COVID-19 medical discussion

[Anastasis 23461]

While I am sure that there will be some new angle certain posters take on this, first US post-exposure prophylaxis RCT of HCQ is negative. 

https://www.nejm.org/doi/full/10.1056/NEJMoa2016638?query=TOC

Abstract

BACKGROUND

Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown.

METHODS

We conducted a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis. We enrolled adults who had household or occupational exposure to someone with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days). The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days.

RESULTS

We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was −2.4 percentage points (95% confidence interval, −7.0 to 2.2; P=0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported.

CONCLUSIONS

After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure. (Funded by David Baszucki and Jan Ellison Baszucki and others; ClinicalTrials.gov number, NCT04308668. opens in new tab.)

[XYZ 2154]

2 hours ago, Anastasis said:

While I am sure that there will be some new angle certain posters take on this, first US post-exposure prophylaxis RCT of HCQ is negative. 

https://www.nejm.org/doi/full/10.1056/NEJMoa2016638?query=TOC

Abstract

BACKGROUND

Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown.

METHODS

We conducted a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis. We enrolled adults who had household or occupational exposure to someone with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days). The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days.

RESULTS

We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was −2.4 percentage points (95% confidence interval, −7.0 to 2.2; P=0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported.

CONCLUSIONS

After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure. (Funded by David Baszucki and Jan Ellison Baszucki and others; ClinicalTrials.gov number, NCT04308668. opens in new tab.)

I thought that Hydroxychloroquine plus Zinc was the fucking winning combination. Why aren’t they testing that?

[Newdoc 3439]

The link is registration required so I will quote the article from a Medacape discussion on Vitamin D and respiratory tract infections. Turns out there is some observational and met-analysis that shows supplements of Vitamin D can have protective results if you have low levels. Natural Vitamin D is best but this appears to be good news.  This is contrary to poor performance of Vitamin D supplements for bone health and CV disease.

“There's also evidence from a meta-analysis of randomized clinical trials of vitamin D supplementation looking at acute respiratory tract infections (upper and lower). This was published in the British Medical Journal 2 years ago, showing that vitamin D supplementation was associated with a significant reduction in these respiratory tract infections. Overall, it was only a 12% reduction, but among the participants who had profound vitamin D deficiency at baseline (such as a blood level of 25-hydroxy-vitamin D of less than 10 ng/mL), there was a 70% lower risk of respiratory infection with vitamin D supplementation.”

[Anastasis 23461]

3 minutes ago, Newdoc said:

Turns out there is some observational and met-analysis that shows supplements of Vitamin D can have protective results if you have low levels.

Assuming that most of us have never had a Vitamin D lab done, what are the general characteristics of people with low D levels?

[BradInATX 9208]

50 minutes ago, Anastasis said:

Assuming that most of us have never had a Vitamin D lab done, what are the general characteristics of people with low D levels?

I believe they lack intangibles

[XYZ 2154]

Isn’t there any study that tries to measure the impact of sun exposure on vitamin D level? For example, let’s say you take a group of people who have office jobs and have minimal exposure to the sun and have low levels of vitamin D, and you have them take their shirt off and sit outside for 10 minutes every day, directly exposed to the sun (no shade), with no sunscreen, and while the sun is up in the sky, let’s say between 10 AM and 2 PM. Do that every day for a month and measure vitamin D level again. Do it 5 minutes instead of 10. Do it every other day instead of every day. Do it once a week. Do it with light skin people, medium-brown skin, and dark skin. What is the combination of lowest sun exposure and highest increase in vitamin D level?
 

It’s like the fucking dermatologists have informed public health policy that we must avoid the sun at all costs, and if we are exposed to it, we must wear UV-blocking sunscreen, and then half of us end up with a vitamin D deficiency.

[Newdoc 3439]

1 hour ago, Anastasis said:

Assuming that most of us have never had a Vitamin D lab done, what are the general characteristics of people with low D levels?

It’s pretty vague. Some attribute fatigue and low energy levels along with mild mood disorders. There are no reliable clinical syndromes that you can diagnose low vitamin D by observation.

[bullzak 415]

On 6/3/2020 at 7:57 PM, XYZ said:

I thought that Hydroxychloroquine plus Zinc was the fucking winning combination. Why aren’t they testing that?

Same here. Thought that was always the deal but dont see reference to it in testing. 

Know zinc has been hard to find. 

[williemackgarza 1826]

It’s pretty vague. Some attribute fatigue and low energy levels along with mild mood disorders. There are no reliable clinical syndromes that you can diagnose low vitamin D by observation.

So pretty much just described 99% of surlycans

[Anastasis 23461]

Vax update.

https://blogs.sciencemag.org/pipeline/archives/2020/06/11/coronavirus-vaccine-update-june-11

CLINICAL TRIALS

Coronavirus Vaccine Update, June 11

By Derek Lowe 11 June, 2020

Since I did a monoclonal antibody update in the last post, here’s one on the vaccine front, where there is a lot of news – and where there are a lot of issues coming up similar to the ones with the antibodies as well. The last vaccine update post was here.

What we’re seeing now is the plan for entering large-scale human trials. The Wall Street Journal‘s Peter Loftus broke the news of the overall plan in the US: Moderna’s candidate was said to be going into Phase III in July, followed by the Oxford/AstraZeneca effort in September, with Johnson & Johnson’s vaccine to follow. But J&J now says that they’re moving up the timetable and negotiating with the NIAID for Phase III trials before then. Moderna has selected 100 micrograms as the Phase III dose, which is what was expected based on their earlier results. Meanwhile, AZ says that they will be scaling up the manufacturing of the Oxford vaccine during the trials themselves, on a risk basis, and it would not surprise me at all to see other companies doing something similar. They’ll basically have to – if one or more of these vaccines reads out well in Phase III, you’d want to get to dosing people as quickly as possible.

Note that Pfizer (and their partner BioNTech) are not part of this government-funded initiative – they’re going it alone, and (as mentioned before) seem to be taking the largest number of potential vaccine candidates into human trials. It’s definitely an effort to be taken seriously. And then you have the Sanofi/GSK work, which has been less in the news, but involves two of the most experienced vaccine companies in the world. So don’t ignore them, either. Merck is in the same category. Another company to keep in mind is Novavax, last mentioned here. They have now announced (no formal report yet) what appear to be very high antibody titers in primate dosing with their vaccine candidate, which they attribute to their proprietary adjuvant. As noted in that article, it’s impossible to directly compare these numbers with those reported in the other primate studies, but these results are certainly of interest. They’re expanding their manufacturing capacity as well.

Things are also moving very quickly in China, although with less information overall. Bloomberg reported that two of the vaccine candidates are being offered to employees of state-run companies who are traveling outside China for work, with data to be collected on that cohort, naturally. The Chinese Phase III trials are something of a mystery, at least to me, because it doesn’t appear (at least from the official figures) that there are any particularly good opportunities for testing them inside China at this point. So it will be interesting to see how those are going to be run, and where.

Unfortunately, that doesn’t look like a problem we’re going to have here in the US. In several states, cases are rising again, and in some others they certainly don’t seem to be falling. As many had predicted, we seem to be in for months of patchy brush-fire types outbreaks in various regions of the country. What will be tricky is coordinating the locations of all those clinical trials – ideally, you’d want them in the areas where the coronavirus is spreading most vigorously, but can those be identified in time to get a trial off the ground? Throw in the “second wave” possibility in the fall for even more uncertainty. In the end, the data will be collected from centers all over the country, and some of them will just have a better signal/noise than the others. I do not envy the folks coordinating all this, nor the ones who will be working up the data under time pressure.

There are other factors – former FDA head Scott Gottlieb noted on his Twitter account today that it doesn’t seem like the NIH/NIAID coordinated trials will be sharing control groups (which in theory is something that could speed things up). In practice, that savings might have been difficult to realize, but it’s interesting that it seems to have been ruled out from the start. It’s also unclear how data on the the US-company vaccine candidates will be collected outside the US, or where, or when. I’ve mentioned manufacturing above, and that’s a huge issue that’s going to be coming more into focus. The various vaccines mentioned have (in many cases) quite different processes for production and purification, adding to the complexity. And don’t forget distribution – the next few months will see (had damn well better see) a lot of preparation for what will be a gigantic worldwide rollout, done on a time scale that’s never been tried before.

Finally, there are political considerations. Aren’t there always. The various companies involved all have an incentive to be the first to announce an effective vaccine, of course – that will be a huge publicity event. On top of that, there is surely a desire on the part of the current administration to be able to announce this before the election in November – and let me be clear, this would be true no matter who was in office, or from which party. I will say, though, that the President’s willingness to promote hydroxychloroquine so far during the pandemic does not bode well for his restraint when it comes to potential treatments. The election season will just make that more fraught. And internationally, one can already see some elbow-throwing between the US and China (and potentially between the US and Europe?) on the origin of the first effective vaccine as well. Russia is part of this as well. National pride is at stake, which also can lead to some otherwise-irrational behavior.

The next few months, then, are not going to be dull. Politics aside, the organization and execution of all these trials will be a huge and complex effort, as mentioned, and when the numbers start coming out of them we’re going to surely be taken by surprise. That’s what clinical trials do; this won’t be different. I’m expecting sudden reversals, and sudden bursts of hope, despair, and confusion. None of us have ever seen anything like what’s coming, and I hope we never have another opportunity to see anything like it again!

[Anastasis 23461]

Another article from Derek Lowe's blog. 

https://blogs.sciencemag.org/pipeline/archives/2020/06/15/what-might-go-wrong

What Might Go Wrong

By Derek Lowe 15 June, 2020

With all of my posts here about vaccines and antibodies, it’s only fair that I spend some time talking about the potential toxicology problems with both of those. I remain optimistic about both categories, but it’s for sure that not all the candidates being advanced are going to make it through. So what sorts of things go wrong?

Well, efficacy, for one: some of them just don’t work so well against their targets. Efficacy is straightforward – well, relatively straightforward. Some of these antibodies and vaccines are just not going to work well enough, either on the absolute scale of not providing enough protection, or on the relative scale of not doing as much as other candidates. This is what Phase II and Phase III trials are for. We’re going to need to know how well these therapies protect people against coronavirus infection, and in the case of the monoclonal antibodies, we’ll also need to know how useful they are when given to people who are already infected.

You know all the arguing that has been going on about the various antiviral ideas, the repurposed drugs and so on? Most of those are arguments about efficacy. And as we’ve seen, even though this is an answerable question, it’s not answerable without a lot of work. We’re going to need to know a new treatment’s effects in various age groups, across male and female patients, people with pre-existing conditions (and those taking various other forms of treatment for them), and so on. What happens if you’re over 70? Or if you have hypertension or asthma? Or are taking one of the therapies for rheumatoid arthritis, for example, that alters immune function? There’s a long list of such questions, and here’s hoping that the upcoming trials will be able to provide real answers to as many of them as possible.

I would not expect all the candidates being tested to be equally efficacious (see below). There’s no way that’s happening. But I don’t expect all of us handicappers to even be able pick the ones a priori that will work the best. Have you ever seen an NCAA basketball tournament play out exactly according to the seeding? Exactly. No, the only way we’re going to sort out efficacy is by clinical results, lots of them, obtained in as well-controlled a way as we can possibly manage. Predictions aren’t worth much at this point. I only hope the picture is reasonably clear once we’ve gotten to the end of the trials, although there is of course no guarantee of that, either.

What about safety? With the repurposed drugs that we’ve been seeing, safety has been overall less of a concern, since they already have a history in human patients. Now, whether that’s always enough, when you’re giving such drugs to people are are ill with a virus that we’re never encountered before, that’s a real question (and is part of the argument about hydroxychloroquine). But some of the things that are coming have never been into people at all. As with any investigational drug, we will have to cross our fingers, taking our best shots based on all the antibody work and vaccine development that has come before.

What does that history tell us to look out for? First, let’s talk about the monoclonal antibodies, where there’s one thing that we have going for us right at the start, in that we are not targeting a human protein. You may have noticed the advertisements for monoclonal antibody drugs tend to list a lot of side effects, but that’s because of their targets. The highest-profile mAb drugs are things modulating immune response and the cell cycle, which are never going to be touched without risk. Targeting any human cell proteins comes with risks, honestly – you can occasionally set off a cytokine-storm response (cytokine release syndrome, CRS) when this process goes awry. (This and some other problems are associated not with the variable target-binding region of the antibody, but with the more constant Fc part of the molecule). But when you’re trying to shut down a pathogen’s protein, well, it’s more full speed ahead.

That said, one thing you want to make sure of is that the antibodies you are administering attack the coronavirus protein and only the coronavirus protein – you don’t want to find yourself hitting a human cell-surface protein without realizing it. There are plenty of autoimmune examples where an inappropriate response is raised to a bystander protein (more on this later in the vaccine section), and you don’t want to jump-start such a thing with a nonselective antibody. There are  other immune responses, lower than outright CRS, that you want to look out for, such as hypersensitivity (which can be immediate or delayed, site-of-injection or more general). The good news here is that the mAbs that are being tested are based on antibodies raised by recovered human patients, so that tells you that these were able to clear the coronavirus without apparently setting off anything else. That’s the biggest factor in the speed with which these new agents are moving into human trials – in many important ways, these antibodies have already been in people. Overall, you would expect some sort hypersensitivity, not a threatening level, is going to probably be the most common adverse event.

But the bad news is that human immune systems vary so widely that you still need to be alert for trouble – that, as you’ll see, is a general theme in all this. Such events are probably going to be low-frequency, but potentially severe, which is just what you don’t want in a clinical development program. Human dosing of the mAbs and the vaccines is going to be wide, fast, and jumpy – accelerated clinical trials with a huge number of patients, but dosed with great attention to any potential adverse events. We’re going to sort these things out by efficacy, of course, but it’s quite possible that we end up with more than one similarly-efficacious therapy and end up ranking them by the incidence of rare side effects.

So let’s talk about the vaccines, then. In this case, we don’t have the already-in-humans advantage that the mAbs have, or at least not to the same degree. What we do know – and it’s no small thing – is that it is possible to raise a useful immune response to the coronavirus, antibodies and T cells, which means that we just have to recapitulate that without the disease itself. That’s as opposed, say, to viral diseases like hepatitis C (or rabies!) where disease-clearing immune responses basically just don’t happen, so that’s good.

Note that we’re going to be trying to raise this through several rather different mechanisms, although they all get to the same place in the end: an immune response which translates to protection against the real viral infection. I’ve done more detailed vaccine posts, but for reference, we have in one group administration of individual viral proteins, or of inactivated (“killed”) virus, or of viral-like particles. You give those direcly and let them set off the immune system. In the other group, you’re looking at co-opting the body’s protein production machinery to (in effect) dose yourself with such proteins. That includes weakened forms of the coronavirus, engineered versions of totally different infectious viruses carrying genetic material for coronavirus proteins rather than their original make-more-virus payloads, or administration of DNA or RNA for those to be taken up by cells and set off such protein production from that direction.

As mentioned, there will be efficacy differences between the different vaccine candidates, and these are just the sorts of things you look out for in a more “normal” development pathway.  Some of them may require larger doses than others (potential manufacturing issues there), and some may require more shots and at different intervals, if so (logistic and manufacturing problems both). Some will have different immunological kinetics (the time it takes to develop a protective response after dosing), and some of them will produce longer-lasting response than others. (It should almost go without saying that that last one is something we’re just not going to know; there are no good ways to predict it). They may behave differently in different populations – different antibody and/or T-cell profiles with younger or older patients, among other things. There are plenty of things to sort out! A big advance that might come out of the Phase II trials (and associated studies) is a marker that can be used going forward, an immune correlate of protection. You would want to be able to say “OK, you have raised a titer of at least X of this particular type of antibody, so that means that yeah, you’re protected”. We don’t have that now (not enough data), but the hope is that we can get closer to that for the Phase III studies.

Past efficacy and on to adverse effects, one thing that has been extensively talked about is antibody-dependent enhancement (ADE), because this has been seen in other vaccine candidates (such as for dengue, where the reasons don’t really apply here) but also in attempts to develop vaccines against the closely-related SARS coronavirus. To be honest, I am getting less and less worried about that as time goes on. The various mAb and vaccine teams have been alert for signs of ADE all along the way, and so far we appear to be in the clear. This doesn’t mean that we can forget about the issue, but it’s not at the top of the worry list, either.

Those earlier worries about hypersensitivity and inappropriate immune responses do apply, though. The classic example intersecting with infectious disease therapy is Guillain-Barré syndrome (GBS). This can be set off after a (sometimes unnoticed) bacterial or viral infection, and involves an immune attack on the myelin sheaths of the nervous system. That’s obviously very bad indeed – although most patients recover, not all of them do, and some of them need intensive care while the myelin damage gets reversed. The exact mechanism of GBS has eluded discovery, despite intensive research – there’s obviously something about the myelin sheaths that are vulnerable to immunologic misidentification, but the details aren’t clear, and the vulnerability varies according to a person’s individual immune system in ways that we cannot yet screen for. So such things will be watched for very carefully indeed.

Even with that, we will not know the real risks of such rare events, because they’re rare. GBS, for example, might occur on the order of one or two people out of a million with the seasonal flu vaccine. You’re only going to see things like that after you’re out in a very large patient population. It’s just not possible to assess something like that in even a rather large clinical trial involving tens of thousands of people. That’s not just the situation with these new coronavirus vaccine candidates; that’s how it is in general. But in this case we’re talking about vaccines that may well be going into hundreds of millions of people as quickly as we can roll them out. If one vaccine candidate gives GBS to 100 people out of a hundred million dosed and another one affects only ten, there is absolutely no way that we will be able to be sure of that before dosing the hundred million people.

I do not want to provide ammunition for the anti-vaccine camp by going into these details, but we can’t ignore medical (and mathematical) reality. All drugs have side effects, and every therapy is a tradeoff. The levels that I’m talking about for something like Guillain-Barré (which is generally not fatal) are, in fact, completely acceptable for preventing a disease like this one. As you see from that link in the paragraph above, they’re acceptable for something like seasonal influenza, which is definitely not as big a problem as the COVID-19 epidemic. State and national governments have already been talking overtly about how many coronavirus deaths are acceptable to avoid shutdowns that harm their economies, and if you’re willing to make that tradeoff, you should jump at the chance to make this one. It’s a much better deal.

This is one of those times when it’s instructive to do the math, as they say. There are (for example) outright fatal immune responses to some drugs (not just vaccines), which are generally very difficult to predict. Think penicillin as the famous example, although there are others. But as shown here, the death rates for these across the population are in the same range as death by lightning bolts (one out of a few million). Now, one should reduce one’s risk of being hit by lightning by not being out in the open during severe thunderstorms, and one should reduce the risk of harming people with a vaccine through careful clinical testing. But (to put it gently) many populations are not showing themselves to be very good at risk reduction these days. I cannot help but picture a bunch of unmasked people in a crowded bar yelling at each other over the music about how they’re not going to let themselves be poisoned by any damned vaccine.

All the issues mentioned are about to become very real as the various antibodies and vaccines move into larger patient populations. Keeping track of everything will not be easy, but, well, here we go!

[Mitch Cumsteen 18547]

It doesn't look like the study has been published yet,  but there is a lot of buzz on dexamethasone reducing mortality in patients on ventilators and oxygen. 

https://www.bbc.com/news/health-53061281

https://nypost.com/2020/06/16/life-saving-coronavirus-drug-dexamethasone-discovered-through-trial/

[Bevo 13566]

50 minutes ago, Mitch Cumsteen said:

It doesn't look like the study has been published yet,  but there is a lot of buzz on dexamethasone reducing mortality in patients on ventilators and oxygen. 

https://www.bbc.com/news/health-53061281

https://nypost.com/2020/06/16/life-saving-coronavirus-drug-dexamethasone-discovered-through-trial/

There were concerns earlier that steroid use was linked to a higher mortality rate. Dexamethasone would have been one of the first drugs investigated in China. I haven't read the articles, but I can only assume that we have improved on the timing, dosage, and/or delivery.

[Liquor and Poker 3659]

What’s the current thinking on surfaces transmission?  Early on we were hearing that the primary vector of transmission was touching surfaces, particularly smooth ones.  Then there were the reports that social distancing is extremely effective in preventing transmission.  Now we see that masks are the most effective way to stop spread.  Those ideas seem to indicate it’s mostly transmitted by breathing. 
 

So where are we on surfaces? Is it still generally believed that you can get it from plastic bags, car interiors, and metal refrigerators?

 

 

[Bevo 13566]

25 minutes ago, Liquor and Poker said:

What’s the current thinking on surfaces transmission?  Early on we were hearing that the primary vector of transmission was touching surfaces, particularly smooth ones.  Then there were the reports that social distancing is extremely effective in preventing transmission.  Now we see that masks are the most effective way to stop spread.  Those ideas seem to indicate it’s mostly transmitted by breathing. 
 

So where are we on surfaces? Is it still generally believed that you can get it from plastic bags, car interiors, and metal refrigerators?

 

 

I think it is safe to say that we should avoid touching anything previously touched by you, casual encounter, or South Austin's mom.

[gmr548 16576]

What’s the current thinking on surfaces transmission?  Early on we were hearing that the primary vector of transmission was touching surfaces, particularly smooth ones.  Then there were the reports that social distancing is extremely effective in preventing transmission.  Now we see that masks are the most effective way to stop spread.  Those ideas seem to indicate it’s mostly transmitted by breathing. 
 
So where are we on surfaces? Is it still generally believed that you can get it from plastic bags, car interiors, and metal refrigerators?
 
 

My understanding is that you can get it from surfaces but at this point it seems pretty clear the primary method of transmission is close contact with a carrier.

It's much easier to end up inhaling a dose of the virus from close interaction is to pick up enough from a surface - which had to be contaminated with enough virus to be infectious, recently enough to transfer to you, and then transfer enough from the surface to your hands, then from hands to face... You get the idea. The chain of transmission is much shorter and the vital load much higher directly from another person. So washing your hands, particilarly when you get home from public, and avoiding touching your face should have you in good shape from a surface standpoint.

[triplehorn 2664]

 

12 hours ago, Mitch Cumsteen said:

It doesn't look like the study has been published yet,  but there is a lot of buzz on dexamethasone reducing mortality in patients on ventilators and oxygen. 

https://www.bbc.com/news/health-53061281

https://nypost.com/2020/06/16/life-saving-coronavirus-drug-dexamethasone-discovered-through-trial/

 

This French flowchart (Dr Raoult) is pre-dexamethasone findings, but observable benefits of dexamethasone probably would start somewhere between late Phase II and Phase III.  The chart shows that Phase II is associated with some lab markers that could help narrow who to give it to and how to time it if there's benefit in detecting the leading edge of the crash. 

 

 

On 6/8/2020 at 7:55 AM, bullzak said:

Same here. Thought that was always the deal but dont see reference to it in testing. 

Know zinc has been hard to find. 

There's quite a bit of international evidence to support application of zn/hcq/az as early as possible to reduce illness severity and need for hospitalization, but in the US today, most of the data that would speak to that is sequestered away in private practices.  Even in countries where early application is the current national standard of care, late application has been formally abandoned due to lack of benefit and potentially greater metabolic risk for an adverse event.

 

 

[triplehorn 2664]

Midstream sneak peek:

WHIP COVID-19 study is an FDA-approved study looking at hydroxychloroquine as a potential preventative medication for healthy, pre-screened individuals

 

"The FDA's decision bars the use of hydroxychloroquine sulfate and a similar drug called chloroquine phosphate from the Strategic National Stockpile for hospitalized COVID-19 patients. But the use of the drug as a prophylaxis, or preventive measure, is not impacted by the FDA decision."

^^^ Folks can wait for the peer reviewed publication to come out to get the complete presentation, but this intervention is available today for anyone interested.  

Edited June 17, 2020 by triplehorn

[triplehorn 2664]

Following up on the above, this is the Detroit Metro Times reporting on a local ongoing FDA-approved study being conducted by Henry Ford Health System.  They are looking at the effects of early application or a prophylactic effect of HCQ on Covid infection in medically stable people.  The CEO of HFHS, Dr. Steven Kalkanis, says "We have analyzed our data and have seen a significantly improved outcome in a group of COVID-19 patients who received hydroxychloroquine." 

That's a heads up.

Re this statement in the reporting: 

Quote

"The FDA's decision bars the use of hydroxychloroquine sulfate and a similar drug called chloroquine phosphate from the Strategic National Stockpile for hospitalized COVID-19 patients. But the use of the drug as a prophylaxis, or preventive measure, is not impacted by the FDA decision.

I take that to mean the feds are sitting on a stockpile of (H)CQ at the SNS that will no longer be available to supply hospitals for hospitalized patients w Covid.  However, the federal SNS stockpile of (H)CQ will be available to distribute to States should they request it for use in some outpatient form of early prevention/intervention.  If we're finally headed there, and this reporting is a real sign, it has the potential to be a morbid exercise to see if there's enough and, if not, where it gets funneled.  Today, some States are more pre-disposed and have been more prepared to adopt this than others.

 

* just a note on prescribing for off-label uses of medication: it is common and it is legal.  the google tells me 1 in 5 prescriptions written in the US is for an off-label use.  20% of scripts written every day in the US are for off-label purposes.  As a separate matter, it doesn't excuse gross incompetence, but nothing should.

 

 

[gmr548 16576]

God damnit I clicked on this thread not knowing triplehorn chose a new venue for the HCQ nonsense.

[triplehorn 2664]

If all you got is to show up and flame, take it elsewhere.  

 

 

[Anastasis 23461]

7 hours ago, triplehorn said:

^^^ Folks can wait for the peer reviewed publication to come out to get the complete presentation, but this intervention is available today for anyone interested.  

Note that the people who are running these trials are specifically trying to prevent the type of "willy nilly" use of HCQ you are continually promoting. They are restricting its use in their health systems to clinical trials.  This is the appropriate posture IMO, not "HCQ is available for anyone interested".  The posture is "Let's evaluate use of HCQ in a controlled context so that we can understand if it actually works." From the longer article linked through in article from the tweet (AAPS, lol). 

Hyzy leads U-M in a multi-center trial launched in April and known as ORCHID, a blinded, placebo-controlled randomized clinical trial that tests hydroxychloroquine’s effectiveness against COVID-19.

Monday’s FDA announcement, he said, “reins in the willy-nilly use” of the drug that began at the height of the pandemic, which was pared following reports of disappointing results and indications the medication could pose cardiac dangers to some patients. 

But it does not end scientific studies to more definitively answer questions about hydroxychloroquine’s potential to treat COVID-19, for which there is not yet a vaccine. 

Henry Ford Health System confirmed Monday that it will continue its WHIP COVID-19 study, which examines hydroxychloroquine, not as a treatment, but rather as a potential preventative medication. Henry Ford's 3,000-participant trial, announced in April, relies on prescreened, healthy frontline workers and first responders.

While the study will proceed, Dr. Steven Kalkanis, chief executive officer of the Henry Ford Medical Group, told Bridge in an email late Monday that Henry Ford will stop using the medication as a treatment for COVID-19 outside of the clinical trial, despite what he characterized as positive results.  

 

2 hours ago, triplehorn said:

Following up on the above, this is the Detroit Metro Times reporting on a local ongoing FDA-approved study being conducted by Henry Ford Health System.  They are looking at the effects of early application or a prophylactic effect of HCQ on Covid infection in medically stable people.  The CEO of HFHS, Dr. Steven Kalkanis, says "We have analyzed our data and have seen a significantly improved outcome in a group of COVID-19 patients who received hydroxychloroquine." 

That's a heads up.

I believe that you are misreading the reporting in the Detroit Metro Times. Kalkanis appears to be referring to a retrospective analysis of data collected during usual care among hospitalized patients, and not the prophy clinical trial data. 

Kalkanis says hydroxychloroquine has been used as a treatment in hospitalized patients, which falls under the FDA's Monday directive. The early results of a retrospective study looking at the drug as a treatment look promising, but the results are not final and still pending peer review.

"We have analyzed our data and have seen a significantly improved outcome in a group of COVID-19 patients who received hydroxychloroquine," he said.

 

Maybe if all you got is a tweet from a quack medical organization and poor reading comprehension, you should take it elsewhere. 

 

 

 

ETA: Just to be clear, I sincerely hope that HCQ shakes out in properly conducted controlled trials, and agree that that research should play out.  All the extent US RCTs are negative, but that doesn't mean that it might not work in one of the other narrow gaps that remain (PreEP and early intervention, for example). But the circus barker like promotion of the product is counterproductive and dangerous, and needs to be curtailed until data can guide its appropriate use. 

Edited June 17, 2020 by Anastasis

[Dahobbs 17526]

2 hours ago, triplehorn said:

I take that to mean the feds are sitting on a stockpile of (H)CQ at the SNS that will no longer be available to supply hospitals for hospitalized patients w Covid.  However, the federal SNS stockpile of (H)CQ will be available to distribute to States should they request it for use in some outpatient form of early prevention/intervention.  If we're finally headed there, and this reporting is a real sign, it has the potential to be a morbid exercise to see if there's enough and, if not, where it gets funneled.  Today, some States are more pre-disposed and have been more prepared to adopt this than others.

No. The EUA allowed the distribution of HCQ for an unapproved use. With its retraction, neither the SNS nor any other manufacturer/distributor may distribute HCQ specifically for Covid-19 in any regard (as a post infection treatment or a prophylactic). It can still be distributed for the purposes for which it is approved. And, healthcare providers can still prescribe it to the same extent they could prescribe any other medication for off-label uses. However, the latter is limited by the standards of the medical profession, requiring the treatment have benefits in excess of the risks. There is no reliable evidence that HCQ provides any benefit in relation to Covid-19. Accordingly, it fails that criteria. As stated by the NIH, HCQ should be given for Covid-19 only in the setting of a clinical trial.

Edited June 17, 2020 by Dahobbs

[triplehorn 2664]

1 hour ago, Dahobbs said:

 There is no reliable evidence that HCQ provides any benefit in relation to Covid-19. Accordingly, it fails that criteria. As stated by the NIH, HCQ should be given for Covid-19 only in the setting of a clinical trial.

I disagree with your first sentence but don’t know how you’re slicing it.  Even so, it’s obviously changing by the day in the US as more trial results come out, including with notable leaking of positive news in this Michigan based early use study.  
 

Regarding your last sentence, do you have an updated link ?  There’s a lot of mixed messaging.  NIH serves a big research function, not so much a regulatory function.  The feds are not blocking it.  However the governing bodies of individual States have a heavy say in what is available for use locally.

My Oregon Governor put a hold on community off-label use of (H)CQ for Covid in late March, which was after off-label use was recognized within the State.  At the time, it was understandable and I have observed it.  I haven’t revisited it lately but do know a person who is hands on with State level public health research and policy.  That person indicated that they are well aware of positive international studies generally and the 2 pre-exposure prophylaxis studies out of India in particular as they seek ways to best protect the front line Oregonians and other high risk groups.  If this Michigan study, or others, support pre-exposure prophylaxis or early application for mitigation, I’d expect there to be some state level shifting here.  There’s very real reason to be hopeful about this pre/early phase use.

[BradInATX 9208]

5 minutes ago, triplehorn said:

I disagree with your first sentence but don’t know how you’re slicing it.  Even so, it’s obviously changing by the day in the US as more trial results come out, including with notable leaking of positive news in this Michigan based early use study.  
 

Regarding your last sentence, do you have an updated link ?  There’s a lot of mixed messaging.  NIH serves a big research function, not so much a regulatory function.  The feds are not blocking it.  However the governing bodies of individual States have a heavy say in what is available for use locally.

My Oregon Governor put a hold on community off-label use of (H)CQ for Covid in late March, which was after off-label use was recognized within the State.  At the time, it was understandable and I have observed it.  I haven’t revisited it lately but do know a person who is hands on with State level public health research and policy.  That person indicated that they are well aware of positive international studies generally and the 2 pre-exposure prophylaxis studies out of India in particular as they seek ways to best protect the front line Oregonians and other high risk groups.  If this Michigan study, or others, support pre-exposure prophylaxis or early application for mitigation, I’d expect there to be some state level shifting here.  There’s very real reason to be hopeful about this pre/early phase use.

Dude just stop, or start your own HCQ thread. Have you seen a single person that has supported you continuing this line of conversation? Have you received a single pos rep from any of this HCQ nonsense? I'm not saying you're right or wrong, just that nobody gives a fuck.

[gmr548 16576]

If all you got is to show up and flame, take it elsewhere.  
 
 

I cannot imagine something less fitting for the banner of this website.

[Dahobbs 17526]

11 hours ago, triplehorn said:

I disagree with your first sentence but don’t know how you’re slicing it.  Even so, it’s obviously changing by the day in the US as more trial results come out, including with notable leaking of positive news in this Michigan based early use study.  
 

Regarding your last sentence, do you have an updated link ?  There’s a lot of mixed messaging.  NIH serves a big research function, not so much a regulatory function.  The feds are not blocking it.  However the governing bodies of individual States have a heavy say in what is available for use locally.

My Oregon Governor put a hold on community off-label use of (H)CQ for Covid in late March, which was after off-label use was recognized within the State.  At the time, it was understandable and I have observed it.  I haven’t revisited it lately but do know a person who is hands on with State level public health research and policy.  That person indicated that they are well aware of positive international studies generally and the 2 pre-exposure prophylaxis studies out of India in particular as they seek ways to best protect the front line Oregonians and other high risk groups.  If this Michigan study, or others, support pre-exposure prophylaxis or early application for mitigation, I’d expect there to be some state level shifting here.  There’s very real reason to be hopeful about this pre/early phase use.

Your post reveals a significant misunderstanding of how the practice of medicine is regulated.

The federal government does not directly regulate the practice of medicine. That job is left to the states and to the medical profession itself. Accordingly, no federal entity is ever going to directly "block" a physician's choice of treatment. Rather, the federal government, through the FDA, regulates the entities that manufacture, label, and distribute medical devices and pharmaceuticals. The FDA tells them what products they can sell, how they can manufacture them, what uses they can advertise for their products, and what they can and must tell the public about the products.

Sometimes the FDA prevents a device or pharmaceutical from being sold at all. Other times the FDA allows the product to be sold, but only for specifically approved purposes. In that latter scenario, since the FDA doesn't regulate the practice of medicine, physicians are not restricted by the federal government from using a product "off-label," that is for purposes other than specifically approved by the FDA. The entity selling the device can't advertise the product for that use, but a physician may still use it. 

Further, while the federal government does not regulate the practice of medicine, entities within the federal government do often provide non-binding guidance for physicians on how to practice medicine. There is no legal penalty for not following this guidance, except for the fact that guidance from the federal government gets incorporated with guidance from within the medical profession (e.g., professional associations like the American Heart Association) into the professional standards expected of healthcare providers. 

Those standards are then enforced by the states, directly through licensing boards, and indirectly through medical malpractice litigation.

Given that context, here is what HCQ stands: (1) it is not approved by the FDA for treating Covid-19, (2) the FDA has concluded that "it is no longer reasonable to believe that oral formulations of HCQ and CQ may be effective in treating COVID-19, nor is it reasonable to believe that the known and potential benefits of these products outweigh their known and potential risks", (3) the NIH has said HCQ should be used only in the setting of a clinical trial; (4) the WHO and other organizations have halted study of HCQ in hospitalized patients; (4) the only studies currently indicating any potential benefit of HCQ generally show a weak benefit and are largely small observational studies and not reliable indicators; (5) a recently published trial on post-exposure prophylaxis shows no benefit.

While continued investigation of HCQ as a prophylaxis should continue for now (and is continuing), the currently available data would not support a physician's decision to prescribe HCQ for Covid-19 (treatment or prophylaxis). Prescribing it now with no demonstrated benefit and given known risks is outside the bounds of the standard of care in the medical community. Accordingly, HCQ use for Covid-19 should be limited to investigation in clinical trials. 

https://www.fda.gov/media/138945/download

https://arstechnica.com/science/2020/06/who-gives-up-on-hydroxychloroquine-for-covid-19-stops-trials/

https://www.nejm.org/doi/full/10.1056/NEJMoa2016638

 

[drt 638]

On 6/16/2020 at 10:23 AM, Mitch Cumsteen said:

It doesn't look like the study has been published yet,  but there is a lot of buzz on dexamethasone reducing mortality in patients on ventilators and oxygen. 

https://www.bbc.com/news/health-53061281

https://nypost.com/2020/06/16/life-saving-coronavirus-drug-dexamethasone-discovered-through-trial/

It's extremely common for treatment of HAPE, so seems like this would make sense.  Kinda gotta wonder why docs in places like Colorado that are used to treating high altitude pulmonary injuries didn't suggest this earlier.

[Liquor and Poker 3659]

Not peer reviewed, so I should just laugh this off, right?  Gave me pause because the study included some work at UT-Galveston and I know a few folks there:

https://www.scmp.com/news/china/science/article/3089476/there-may-be-no-immunity-against-covid-19-new-wuhan-study

[triplehorn 2664]

1 hour ago, Dahobbs said:

Your post reveals a significant misunderstanding of how the practice of medicine is regulated.

The federal government does not directly regulate the practice of medicine. That job is left to the states and to the medical profession itself. Accordingly, no federal entity is ever going to directly "block" a physician's choice of treatment. Rather, the federal government, through the FDA, regulates the entities that manufacture, label, and distribute medical devices and pharmaceuticals. The FDA tells them what products they can sell, how they can manufacture them, what uses they can advertise for their products, and what they can and must tell the public about the products.

Sometimes the FDA prevents a device or pharmaceutical from being sold at all. Other times the FDA allows the product to be sold, but only for specifically approved purposes. In that latter scenario, since the FDA doesn't regulate the practice of medicine, physicians are not restricted by the federal government from using a product "off-label," that is for purposes other than specifically approved by the FDA. The entity selling the device can't advertise the product for that use, but a physician may still use it. 

Further, while the federal government does not regulate the practice of medicine, entities within the federal government do often provide non-binding guidance for physicians on how to practice medicine. There is no legal penalty for not following this guidance, except for the fact that guidance from the federal government gets incorporated with guidance from within the medical profession (e.g., professional associations like the American Heart Association) into the professional standards expected of healthcare providers. 

Those standards are then enforced by the states, directly through licensing boards, and indirectly through medical malpractice litigation.

Given that context, here is what HCQ stands: (1) it is not approved by the FDA for treating Covid-19, (2) the FDA has concluded that "it is no longer reasonable to believe that oral formulations of HCQ and CQ may be effective in treating COVID-19, nor is it reasonable to believe that the known and potential benefits of these products outweigh their known and potential risks", (3) the NIH has said HCQ should be used only in the setting of a clinical trial; (4) the WHO and other organizations have halted study of HCQ in hospitalized patients; (4) the only studies currently indicating any potential benefit of HCQ generally show a weak benefit and are largely small observational studies and not reliable indicators; (5) a recently published trial on post-exposure prophylaxis shows no benefit.

While continued investigation of HCQ as a prophylaxis should continue for now (and is continuing), the currently available data would not support a physician's decision to prescribe HCQ for Covid-19 (treatment or prophylaxis). Prescribing it now with no demonstrated benefit and given known risks is outside the bounds of the standard of care in the medical community. Accordingly, HCQ use for Covid-19 should be limited to investigation in clinical trials. 

https://www.fda.gov/media/138945/download

https://arstechnica.com/science/2020/06/who-gives-up-on-hydroxychloroquine-for-covid-19-stops-trials/

https://www.nejm.org/doi/full/10.1056/NEJMoa2016638

 

Thanks for taking the time.  Regarding questions around how the practice of medicine is regulated, I'm not aware of anything I've previously said that contradicts what you posted or that reveals a misunderstanding on my part.  A few posts above I specifically drew attention to States playing a primary role in regulating medical practice which naturally creates differences between States in what is available.  Obviously this spans a number of different medical procedures and for what purposes various treatments can be prescribed.  I pay attention to what my State authorizes and have always observed that.  Off label-use of the med under scrutiny is permitted in some States at this time.   

Regarding the links you posted, there's nothing new in there.  The WHO and NEJM articles relate only to studies done in hospitalized patients and post-exposure prophylaxis.   The fda.gov letter is interesting in that the general language around the FDA/EUA for use in "hospitalized" patients is dropped.  Not sure if that is a result of the letter-writer being casual or not.   

Of note from your second link:

"The WHO noted in its announcement today’s decision to end hydroxycloroquine’s use in the Solidarity trial, which looks at stopping COVID-19, “does not apply to the use or evaluation of hydroxychloroquine in pre- or post-exposure prophylaxis in patients exposed to COVID-19.”

First, what your link coveys is that this medication still remains under active investigation as a viable intervention albeit with a more narrowed focus.  So yes, it's relevant for consideration and discussion.  It leaves pre-exposure prophylaxis and early post-exposure mitigation of illness severity to be elaborated.  Internationally, there are positive signs in both contexts, but nothing definitive at this time.  Until results of additional ongoing studies are produced, positive or negative, I'll leave it that.  

 

 

[drt 638]

Remedy's website lists both of these antibody tests as the ones that they're using.  https://www.360dx.com/immunoassays/study-finds-abbott-coronavirus-serology-test-more-accurate-euroimmun-test#.XuuFZmhKiUk  If you actually go to the pdf of the study in question (https://academic.oup.com/clinchem/advance-article/doi/10.1093/clinchem/hvaa120/5836557) their conclusion is that neither are very good in the first 14 days following symptom onset.

Looks like the Abbot test is slightly better. Makes me wonder which one I received, and how all this relates if we never had symptoms or had very mild symptoms.

[triplehorn 2664]

This question has come up here previously - is there a difference in incidence and/or clinical course of Covid in patients with Rheumatic Diseases who are on disease-modifying antirheumatic drugs (DMARDs)?  Based on this report, there appears to be a pre-exposure preventative effect as well as illness severity mitigating effect for Covid:

Clinical Rheumatology:  Impact of anti-rheumatic drugs and steroids on clinical course and prognosis of COVID-19

 

Quote

"Our data show a small incidence of COVID-19 among RD outpatients and a small presence of RD patients among subjects hospitalized for COVID-19. When COVID-19 occurred in RD patients, it had a better course and a good prognosis. DMARDs seem to protect against a worse prognosis, as no hospitalized patient was taking DMARDs and the percentage of RD outpatients treated with DMARDs was significantly lower among subjects with COVID-19. Interestingly, our study first shows that hospitalized patients taking steroids for RDs or other diseases may have clinical parameters and a prognosis better than other hospitalized patients."

 

[triplehorn 2664]

After expecting to rapidly enroll 2000 subjects, NIH early intervention study gets shuttered due to only enrolling 20 patients since the start of May.  

BULLETIN—NIH Clinical Trial Evaluating Hydroxychloroquine and Azithromycin for COVID-19 Closes Early

Quote

June 20, 2020

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has stopped enrollment in its clinical trial evaluating whether hydroxychloroquine and azithromycin can prevent hospitalization and death from coronavirus disease 2019 (COVID-19). This action was taken because NIAID, the study leadership and the independent data and safety monitoring board (DSMB) overseeing the trial determined that the rate of participant enrollment has been inadequate for the trial to meet its objectives in a timely manner. No safety concerns were associated with the trial.

Launched in May 2020, the NIAID-sponsored Phase 2b trial aimed to determine whether a short course of hydroxychloroquine and azithromycin could safely and effectively prevent disease progression among adults with mild-to-moderate COVID-19. Hydroxychloroquine is approved by the Food and Drug Administration to treat autoimmune diseases and to prevent and treat malaria. Preliminary evidence had suggested that the drug, alone or in combination with the FDA-approved antibiotic azithromycin, might benefit people with COVID-19. 

Although recent research suggests that hydroxychloroquine may not be an effective treatment for patients hospitalized with COVID-19, the question of whether it offers benefit when given early in the course of the disease remains unanswered. The NIAID study, conducted by the AIDS Clinical Trials Group (ACTG), sought to fill this knowledge gap by testing it in a randomized, placebo-controlled trial—considered the gold standard for determining whether an intervention can benefit patients.

The study, conducted at ACTG sites across the United States, planned to rapidly enroll approximately 2,000 adults who had laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19, and were experiencing symptoms consistent with COVID-19. Participants were randomly assigned to receive either hydroxychloroquine and azithromycin or matching placebo pills to take at home for seven days.  

Since its launch in May, however, the study had enrolled only 20 participants, despite efforts by the study sites to enhance recruitment, raising concerns that it would not be feasible to continue the trial to full enrollment. On June 15, FDA revoked an Emergency Use Authorization(link is external) that had allowed hydroxychloroquine and the related drug chloroquine to be prescribed to hospitalized adolescents and adults with COVID-19. This revocation does not apply to clinical trials and is specific to hospitalized individuals rather than outpatients. However, the decision could further dampen enthusiasm for enrollment in studies evaluating these drugs.

Based on these considerations and in close consultation with the study team, NIAID determined that it is highly unlikely that the ACTG trial, known as A5395, would be able to enroll to completion and meet its intended objectives. The DSMB concurred with this assessment and agreed it would be best to close the trial. Participants, site investigators, institutional review boards and regulators are being notified of this decision. The study team is working with the clinical trial sites to ensure that participants in the trial receive appropriate care.

NIAID remains committed to identifying safe and highly effective treatments for COVID-19. The Institute recently launched a trial evaluating remdesivir plus the anti-inflammatory drug baricitinib for treatment of hospitalized adults with COVID-19. Additional studies, including outpatient studies, are in the planning stages.

 

 - "No safety concerns were associated with the trial."

- "Preliminary evidence had suggested that the drug, alone or in combination with the FDA-approved antibiotic azithromycin, might benefit people with COVID-19." 

- "Although recent research suggests that hydroxychloroquine may not be an effective treatment for patients hospitalized with COVID-19, the question of whether it offers benefit when given early in the course of the disease remains unanswered."

 

what in the hell. unfortunate doesn't begin to describe it.

[Captainant 27635]

Holy fuck dude, stop. 

[triplehorn 2664]

It's the latest information on very relevant NIH research. It's a medical discussion thread.  I've been posting on this thread from the beginning.   Try the ignore function instead of thread shitting.

[Liquor and Poker 3659]

I keep seeing these clips of Indian officials walking down the street with huge foggers or spraying down huge crowds of people sitting on the ground with firehoses of chemicals (the people even obediently turn around on command so they can get soaked on both sides).

How can that be anything but a gesture to control fear?  I guess also showers. 

[zork 629]

Quote

Ascientist known for his contrarian takes to dire COVID-19 predictions has released a paper claiming that antibody evidence suggests the median coronavirus infection fatality rate for those under 70 is just 0.04%. 

The estimate throws into sharp relief the lopsided mortality figures for the disease, which has claimed an inordinate number of elderly people across the planet while leaving younger individuals mostly unscathed. 

John Ioannidis, a professor of epidemiology and population health at Stanford University, argues in a paper published earlier this month that COVID-19 "seroprevalence studies," which measure infection rates using the presence of antibodies in blood samples, "typically show a much lower fatality than initially speculated in the earlier days of the pandemic."

"It should be appreciated," he writes in the paper, "that [the fatality rate] is not a fixed physical constant and it can vary substantially across locations, depending on the population structure, the case-mix of infected and deceased individuals and other, local factors."

In the paper, which has not yet been peer-reviewed, Ioannidis surveyed 23 different seroprevalence studies and found that "among people <70 years old, infection fatality rates ranged from ... 0.00-0.23% with median of 0.04%." 

The median fatality rate of all cases, he writes, is 0.26%, significantly lower than some earlier estimates that suggested rates as high as over 3%. 

In the paper, Ioannidis acknowledges that "while COVID-19 is a formidable threat," the apparently low fatality rate compared to earlier estimates "is a welcome piece of evidence."

"Decision-makers can use measures that will try to avert having the virus infect people and settings who are at high risk of severe outcomes," he writes. "These measures may be possible to be far more precise and tailored to specific high- risk individuals and settings than blind lockdown of the entire society."

https://justthenews.com/politics-policy/coronavirus/stanford-prof-median-infection-fatality-rate-coronavirus-those-under-70

[drt 638]

Not yet peer reviewed, so might as well be something you or I wrote on the internet.  And I'm shocked that "Ascientist known for his contrarian takes to dire COVID-19 predictions"  might conclude that come to the conclusion that based on antibody testing the fatality rate isn't as high as initial estimates.

[jimmyjazz 45887]

I'm sure I could dig back and find this, but maybe someone can provide a quick answer informed by current science:

What is the expected "hang time" for aerosolized particles indoors?  One of my wife's best friends owns a dance studio and her employee who did routine after-class cleaning quit.  The owner can't do it all herself so she asked my wife to help out.  I'm just wondering how long is a reasonable amount of time to wait after classes before entering the facility.  All kids wear masks while in class . . . but, kids.  All are screened for fever before class as well, but that's certainly not diagnostically robust.

We want to help her out, as she has always been super helpful to us, but I need to know the risks.

[triplehorn 2664]

18 hours ago, triplehorn said:

It's the latest information on very relevant NIH research. It's a medical discussion thread.  I've been posting on this thread from the beginning.   Try the ignore function instead of thread shitting.

I'm not going to be initiating any more HCQ research, news, or opinion after this post on this or any thread.  I'm open to dispassionate discussion about it in the future, but that won't be until others are on board, which isn't now. 

Why it matters?   Understanding HCQ applies beyond this pandemic.  That is because of its potential importance fighting RNA viruses as a class.  One common shared trait of RNA viruses essential for viral replication is the use of RNA-dependent RNA polymerase (RdRp).  If you find agents that inhibit the function of this enzyme, you potentially have a tool with a broader spectrum to fight a variety of pathogenic RNA viruses.   Remdesivir inhibits this enzyme, and this is also a mechanism of action enhanced by and demonstrated for HCQ in vitro. 

The Achilles heel of Remdesivir, for one, is that it has to be administered IV and is very expensive.  The major limitations of technical IV use and high cost make it unsuitable for broad application to mild/mod severity, non-critical cases - a large percentage of whom would develop no complications without any intervention.  But what if attacking RdRp for meaningful life saving and organ protecting is dependent on hitting the infection early and hard, where doing so means you have to expose a lot of people early to a treatment who would otherwise not develop complicated illness and hospitalization?  In that case you need something that is safe, easy to administer, and inexpensive (cheaper per day than OTC TheraFlu)   HCQ checks those 3 boxes.  The most important question to be answered is if early application is a key clinical outcome differentiator for RdRp inhibiting meds. This key question relates to all the 'vir meds in the current mix and HCQ.  How many other meds in the mix check those boxes, or even two of them?  

Because of the active threat of recurrent deadly pandemics for years to come from various RNA viruses beyond this novel coronavirus, there is a huge amount of medical money in the balance globally.  Some are primarily motivated by profit. We rely on publicly funded research to answer these questions about checking those 3 boxes, because Big Pharma has no interest in offering a helping hand or paying for studies that could tip the scale towards a safe, cheap, easy to take generic like HCQ.  It's why the NIH early intervention study getting shut down is such a setback.  It's not stopping other studies being done here and internationally though.

Stalled and late-start domestic studies notwithstanding, today the results of a randomized controlled trial (the elusive RCT) became public from a Chinese study which demonstrate superiority of both Chloroquine and Hydroxychloroquine over control when used for early intervention in Covid-19:

Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized controlled study

 

Quote

 

When you get this degree of decreased recovery time, it follows that peak severity of illness should also be less.  Less of everything bad.

 

[triplehorn 2664]

Gilead to start testing inhaled remdesivir, eyeing earlier COVID-19 use

 

Quote

The company’s intention is very clear: reaching patients earlier, before their disease worsens and becomes harder to treat. “An inhaled formulation would be given through a nebulizer, which could potentially allow for easier administration outside the hospital, at earlier stages of disease,” O’Day said.

[...]

What he didn’t mention was that the drug’s benefits actually decreased in mild or moderate patients—though that patient population was too small to be conclusive—just as it didn’t much help those critically ill patients on invasive ventilation. The company recently said in its own phase 3 Simple trial, moderate patients on remdesivir were 65% more likely to see their clinical symptoms improve than those on standard treatment alone.

But as Evercore ISI analyst Umer Raffat noted at the time, the ACTT-1 readout is still missing data on whether patients who take remdesivir soon after symptom onset fare better.

Getting an antiviral early to potentially stop disease progression is an appealing idea, and it will be the focus of Gilead’s next wave of clinical development. New studies will also test the IV formulation in the outpatient setting at places such as infusion centers and nursing homes.

“For patients who are at high risk of disease progression, it could be particularly beneficial to start treatment outside the hospital,” O’Day argued. “Our hope is that earlier intervention could help patients avoid hospitalization altogether.”

yep. This is a direct attempt to work around that Achilles heel I mentioned just above. 

Edited June 23, 2020 by triplehorn

[Bevo 13566]

Fuck, I've been drunk since February. Never and I repeat never play the drinking game where every time triple says the word hydroxychloroquine you have to take a shot.

Edited June 23, 2020 by Bevo

[Anastasis 23461]

I guess an unblinded study of N=15 people on HCQ that includes randomized assignment is better than a letter to the editor.

BTW, if you track the attrition flow of that study, you see how poorly executed the study was. They enrolled and randomized people who did not have COVID infection, and people who were asymptomatic were enrolled and randomized but excluded from the analysis.  They don't have their protocol published, but I would like to see their pre-planned SAP. 

[Txzen 498]

On 6/22/2020 at 12:37 PM, jimmyjazz said:

I'm sure I could dig back and find this, but maybe someone can provide a quick answer informed by current science:

What is the expected "hang time" for aerosolized particles indoors?  One of my wife's best friends owns a dance studio and her employee who did routine after-class cleaning quit.  The owner can't do it all herself so she asked my wife to help out.  I'm just wondering how long is a reasonable amount of time to wait after classes before entering the facility.  All kids wear masks while in class . . . but, kids.  All are screened for fever before class as well, but that's certainly not diagnostically robust.

We want to help her out, as she has always been super helpful to us, but I need to know the risks.

I think the issue (for me) would be an indoor area where a lot of exertion has occurred. The more and deeper you breathe, the more droplets you will generate

There's a fair amount of data out there on survival or aerosols of this coronovirus family. I think the time component of aerosol infectivity is still in the period of understanding, and it certainly depends on the size of the droplet, the temperature at least:

• "...airborne coronavirus MERS-CoV exhibited strong capability of surviving, with about 64% of microorganisms remaining infectious 60 min after atomization at 25 °C and 79% relative humidity (RH) (9). On the other hand, rapid virus decay occurred, with only 5% survival over a 60-min procedure at 38 °C and 24% RH, indicative of inactivation. Recent experimental studies have examined the stability of SARS-CoV-2, showing that the virus remains infectious in aerosols for hours (12) and on surfaces up to days". link
• "The SARS-CoV-2 virus has been found to remain viable in aerosols for 3 h, while it, in the form of droplets, is more stable on plastic and stainless steel, copper, cardboard, and glass with durations detected up to 72, 4, 24, and 84 h, respectively. In comparison, the SARS-CoV virus was also found to be airborne in the form of aerosols for 3 h, indicating that both SARS viruses behave more or less in the same manner in the air. Nevertheless, the SARS-CoV virus remains stable and viable in the form of droplets on plastic and stainless steel, copper, cardboard, and glass with durations (half-lives) lasting to 72, 8, 8, and 96 h, respectively." link, and the original NEJM paper which shows at least 3h of aerosol data: NEJM

[DDD Dad 14325]

On 6/23/2020 at 10:19 AM, Bevo said:

Fuck, I've been drunk since February. Never and I repeat never play the drinking game where every time triple says the word hydroxychloroquine you have to take a shot.

Sorta like my daily headaches from drinking every night.

[jimmyjazz 45887]

6 minutes ago, Txzen said:

I think the issue (for me) would be an indoor area where a lot of exertion has occurred. The more and deeper you breathe, the more droplets you will generate

There's a fair amount of data out there on survival or aerosols of this coronovirus family. I think the time component of aerosol infectivity is still in the period of understanding, and it certainly depends on the size of the droplet, the temperature at least:

• "...airborne coronavirus MERS-CoV exhibited strong capability of surviving, with about 64% of microorganisms remaining infectious 60 min after atomization at 25 °C and 79% relative humidity (RH) (9). On the other hand, rapid virus decay occurred, with only 5% survival over a 60-min procedure at 38 °C and 24% RH, indicative of inactivation. Recent experimental studies have examined the stability of SARS-CoV-2, showing that the virus remains infectious in aerosols for hours (12) and on surfaces up to days". link
• "The SARS-CoV-2 virus has been found to remain viable in aerosols for 3 h, while it, in the form of droplets, is more stable on plastic and stainless steel, copper, cardboard, and glass with durations detected up to 72, 4, 24, and 84 h, respectively. In comparison, the SARS-CoV virus was also found to be airborne in the form of aerosols for 3 h, indicating that both SARS viruses behave more or less in the same manner in the air. Nevertheless, the SARS-CoV virus remains stable and viable in the form of droplets on plastic and stainless steel, copper, cardboard, and glass with durations (half-lives) lasting to 72, 8, 8, and 96 h, respectively." link, and the original NEJM paper which shows at least 3h of aerosol data: NEJM

Thanks . . . the 2nd article shows a half-life plot indicating roughly 1 hour half life.  I assume that means 50% viability after 1 hour, 25% after 2 hours, 12.5% after 3 hours, etc.?

[Txzen 498]

That's probably a fair interpretation of the data, the question then is how many particles (and how unlucky) do you have to be to contract it. But it's measuring the actual number of viral particles (titer), and note that we're starting with a pretty large number, and that's a log scale graph. 

These are all mechanically-generated aerosols, and there are other studies out there which say you've got measurable virus farther out to 16h : link

There's some additional consideration that aerosols are not always so easily generated in real life, and the dynamics of a normal room (like an OR) could be different: Link

Quote

“These are only generated under very specific circumstances during certain hospital procedures,” she explains, such as bronchoscopy or intubation. That could actually mean these findings – which saw COVID-19 aerosols created using a nebulizer – hold some good news for ongoing coronavirus treatment. 

“This data suggests that aerosolized virus half-life is measured in hours,” Dr. Rasmussen suggests, “and aerosols generated by these medical procedures will not persist for days, for example in the hospital procedure rooms.”

“Furthermore, both viruses also showed a 3-log decrease in infectious virus on stainless steel and plastic surfaces after 48-72 hours,” she added. “This suggests that, while viruses can stay on some surfaces for days, their infectious titer is greatly reduced (1000-fold).”

 

[Anastasis 23461]

Any geneticists want to translate this thread for us.

Sounds like the ABO blood type signal is not being replicated in this analysis, but there are some other gene candidates related to immune response?

 

 

 

Edited June 29, 2020 by Anastasis

[GRHorn 105]

No new studies listed here, but some interesting recommendations from the American Academy of Pediatrics related to school in the fall.

 

 

[Post Oak 20208]

Sure that should be the "goal".

Not gonna happen though