you apply and extrapolate India's CFR to US cases, we would have about 70K fewer deaths today.  Is that all due to dispensing 100M HCQ doses to the population for free?  No, that's oversimplifying.  But you can sure as shit say that it's not making things worse.

 

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Got this from Oregon Health Authority today:

 

"PORTLAND, Ore. — As of mid-June, 1% of Oregonians without COVID-19 had evidence of past infection of the virus in their blood, which is 10 times higher than the reported rate of infections obtained through conventional testing, according to a new study.

Oregon Health Authority epidemiologists who authored the study, which appears today in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (MMWR), found that nine of 897 blood specimens collected from 19 health care facilities around Oregon between May 11 and June 15, 2020, contained antibodies against the virus that causes COVID-19.

The study also suggested that rates of infection increased with age, with no antibodies detected in the blood of pediatric patients 17 and younger. The rate was 0.4-0.5% in those ages 18-64; and 1.6-2.1% in those 65 and older.

The results indicate a “substantial” proportion of Oregon residents have undiagnosed and unreported infection from COVID-19. [...]"

 

---> If our rate of infection is appx 10 times higher than conventional testing suggests, and considering we haven't been hit hard yet, that could have substantial implications on the timeline to reach herd immunity in other states that are being/have been walloped.  Graphs are hinting that that is what appears to be coming into focus right now on a US regional (and select international) basis.

----> "no antibodies detected in the blood of pediatric patients 17 and younger."   hmmmm.

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6 hours ago, triplehorn said:

Regarding the path to herd immunity, restrictive measures alter the shapes of the curves, but the the area under the curves are the same unless definitive interventions like vaccines are available before herd immunity occurs.  Other available meds like HCQ and Ivermectin could conceivably help approach the end game of herd immunity more safely and with a lot less mortality.

Regarding HCQ as an early intervention to reduce need for hospitalization and death take note of this:

Over 3 Cr N95 masks, 1.28 Cr PPEs, 10 Cr HCQ tablets given to states, UTs by Centre for free

That is 108 Million doses of HCQ that have been distributed to India's population so far, provided by the Indian govt for free.

With 2.5M Covid cases, India ranks 3rd in the world behind the US and Brazil.  India's CFR is at about 1.9 to 2 while the US is at about 3 to 3.1.  If you apply and extrapolate India's CFR to US cases, we would have about 70K fewer deaths today.  Is that all due to dispensing 100M HCQ doses to the population for free?  No, that's oversimplifying.  But you can sure as shit say that it's not making things worse.

 

Indians are much better at social distancing and as a society they are more willing to follow the govt edicts.

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28 minutes ago, Parliament said:

I'm a high-functioning idiot, and it does me no good to read this whole thread to figure out out for myself. So just tell me: Is there the real chance an effective vaccine won't happen? There's a lot more to it than shoveling money into research.

 

 

Well we've never developed an effective vaccine for any of the other coronaviruses that infect humans in large numbers on an annual basis, and have for centuries or millennia.  

So we've got that going against us, which isn't nice.

On the other hand, I don't believe there's ever been such a concentrated effort to develop a vaccine against a coronavirus, as what we're seeing now, on a global scale.  So, we can keep our hope in the ingenuity and perseverance of human beings.

That said, I don't really believe we'll ever have a truly effective vaccine against this, and I don't believe we can make any public health policy decisions based on the assumption that we will.  I think we're ultimately going to have to learn to live with this among us, it will become less lethal as each year goes by, and eventually will be just one of the group of coronaviruses that spread each year and cause illnesses in human beings, like the common cold.

 

 

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58 minutes ago, Parliament said:

I'm a high-functioning idiot, and it does me no good to read this whole thread to figure out out for myself. So just tell me: Is there the real chance an effective vaccine won't happen? There's a lot more to it than shoveling money into research.

I tend to agree with @utee94 's take above.

However, here's the NYT op-ed penned by Prof. Akiko Iwasaki (the same Yale immunobiologist whose thread I posted in the last page or so on identifying disease trajectory clusters and early immune signatures predictive of bad outcomes, the role of inflammasomes with special attention to IL-1B and IL-18) on the likelihood of a covid vaccination.  Read it carefully though and take note of the emphasis on T cell immune function:

Scared That Covid-19 Immunity Won’t Last? Don’t Be : Dropping antibody counts aren’t a sign that our immune system is failing against the coronavirus, nor an omen that we can’t develop a viable vaccine.

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Within the last couple of months, several scientific studies have come out — some peer-reviewed, others not — indicating that the antibody response of people infected with SARS-CoV-2 dropped significantly within two months. The news has sparked fears that the very immunity of patients with Covid-19 may be waning fast — dampening hopes for the development of an effective and durable vaccine.

But these concerns are confused and mistaken.

Both our bodies’ natural immunity and immunity acquired through vaccination serve the same function, which is to inhibit a virus and prevent it from causing a disease. But they don’t always work quite the same way.

And so a finding that naturally occurring antibodies in some Covid-19 patients are fading doesn’t actually mean very much for the likely efficacy of vaccines under development. Science, in this case, can be more effective than nature.

The human immune system has evolved to serve two functions: expediency and precision. Hence, we have two types of immunity: innate immunity, which jumps into action within hours, sometimes just minutes, of an infection; and adaptive immunity, which develops over days and weeks.

Almost all the cells in the human body can detect a viral infection, and when they do, they call on our white blood cells to deploy a defensive response against the infectious agent.

When our innate immune response is successful at containing that pathogen, the infection is resolved quickly and, generally, without many symptoms. In the case of more sustained infections, though, it’s our adaptive immune system that kicks in to offer us protection.

The adaptive immune system consists of two types of white blood cells, called T and B cells, that detect molecular details specific to the virus and, based on that, mount a targeted response to it.

A virus causes disease by entering cells in the human body and hijacking their genetic machinery so as to reproduce itself again and again: It turns its hosts into viral factories.

T cells detect and kill those infected cells. B cells make antibodies, a kind of protein that binds to the viral particles and blocks them from entering our cells; this prevents the replication of the virus and stops the infection in its tracks.

The body then stores the T and B cells that helped eliminate the infection, in case it might need them in the future to fight off the same virus again. These so-called memory cells are the main agents of long-term immunity.

The antibodies produced in response to a common seasonal coronavirus infection last for about a year. But the antibodies generated by a measles infection last, and provide protection, for a lifetime.

Yet it is also the case that with other viruses the amount of antibodies in the blood peaks during an infection and drops after the infection has cleared, often within a few months: This is the fact that has some people worried about Covid-19, but it doesn’t mean what it might seem.

That antibodies decrease once an infection recedes isn’t a sign that they are failing: It’s a normal step in the usual course of an immune response.

Nor does a waning antibody count mean waning immunity: The memory B cells that first produced those antibodies are still around, and standing ready to churn out new batches of antibodies on demand.

And that is why we should be hopeful about the prospects of a vaccine for Covid-19.

A vaccine works by mimicking a natural infection, generating memory T and B cells that can then provide long-lasting protection in the people who are vaccinated. Yet the immunity created by vaccines differs from the immunity created by a natural infection in several important ways.

Virtually all viruses that infect humans contain in their genomes blueprints for producing proteins that help them evade detection by the innate immune system. For example, SARS-CoV-2 appears to have a gene dedicated to silencing the innate immune system.

Among the viruses that have become endemic in humans, some have also figured out ways to dodge the adaptive immune system: H.I.V.-1 mutates rapidly; herpes viruses deploy proteins that can trap and incapacitate antibodies.

Thankfully, SARS-CoV-2 does not seem to have evolved any such tricks yet — suggesting that we still have an opportunity to stem its spread and the pandemic by pursuing a relatively straightforward vaccine approach.

Vaccines come in different flavors — they can be based on killed or live attenuated viral material, nucleic acids or recombinant proteins. But all vaccines consist of two main components: an antigen and an adjuvant.

The antigen is the part of the virus we want the adaptive immune response to react to and target. The adjuvant is an agent that mimics the infection and helps jump-start the immune response.

One beauty of vaccines — and one of their great advantages over our body’s natural reaction to infections — is that their antigens can be designed to focus the immune response on a virus’s Achilles heel (whatever that may be).

Another advantage is that vaccines allow for different kinds and different doses of adjuvants — and so, for calibration and fine-tuning that can help boost and lengthen immune responses.

The immune response generated against a virus during natural infection is, to some degree, at the mercy of the virus itself. Not so with vaccines.

Since many viruses evade the innate immune system, natural infections sometimes do not result in robust or long-lasting immunity. The human papillomavirus is one of them, which is why it can cause chronic infections. The papillomavirus vaccine triggers a far better antibody response to its viral antigen than does a natural HPV infection: It is almost 100 percent effective in preventing HPV infection and disease.

Not only does vaccination protect against infection and disease; it also blocks viral transmission — and, if sufficiently widespread, can help confer so-called herd immunity to a population.

What proportion of individuals in a given population needs to be immune to a new virus so that the whole group is, in effect, protected depends on the virus’s basic reproduction number — broadly speaking: the average number of people that a single infected person will, in turn, infect.

For measles, which is highly contagious, more than 90 percent of a population must be immunized in order for unvaccinated individuals to also be protected. For Covid-19, the estimated figure — which is unsettled, understandably — ranges between 43 percent and 66 percent.

Given the severe consequences of Covid-19 for many older patients, as well as the disease’s unpredictable course and consequences for the young, the only safe way to achieve herd immunity is through vaccination. That, combined with the fact that SARS-CoV-2 appears not to have yet developed a mechanism to evade detection by our adaptive immune system, is ample reason to double down on efforts to find a vaccine fast.

So do not be alarmed by reports about Covid-19 patients’ dropping antibody counts; those are irrelevant to the prospects of finding a viable vaccine.

Remember instead that more than 165 vaccine candidates already are in the pipeline, some showing promising early trial results.

And start thinking about how best to ensure that when that vaccine comes, it will be distributed efficiently and equitably.

For comparison, look at this from the CDC today:

CDC gives three-month window of immunity after COVID-19 infection   

I'm not even sure what stock to put into anything coming out of the "CDC" today.  It's been perversely undermined, obstructed, and manipulated since January.  (I had a recent talk with a med student with friends employed at CDC who describe jaw dropping fuckery going on from the beginning inhibiting their standard responses and function during a pandemic).  To me, "3 month window" translates as a message that "errbody gets a $$$hot no matter if you've already had it or not!"  Contrast that with what Iwasaki wrote in the NYT above.

The more pressing question emerging today is 'do we even need a vaccine for Covid'.

 

Edited by triplehorn
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7 hours ago, triplehorn said:

Regarding the path to herd immunity, restrictive measures alter the shapes of the curves, but the the area under the curves are the same unless definitive interventions like vaccines are available before herd immunity occurs.

This isn't true. There is some pretty good information out there regarding R effective.

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Here's a presentation by Prof. Iwasaki on the multidisciplinary collaboration at Yale med on their work studying Covid pathogenesis.  I had to watch this a couple times even though she does a pretty remarkable job of making it understandable.  The first part discusses their use of mice transduced to express the human ACE2 receptor.  That allowed them to selectively observe what kinds of effects the virus has on human cell signaling as a function of immune response.  The second part discusses their work studying human Covid patients and observed differences related to disease outcomes.  Additional work they did observing gender differences is notable.

People who fare better have a robust initial immune response with corresponding viral load reduction .  Those who fare worse have a delayed response in some respects with an apparent inability to lower and clear viral load.  The persistence in viral load, or inability to reduce it in some people, drives the continued inflammatory response with irregular features.  She points out that their study doesn't look at what is happening right at inception (when people are infected but not yet identified as sick for study) to understand differences.  But a lot sure seems to point to  in T cell numbers and function for bringing the infection to heel, or not.

 

 

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I wanted to summarize the Prof. Iwasaki presentation at the bottom of last page, the transgenic mouse study in particular.

She describes how the coronavirus viral genome codes for multiple genes that interfere with our own cell signaling and recognition: interferon production, IFN receptor signaling, and innate INF induction and signaling pathways.  The betacoronaviruses (like MERS, SARS1) are known to code for multiple evasion molecules.

Her team studied the molecular cellular process of Covid infection using their ACE2 expressing transgenic mice.  They selectively interfered with host innate immune responses by blocking mouse interferon regulatory transcription factors, IRF-3 and 7, integral transcription factors that drive Type I and Type III interferon production.  They also knocked out the mouse Type I interferon receptor.  They observed that covid virus induces interferon production despite key innate host signaling pathways being blocked.  So it's a function of the viral hack that its genome products appear to be driving the induction of pro-inflammatory pathways outside of our own regulatory signaling.  The thinking follows that the higher the viral load, and the extent to which it grows without early suppression, the greater the volume of direct viral signaling for induction IFN to the point where it becomes pathologic. 

Two of several things that appear to be linked to Covid demise are advanced age and low Vit D.  Both have links to diminished innate T cell function, which is important for what we use to fight infection before antibodies are available to further suppress an ongoing infection.  When our early initial viral suppression (T cell) is weak, we're more likely to have viral load grow to a point where direct viral amplification of pro-inflammatory pathways causes an array of bad things that can disable or kill us. 

It underscores the importance of slowing and containing the growth of viral load, and slowing or suppressing potentially key contributory inflammatory pathways, as early as possible, until even elderly with co-morbidities can clear it.

Iwasaki's Conclusion slides:

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Screen Shot 2020-08-17 at 5.59.18 PM

Screen Shot 2020-08-17 at 5.57.04 PMScreen Shot 2020-08-17 at 6.01.15 PM

 

Edited by triplehorn
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What's this? JAK Inhibitors, a class of drug also used to treat rheumatoid arthritis appear to offer a targeted mechanism to counter the maladaptive immune inflammatory response associated with severe covid disease; particularly thought to be beneficial when applied as early as possible in the infection.  Sounds familiar.

What I'd like to see is an HCQ study with a control looking at Covid patients' before and after chemokine and cytokine levels guided by insights from Iwasaki's Yale collab immune signature work.  Yale collab also found that increased IL-18 was the molecule MOST associated with covid mortality.  That relates to inflammasome activation.  HCQ has been shown to suppress inflammasome activation, not to mention its use in treating rheumatoid  arthritis.  There already is a lot of evidence pointing to substantial benefits of HCQ when applied in the outpatient early first stage of Covid.  I suspect that looking at its specific anti-inflammatory actions as it relates to Covid pathology will help explain more specifically why it appears to be beneficial in the clinical setting, and is safe.  I don't see a reason they couldn't look for a HCQ/immune mechanistic effect using the Covid infected transgenic mice.

Edited by triplehorn
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I had my first appointment yesterday at one of the research labs here in Austin doing the vaccine trial for Moderna. The nasal swab was as uncomfortable as advertised. They took 8 vials of blood, which seemed excessive. Then I got the injection.

The injection site started to get sore last night and was a little worse this morning, but it felt about the same as when I get the flu shot.  Pretty tender when I raise my arm. Since there is a decent amount of soreness maybe I did get the actual vaccine?  I hope so, anyway, I go back in a month to get the second injection, plus another nasal swab.

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