Can touching a barbell in the gym get you sick with the coronavirus?

[ickyrica]

If lockdown status brings the US a 20% death rate then Sweden must be filling up with bodies. They never shut life down, oh the humanity!

How Sweden has faced the coronavirus without a lockdown | Boston.com

Thank God for the intimate wisdoms that @master.on bestows upon us all! We would be blind, lost in the big scary world if it weren't for him!!

 

[Michael Scally MD]

 

[Michael Scally MD]

COVID-19 & Farts ...

I just saw a post about "If a fart can make it through underwear and a pair of jeans, how can a mask made of cloth save you from covid? Asking for a friend..[sic]" Well, firstly, thank you for the question! As a scientist (specifically a chemist, I am absolutely qualified to 1/9

answer this question! Let's consider the size of the molecules that make up the stink smell in farts. We'll focus on one particular example, as the others are similarly sized (when compared to the size of a virus). Methanthiol (CH3SH), like a number of thiol (-SH) containing 2/9

molecules, smells! When you work with it enough (as I have), it smells like incredibly intense garlic; though many would just say it smells putrid. If you want everyone to hate you, walk through a hallway carrying an open container of thiol compounds. Ask my former student 3/9

and colleagues, they all remember that day! Well, CH3SH is a rather small molecule with a diameter around 4*10^-10 m (0.4 nm, about 1.6*10^-8 inches). By comparison, viruses typically range in diameter from about 20 nm up to about 400 nm (J. Biol. Phys., 2013, 39(2), 215), 4/9

with COVID-19 being around 60-140 nm (Cell. Mol. Immun., 2020, doi.org/10.1038/s41423…). The difference in sizes of the COVID-19 virus and a common odorant in farts is 2-3 orders of magnitude (100–1000 times the diameter of the smaller methanethiol). An N95 mask is capable 5/9

of filtering 95% of a test aerosol containing average particle size of 300 nm (from the CDC: blogs.cdc.gov/niosh-science-…). Basically, an N95 mask has a tight weave pattern with multiple layers that serve as a barrier to larger structures (like viruses, or simply spittle). 6/9

While the benefits of a specific mask will depend on the fabric and construction of the mask (not to mention how it is worn), having some form of barrier between an infected individual and a healthy individual is far superior to open air allowing for the transfer of virus 7/9

(along with other matter) between those individuals. Lastly, to argue that “since I can smell a fart through a mask, there's no point in wearing a mask to protect me against viruses” is like securing a medieval castle with a gate to keep out invading horsemen, 8/9

but arguing that because roaches can still enter that there is no point in having a gate. Clearly you have not considered that the horseman is the greater threat. 9/9

Thread by @MakalMakal: I just saw a post about "If a fart can make it through underwear and a pair of jeans, how can a mask made of cloth save you from covid? Aski…

 

[ickyrica]

COVID-19 & Farts ...

I just saw a post about "If a fart can make it through underwear and a pair of jeans, how can a mask made of cloth save you from covid? Asking for a friend..[sic]" Well, firstly, thank you for the question! As a scientist (specifically a chemist, I am absolutely qualified to 1/9

answer this question! Let's consider the size of the molecules that make up the stink smell in farts. We'll focus on one particular example, as the others are similarly sized (when compared to the size of a virus). Methanthiol (CH3SH), like a number of thiol (-SH) containing 2/9

molecules, smells! When you work with it enough (as I have), it smells like incredibly intense garlic; though many would just say it smells putrid. If you want everyone to hate you, walk through a hallway carrying an open container of thiol compounds. Ask my former student 3/9

and colleagues, they all remember that day! Well, CH3SH is a rather small molecule with a diameter around 4*10^-10 m (0.4 nm, about 1.6*10^-8 inches). By comparison, viruses typically range in diameter from about 20 nm up to about 400 nm (J. Biol. Phys., 2013, 39(2), 215), 4/9

with COVID-19 being around 60-140 nm (Cell. Mol. Immun., 2020, doi.org/10.1038/s41423…). The difference in sizes of the COVID-19 virus and a common odorant in farts is 2-3 orders of magnitude (100–1000 times the diameter of the smaller methanethiol). An N95 mask is capable 5/9

of filtering 95% of a test aerosol containing average particle size of 300 nm (from the CDC: blogs.cdc.gov/niosh-science-…). Basically, an N95 mask has a tight weave pattern with multiple layers that serve as a barrier to larger structures (like viruses, or simply spittle). 6/9

While the benefits of a specific mask will depend on the fabric and construction of the mask (not to mention how it is worn), having some form of barrier between an infected individual and a healthy individual is far superior to open air allowing for the transfer of virus 7/9

(along with other matter) between those individuals. Lastly, to argue that “since I can smell a fart through a mask, there's no point in wearing a mask to protect me against viruses” is like securing a medieval castle with a gate to keep out invading horsemen, 8/9

but arguing that because roaches can still enter that there is no point in having a gate. Clearly you have not considered that the horseman is the greater threat. 9/9

Thread by @MakalMakal: I just saw a post about "If a fart can make it through underwear and a pair of jeans, how can a mask made of cloth save you from covid? Aski…

@NorthMich farts vs covid. The idea has legs to it haha

 

[DrinkFlintWater]

N.J. gym owner charged with ignoring order to stay closed during coronavirus pandemic

 

[LeoTC]

View attachment 129416

There's a shocking number of videos on Pornhub that disprove this example.

I seriously don't know how some of you have the energy to argue with the @master.on types at this point.

I'm so far beyond burnt out dealing with Covid zealots it's not funny. They're actually worse than the keto and vegan preachers.

 

[ickyrica]

I seriously don't know how some of you have the energy to argue with the @master.on types at this point.

covid boredom mainly.

 

[LeoTC]

covid boredom mainly.

Fair enough.

 

[Old]

There's a shocking number of videos on Pornhub that disprove this example.

I seriously don't know how some of you have the energy to argue with the @master.on types at this point.

I'm so far beyond burnt out dealing with Covid zealots it's not funny. They're actually worse than the keto and vegan preachers.

Veganism has reached the status of religion. What I can't figure out is how many of them are fascinated with and advocates for Wolves - obligate carnivores. TILT. I meat [pun] these in NY and have met them in Yellowstone staring at wolves through binoculars, logging their kills and social structure. They name each wolf but the elk and bison are just 'ungulates'. But then most religions I just don't 'get'.

COVID-19 & Farts ...

I just saw a post about "If a fart can make it through underwear and a pair of jeans, how can a mask made of cloth save you from covid? Asking for a friend..[sic]" Well, firstly, thank you for the question! As a scientist (specifically a chemist, I am absolutely qualified to 1/9

answer this question! Let's consider the size of the molecules that make up the stink smell in farts. We'll focus on one particular example, as the others are similarly sized (when compared to the size of a virus). Methanthiol (CH3SH), like a number of thiol (-SH) containing 2/9

molecules, smells! When you work with it enough (as I have), it smells like incredibly intense garlic; though many would just say it smells putrid. If you want everyone to hate you, walk through a hallway carrying an open container of thiol compounds. Ask my former student 3/9

and colleagues, they all remember that day! Well, CH3SH is a rather small molecule with a diameter around 4*10^-10 m (0.4 nm, about 1.6*10^-8 inches). By comparison, viruses typically range in diameter from about 20 nm up to about 400 nm (J. Biol. Phys., 2013, 39(2), 215), 4/9

with COVID-19 being around 60-140 nm (Cell. Mol. Immun., 2020, doi.org/10.1038/s41423…). The difference in sizes of the COVID-19 virus and a common odorant in farts is 2-3 orders of magnitude (100–1000 times the diameter of the smaller methanethiol). An N95 mask is capable 5/9

of filtering 95% of a test aerosol containing average particle size of 300 nm (from the CDC: blogs.cdc.gov/niosh-science-…). Basically, an N95 mask has a tight weave pattern with multiple layers that serve as a barrier to larger structures (like viruses, or simply spittle). 6/9

While the benefits of a specific mask will depend on the fabric and construction of the mask (not to mention how it is worn), having some form of barrier between an infected individual and a healthy individual is far superior to open air allowing for the transfer of virus 7/9

(along with other matter) between those individuals. Lastly, to argue that “since I can smell a fart through a mask, there's no point in wearing a mask to protect me against viruses” is like securing a medieval castle with a gate to keep out invading horsemen, 8/9

but arguing that because roaches can still enter that there is no point in having a gate. Clearly you have not considered that the horseman is the greater threat. 9/9

Thread by @MakalMakal: I just saw a post about "If a fart can make it through underwear and a pair of jeans, how can a mask made of cloth save you from covid? Aski…

I find farting in public helps ensure social-distancing compliance of those around me.

 

[Old]

Regarding the problems of manipulation of the data and insufficient testing...

I really liked the article's careful explanation of the differences between:

Case fatality rate vs. infection fatality rate

Most people don't know the difference. Many think the terms are interchangeable or use them both as an indicator of the "death rate". This is either from ignorance or politicization or both.

For example, I've frequently seen people compare Covid-19 case fatality rate to standard influenza infection fatality rate. This is an apples and oranges comparison. It exaggerates danger of Covid-19.

And now, people are comparing the estimated Covid-19 infection fatality rate to standard influencza case fatality rate. Also apples and oranges. It minimizes the severity of Covid-19.

Here is the author's explanation of the difference:

'But the two numbers describe different things: The first is a case fatality rate, reflecting deaths among people with confirmed diagnoses of covid-19. The second is the infection fatality rate, extrapolated from the antibody surveys.

'In other words, both numbers can be correct, and useful.

'“Those higher numbers of case fatality rates, they’re still true,” Viboud said. “It’s your probability of dying if you’re clinically sick with it, which is something that people may care about, too.”

'Moreover, the fatality rate of a virus, however it is defined, is not an innate feature of the pathogen. It depends on many variables, including the age and health of the population and access to health care. Timing matters, too: In China the fatality rate was high during the initial phase of the outbreak, when hospitals were overwhelmed and doctors struggled to cope with the crisis.

[...]

'A commonly cited statistic about seasonal flu is that it has a fatality rate of 0.1 percent, That, however, is a case fatality rate. The infection fatality rate for flu is perhaps only half that, Viboud said. Shaman estimated that it’s about one-quarter the case fatality rate.'

Source: https://www.washingtonpost.com/heal...c215d8-87f7-11ea-ac8a-fe9b8088e101_story.html​

Certainly we don't see a 1/1000 death rate from flu. A couple years back with a particularly bad season, the CDC put cases at 45,000,000 and deaths at 61,000 - that's 18/100,000 which far less than 0.1%

When looking at the CDC statistics for flu, the numbers are rounded and it takes about 3 years to compile them. So covid 19 numbers will take years too.

More important than the actual numbers, one doctor pointed out the more obvious which is that past flues don't overwhelm hospitals as has happened in some cities.

But not all places. Hospitals where I live have few cases and are largely empty waiting for trouble to come. Upstate NY is estimated with antibody tests to have had only 3.5% exposure - so its slow and without 'overwhelming'.

A big problem is that the policy of not allowing family members including health care advocates to stay with the patient is causing many to not go to the ER when they should. Apparently this is not unique to NY (perhaps a CDC guideline).

 

[Michael Scally MD]

A Prophet of Scientific Rigor—and a Covid Contrarian
John Ioannidis laid bare the foibles of medical science. Now medical science is returning the favor.
A Prophet of Scientific Rigor—and a Covid Contrarian

Ioannidis has been a fixture in medical-school curricula for years, achieving something akin to hero status. He’s one of the most-cited scientists of any type in the world, and may be peerless on this metric among physicians. Amazingly, he’s earned all this acclaim by dedicating his career to telling the fields of biomedicine (and others, too) how shoddy they are, and how little trust one should have in their published research.

But now the scientist celebrated for showing colleagues how their studies are screwed up has a new claim to fame. Its very different vibe is reflected in the faces of the medical students I’m addressing. Almost literally overnight Ioannidis has himself become a case study in how to screw up a medical study. And not just any study: this one concludes that Covid-19 isn’t all that dangerous; that the current lockdowns to prevent its spread are a bigger threat to public health than the actual disease. In other words, Ioannidis’ views on the pandemic sound closer to those of the governor of Georgia than to Anthony Fauci’s.

Let’s face it, the field of epidemiology hasn’t so far covered itself in glory with regard to the coronavirus crisis. The field was for the most part fatefully slow to recognize that a pandemic was aborning; later on, it produced a stream of conflicting and sometimes wildly off-the-mark assessments of infection and mortality rates, and where they might be heading.

But even in this fast-paced and sloppy context, Ioannidis’ study is seen as standing out. Not just for its methodological weaknesses, but for the apparent wrongness of its main conclusions—and the risk that these could have a harmful influence on public-health recommendations. In a nutshell, Ioannidis and his study co-authors tested about 3,300 residents of California’s Santa Clara County for antibodies to the new coronavirus. The results, according to Ioannidis, imply that the disease isn’t nearly as deadly as believed. “Based on what we’re seeing now, the fatality of the virus is more or less the same as influenza, about 0.1 percent,” he says. “Most of the earlier data was completely bogus.”

…

The prevailing take now is that Ioannidis has fallen prey to the very sorts of biases and distortions that he became revered for exposing in others. If that’s what happened, it will be a twist that Ioannidis himself had prophesied to me ten years ago in Greece. “If I did a study and the results showed that in fact there wasn’t really much bias in research, would I be willing to publish it?” he said then. “That would create a real psychological conflict for me.” Ioannidis was acknowledging that he’s invested in showing that other scientists tend to get it wrong, and that he might end up being skeptical of data suggesting they are, in fact, getting it right.

Now Ioannidis’ claims about Covid-19 may be pulled by the gravity of his commitment to being the one who sees where everyone else went wrong. There’s a meta-meta-science lesson in there, too, and one we’ve sometimes seen before: Bias is so powerful a force in scientific research that even a grandmaster of research into bias can eventually trip over it.

 

[Michael Scally MD]

[OA] Testosterone, A Key Hormone in The Context of COVID-19 Pandemic

Daily data show that entire population with SARS-CoV2 is 58% made of males [1–3]. The difference in the number of cases reported by gender increases progressively in favor of male subjects up to the age group ≥60–69 (66.6%) and ≥70–79 (66.1%), with the exception of the 20– 29 years and 30–39 years group in which the number of female subjects it is slightly higher. Furthermore, higher lethality is in favor of male subjects in all age groups. Deaths among 30–39ys are 82.4% males; among 40-49ys are 73.1% males; among 50-59ys are 78.5% males; among 60- 69ys are 79.7% males; among 70-79ys are 79.6% males; among 80- 89ys are 66.9% males [4].

The initial clinical manifestation of COVID-19 is pneumonia, although gastrointestinal symptoms and asymptomatic infections are described, the latter has not yet been definitely assessed [5]. The infection can progress to severe disease with dyspnoea and chest symptoms corresponding to pneumonia in the second or third week of a symptomatic infection. Clinical data show decreased oxygen saturation, changes visible through chest X-rays and other imaging techniques. Furthermore, lymphopenia appears to be common, and an increase of inflammatory markers (C-reactive protein and pro-inflammatory cytokines) has been reported [6].

1. Is low testosterone a promoter of COVID-19 infection? …

2. Is high testosterone a promoter of COVID-19 infection? …

The elucidation of the role of testosterone in the battle towards COVID-19 infection turns out to be an urgent need.

Pozzilli P, Lenzi A. Testosterone, a key hormone in the context of COVID-19 pandemic [published online ahead of print, 2020 Apr 27]. Metabolism. 2020;154252. doi:10.1016/j.metabol.2020.154252 https://www.metabolismjournal.com/article/S0026-0495(20)30116-5/pdf

 

[Michael Scally MD]

The US compared with the rest of the world, May 1st, #COVID19
8 times as many expected confirmed cases
6.5 times as many expected deaths
based on population ...

 

[Michael Scally MD]

One of, if not the best performing model for #COVID19 in the US, by @youyanggu Youyang Gu (@youyanggu) | Twitter, predicts 170,000 deaths (98-293 range) by August.

Current Projection for US (Updated Daily - Last Updated: May 1): Current Total: 62,993 deaths | Projected Total: 170,041 deaths by Aug 4, 2020 (Range: 98-293k). Currently Infected: 0.6% | Total Infected: 2.8%. COVID-19 Projections Using Machine Learning

 

[Michael Scally MD]

FDA Emergency Use Authorization (EUA) for Emergency Use of Remdesivir

Based on review of the topline data from the randomized, double-blinded, placebo-controlled trial conducted by NIAID (NCT04280705) and from the Gilead-sponsored open-label trial that evaluated different durations of remdesivir (NCT04292899), it is reasonable to believe that the known and potential benefits of RDV outweigh the known and potential risks of the drug for the treatment of patients hospitalized with severe COVID-19.

Having concluded that the criteria for issuance of this authorization under 564(c) of the Act are met, I am authorizing the emergency use of remdesivir for treatment of COVID-19 …

https://www.fda.gov/media/137564/download

 

[Old]

[OA] Testosterone, A Key Hormone in The Context of COVID-19 Pandemic

Daily data show that entire population with SARS-CoV2 is 58% made of males [1–3]. The difference in the number of cases reported by gender increases progressively in favor of male subjects up to the age group ≥60–69 (66.6%) and ≥70–79 (66.1%), with the exception of the 20– 29 years and 30–39 years group in which the number of female subjects it is slightly higher. Furthermore, higher lethality is in favor of male subjects in all age groups. Deaths among 30–39ys are 82.4% males; among 40-49ys are 73.1% males; among 50-59ys are 78.5% males; among 60- 69ys are 79.7% males; among 70-79ys are 79.6% males; among 80- 89ys are 66.9% males [4].

The initial clinical manifestation of COVID-19 is pneumonia, although gastrointestinal symptoms and asymptomatic infections are described, the latter has not yet been definitely assessed [5]. The infection can progress to severe disease with dyspnoea and chest symptoms corresponding to pneumonia in the second or third week of a symptomatic infection. Clinical data show decreased oxygen saturation, changes visible through chest X-rays and other imaging techniques. Furthermore, lymphopenia appears to be common, and an increase of inflammatory markers (C-reactive protein and pro-inflammatory cytokines) has been reported [6].

1. Is low testosterone a promoter of COVID-19 infection? …

2. Is high testosterone a promoter of COVID-19 infection? …

The elucidation of the role of testosterone in the battle towards COVID-19 infection turns out to be an urgent need.

Pozzilli P, Lenzi A. Testosterone, a key hormone in the context of COVID-19 pandemic [published online ahead of print, 2020 Apr 27]. Metabolism. 2020;154252. doi:10.1016/j.metabol.2020.154252 https://www.metabolismjournal.com/article/S0026-0495(20)30116-5/pdf

Nice article illustrating the pros and cons for both arguments.

It would be useful to document the severity of Covid-19 in those who regularly use AAS. As well as those on androgen suppression therapy.

While very-high T would technically be another category as would very-low T, the extreme contrasts might assist in better understanding the role of T and cases and death by this pathogen. Both extremes are generally considered inflammatory but with different density of ARs.

Another point mentioned was the number of CAG repeats. So when separating socioeconomic conditions, do men of African decent (shortest CAG repeats) die more than those of Asia decent (longest CAG repeats)? This article was from Italy, so presumably this age/gender data was mainly caucasians (who are in between with ~21 CAG repeats). In short, is there a race component to Covid-19?

Also, why are cases higher for women in the 20-39 year range when male T is at its highest?
And deaths for males progressively improves with age from 30-79 as T production gradually decreases?

As the author said, elucidation of the role of testosterone is needed.

 

[Michael Scally MD]

Remdesivir, an antiviral drug designed to treat both hepatitis and a common respiratory virus, seemed fated to join thousands of other failed medications after proving useless against those diseases. The drug was consigned to the pharmaceutical scrap heap, all but forgotten by the scientists who once championed it.

But on Friday, the Food and Drug Administration issued an emergency approval for remdesivir as a treatment for patients severely ill with Covid-19, the disease caused by the coronavirus.

The story of remdesivir’s rescue and transformation testifies to the powerful role played by federal funding, which allowed scientists laboring in obscurity to pursue basic research without obvious financial benefits. This research depends almost entirely on government grants.

…

The F.D.A. rushed to approve remdesivir under emergency use provisions, after a federal trial demonstrated modest improvements in severely ill patients.

The trial, sponsored by the National Institute of Allergy and Infectious Diseases, included more than 1,000 hospitalized patients and found that those receiving remdesivir recovered faster than those who got a placebo: in 11 days, versus 15 days.

But the drug did not significantly reduce fatality rates, and some critics noted that the trial’s primary endpoint — its measure of success — had been greatly simplified to emphasize time to recovery.

A half-dozen experts contacted by The Times on Thursday said the change was necessary. Officials at N.I.A.I.D. said biostaticians urging the revision had not seen the data and were not aiming for a particular result.

 

[Michael Scally MD]

I am truly sorry to say, Remdesivir is probably worthless, and we are seeing some fascinating drug company shenanigans, a thread. Thread by @MarkHoofnagle: I am truly sorry to say, Remdesivir is probably worthless, and we are seeing some fascinating drug company shenanigans, a thread. First, the…

First, the pretest probability that an infused, small-molecule inhibitor of a virus would improve mortality in symptomatic patients was already pretty low. Unfortunately, antivirals work poorly in acute disease. This has to do with their mechanism@of action, and host response.

Antivirals usually target some aspect of viral replication/assembly/transmission. Remdesivir is a clever pharmacologic prodrug that inhibits a key piece of RNA viruses that mammals don’t have - the RNA-dependent RNA polymerase, and inhibits viral replication.

Unfortunately, by the time you are symptomatic with a virus, you are usually already high/peak viral load. So, when you give an antiviral to someone who is already ill, the damage from the virus is largely done. It’s there in big numbers and in the cells.

Consistent with this, the Lancet paper on the remdesivir trial in China shows no impact on viral load clinically.



Pick your metaphor. The cat is out of the bag. The damage is done. At this point the host response to virus is activated, and your body is suppressing replication through a variety of mechanisms (which also make you feel terrible).

So how could inhibiting RDRP after the fact help? The answer is, it probably doesnt. It certainly didn’t in this trial - no difference, not even a trend in mortality, but in subgroup analysis maybe shortened disease duration in early/mild disease. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltext

Now, critics of stupid drugs that should never have been stockpiled by govts say, “sounds like Tamiflu!” Yes. This is the same as Tamiflu, which also maybe shortens flu by a day, but otherwise is a largely useless antiviral (and actually harmful with bad side effect profile).

Fortunately, side effects of remdesivir did not seem severe in this trial with only about 3x as many patients stopping than placebo, some rashes, nothing life threatening.

Where do the Shenanigans come in? Well, remember how maybe this Chinese trial showed a shortened course in a subset of patients? Like tamiflu? But didn’t change mortality?

Well a month ago the NIAID trial changed their endpoints to remove death and instead look at dz duration.

No really. They changed the destination half way through the race to match the only positive outcome of another trial, that they (or Gilead at least) certainly had a copy of the paper once it was submitted to Lancet.

Shenanigans! Get a broom!

Since NIH remdesivir trial is in the news...

was there an explanation about why the primary outcome (now positive) was changed last month to 'time until clinical recovery?'




This is like declaring a race and then when you realize you’re not going to win, declaring the destination was actually wherever you are standing at the moment.

Then, even more fishy, *the same day* as this Lancet trial is release, Gilead and NIAID claim a “positive trial” and they’ve “shortened the course of the disease significantly”. Notably, the mortality benefit did not reach significance.

By the end of the day, reports that FDA is going to emergently approve remdesivir for treatment of COVID.

Gilead gets what they want. No one will want to be in a control arm in further trials and they will argue all future trials must be noninferiority.

Before we have the answer whether this drug actually changes anyone’s destiny, it’s going to become the gold standard therapy. We will likely now never know if (the unlikely possibility) it changes mortality.

Absolute genius. You have to salute them. On the day a negative trial of their drug is reported, based on a press release they took over the news cycle, and with some midstream edits to their endpoints their now “positive” trial wins them FDA approval and a halted trial.

It’s an infusion, once symptomatic, you need an admission, a test, etc., really even symptoms are probably too late a goal for such a therapy to work. Prophylaxis (like Gilead’s Truvada/PreP would be better - but unworkable in its current form.

Either way, a big win for Gilead, but I’m unimpressed with any if the evidence presented so far that this is a game changer.

 

[master.on]

Remdesivir, an antiviral drug designed to treat both hepatitis and a common respiratory virus, seemed fated to join thousands of other failed medications after proving useless against those diseases. The drug was consigned to the pharmaceutical scrap heap, all but forgotten by the scientists who once championed it.

But on Friday, the Food and Drug Administration issued an emergency approval for remdesivir as a treatment for patients severely ill with Covid-19, the disease caused by the coronavirus.

The story of remdesivir’s rescue and transformation testifies to the powerful role played by federal funding, which allowed scientists laboring in obscurity to pursue basic research without obvious financial benefits. This research depends almost entirely on government grants.

…

The F.D.A. rushed to approve remdesivir under emergency use provisions, after a federal trial demonstrated modest improvements in severely ill patients.

The trial, sponsored by the National Institute of Allergy and Infectious Diseases, included more than 1,000 hospitalized patients and found that those receiving remdesivir recovered faster than those who got a placebo: in 11 days, versus 15 days.

But the drug did not significantly reduce fatality rates, and some critics noted that the trial’s primary endpoint — its measure of success — had been greatly simplified to emphasize time to recovery.

A half-dozen experts contacted by The Times on Thursday said the change was necessary. Officials at N.I.A.I.D. said biostaticians urging the revision had not seen the data and were not aiming for a particular result.

I am truly sorry to say, Remdesivir is probably worthless, and we are seeing some fascinating drug company shenanigans, a thread. Thread by @MarkHoofnagle: I am truly sorry to say, Remdesivir is probably worthless, and we are seeing some fascinating drug company shenanigans, a thread. First, the…

First, the pretest probability that an infused, small-molecule inhibitor of a virus would improve mortality in symptomatic patients was already pretty low. Unfortunately, antivirals work poorly in acute disease. This has to do with their mechanism@of action, and host response.

Antivirals usually target some aspect of viral replication/assembly/transmission. Remdesivir is a clever pharmacologic prodrug that inhibits a key piece of RNA viruses that mammals don’t have - the RNA-dependent RNA polymerase, and inhibits viral replication.

Unfortunately, by the time you are symptomatic with a virus, you are usually already high/peak viral load. So, when you give an antiviral to someone who is already ill, the damage from the virus is largely done. It’s there in big numbers and in the cells.

Consistent with this, the Lancet paper on the remdesivir trial in China shows no impact on viral load clinically.

View attachment 129528

Pick your metaphor. The cat is out of the bag. The damage is done. At this point the host response to virus is activated, and your body is suppressing replication through a variety of mechanisms (which also make you feel terrible).

So how could inhibiting RDRP after the fact help? The answer is, it probably doesnt. It certainly didn’t in this trial - no difference, not even a trend in mortality, but in subgroup analysis maybe shortened disease duration in early/mild disease. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltext

Now, critics of stupid drugs that should never have been stockpiled by govts say, “sounds like Tamiflu!” Yes. This is the same as Tamiflu, which also maybe shortens flu by a day, but otherwise is a largely useless antiviral (and actually harmful with bad side effect profile).

Fortunately, side effects of remdesivir did not seem severe in this trial with only about 3x as many patients stopping than placebo, some rashes, nothing life threatening.

Where do the Shenanigans come in? Well, remember how maybe this Chinese trial showed a shortened course in a subset of patients? Like tamiflu? But didn’t change mortality?

Well a month ago the NIAID trial changed their endpoints to remove death and instead look at dz duration.

No really. They changed the destination half way through the race to match the only positive outcome of another trial, that they (or Gilead at least) certainly had a copy of the paper once it was submitted to Lancet.

Shenanigans! Get a broom!

Since NIH remdesivir trial is in the news...

was there an explanation about why the primary outcome (now positive) was changed last month to 'time until clinical recovery?'

View attachment 129529


This is like declaring a race and then when you realize you’re not going to win, declaring the destination was actually wherever you are standing at the moment.

Then, even more fishy, *the same day* as this Lancet trial is release, Gilead and NIAID claim a “positive trial” and they’ve “shortened the course of the disease significantly”. Notably, the mortality benefit did not reach significance.

By the end of the day, reports that FDA is going to emergently approve remdesivir for treatment of COVID.

Gilead gets what they want. No one will want to be in a control arm in further trials and they will argue all future trials must be noninferiority.

Before we have the answer whether this drug actually changes anyone’s destiny, it’s going to become the gold standard therapy. We will likely now never know if (the unlikely possibility) it changes mortality.

Absolute genius. You have to salute them. On the day a negative trial of their drug is reported, based on a press release they took over the news cycle, and with some midstream edits to their endpoints their now “positive” trial wins them FDA approval and a halted trial.

It’s an infusion, once symptomatic, you need an admission, a test, etc., really even symptoms are probably too late a goal for such a therapy to work. Prophylaxis (like Gilead’s Truvada/PreP would be better - but unworkable in its current form.

Either way, a big win for Gilead, but I’m unimpressed with any if the evidence presented so far that this is a game changer.

It looks like remdesivir is worthless

...and most of the FDA committee who approved it, is in Gilead's pocket.

 

[Michael Scally MD]

Relaxed regulations, misinformation, and a big potential payout are reminiscent of the conditions that cultivated Theranos.

In November 2015, the U.S. House of Representatives held a hearing about draft guidance from the U.S. Food and Drug Administration (FDA) about closing a regulatory loophole exploited by Theranos. However, the draft guidance was never put into law, with one congressman objecting, “Why in the world would a lab develop a test that wasn’t safe and accurate?” The short answer: because its founder wanted to become the world’s youngest self-made female billionaire.

We’ve seen the U.S. Centers for Disease Control and Prevention (CDC) flounder as it scrambled to develop a test for SARS-CoV-2, heard President Trump blame Obama-era regulations for the lack of tests, and are now hearing about serology tests that can determine if we can go back to work.

Because of my role in exposing the Theranos scandal and starting a diagnostic company of my own, I have been asked countless times: “What is going on with coronavirus testing?” While there is certainly value in moving as fast as possible during this crisis, I am worried that we are creating an environment that facilitates many of the same mistakes Theranos made.

Theranos spent 15 years and nearly a billion dollars of venture capital and only got FDA clearance for one test — oral herpes, which is more commonly diagnosed by simple visual inspection than with a blood test. How can so many years and dollars result in such astonishing failure? Sure, bad scientific methods, poor engineering, terrible management, uninformed investors, a negligent board, and fraud played a part. But from my perspective, our worst and most pervasive sin was a simple one: cutting corners. We “launched” a product that claimed to perform hundreds of tests from a single drop of blood when in reality we could only do one. We needed to launch more tests, we needed to test more patients, and we needed to do so quickly. If there was a corner that could be cut, it was gone.

The deadline to get SARS-CoV-2 tests working and distributed was not artificial — Covid-19 was coming, whether we were prepared for it or not. And just like at Theranos, sweet talking, half-truths, and unfounded optimism were not going to help. The CDC rushed to develop and distribute a test, and the first tests were sent out on February 5, just weeks after development began. However, many labs found that the negative controls from the test kits produced positive results. This was a clear sign that the tests were not working. By the end of February, the CDC said it had only tested 1,235 people for SARS-CoV-2. For reference, South Korea had tested over 100,000 people by that time. On February 29, the FDA released a policy to guide the private sector in the development of tests for SARS-CoV-2.

The policy itself includes validation requirements that must be met in order to market a test using the FDA’s Emergency Use Authorization for SARS-CoV-2. To me, the validation requirements are remarkably relaxed. Under the section “Clinical Evaluation,” the “FDA recommends that laboratories confirm performance of their assay… by testing a minimum of 30 contrived reactive specimens.” Rather than test samples from patients who actually have Covid-19, labs can take 30 healthy samples, add SARS-CoV-2, and test those. This allows labs to start testing patients without ever validating that their test works in real-world circumstances.

…