Fear and Loathing, a Rat Flu Odyssey

[The SnowShow]

I think everybody reacts different/ strains are different so besides the fact Trump isnt really out of the woods yet maybe the strain he got wasn't the same as what the next person will get and obviously Trump didnt react like the 200,000+ dead Americans

Yea and he also may have received a low viral load too.

[tetzen]

My wife just told me there are currently about 50,000 doses of Regeneron available. That's enough to cover one day of new cases in the U.S....

Trying to find remdesivir at the moment for the FIL and it's nearly fucking impossible to locate (particularly with them being out of country). Not even bothering with a regeneron search. The sister is getting hospitalized as well now, so things are worsening. The hope is this is the worst of it and the situation starts reversing.

[old goat]

At this point, I think It's obvious he hasn't tested negative. And we should assume he hasn't, until they tell us he has. And even then, we will be skeptical, because it's Trump.

Someone who was exposed to him in the time before he announced he was positive should sue for the information and get an emergency injunction to give up the information. And if anyone contacted the virus from him when he should have been isolating they should sue as well. While HIPPA protects details of Trump's case, information about possible contacts when someone was contagious is not protected for communicable diseases.

Well, it's very hard to get the white balance correct when he has more orange spray tan than usual going to hide his pale face. Anyone out there want to try to color correct that?

Dude looks wrecked and I'd guess his normal makeup artist walked off the job.

I don't think that's spray on--his cheeks look solid, like there's a half inch rigid coating. I think his makeup was done by a mortician.

[total_immortal]

Someone who was exposed to him in the time before he announced he was positive should sue for the information and get an emergency injunction to give up the information.

Ummm...based on previous lawsuits against him, I don't think you'll get much info even if the court rules in your favor.

[KQ]

Trying to find remdesivir at the moment for the FIL and it's nearly fucking impossible to locate (particularly with them being out of country). Not even bothering with a regeneron search. The sister is getting hospitalized as well now, so things are worsening. The hope is this is the worst of it and the situation starts reversing.

I'm so sorry. Hoping for the best for your family.

[old goat]

Ummm...based on previous lawsuits against him, I don't think you'll get much info even if the court rules in your favor.

A court could order his doctor to release the information. I don't think a career military doctor would defy a court order. And given the time sensitive nature of the problem I don't think the courts would dick around with the issue for weeks or months or years.

[LegoSkier]

My wife just told me there are currently about 50,000 doses of Regeneron available. That's enough to cover one day of new cases in the U.S....

Ooh. Time for a bioprocess engineering nerd out (specialty of my Master’s degree)…

I've been in a few FB discussions with people knowledgeable including a former Prof who basically invented the modern way to produce monoclonal antibodies at scale, and this is going to be a tough one. Classically, monoclonals are produced in very limited quantities for things like cancer treatment. Sure lots of people get cancer every year, but even that is obviously not nearly at the scale of an infectious disease like covid. There are only a few manufacturing lines in the world that can pump these things out at a large scale and those are usually going full tilt producing the existing monoclonal products. This is not like a car line where you just add a shift to make more stuff.

Once you have an antibody (or in this case two), you have to first get to lab-scale for initial development of how you actually produce the stuff. So what you are trying to do is identify what particular cell line will be used to produce the antibody. Usually this is a line of Chinese Hamster Ovary (CHO) cells. Some therapeutic proteins can be produced in bacterial or even yeast cells but antibodies generally require a level of folding (Glycosylation) that those cells can’t handle so you have to use the more finicky mammalian cells.

So let’s say you have figured out the cell lines you are going to use to produce the thing (completed previous step), now you have to scale-up to a pilot plant scale to supply clinical trials. This is getting the production up to around 500L batch size. The important thing here is product titer. Meaning how many grams of antibody you can produce per liter of cell culture. Good manufacturing lines can do about 3g/L. So think about that…Trump got a one time dose of 8g of the cocktail. That means there had to be 8g/3g/L = 2.66 L of cell culture to produce his single dose. Or a 500L pilot will produce 500 * 3 / 8 = 187 doses per batch. OK for a small trial but not much more.

Each batch run takes a couple of weeks as fed-batch cell culture works by continuously feeding the cells to fatten them up while they produce a lot of protein. But that’s only the first step. Then you have to:
- Break them apart to release your target protein.
- Run them through one or more initial filtration stages to get out all the big chunks.
- Run them through a chromatography column to actually pull out the protein. Chromatography medium is super expensive. Like I observed a 1 meter diameter production column being packed with new gel once and that was over a million dollars in gel.
- Then there are more filtration and ultrafiltration steps to get out as many other fine bits as you can.
- Then you lyophilize (freeze dry) it in bulk.
- Then you usually ship it to a fill-finish site (usually somewhere else than the culture plant) to get it put into purified saline (or whatever delivery medium) and packaged in dose sized units.

All this takes probably at least a couple of weeks or more. Usually on a full production line, you have several bioreactors going so you can have multiple batches going at different growth stages. A plant might have four 12,000 L reactors so in this case each 12k batch would produce 12000 L * 3 / 8 = 4500 8g doses per batch. Not bad but this is still not something that produces a widely available drug. It’s definitely not like producing Tylenol. Oh yea, did I mention that CHO cells are susceptible to viruses (especially mouse viruses), so if you step on mouse crap on your way into work you can kill off a whole batch and bring down a plant for cleaning? That’s why these plants are big buildings that are entirely BSL2 environments where you have to go full bunnysuit to step into one.

For a set of pics of what these things look like (including the one I interned at in Oceanside, CA) look at https://www.gene.com/stories/the-bea...-manufacturing

Note that Regeneron doesn’t have shit for manufacturing capacity so they signed a deal with Roche (which owns Genentech) to scale up this cocktail. So the pics in that link are probably the exact equipment that will be producing this at scale.

[total_immortal]

A court could order his doctor to release the information. I don't think a career military doctor would defy a court order. And given the time sensitive nature of the problem I don't think the courts would dick around with the issue for weeks or months or years.

I was just noting that this administration has not complied with a single court order or subpoena and I don't think this would be the one to break that trend. They'll just appeal it until either it reaches the supreme court or public interest disappears.

[adrenalated]

Thanks for that explanation Lego!

[Toadman]

Stadiums? So college and pro stadiums can be full?! Holleee fuck.

I'M GOING TO DISNEY WORLD!!!!

[SorryBro]

Lego, thanks for that. Actual knowledge from scientists is always in short supply. Really appreciate you taking the time to type that out.


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[Laps]

“The important thing here is product titer.”

Huh huh, he said “titer”.

But seriously, great info. Thanks.


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[old goat]

One issue with drug companies ramping up to make a lot of antibody is the Prestige Ameritech affair--where the govt signed a contract for a lot of N95's for the H1N1 pandemic, the company massively expanded capacity, the pandemic ended, the govt stopped buying masks, the company laid off most of its workforce and nearly went bankrupt. Any company thinking of investing heavily in making monoclonal antibodies or anything else for the pandemic has to look at that and question the wisdom of the investment.

We still haven't managed to ramp up N95 production in this country--nurses are still using a mask for a week. How do we expect to create the capacity to make huge quantities of monoclonal antibody? And we certainly can't depend on another country to do it for us.

[gravitylover]

Right on Lego! Thanks for that.

[tetzen]

That was a good explanation Lego. I've read up on some of the production work for the H1N1 vaccine and I have a lot of respect for what goes into creating that manufacturing capability. People were bitching about big-Pharma pre-pandemic and even still now. I think they are right to in certain instances. However, the intricacy with which these manufacturing processes have to be planned is pretty mind boggling. If even one portion of the process gets exposed to contamination, you can write off an entire line of production, not to mention if they discover an adverse event down the line during consumption as well.

It certainly justifies the prices in some of these cutting edge medicines until the economies of scale catch up.

[Adolf Allerbush]

Trying to find remdesivir at the moment for the FIL and it's nearly fucking impossible to locate (particularly with them being out of country). Not even bothering with a regeneron search. The sister is getting hospitalized as well now, so things are worsening. The hope is this is the worst of it and the situation starts reversing.

Man, that's rough. Hoping things get better.

[bigdude2468]

Northwestern University on Thursday released the findings of a study that found using a more accurate antibody test that 20% of Chicagoan's have developed antibodies. They say the standard blood test misses 25% of the instances. Researchers expected it to be significantly higher than previous estimates but not 20%. Per N'Western this matches with some estimates that the number of covid cases is 10 times higher than the confirmed cases.

[jono]

Do you have a link to anything on that study, by chance? Quick search brought me to this description of a great way to bias the results to the high side through selection:

Nearly 1 in 5 Chicago residents who sent blood-spot samples to Northwestern University researchers tested positive for antibodies to the coronavirus that causes COVID-19, according to preliminary results of an ongoing study.

But I didn't run across any links to actual study data. Thanks!

[schuss]

Yeah, if it's volunteered samples I'd worry a lot about audience bias

[bigdude2468]

Yeah, if it's volunteered samples I'd worry a lot about audience bias

Not specifically volunteers. N’Western sent the test packs to people in specific zip codes that were adjoining and had either high and low confirmed cases. Test only requires a finger prick. They believe the regular veinous test results in too few people getting the test. I have no other info.

[jono]

Hopefully they publish soon. Devil's in the details trying to know whether the headline should be "20% of Chicago tests positive" or "80% of people in Chicago who think they had it test negative." Probably neither.

[Name Redacted]

Dealing with a possible exposure right now. 11 days out now and I'm still asymptomatic. Just got tested yesterday. The whole timeline and testing thing was pretty eye opening to me. Such a mind fuck to wait two days for a test then another 2-3 for results.

I now truly believe that we are all destined to eventually get the damn virus and hope for the best. Stave it off as long as your can, maybe new treatments will give you a better chance if things go south.

[wooley12]

Pulled the trigger on a new mask for fall/winter.

Translation - "THE WORST IS YET TO COME"

[Casey E]

Colateral damage up north, poor RV’ers huddling in “warm” B.C.


Canadian snowbirds flock west as winter looms, but space is at a premium

http://[/https://globalnews.ca/news/...d-coronavirus/

[KQ]

just another potential wrinkle:

Mom loses hearing in one ear after mild Covid-19 infection