When will there be enough evidence that vaccines reduce asymptomatic carriage (e.g. risk of transmission) to be able to change guidelines for vaccinated people not being a risk to unvaccinated? Also, how should vaccinated people be tested (if at all?) given PCR sensitivity issue?
As we discussed before, this Singapore study is the most compelling I've seen that asymptomatic infection less likely to transmit (4 fold) than symptomatic infection: thelancet.com/journals/lance…
And this study from Catalonia, Spain also told us that viral load of index cases is the most predictive factor of spreading the virus to others
thelancet.com/journals/lanin…
Now combine this with the fact that 2 studies on Feb 8 demonstrated that nasal viral load massively reduced after vaccination-here is 1st from Pfizer in Israel where >75% of those >60 yrs were >14 days post-first dose compared to 25% of those 40-60 yrs
medrxiv.org/content/10.110…
CT (cycle threshold) of 16,297 positive qPCR tests reported from Dec 1st to Jan 31st in these 2 age groups (lab didn't know vaccination status). Hypothesis- if vaccines reduce
viral load, difference in CT values between the two age group should be seen in late Jan but not before.
Consistent with hypothesis no difference in CT values in two age groups before Jan 15th - after that, stark difference, much higher CT values (lower viral loads) in >60 yr old age group. 2nd study from Feb 8 is here and tweeted before
medrxiv.org/content/10.110…
Following inoculation with Pfizer mRNA vaccine, viral load is reduced 4-fold for infections occurring 12-28 days after the first dose of vaccine (and that is just first dose!). So, important question becomes- if you want to test someone after vaccine, should you use
oversensitive PCR test & not incorporate CT? I would argue (along with @michaelmina_lab) that - if you must test after vaccination, use a rapid antigen test to assess infectiousness if your question is - can this person transmit (seems less & less likely)
academic.oup.com/cid/advance-ar…
And with that I am taking a day off Twitter to work. Good night all!

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More from @MonicaGandhi9

15 Feb
Simplest way I can think of to fix the vaccine supply shortage is to authorize J&J vaccine tomorrow (instead of waiting for Feb 26 FDA hearing date). Then you will say - oh no, not as effective? And I will say yes, it is for severe disease & variants!
abc7news.com/covid-19-san-f…
And you will say, show me the data on J&J vaccine again? And I will say please please watch this short 30 minute video (6 minutes to 36 minutes) - all data here and a rhapsody in blue to T cells
And you will say - honey, I don't have time to watch you prattle on for 33 minutes - show me the key slides? And I will say - I really want you to see ALL the data but okay here
Read 5 tweets
12 Feb
This study is going to tickle your T cells! A lot of what will happen with the variants will be determined by how well your vaccine-induced T-cell response cross reacts to them. Here is UK study of vaccinated people (Pfizer x 2) then exposed to new
researchsquare.com/article/rs-226…
variants circulating (B.1.1.7 UK, B.1.351, SA) compared to cohort who recovered from natural infection (with non-variants) in spring 2020. Those who had recovered from natural infection with the "spring" (non-variant) virus had less effective antibody responses (reduced with UK
variant, couldn't neutralize the B.1.351 strain). But T cells remained protective likely because it forms responses to epitopes ('bits') across the whole spike protein. Same true with those who got 1 dose of vaccine- robust and complex T-cell response to the variants
Read 4 tweets
1 Feb
okay let's put it specifically from NYT since everyone thinks I am Pollyanna: "In official language of research science, vaccine is typically considered effective only if it prevents people from coming down with any degree of illness..."
nytimes.com/2021/02/01/bri…
"With a disease that’s always or usually horrible, like ebola or rabies, that definition is also the most meaningful one.
But it’s not the most meaningful definition for most coronavirus infections. Whether you realize it or not, you have almost certainly had a coronavirus. "
"Coronaviruses have been circulating for decades if not centuries, and they’re often mild. The common cold can be a coronavirus. The world isn’t going to eliminate coronaviruses — or this particular one, known as SARS-CoV-2 — anytime soon. Yet we don’t need to eliminate it for"
Read 5 tweets
1 Feb
Efficacy refers to how a drug/vaccine does in a clinical trial; effectiveness refers to how it does in the "real world". Nice preprint on the effectiveness on the Pfizer vaccine which has arrangement with Israel to get data weekly as it rolls out
medrxiv.org/content/10.110…
503,875 individuals (mean age 59·7 years); 351,897 had 13-24 days of follow-up. Cumulative incidence of infection was 0·57% days 1-12 and 0·27% days 13-24. Relative risk reduction 51.4% after 1st dose with more expected after 2nd. Real world looks as good as trial, exciting!
By the way, for my academic friends, this is clearly being reviewed at Lancet with the decimal point in the middle and the "evidence before this study" part at the beginning!
Read 6 tweets
1 Feb
One thing that struck me tonight is that the UK roll-out of vaccine is much more in line with public health and practicality than US rollout which is much more 'academic'. For those in academia, you know what I mean but we pay attention to every single detail of the trials-
In fact, an academic ID doctor worth their salt better know which HIV trial of the new injectable HIV medications allowed in a K103N mutation or not. However, when it comes to achieving herd immunity, we do not need 100% of the population to have 100% protection- we need as many
people as possible to get vaccinated as soon as possible with any of these vaccines, all of which encode for the entire spike protein and are very immunogenic. So, the UK authorized AZ/U of Oxford vaccine, Moderna, & Pfizer because the more you authorize the more supply you have.
Read 7 tweets
30 Jan
And then wanted to explain why you should be beaming ear-to-ear about vaccine data. Why would an infection trigger all of this testing, masking, life halting? Because severe illness/hospitalizations/deaths occur. All vaccines to date prevented hospitalizations/deaths completely.
Severe illness prevented completely in Moderna/Pfizer/AztraZeneca trials; 85% across regions (even in South Africa - South Africa variant there) in J&J trials and immune response from 1 dose may keep on giving (remember, outcomes evaluated 14-28 days out due to expediency)
But as I wrote yesterday, immunogenicity from 1 dose of J&J likely extends beyond 14-28 days - keeps on going so likely more protection over time - see graphs in this paper. Two-dose trial still going. Finally, S. Africa variant is one with less protection
nejm.org/doi/full/10.10…
Read 6 tweets

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