Private channel session 238

29 messages over 1h 37m, 2020-07-23 – 2020-07-23.

A “conversation” here is an activity session — a run of messages with under 60 minutes of silence inside it. The channel had no native conversation boundaries.

2020-07-23 07:35 Kristian G. Andersen open PDF p.103

Might be worth tuning in for: https://twitter.com/CellPressNews/status/1286096187754459142?s=20 @Robert Garry, we need to discuss challenge trials at some point :wink:.
2020-07-23 07:49 Robert F. Garry open PDF p.103

Wow - that Cell discussion with Gao and Shi should be fun...Not sure I can bring you over to the "dark side" and Ithink it is possible someone could die, but - yeah IMO - controlled trials better than "wild" trials given the circumstances.
2020-07-23 07:56 Kristian G. Andersen open PDF p.103

Yeah, should be interesting. George popped up on a NASEM meeting last week and it was pretty interesting to get his take. A little different than here in the US... I say we just make the whole of Florida a challenge trial :wink:
2020-07-23 08:14 Andrew Rambaut open PDF p.103

I am talking to Wellcome Vaccines dept tomorrow about challenge trials. They are considering which stocks to manufacture. I am not that sure what to tell them other than a basal D614G.
2020-07-23 08:44 Kristian G. Andersen open PDF p.103

Yeah, NIAID asked us about getting an isolate from a "mild infection"... Well, mild, severe, moderate, chances are they're all the same. I agree on getting something as basal on the tree as possible (that's assuming D614G _does not_ show resistance to neutralization - which is a real concern (e.g., GP A82V in Ebola does that).
2020-07-23 08:45 Andrew Rambaut open PDF p.104

Jeremy's preprint suggests it is sensitive to ABs
2020-07-23 08:45 Andrew Rambaut open PDF p.104

But I guess the point is it is the dominant form and will remain so.
2020-07-23 08:45 Kristian G. Andersen open PDF p.104

The UK has been playing hard and loose with viruses in the past, so I wouldn't be surprised if we'd see challenge trials from them. IMO, this virus is much too dangerous with too many uncertain long-term effects to deliberately infect people - especially given the HUGE number of cases we have in this country.
2020-07-23 08:46 Kristian G. Andersen open PDF p.104

Yeah, everything is basically D614G by now, so that's kinda the virus we need to make sure the vaccine works against - but I'm not really concerned there's a difference between Doug and Dougless here.
2020-07-23 08:47 Andrew Rambaut open PDF p.104

I agree that it is probably unnecessary - just try the vaccine.
2020-07-23 08:48 Kristian G. Andersen open PDF p.104

Let's just immunize Florida and see what happens.... :smiling_imp:
2020-07-23 08:51 Robert F. Garry open PDF p.104

I could get begind that
2020-07-23 08:51 Robert F. Garry open PDF p.104

but unfortunately it's not what they doinghttps://www.forbes.com/sites/brucejapsen/2020/06/02/fauci-modernas-phase-3-covid-19-vaccine-trial-will-include-30000-young-and-old-individuals/#316e15174f75
2020-07-23 08:52 Kristian G. Andersen open PDF p.104

I'm _super_ worried about Moderna... Just not convinced that thing is safe.
2020-07-23 08:53 Robert F. Garry open PDF p.104

Basically for Moderna they are immunizing/placeboing 30,000 people then sending them out to see how many get infected.
2020-07-23 08:53 Kristian G. Andersen open PDF p.104

They _really_ need to do that trial in high-transmission areas - i.e., not the North East!
2020-07-23 08:53 Robert F. Garry open PDF p.104

Agree - maybe not safe but even more dangerous - it may not work at all or very well - either would be a setback.
2020-07-23 08:55 Kristian G. Andersen open PDF p.105

Yeah, it's unclear to me - definitely appear to be "not safe", but as you say - it could be even worse. I'm super worried this is going to be Trump's next political trick - he would have _no_ hesitation pushing a vaccine through where we have very little or no data on population-wide safety
2020-07-23 08:58 Robert F. Garry open PDF p.105

A small controlled trial of 300 people - maybe fewer- would get you the same information - does it work? you could have an answer in less than a month then move on to the next one if it doesn't. What are they telling these 30,000people - go out to bars? try to get infected. Probably not, but if they are giving them the proper advice - mask upsocial distance etc - you should have VERY FEW infections in the 30,000. Who did the power calculation to get30K?
2020-07-23 09:00 Robert F. Garry open PDF p.105

Population-wise safety another issue - I doubt that any of the 30,000 are in at risk groups - old - respiratory illness,obesity etc.
2020-07-23 09:00 Kristian G. Andersen open PDF p.105

Yup, very true - I'm just very worried that those 300 people wouldn't fully understand what they're signing up for. Need the safety data on the vaccine in any case, which already requires a lot of people - but I guess it depends onwhether we want (a) safety, or (b) efficacy data first. If the latter, challenge trial makes sense.
2020-07-23 09:01 Robert F. Garry open PDF p.105

Yes - it's definitely Trumps next trick for sure....
2020-07-23 09:02 Kristian G. Andersen open PDF p.105

He'd push it through - _even_ if we knew it was unsafe or even dangerous. No doubt. And that's bloody terrifying.
2020-07-23 09:02 Robert F. Garry open PDF p.105

Enough safety data should be there in the Phase I and II trials - you're right that the Moderna safety data is HIGHLY suspect.
2020-07-23 09:06 Kristian G. Andersen open PDF p.105

If I were a betting man, I'd put my money on ChAdOx1 and Sinovac - I'd forget anything RNA- or DNA-based for now- it's just too early for those platforms.
2020-07-23 09:08 Robert F. Garry open PDF p.105

"fully understand what they're signing up for" - lay it out for them - they might die. We've got a 1000 dying each day just in the US. Yes - some trial participants could die - I think it's less likely with the better treatment regiments -dexy, remdesivir if they get in trouble - give them Ho or Crowe's MAbs.
2020-07-23 09:10 Robert F. Garry open PDF p.105

AGree about the RNA/DNA - There are other vectors that could work too - even VSV- the devil we know....
2020-07-23 09:11 Kristian G. Andersen open PDF p.105

True - maybe Ad26 too (I don't know enough about that one). Ad5 does not seem appealing, although I'm pretty sure China will approve it (CanSino).
2020-07-23 09:12 Robert F. Garry open PDF p.106

In my mind you definitely want the efficacy data first. If it doesn't work in young and health it won't work in the old and compromised.