COVID-19: Vaccine/antidote and testing procedures Megathread [Mod Warning - Post #1]

Hmmzis

CelticRambler, could you please link to the treatments you mentioned there? I'm perosnally not aware of any mABs currently in production, let alone in use, that would work against SARS-cov-2.

While Remdesivir showed some good indications, it has a very inconclusive effect on death rate and it requires hospitalisation.
Tocilizumab looked like it should help at later stages, in practice it's less than stellar and causes complications with secondary infections.

Interferon looks good in trials, but needs to be given early to have an effect. This requires very rapid testing available to the masses and people injecting themselves with it.

Existing antivirals have a somewhat meager effect for some reason. Favipiravir should have worked better, the Russians are using it, but their death rates are still very high. Japan is using it as well, their numbers look better though.

The best results so far have been from improvements in standard care. Less preassure on vents, not putting on vents in the first place, prone position, CPAP, higher O2 concentrations etc. All of that requires ICU capacity though and smart experienced doctors, both of which are in short supply, hence the severe restrictions on society. This has brought the ICU survival rate from 20% to almost 80%.

With all the above the IFR is still at best 8-10x worse than for any flu out there.

So it's either, or a combination of:

Effective prophylactics (none on the horizon)
Vaccines (in human trials, mixed results for some)
Actually effective treatments (apart from stadard care, not much available, lot of promises though)

To get back to normality without allowing the virus to cull a non-trivial amount of our population.

CelticRambler

hmmm wrote: »

We should select a small number of the top candidate vaccines, the same approach as other countries are taking.

There are no "top candidate" vaccines. None of those under development have been comprehensively tested, not for safety, nor for efficacy. Just because the US is throwing billions at an idea doesn't make it any more likely to succeed, and if you dig into the details of each candidate vaccine, you'll find that many of the 100-odd are based on one of a very small number of hypothesised mechanisms. If one doesn't work, none of the others in the same category will work.

It is equally likely that any successful vaccine will be developed by a small lab as one of the giants, and the licence to produce it will be bought up by one of the major pharma companies. At that point, any options to purchase previously signed will expire.

In addition, there's a sound biological reason for delivering the first vaccines to whatever country is suffering the worst outbreak at the time, and that almost certainly won't be Ireland or anywhere else in the EU. So whatever agreement was signed in the distant past would be set aside for the greater good, and Ireland would get their allocation a few months later.

When you're looking at a delivery timeframe of up to fifteen years, three months here or there won't make a jot of difference to the economy.

CelticRambler

Hmmzis wrote: »

CelticRambler, could you please link to the treatments you mentioned there? I'm perosnally not aware of any mABs currently in production, let alone in use, that would work against SARS-cov-2.

Will do, later/tonight, when I have time to dig through my references!

In the meantime, you've highlighted an important point in that the very best results (so far) have been achieved by nursing, not medication. This corresponds also to the best control of the outbreak, which is considerably better in "deprived" economies where they had/have very poor access to ICU facilities and millions of individual tests. Greece remains the shining example in Europe of how to manage an epidemic through movement restrictions; and several African nations have shown how testing should be done when you're short of reagents: en masse, not case-by-case for the sake of political gain.

hmmm

CelticRambler wrote: »

In addition, there's a sound biological reason for delivering the first vaccines to whatever country is suffering the worst outbreak at the time, and that almost certainly won't be Ireland or anywhere else in the EU. So whatever agreement was signed in the distant past would be set aside for the greater good, and Ireland would get their allocation a few months later.

No different to Swine Flu, the rich countries who pay first are going to get the vaccine first. And it's very obvious who the leading vaccine candidates are, most of the 120 in development are nowhere near entering clinical trials.

Your 15 year estimate for a vaccine is outlandish.

You seem to be intent on twisting my words, so last I'll say on this with yourself.

plodder

One interview that was posted here the other day made the point that vaccines will be manufactured (with completely independent supply chains) such that different parts of the world (the US being one unit for example) will get it at the same time.

ShineOn7

CelticRambler wrote: »

When you're looking at a delivery timeframe of up to fifteen years, three months here or there won't make a jot of difference to the economy.

Covid will be a distant memory in 5 years, let alone 15

Hector Savage

15 years for a vaccine!! ????

Well f*ck this sh*t anyway, time to just say f*ck it and open up, can you imagine society with 15 years of this crap ?

Mad Max sort of world I'd imagine...

Hmmzis

Exercise:

https://www.sciencedirect.com/science/article/pii/S0306987720309658

It's a good idea even without covid around, given all that sitting in the house and/or working from home.

stephenjmcd

Another vaccine gone into trial in Australia this time from Novavax. Not sure what they'll learn bar how safe it is seeing as the virus doesn't appear to be prevalent in the country

https://www.forbes.com/sites/alexknapp/2020/05/25/novavax-is-beginning-clinical-trials-of-its-coronavirus-vaccine/

ShineOn7

A stat that's worth repeating: Something like 80% of these things never make it out of the lab (I think it could be even closer to 90%)

I believe we'll either have very effective treatments and/or a very low R0 on it worldwide long before we see a working vaccine

In the meantime we'll get another "New vaccine!" headline at least twice a week for the next couple of months

hmmm

stephenjmcd wrote: »

Another vaccine gone into trial in Australia this time from Novavax. Not sure what they'll learn bar how safe it is seeing as the virus doesn't appear to be prevalent in the country

https://www.forbes.com/sites/alexknapp/2020/05/25/novavax-is-beginning-clinical-trials-of-its-coronavirus-vaccine/

They can do Phase 1 and 2 quite happily in their own country. Phase 3 is the difficult one that really requires active virus circulation.

Novavax got $384m from CEPI, this is another one of the leading candidates. There's apparently 10 vaccines already in human trials, after this the main realistic contenders are probably J&J and Merck. CEPI have funded 9 per this report: https://www.technologynetworks.com/biopharma/product-news/cepi-announces-a-ninth-covid-19-vaccine-development-partnership-334379

"To date, CEPI has provided initial support and funding to Curevac, Inc., Inovio Pharmaceuticals, Inc., Moderna, Inc., Novavax, Inc., The University of Hong Kong, The University of Oxford, The University of Queensland and a consortium led by Institut Pasteur to develop COVID-19 vaccine candidates."

hmmm

Some interesting news in this report:
https://www.irishtimes.com/business/health-pharma/merck-leaps-into-covid-19-development-fray-with-vaccine-drug-deals-1.4262911

"Merck, which has largely kept to the sidelines of the race for Covid-19 treatments, said it was buying Austrian vaccine maker Themis Bioscience and would collaborate with research nonprofit IAVI to develop two separate vaccines."

"Last week, Dr. Francis Collins, director of the National Institutes of Health, said Merck’s vaccine, and those from Johnson & Johnson and Sanofi, are a month or two behind Moderna’s, but may get added to large efficacy trials this summer as they wrap up early-stage studies."

"Ridgeback’s pill, EIDD-2801, is designed to block virus reproduction, and has shown promise in animal studies of multiple coronaviruses, including SARS-CoV-2. It has also been shown to be safe and well tolerated in early stage trials.

Mr Frazier compared it to Gilead Sciences’ remdesivir, but it would be a pill, rather than an intravenous infusion. Efficacy trials will start later this year.

“If the drug works, we would be able to produce billions of doses,” he added."

2u2me

Never before have RNA vaccines been used on humans. The Thai's are now experiementing on monkeys with a view for them to work on humans.

It would be a much faster and cheaper to market vaccine; will we take this up when it becomes available?

I'd imagine this will be the vaccine that will be available first.

Hmmzis

2u2me wrote: »

Never before have RNA vaccines been used on humans. The Thai's are now experiementing on monkeys with a view for them to work on humans.

It would be a much faster and cheaper to market vaccine; will we take this up when it becomes available?

I'd imagine this will be the vaccine that will be available first.

There should be (hopefully) some vaccines available sooner than next year.

That said, I'm eager to see the challenge data from their NHP trials. Would the first proper data showing if and how protective the response from an mRNA vaccine is. Moderna still haven't published anything from their trials.

Duke of Url

2u2me wrote: »

Never before have RNA vaccines been used on humans.

They are being used on humans

RNA vaccines are currently on human trials In the US

hmmm

https://www.youtube.com/watch?v=OLyAGftI3QY

Hmmzis

https://pubmed.ncbi.nlm.nih.gov/32412891/

Very small N, could do with a larger trial.

hmmm

https://blogs.sciencemag.org/pipeline/archives/2020/05/26/coronavirus-vaccine-update-may-26

Interesting summary of where we are at.

is_that_so

Another interesting study on antibody levels, specifically in mild cases.
https://www.theguardian.com/world/2020/may/27/french-team-finds-mild-coronavirus-infection-does-lead-to-antibodies

Hmmzis

One more to the pre-existing cross-reactive T cell pile:

https://www.biorxiv.org/content/10.1101/2020.05.26.115832v1

With a twist though:

NSP7-specific T cells showed recognition of protein fragments with low homology to "common cold" human coronaviruses but conserved among animal betacoranaviruses

If that's not a blatant typo, then it's a very, very interesting find. The other papers were speculating that the cross reactive T cells were form previous Common Cold infections. This is stating the opposite while citing the commonality with other animal betacoronaviruses.

They have also verified that the SARS-cov and SARS-cov-2 recovered patients very rarely had those T cells.

Half of them (9/18) possess T cells targeting the ORF-1 coded proteins NSP7 and 13, which were rarely detected in COVID-19- and SARS-recovered patients

stephenjmcd

https://www.rte.ie/news/business/2020/0528/1143101-glaxosmithklines-vaccine-work/

Hmmzis

Move over mRNA, repRNA has entered the ring.

https://www.biorxiv.org/content/10.1101/2020.05.28.121640v1.full.pdf+html

Looks like a good preclinical result. I like that they tried it on older (17m) mice as well. Both single dose and boosters were tested and checked. Really good titres from both aproaches. T cell responses got ellicited in both regiments as well. Same results un NHPs as in mice.

Not sure about their claims of production speed, but by the sounds of it looks to be a bit simpler than most other approaches.

Phase 1 clinical trials next.

hmmm

Hmmzis wrote: »

Move over mRNA, repRNA has entered the ring.

Even if this is a pretty awful situation, it's great to see the huge acceleration in medical technologies this is causing - some of these small companies are getting hundreds of millions flung at them. The US Department of Defence were already taking an interest in companies like Moderna in case we ever faced a biological attack, who could create a new vaccine in days if needs be (in theory, if the technology works - and looks like we are about to find out).

I heard an interview with Larry Summers yesterday (famous US economist for those who don't know), and he said that he estimates the US economy is losing 10 billion a day. His argument was that the governments should be funnelling billions into vaccines, testing and treatments, even though most will fail, because saving even a few days of development time would generate such an enormous return.

hmmm

I thought the Chinese were testing a monoclonal already? Anyway, in human testing now and Eli are going straight into manufacturing.

https://www.biopharma-reporter.com/Article/2020/06/02/Eli-Lilly-s-COVID-19-antibody-begins-trials

Gael23

Is this vaccine in September going to happen?

Hmmzis

Gael23 wrote: »

Is this vaccine in September going to happen?

Maybe, maybe not. Given recent events they might even be able to test it in Ireland.

Hmmzis

hmmm wrote: »

I thought the Chinese were testing a monoclonal already? Anyway, in human testing now and Eli are going straight into manufacturing.

https://www.biopharma-reporter.com/Article/2020/06/02/Eli-Lilly-s-COVID-19-antibody-begins-trials

This is good news for a change. All the best to them, hope the results bring a resounding success. We so damn need it.

hmmm

Gael23 wrote: »

Is this vaccine in September going to happen?

The discussions I've seen say that the general public are unlikely to see a vaccine before mid next year at the very earliest, and that's assuming most things go well in trials.

There may be doses available of a vaccine for high-risk people (e.g. medical staff), depending on the generosity of the producing nations, later this year - if everything goes well again.

We should hopefully have a monoclonal antibody this year which can be used to treat people in hospitals.

is_that_so

Another trial looking at repurposing something in common use - Ibuprofen

https://www.bbc.com/news/health-52894638

Mike3287

is_that_so wrote: »

Another trial looking at repurposing something in common use - Ibuprofen

https://www.bbc.com/news/health-52894638

They don't have a clue at this stage

Ibuprofen was supposed to make it worse in March and now in June it makes it better