Covid vaccine development

[roger wiegand]

Derek Lowe writes an incredibly good, readable, and very reliable blog on topics across medicinal chemistry and drug development. (lots of picky fact checkers read it and he is very responsive about making corrections as required) Here is his most recent summary of corona virus vaccine development, with links to the underlying data, if you're interested in a pretty comprehensive picture of what's happening. Bottom line-- a ton of activity and a myriad of approaches; preliminary data from early safety studies and antibody/T cell responses look promising for several candidates. We should see the beginnings of efficacy data soon; it will take longer to get the candidates into enough patients to assess safety in a broad population.

https://blogs.sciencemag.org/pipeline/archives/2020/09/03/coronavirus-vaccine-roundup-early-september

[Michael Weber]

Thanks. Mostly over my head but it’s comforting to know there are internet sources with actual reliable information about this subject. Interesting comment about the Russian vaccine. And I found a link to some edgy cartoons.

[Mike Henderson]

Wow, good stuff. Thanks for posting that. There's a lot there that I didn't know.

Mike

[Ed Aumiller]

Roger, thanks...

[roger wiegand]

Derek had a post earlier in the week on the subject of cold chain distribution that makes sobering reading. I faced that problem big time in getting heat-sensitive materials in and out of Sub-Saharan Africa, but at least a couple of the current leading candidates require storage at -80C (-112 F), something that may not be feasible even in the US, at least in part to an ongoing shortage of dry ice. Most physicians offices are clearly not prepared to provide appropriate storage. There is potential to waste a huge amount of material due to spoilage.

The logistics of storage and distribution are all problematic, availability of glass vials for packaging is a big concern now, for example. These problems are all solvable given competent management, time, and money, at least in resource-rich countries; but they are part of my sticking to thinking it will easily be the middle of next year before widespread vaccine coverage is accomplished in the US, developed countries in Asia, and Europe. I'd love to be surprised. Sadly I suspect the folks in Africa and south Asia are going to get the short end of the stick yet again; their needs won't be prioritized

[Stan Calow]

This is an interesting podcast to a Planet Money story on what it has taken just to maintain capacity to produce enough influenza vaccine for a potential outbreak in the US: https://www.npr.org/2020/03/06/812943907/episode-977-wheres-the-vaccine Essentially, the government has contracts in place for enough chickens (in classified locations) to produce 900,000 eggs, per day, for several months at a time. The government buys the eggs whether they're used or not. Otherwise the free market does not support maintaining the capacity to react on short notice to a influenza pandemic. Imagine the logistics and supply issues they will have to iron out for a COVID vaccine on top of that. So when the scientists say "we will have a vaccine by XXXX", that only means they will have identified an effective one, not that they have full production capability. Its economics as much as science.

[Mike Soaper]

As a reference to the needed storage temp of -112F, the surface temp of dry ice is about -109F

Thanks for the info and work Roger

[Mike Soaper]

Not particarly vaccine related, but some might find it interesting

AHNA COVID-19 Update Tuesday, August 25, 2020
American Holistic Nurses Association (AHNA)

https://www.ahna.org/Portals/66/Docs/Resources/COVID-19/COVID-19%20Update%20August%2025%202020.pdf?ver=2020-08-27-142028-810

[Jim Matthews]

Covid-19 is a new (novel) virus with no precursors in the human population.

It is pernicious because it is contagious, even in asymptomatic carriers. The coronavirus that caused Sars-1 was transmissable only by those obviously sick.


https://nationalinterest.org/blog/reboot/no-coronavirus-wont-just-go-away-sars-did-161346

[roger wiegand]

Vaccine development is a lot like drug development, but with a somewhat higher success rate, at least for traditional approaches. 90% of the work and investment happens after you have a candidate molecule that appears to work in model systems, and most of those candidates fail in the clinic.

[Ken Fitzgerald]

Thanks for the article Roger! It was an informative and interesting read.

[Andrew Joiner]

Thanks for that link Roger. Derek's wrapup is encouraging :
===============
Wrapup
Dang, that’s a lot of vaccine candidates. And as you can see, it’s a long-tail distribution – there are some big ones that everyone knows about, but a lot of people are bringing a lot of technologies to bear on the problem. This makes me think that we’re going to have a multichapter story, in the end. There will be the first vaccines approved, then the second wave, then the improvements on those, until we have (with luck, hard work, skill, and lots of money) tossed this virus out of the human population and back to the bats, pangolins, or whoever had it in the first place.
An excellent side effect is that vaccine technology will never be the same after this – it’s going to be like aircraft design before and after World War II, and for many of the same reasons. This whole pandemic has been awful, in many different ways, but we’re going to come out of it stronger and more capable than when we went in.

[Tyler Bancroft]

Derek Lowe's a treasure. I've been reading his blog for years. If you need a bit of light reading, try his "Things I Won't Work With" series. (https://blogs.sciencemag.org/pipeline/archives/2010/02/23/things_i_wont_work_with_dioxygen_difluoride)

[roger wiegand]

I love it every time there's a "things I won't work with" post! It's good to have at least passing familiarity with chemistry (and chemists!) to fully appreciate them. (NB, I am a biologist; my job was to kill all the beautiful compounds the chemists produced by discovering nasty truths about their (lack of) activity, toxicity, or bioavaliability.:))

I suppose there could be a related woodworking thread. Particle board might not be so exciting as a topic though.

[Curt Harms]

I love it every time there's a "things I won't work with" post! It's good to have at least passing familiarity with chemistry (and chemists!) to fully appreciate them. (NB, I am a biologist; my job was to kill all the beautiful compounds the chemists produced by discovering nasty truths about their (lack of) activity, toxicity, or bioavaliability.:))

I suppose there could be a related woodworking thread. Particle board might not be so exciting as a topic though.

So you were a killjoy then:D. Thanks for your input here, it's nice to hear from someone who knows what they're talking about.

[Robert Engel]

Covid-19 is a new (novel) virus with no precursors in the human population.

It is pernicious because it is contagious, even in asymptomatic carriers. The coronavirus that caused Sars-1 was transmissable only by those obviously sick.


https://nationalinterest.org/blog/reboot/no-coronavirus-wont-just-go-away-sars-did-161346

Granted COVID is serious but coronaviruses are the category of common cold viruses. COVID is novel in the sense of an immunologically naive pollution, not that it is a new class of virus.

Contrary to what much of the public has been led to believe, its been known from very early on that children are not significant sources of infection. There is now evidence the same is true of asymptomatic adults, which prompted the CDC to recommend that asymptomatic people need not be tested.

The CDC estimates only 6% of COVID deaths were actually due to COVID alone. This astounding revelation puts an entirely different face on this pandemic, does it not? perhaps the US does not account for 20% of all deaths worldwide. It was hard to believe anyway.

But even with this revelation, even what we know about testing, who is susceptible, even in the face of an obviously flattened curve, some areas are still locked down and mask mandates are still in force. We hear a candidate vow to “follow the science” and impose a 3 month national mask mandate, even though the pandemic is obviously waning?

COVID has followed a predictable biological course, it’s one remarkable feature was being contagiousness, NOT it’s lethality! And the wonderfully awesome human immune system is functioning as it’s been programmed to for millennia. It wasn’t masks or draconian lockdowns That did it.

[Mike Henderson]

The CDC estimates only 6% of COVID deaths were actually due to COVID alone.

I suppose that what you mean is that 6% of the people who died while infected with COVID had no underlying conditions that contributed to their death, such as heart disease, diabetes, etc.

It's still COVID that precipitated the death of the other 94%. Most would not have died at that time without the COVID infection.

Mike

[Stan Calow]

The usual way of tracking any illness, is to attribute premature death to the proximate cause. Even if you were obese with diabetes and a heart condition, if COVID makes you die sooner than you would have, thats a negative consequence of the infection. Death rate is not the only measure of concern. Large numbers of sick people, using up resources, and unable to function, are also significant negative impacts.

[Jim Becker]

I suppose that what you mean is that 6% of the people who died while infected with COVID had no underlying conditions that contributed to their death, such as heart disease, diabetes, etc.

It's still COVID that precipitated the death of the other 94%. Most would not have died at that time without the COVID infection.

Mike

THis is true and CDC and other Epidemiologists have clarified this emphatically since the 6% number was being misrepresented in various ways. COVID19 was still the primary cause of death to those with underlying conditions who contracted the disease that made them more succeptiable to the same. CDC has also clarified the testing thing...

[Nicholas Lawrence]

I suppose that what you mean is that 6% of the people who died while infected with COVID had no underlying conditions that contributed to their death, such as heart disease, diabetes, etc.

It's still COVID that precipitated the death of the other 94%. Most would not have died at that time without the COVID infection.

Mike

I have concerns with the data. Hospitals can access COVID funds if the person is reported as having COVID, so there is a potential financial incentive to code things as being related to COVID whether they actually are or not. There are also some reports of things that are statistically unlikely (reports of some providers who have never reported a negative test result to CDC for example).

There have also been some prominent incidents of large scale false positives.

The yardstick that makes the most sense to me is the "excess death" numbers that have been discussed in various studies. They compare the monthly or annual deaths to the monthly or annual averages over the last five years. It is hard to think of a way those numbers could be manipulated, assuming someone wanted to do that.

I have not looked lately, but earlier in the pandemic those numbers suggested the virus was killing people far earlier than we knew at the time, and that the total number of deaths caused by the virus was actually higher than the reported case numbers. I would not be surprised if that were still the case.

[Tyler Bancroft]

I love it every time there's a "things I won't work with" post! It's good to have at least passing familiarity with chemistry (and chemists!) to fully appreciate them. (NB, I am a biologist; my job was to kill all the beautiful compounds the chemists produced by discovering nasty truths about their (lack of) activity, toxicity, or bioavaliability.:))

Neuroscientist here. His "things I won't work with" posts make me grateful I didn't become a bench scientist...

[roger wiegand]

Stuff that explodes if you even think about it is pretty exciting though...

[Tyler Bancroft]

Stuff that explodes if you even think about it is pretty exciting though...


Are you sure you aren't an engineer? ;)

[Robert Engel]

Jim, if you'll do some checking the CDC guidelines to doctors on reporting a COVID death are quite nebulous, even to the point if the attending physician thinks its COVID, even without a + test, there is a place to indicate that on the CDC report form.

This, combined with the PCR test is blowing up the numbers.

When COVID is a contributing cause of death, that is not the same as the cause of death. For example, a person with COPD who contracts the flu, is reported as death due to COPD complicated by influenza not as an influenza death.

But its even worse than that, in many cases ANY death in a COVID + person is reported as a COVID death, such as car accidents, cancer deaths, etc. This was brought to light by the audit done by Gov. Polis in CO where fully 25% of "COVID deaths" were removed from the data.

Regardless, it is undeniable there are huge problems with the COVID data. The CDC has lost credibility due its faulty reporting protocols, which I believe stems from its bureaucracy. I wouldn't put a lot of stock in "the CDC clarifying" anything.

I'm trying to make the point that the lethality of the virus is being overblown by the media.

This virus is not the killer virus the public believes it is. The risk for a 50 to 64 year old of hospitalization is 1 in 790,000 and of death only 1 in 6,670,000. Reference here. (the risk for a 50 to 64 year old of hospitalization is 1 in 790,000 and of death only 1 in 6,670,000.) We know who the susceptible are, we know who are at the least risk. Global mandates such as masking the public simply do not work and there is ample evidence. If masks worked, we would have everyone in an elder care facility in a mask during flu season!

I and many, many others believe colossal mistakes, with far reaching effects. Data will be forthcoming on suicides, divorce, drug abuse, child abuse, etc. and I predict they will be shocking.

I am also very confident when the COVID data is retrospectively analyzed, we will find the US represents no where near 1/5 of the world's COVID deaths.

[Jim Becker]

We will have to agree that we disagree, Robert. The epidemiologists that I have regular contact with...including my spouse...also disagree.

[Jim Matthews]

Late to the party.

I follow "Medlife crisis" on YouTube.
He takes a stringent, data driven approach to epidemiology. He was one of the first to openly caution about broad extrapolations and explain why no clear answers are available in chaotic times.

https://www.youtube.com/channel/UCgRBRE1DUP2w7HTH9j_L4OQ