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COVID-19 Pandemic: Transmissions, Deaths, Treatments, Vaccines, Interventions and More...

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Even though the study used the gold standard methodology of conducting clinical research, outside researchers saw significant limitations. The study was conducted in an unusual way: over the internet, without patients being seen by study doctors. The fact that patients self-reported their data and that one in five did not take all their doses of the study drug, as well as the study’s small size, made him less than confident that the study could entirely rule out that hydroxychloroquine had some preventative effect While the initial infections had to be confirmed with a diagnostic test, the researchers also counted patients who had symptoms consistent with disease, in part because testing wasn’t available.

They only PCR tested a handful of patients and did everything by phone interview without any doctors involved. Sounds useful. Hey I still say I have no evidence if it works or not. But let us be honest. If the conclusion said it worked but with those same limitations you would be saying it was complete garbage. And you would probably be right.

I've said all along that "proving" efficacy of any prophylactic (either pre or post exposure) would be very difficult, since the vast majority of people aren't getting COVID right away (it's only estimated to be ~10%, even with close exposure, although at least in this case they feel they had a reasonably well-documented close exposure), meaning a large trial would be required to discern any differences.

And while there were limitations, which the author acknowledged, the study design and execution were still light years ahead of the Indian prophylaxis study you posted, which actually was absolute garbage. In this case they had known close exposure and tried very hard to ensure treatment and control groups adhered to dosing by sending them the meds and following up on taking them. This is about as good as one can do in a non-hospitalized setting.

So, actually, given that the trial was probably run as well as could be expected, I don't think I ever would've called it garbage. I would have definitely questioned any report of minor efficacy given the limitations, but if we had seen a home run in efficacy, I would have probably called my doctor up to get some. Unfortunately, clearly I was right that HCQ was unlikely to be effective as a prophylactic. You have no idea how much I'd rather have been wrong. I have no desire to remain quarantined for 3, 6, 12 more months.
 
I've said all along that "proving" efficacy of any prophylactic (either pre or post exposure) would be very difficult, since the vast majority of people aren't getting COVID right away (it's only estimated to be ~10%, even with close exposure, although at least in this case they feel they had a reasonably well-documented close exposure), meaning a large trial would be required to discern any differences.

And while there were limitations, which the author acknowledged, the study design and execution were still light years ahead of the Indian prophylaxis study you posted, which actually was absolute garbage. In this case they had known close exposure and tried very hard to ensure treatment and control groups adhered to dosing by sending them the meds and following up on taking them. This is about as good as one can do in a non-hospitalized setting.

So, actually, given that the trial was probably run as well as could be expected, I don't think I ever would've called it garbage. I would have definitely questioned any report of minor efficacy given the limitations, but if we had seen a home run in efficacy, I would have probably called my doctor up to get some. Unfortunately, clearly I was right that HCQ was unlikely to be effective as a prophylactic. You have no idea how much I'd rather have been wrong. I have no desire to remain quarantined for 3, 6, 12 more months.
The only significant finding in his study was that a significant number HCQ patients did not adhere 100% to the trial as compared to patients taking placebo. This study might not be as bad as India HCQ prophylaxsis but it is not high quality. I am ashamed of myself for not reading more carefully on how this study is being implemented. Almost no clinical diagnosis ignores asymptomatics. No testing to confirm symptoms as CV19. 1 in 5 patients did not take the HCQ regiment in full. 75% of HCQ patients did not fully comply with trial. On top of all that, it was not even a prophylactic study. It was patients who already had been exposed to the disease for up to 4 days. Let's see if HCQ uninfects people who might already be infected???

So what this study tells us is that HCQ cannot uninfect people who have been infected for 1 to 4 days already and eventually show symptoms of CV19, but are not actually confirmed to have CV19 by test. Brilliant work.

LOL
 
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Some good news on tocilizumab, an IL-6 receptor antagonist (aimed at reducing the "cytokine storm" of respiratory over-inflammation seen in many patients), which was shown to reduce mortality by 45% in patients with severe COVID symptoms in this observationally controlled (not placebo-controlled, so not the highest standard) trial run out of the U of Michigan. This is just a preprint, though, so the usual caveats, especially as the treatment group was slightly younger and slightly less likely to have underlying pulmonary disease (so the effect might be exaggerated a bit), but I'm guessing this might be enough for this to become part of standard care for such patients, despite the finding that it also doubled the risk of superinfection.

Question: Can therapy with the IL-6 receptor antagonist tocilizumab improve outcomes in patients with severe COVID-19 illness requiring mechanical ventilation?

Findings: In this observational, controlled study of 154 patients, receipt of tocilizumab was associated with a 45% reduction in the hazard of death, despite twice the frequency of superinfection (54% vs 26%), both of which were statistically significant findings.

Meaning: Tocilizumab therapy may improve survival in patients with COVID-19 illness requiring mechanical ventilation. These results can inform clinical practice pending the results of randomized clinical trials


https://www.medrxiv.org/content/10.1101/2020.05.29.20117358v1.full.pdf
 
Some good news on tocilizumab, an IL-6 receptor antagonist (aimed at reducing the "cytokine storm" of respiratory over-inflammation seen in many patients), which was shown to reduce mortality by 45% in patients with severe COVID symptoms in this observationally controlled (not placebo-controlled, so not the highest standard) trial run out of the U of Michigan. This is just a preprint, though, so the usual caveats, especially as the treatment group was slightly younger and slightly less likely to have underlying pulmonary disease (so the effect might be exaggerated a bit), but I'm guessing this might be enough for this to become part of standard care for such patients, despite the finding that it also doubled the risk of superinfection.

Question: Can therapy with the IL-6 receptor antagonist tocilizumab improve outcomes in patients with severe COVID-19 illness requiring mechanical ventilation?

Findings: In this observational, controlled study of 154 patients, receipt of tocilizumab was associated with a 45% reduction in the hazard of death, despite twice the frequency of superinfection (54% vs 26%), both of which were statistically significant findings.

Meaning: Tocilizumab therapy may improve survival in patients with COVID-19 illness requiring mechanical ventilation. These results can inform clinical practice pending the results of randomized clinical trials


https://www.medrxiv.org/content/10.1101/2020.05.29.20117358v1.full.pdf
I am hopeful for tocilizumab. We need a treatment for severe cases and this could make a HUGE impact on death rates.
 
They aren't spikes or in real trouble as you posted all that crap he said. No spikes! No state is in trouble even by the standards his graph showed, which are very inaccurate mathematical graph.
tell that to all the dead people. Beer man by day, mathematical expert who makes better graphs than those in science by night.
 
The Sweden Experiment with Limited Social Distancing...

It's certainly not "over" yet, but they're doing far worse than their similarly situated, similarly low population density Nordic neighbors, Norway and Finland, especially in deaths, which is what really matters; these neighbors are also doing much more testing per capita (and tracing) and practicing much more aggressive social distancing. Cases per 1MM are less different, likely because of far less testing. I threw Denmark, Iceland and Germany in, too, even though their densities are a bit different. And Latvia, Lithuania, and Estonia, which are just a bit above Sweden in density are also doing much better than Sweden, with all of them below 40 deaths/1MM.

Sure Sweden is doing better than some of the much more densely populated countries, but on a density basis they're pretty much a very bad outlier. Ireland, though has about 3X the density as Sweden and has similar deaths/1MM and Spain at 4-5X the density of Sweden has 2X the death rate per 1MM as Sweden. Germany is an outlier in the other direction with 10X the density of Sweden (and is more dense than all the major EU countries other than the UK), but has a death rate of only 79/1MM - they've been the model country with regard to early/aggressive testing, tracing/isolating and social distancing (along with Denmark).

Country......Cases/1MM.......Deaths/1MM........Tests/1MM.....Density (per sq mi)
Sweden..........2088......................256.....................11K.....................56
Finland.............902.......................38.......................17K....................43
Norway............1427......................39.......................31K....................41
Iceland............5266......................29......................141K.....................8
Denmark.........1580......................78.......................33K...................345
Germany.........1945......................79.......................30K...................576

https://www.bbc.com/news/world-europe-52395866

https://www.worldometers.info/coronavirus/#countries

...and What It Might Mean for Sweden and the US (and more)

Some from Sweden also recently said they thought they'd be at "herd immunity" in several weeks. My guess is that's a pipe dream. Sweden has 1800 positive viral cases per 1MM, which is 0.18%, while NY has 15K cases per 1MM, which is 1.5% viral cases and NY's antibody sampling shows 15% actually with antibodies right now (were infected) or about 10X the level of cases. If Sweden had a similar ratio, they'd have 1.8% of their population with antibodies (10X 0.18%), which is almost nothing compared to herd immunity estimates of 54% if the transmission rate, R0, is 2.2 (as thought awhile back) or 82% if R0 is 5.7 (as more are thinking now).

https://www.cnbc.com/amp/2020/04/22...immunity-in-weeks.html?recirc=taboolainternal

However, they're saying Stockholm has 11% with antibodies, although Stockholm is far more densely populated than the rest of the country, as the country, overall has 64 people per sq mi, (near last in Europe) vs. Stockholm's 13,000 per sq mi (200X more densely populated) - so maybe it's possible for both to be true, ie.., 11% antibodies in Stockholm (which has 22% of Sweden's population) and 1.8% of Sweden with antibodies, overall (11/1.8 = 6 and 100/22 = 4.5).

So, if Sweden, right now is only at 1.8% of the population infected with antibodies, they have a very long way to go to reach herd immunity, which looks to be 20-30X their current infection%, meaning that's theoretically 20-30X more hospitalized/dead than they have now, assuming no interventions or great treatments/cures before then. That's a worst case, as infections would slow down as an area nears herd immunity, plus very low density locations might simply not sustain infections through the population - which could also be true for swaths of middle America, although those hotspots in meatpacking plants and small town flare-ups should be scaring the crap out of Middle America, but they don't seem to be.

Same is possible in the US if we're not smart about how we reopen and are not ready to stamp out flareups as they occur (with aggressive testing/tracing/isolating). We might be at ~3% of the US that have been infected, I'd guess, just roughly based on comparison to NY's data, where 15% have antibodies and 1.5% have tested positive for the virus (10X ratio), so that the US with 0.3% tested positive for the virus (1MM of 330MM) would then be 3.0% with antibodies (10X).

So, if the US, right now is only at 3% of the population infected with antibodies, we also have a very long way to go to reach herd immunity, which looks to be 15-25X their current infection%, meaning that's theoretically 15-25X more hospitalized/dead than we have now, assuming no interventions or great treatments/cures before then. Infections should slow down quite a bit once above 30-40% infected (less targets and less infected), so I doubt we're talking truly 15-25X more hospitalized dead, but I think 10-15X more is definitely a risk. That's 10-15X the 60K deaths we've seen - over whatever time it would take to reach herd immunity if we're not practicing any interventions (probably 6+ months).

We better hope we get a spring/summer lull, like we do with the flu to give us more time to develop treatments/cures/vaccines by fall and to improve our infrastructure for massive testing/tracing and isolating, just in case the next wave is strong. If there's no seasonal lull, we're likely in for a very bad time in this country if we reopen too aggressively and without a good testing/tracing infrastructure in place. Our other hope is that maybe, somehow, our antibody tests are off and many more have been infected than we know (or are somehow immune) - but hope isn't a strategy.

Update on Sweden, as the architect of their much more "hands off" approach to lockdowns and distancing is now admitting they probably didn't get it quite right, as Sweden continues to do badly especially relative to their similarly situated Nordic neighbors, who took much more aggressive interventions, as Sweden has about 8-10X the death rate of Norway/Finland with similar population density. Sweden now also has the highest per capita death rate in the world over the past few weeks. Where's T with his praise for how well Sweden handled this pandemic?

Anders Tegnell, Sweden’s state epidemiologist, agreed with the interviewer on Sveriges Radio that too many people had died in the country. “If we would encounter the same disease, with exactly what we know about it today, I think we would land midway between what Sweden did and what the rest of the world did,” said Mr Tegnell in the interview broadcast on Wednesday morning.

Mr Tegnell’s admission is striking as for months he has criticised other countries’ lockdowns and insisted that Sweden’s approach was more sustainable despite heavy international scrutiny of its stubbornly high death toll.

The public mood in Sweden appears to have shifted somewhat since neighbouring Norway and Denmark last week opened their borders to each other but not their close neighbour. Sweden has reported a much higher death toll relative to its population size than Norway.


https://www.ft.com/content/dae6d006-9adc-46d5-9b4e-79a7841022e8
 
Anybody with a ounce of common sense knows this pandemic is far from over.
SD, masks, testing are all imperatives. Hopefully the 2nd wave this Fall; which is happening; will be less impactful and nothing like the 2nd wave of 1918-1919.
Well you should be telling this to those protesters and vandals in the streets for the past 9 days... not people typing on this sports forum...sure it will come back but most won’t pay attention to the people who were directing us in our states...and don’t let someone put you into a nursing home / assisted living facility...,in the famous words of Andrew Cuomo “ I would not put my mother into a nursing home”... no Andrew but you we’re ok with it for 6 k now dead seniors the past several months... another idiot of white privilege.
 
Well you should be telling this to those protesters and vandals in the streets for the past 9 days... not people typing on this sports forum...sure it will come back but most won’t pay attention to the people who were directing us in our states...and don’t let someone put you into a nursing home / assisted living facility...,in the famous words of Andrew Cuomo “ I would not put my mother into a nursing home”... no Andrew but you we’re ok with it for 6 k now dead seniors the past several months... another idiot of white privilege.
Ive been saying this for months now. Get the people out of nursing homes into bigger spacious buildings that they can be spread out. There are plenty of empty schools, office buildings and hotels that can handle them much better then the corals they live in called Nursing homes and assisted living facilities.
 
You're talking to a brick wall. He said less than 2 weeks ago that the mortality rate of the virus is 5% LOL. He "likes" all the comments where a spike in cases gets pointed out. You're only going to hurt yourself lol.
So true. His posts today highlight how stupid and biased he his. Him and the person talking about super spreaders from Brazil yesterday like it was something new. The first cases in the US were in Washington and soon after right here in Montgomery County PA started by a single individual. That is how this virus works and everyone except him knew about it from the beginning.
 
So true. His posts today highlight how stupid and biased he his. Him and the person talking about super spreaders from Brazil yesterday like it was something new. The first cases in the US were in Washington and soon after right here in Montgomery County PA started by a single individual. That is how this virus works and everyone except him knew about it from the beginning.
hahahaha a single individual in Montomgoery County PA started it all!!!! You're a loon. We laugh at you.
 
And who infected the other thousands after ??? Ya no crap one person started infecting other people
That person was the first confirmed person to spread the virus in PA. But like many others returning from trips abroad starting spreading it all over. Do you even read factual news or just those that fit your agenda. Go away please.
 
That person was the first confirmed person to spread the virus in PA. But like many others returning from trips abroad starting spreading it all over. Do you even read factual news or just those that fit your agenda. Go away please.
ya no duh it was people who were returning from trips bringing it here. How else would it get here? By swimming??
 
While the "adults" are arguing, hundreds of thousands of young people are literally risking their lives to deal with racial injustice that is way overdue to be dealt with once-and-for-all.

Most (the vast vast majority) of Democrats and liberals wants and prays that mortality rates are down, the severity of those who get the virus, recover with less suffering and that come this Fall there will be better treatments and we will well be on our way to a cure.

So all of the people who are fighting with each other like a bunch of eight year olds, kindly STFU.
 
The only significant finding in his study was that a significant number HCQ patients did not adhere 100% to the trial as compared to patients taking placebo. This study might not be as bad as India HCQ prophylaxsis but it is not high quality. I am ashamed of myself for not reading more carefully on how this study is being implemented. Almost no clinical diagnosis ignores asymptomatics. No testing to confirm symptoms as CV19. 1 in 5 patients did not take the HCQ regiment in full. 75% of HCQ patients did not fully comply with trial. On top of all that, it was not even a prophylactic study. It was patients who already had been exposed to the disease for up to 4 days. Let's see if HCQ uninfects people who might already be infected???

So what this study tells us is that HCQ cannot uninfect people who have been infected for 1 to 4 days already and eventually show symptoms of CV19, but are not actually confirmed to have CV19 by test. Brilliant work.

LOL
It was a post-exposure prophylactic study, with strong exposure criteria for everyone, so that shouldn't be a variable and since treatments started in similar fashion for each group with respect to days after exposure, not sure why that seems to be an issue for you (especially since the number who became infected is very close to what they expected). If it worked to prevent a diagnosable infection we would've seen it, but it didn't - it had nothing to do with "uninfecting" anyone. Agree it would've been better to have PCR viral tests, but the symptomatic diagnosis was done by doctors blinded to treatments, at least (plus we know those PCR tests suffer from significant false negative rates).

Boulware also has a true prophylactic (no known exposure) trial and a trial in mildly symptomatic COVID patients (including the ones who developed infections while on this trial) going on in parallel. In addition, nearly as many in the placebo group also didn't fully comply with the treatment - and part of the reason more on HCQ didn't comply was there was a statistically greater number on HCQ who reported side effects, which is a valid reason to stop taking a medication. Also, for what it's worth, the subset of people also taking zinc (20%) showed no difference from those not taking zinc in either arm.

The only way to do these studies with very high confidence is to dose people known to be uninfected/unexposed (almost impossible to ensure unexposed, though) with treatment/placebo and then subject them to significant controlled viral exposure, but that's unethical, obviously. Here's an interview with Dr. Boulware if anyone is interested.

 
It was a post-exposure prophylactic study, with strong exposure criteria for everyone, so that shouldn't be a variable and since treatments started in similar fashion for each group with respect to days after exposure, not sure why that seems to be an issue for you (especially since the number who became infected is very close to what they expected). If it worked to prevent a diagnosable infection we would've seen it, but it didn't - it had nothing to do with "uninfecting" anyone. Agree it would've been better to have PCR viral tests, but the symptomatic diagnosis was done by doctors blinded to treatments, at least (plus we know those PCR tests suffer from significant false negative rates).

Boulware also has a true prophylactic (no known exposure) trial and a trial in mildly symptomatic COVID patients (including the ones who developed infections while on this trial) going on in parallel. In addition, nearly as many in the placebo group also didn't fully comply with the treatment - and part of the reason more on HCQ didn't comply was there was a statistically greater number on HCQ who reported side effects, which is a valid reason to stop taking a medication. Also, for what it's worth, the subset of people also taking zinc (20%) showed no difference from those not taking zinc in either arm.

The only way to do these studies with very high confidence is to dose people known to be uninfected/unexposed (almost impossible to ensure unexposed, though) with treatment/placebo and then subject them to significant controlled viral exposure, but that's unethical, obviously. Here's an interview with Dr. Boulware if anyone is interested.


My problem is that it was not a prophylactic study. If someone was exposed and got enough viral load, they would be infected. You could give them HCQ on days 1 thru 4 to see if it prevents them from developing symptoms, but you should be testing each patient by PCR to confirm infection and then tracking impact to viral load. Without PCR tests you have no idea how many from each group were actually infected as asymptomatics make up a substantial pct of infections. Also, Day 1 had the least number of patients and Day 4 the most. So the majority of infected patients had been for multiple days before prophylactic treatment? So the goal was to give HCQ a few days after and see if it "uninfected" infected patients?

BTW, here are the infection rates for each combination of days after exposure and HCQ/non-HCQ from his study:


Day --------> non-HCQ------>HCQ
1 ----------> 12.7 -------------> 6.5
2 ----------> 17.0 ----------> 12.0
3 ----------> 14.5 ----------> 12.2
4 ----------> 12.4 ----------> 14.5
 
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Three of the authors of that Lancet-published study on HCQ have retracted it because they cannot verify the data are accurate. Surgisphere will not share the full dataset with the authors of the study.
 
Posted about the fall from grace of the CDC last week, above (and 3 months ago), and then out comes an article from WaPo detailing how Commissioner Redfield now has the gall to suggest that the CDC "kept eyes" on the spread of the coronavirus and implying widespread testing wouldn't have done much good.

https://www.washingtonpost.com/heal...nds-failure-spot-early-coronavirus-spread-us/

The director of the Centers for Disease Control and Prevention on Friday defended the agency’s failure to find early spread of the coronavirus in the United States, noting that surveillance systems “kept eyes” on the disease.

“We were never really blind when it came to surveillance” for covid-19, the disease caused by the virus, CDC chief Robert R. Redfield said. Even if widespread diagnostic testing had been in place, it would have been like “looking for a needle in a haystack,” he said.


Redfield's attempt to create a rationalization to shift the focus from the Trump Administration’s grossly and historically incompetent handling of the coronavirus is simply clumsy and transparent. Essentially, the argument seems to be that "nothing could have been done" and the resulting pandemic tragedy in the US was unavoidable. None of that is accurate.

As I and others have detailed countless times, if we had simply followed the South Korea/Taiwan model (which we already had in our pandemic playbook) of early aggressive testing, tracing and isolating, augmented by mask-wearing and distancing, we would have likely saved at least tens of thousands of American lives if not 90,000 or more. This is another embarrassment for the CDC.

Historically, in the regulatory oversight world, "capture" meant that regulatory agencies, like the EPA, OSHA, CDC, etc., were being or at risk of being "captured" by industrial concerns intent on weakening/negating regulations they saw as burdensome and that cut into profits, even if they were protecting safety and/or the environment for the greater public good.

But now we have the Administration being the drivers of such capture and it's gone beyond capture to pure whitewashing of this situation, despite the obvious science that testing would have revealed how much the virus had spread and allowed a much earlier response, probably saving most of the American lives lost. As Michael Worobey, an evolutionary biologist and author of a recent paper detailing the early spread of the virus said in the article:

“It would be absurd to not recognize that there were some failings in the way testing was rolled out,” Worobey said. He said details of the introduction and spread of the virus are crucial to understanding exactly what happened and what could be done to prevent future outbreaks.

“When a plane crashes, it’s very impressive the way these thing are investigated right down to every single fragment of debris so that we figure out what went wrong without trying to brush anything under the carpet,” he said.

Another scathing review of the ineptitude of the CDC and how they've been completely sidelined by the Administration, whereas in every other previous infectious disease outbreak, they led the Federal effort to figure out what was going on and to communicate guidance to Americans with regular press briefings. It's sad to see what has happened to this once proud world-leading agency.

https://www.nytimes.com/2020/06/03/us/cdc-coronavirus.html
 


Three of the authors of that Lancet-published study on HCQ have retracted it because they cannot verify the data are accurate. Surgisphere will not share the full dataset with the authors of the study.

One might ask why they didn't do a more thorough review of the data beforehand. This is a sad chapter in scientific research. I assume the ivermectin and ACE-inhibitor studies, which also relied on Surgisphere data, will also be retracted.

IMO, none of this changes the conclusion reached by most studies on the lack of efficacy of HCQ in hospitalized patients, but it certainly should lead to a sigh of relief that the claim of significantly increased arrhythmias and mortality are likely not supported.
 
Another scathing review of the ineptitude of the CDC and how they've been completely sidelined by the Administration, whereas in every other previous infectious disease outbreak, they led the Federal effort to figure out what was going on and to communicate guidance to Americans with regular press briefings. It's sad to see what has happened to this once proud world-leading agency.

https://www.nytimes.com/2020/06/03/us/cdc-coronavirus.html
NY times. Lol
 
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