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Aaron Richterman, MD Profile picture
@AaronRichterman
Jan 12, 2021 • 27 tweets • 11 min read • Read on X
Interesting poll. Selection/response bias aside, majority picked a low probability, but 40% still thought there was 10+% prob that vaccines will not substantially prevent transmission. This is why I have become convinced this concern is highly unlikely (borderline implausible) 🧵
1. Data from screening PCR at the time of the 2nd moderna mrna vaccine, showing reductions in asymptomatic PCR positivity. This is before the 2nd dose and if anything will underestimate effect. Will have additional confirmation from unblinding pcr and ab

2. Data from AZ vaccine chadox study is a mess, but they did weekly PCR screening and points in the same direction.
thelancet.com/action/showPdf… Image
3. We aren't reinventing immunology and need to consider our priors based on experience with other vaccine-preventable infections.

3b. Another thread from @MonicaGandhi9 on this

3c. The interesting counterargument involves requirement of IgA for upper resp tract mucosal immunity (vs IgG to prevent LRT symptomatic disease). However, as @leela_davies points out, IgG-generating vaccines prevent transmission in other resp viruses

4. Even if we assume vaccines ONLY prevent symptomatic disease, turning all into asymptomatic infections, there is a solid body of evidence 👇 (inc systematic reviews from @mugecevik and @nicolamlow) that this alone would substantially reduce transmission

5. Based on this, I think the possibility that these vaccines don't meaningfully reduce transmission (to the point that populations can move back towards normal life in due course) is low enough that we should treat this as a mostly theoretical concern at this point.
6. An enduring lesson of this pandemic (& others) is the need to communicate uncertainty honestly (in both directions). Of course its reasonable to be careful, but lets not forget that this theoretical concern is being cited as a reason not to get the vax
7. implications of monoclonal post-exposure prophylaxis data on transmission

8. More on why reducing symptoms/severity w vaccines will probably reduce transmission

8a. (Aside - Good paper with biases to be mindful of when comparing secondary attack rates of symptom/asymptomatic in households (page 19). h/t @mugecevik)

dash.harvard.edu/handle/1/37366… Image
9. Some more discussion on Moderna dose 2 testing
10. Implications from regular pcr monitoring after natural infection. Less infections, lower viral load, more asymptomatic. Will reduce transmission.
10a. That said, similar caveats as below re whether those were even all reinfections.
11. More data from the Oxford/az randomized clinical trial. Vaccinated ppl who developed infection had lower viral loads and were pcr+ for one week shorter time relative to placebo. True for both asymptomatic and symptomatic cases. =>reduced transmission

papers.ssrn.com/sol3/papers.cf… ImageImage
12a. And real world data from Israel. Interesting analysis inferring vaccine status by age and following cycle thresholds over time, suggesting lower VL in vaccinees w infection. Cool time series. Caveat: unclear what symptom status is but assume mostly symptom prompted testing.
12b. Here are the pre-prints from the two real-world Israel studies of time series w viral load reduction after mrna vaccination. Some limitations including unknown symptom status, but suggestive.
medrxiv.org/content/10.110…
medrxiv.org/content/10.110… ImageImage
13. Nice study of healthcare workers after Pfizer vaccine with regular PCR screening every 2 weeks. They found 70% reduction in all infections (asx or sx) dose1+3wks, 85% dose2+1wk. May be overestimated if vaccine ⬇️ duration of pcr+, but expect large transmission ⬇️ Image
13a. Link for that last study: papers.ssrn.com/sol3/papers.cf…
14. 75% protection against asymptomatic seroconversion in J&J vaccine trial.
14a. Important for those worried about b1.351. While this prelim analysis of asymptomatic infection after j&j is based on 29% completed serology data, most of the serologies from South Africa had been done. Image
15. No posted pre print yet but if this holds we now have 3 lines of evidence suggesting 85-90% reduction in all infections by the mrna vaccines (moderna RCT, Pfizer UK regular screening healthcare workers, 👇🏻 Israel regular screening).
H/t @EricMeyerowitz
15a. There is a little separation in the first few days so will need to see what kind of adjustment has been made here.
16. On interpreting cross-sectional pcr during vaccine trials (i.e. moderna asymptomatic swabs at the time of dose 2)

ImageImage
17. Another study with regular (weekly) asymptomatic screening of hcw finds large reduction in pcr+ after Pfizer vaccine. The case for a large transmission reduction w vaccine seems closed at this point but will keep collecting these for now.

authorea.com/users/332778/a…
17a. At least until these stop coming on a daily basis...

nytimes.com/live/2021/03/0…

google.com/amp/s/www.wire…

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More from @AaronRichterman

Aaron Richterman, MD Profile picture
May 31, 2023
Over 100 governments in low- and middle-income countries have introduced anti-poverty cash transfer programs over the last 3 decades

In new research, we examined the effects of these initiatives on the ultimate health outcome — mortality

Published today in @Nature /1 Image
We used >80 national surveys in 37 low- and middle-income countries to create longitudinal survival datasets for 4 million adults & 3 million children 2000-2019

About 1/2 the countries started cash transfer programs, & 1/2 the programs were unconditional (no strings attached) /2 Image
We used difference-in-difference models to show these programs led to a 20% reduction in mortality for women, and an 8% reduction in risk of death for children under 5
/3 Image
Read 8 tweets
Aaron Richterman, MD Profile picture
Nov 16, 2021
New pre-print from @EricMeyerowitz and me reviewing loads of new Delta transmission data.

One area we cover — updates on vaccines' effects on transmission in the Delta era 🧵 1/24

papers.ssrn.com/sol3/papers.cf…
First, to review, vaccines can provide:
-direct protection (reduction in infx/disease among vaccinated ppl)
-indirect protection (reduction in infection among all community members through ⬇️ transmission)
/2
nature.com/articles/s4157…
Indirect protection can be generated by
1) ⬇️ risk of infection (if person not infected, cannot transmit)
2) ⬇️ infectiousness of vaccinated person w infection

Prior to delta, 1) + 2) = substantial transmission reduction of 75%+. Our pre-delta review:
/3
academic.oup.com/ofid/advance-a…
Read 24 tweets
Aaron Richterman, MD Profile picture
Aug 24, 2021
As @mugecevik points out, despite the recent proliferation of vaccine studies using routinely collected testing data, the majority of these cannot be reliably be used to estimate VE vs all infections because they do not use systematic testing and/or control for confounding.
Vaccine protection against all infections is one important way (of several) that vaccines reduce transmission (discussed👇). Here is an updated table of high-quality studies assessing VE against infection, including just 3 from the delta era at the bottom
academic.oup.com/ofid/advance-a…
When using regular (or cross-sectional) systematic testing to estimate VE, you are really measuring VE against a composite of infection and duration of PCR-positivity, as highlighted recently by @dylanhmorris.
Fascinating discussion of these methods here sciencedirect.com/science/articl…
Read 4 tweets
Aaron Richterman, MD Profile picture
Aug 11, 2021
This 👇claim arises principally from Israeli data (which is unpublished in any form so will withhold judgment) and from the UK REACT 1 study, rounds 12 & 13. But... is the REACT 1 data likely to be solely explained by delta? 🧵
(study link spiral.imperial.ac.uk/handle/10044/1…)
This is the table in question. You can see VE of a combination of AZ/MRNA vs symptomatic infection was 83% (19-97%) in round 12, but only 59% (23-78%) in round 13. The concern of course is that this drop in VE is due to delta, which had completely taken over by round 13 /2
However, while 100% of the isolates identified in round 13 were delta, 80% in round 12 were also delta (20% were alpha). Any effect of delta on VE should have been partially seen in round 12. /3
Read 7 tweets
Aaron Richterman, MD Profile picture
Jul 31, 2021
The question at hand: what is the relative transmission potential of a vaccinated person who becomes infected with delta? This 👇new report from Singapore is much more informative on this question than the CT data released so far from Ptown and Wisconsin.
medrxiv.org/content/10.110…
First, importantly, reducing transmission potential of a person who becomes infected is only one component on the transmission reduction effect of the vaccines. The other: reducing the likelihood of becoming infected in the first place. We discuss here👇
academic.oup.com/ofid/advance-a…
We still await definitive evidence from systematic sampling on the ? of overall infection risk reduction with vaccination, but w strong protection vs symptomatic disease, expect that there will still be substantial protection (50+%) vs overall infection
nejm.org/doi/full/10.10…
Read 10 tweets
Aaron Richterman, MD Profile picture
Dec 19, 2020
Thankful to Singapore for surveillance systems that allow for the detailed studies required to truly assess the relative transmission risk of asymptomatic vs symptomatic cov-2 👇, which they find to be much higher in those who develop symptoms /1

thelancet.com/journals/lance…
couple points:

1. Use of serology to stratify recency infection was a nice addition

2. A better description of asymptomatic definition would be helpful. We go through this thorny issue here👇 @mugecevik @EricMeyerowitz @BogochIsaac @nicolamlow

/2
thelancet.com/journals/lanin…
This is consistent with limited data summarized in several nice recent systematic reviews:

1. Transmission potential appears lower in asymptomatic infection from @nicolamlow and team ncbi.nlm.nih.gov/pmc/articles/P…
/3
Read 6 tweets

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