Thread by @profshanecrotty

This is a very nice study of the AstraZeneca/Oxford (AZ) ChAdOx vaccine in the UK (with a  challenging title!).
ssrn.com/abstract=37791…

There are several novel findings in this study, including:

* 75% protection against ASYMPTOMATIC infections, (w/new definition).

* Protection against symptomatic infections was similar for B117 (the UK variant).

* Even though ChAdOx antibodies were 9x weaker against B117.

* Protection against asymptomatic B117 appears mostly lost.

On the topic of vaccine protection from asymptomatic infections:

There have been limited data on vaccine protection from asymptomatic infections, which has important implications for transmission of virus.

There is a piece of data from the Moderna vaccine trial indicating that vaccine may prevent 66-ish% of asymptomatic infections.

https://twitter.com/profshanecrotty/status/1339375764806897665?s=20

There are previously data from ChAdOx vaccine trials on this topic, but the data have been all over the place.

In this new study, they required that asymptomatic cases be defined as PCR+ samples that could be sequenced. By that metric, two doses of the ChAdOx vaccine was about 75% protective against asymptomatic infection with the 'regular' SARS2 strain. That's very good!

Their stated rationale for their definition of asymptomatic cases is the QC problem with asymptomatic PCR+ cases I have been saying for a while:

While that QC is relatively stringent, given that viral transmission likely requires relatively high viral loads (no infectious virus is isolated with high Ct PCR samples), I think this is a good QC metric for defining meaningful asymptomatic infections.

To that point, this study also assessed viral loads and infection duration in vaccinated versus unvaccinated people, and viral loads were substantially lower (higher Ct) in vaccinated people. Both for asymptomatic and symptomatic COVID cases.

Possibly 10x on average, but they don't state that. Additionally, vaccinated people had virus for much shorter periods of time-- a week less, on average. In each case, very good news!

This is the first public data for any COVID vaccine on these viral load topics, so it is quite a valuable contribution.

On the topic of vaccine protection from B117 (the "UK variant") :
The study also has valuable data on AZ COVID vaccine protection against B117 infections.

ssrn.com/abstract=37791…

ChAdOx protection against symptomatic infections was similar for B117 and the parental strain. (75% vs 84% with plenty of overlap.) However, protection against asymptomatic B117 dropped to about 25% protection, from 75%.

What to make of that? Well, the case numbers are too small to make much of a conclusion, but the other big piece of data in the paper is this:

AZ vaccine neutralizing antibodies were 9x worse against B117.

That is a surprisingly large loss. Most studies have reported between no effect and a 2x effect of neutralization of B117, both for COVID-19 cases and vaccinated people.

The authors comment that not all neutralization techniques are giving equivalent results between labs--that is definitely true--and they have used a live virus assay here.

Still, other labs have used live virus assays and seen much more mild effects. E.g. Menachery and Suthar. No effect on antibodies from COVID cases, and perhaps a 2x effect on neutralizing antibodies from Moderna vaccinated people.
medrxiv.org/content/10.110…

The data imply that the AZ ChAdOx COVID vaccine may have particularly poor antibody potency against SARS2 variants. Head-tp-head experiments are necessary for such a conclusion, and it will be important to see such experiments done.

Plausibly, T cells plus residual antibody activity against B117 with the ChAdOx vaccine may be good at preventing even mild symptomatic COVID-19. That is generally an encouraging sign for vaccines functioning against variants.

Overall, quite a scientifically rich study!