Thread by @michaelzlin

Earlier I proposed a simple public health philosophy: "identify the worst-case scenario using the most up-to-date science and recommend easy things that can mitigate that"

No claim to originality; would hope it's the default PH approach actually

Let's apply it now to J&J vax...

https://twitter.com/michaelzlin/status/1406326680948334596

10 million Americans have received the J&J vaccine. That's a big enough group for PH officials to care about. They have a vaccine with measured efficacy of ~70% for symptomatic disease and ~90% for hospitalization or severe disease (on a mix of original and alpha strains)

All good, and if we have already vaccinated >75% of people ≥12yo in the US with RNA vaccines, maybe good enough. We'd reach herd immunity, mostly due to the RNA vaccines' ~90% efficacy against all disease, i.e. R0 becomes <1.

But we've only fully vaccinated ~50% of eligible people and Delta with enhanced transmissibility is on the rise (already causing a big surge in Missouri and Arkansas). What's the worst-case scenario?

Worst case scenario, is that we have a widespread Delta wave in the fall. Actually that's the medium-case scenario; modeling predicts a fall surge that's 20% the size of the past winter wave, which itself was massive (causing 400,000 lives).
cnn.com/2021/06/21/us/…

The worst-case scenario is Delta can percolate enough in unvaccinated or partly immunized (50% of the US population) or JNJ-immunized (only partly protected vs disease) through the summer to mutate to even more transmissible/evasive forms, or some new variant emerges from abroad.

The prediction of partial disease prediction for JNJ recipients derives from JNJ's 60% efficacy against disease from the Beta B.1.351 variant, which appears similarly evasive as Delta against vaccine-elicited antibodies. @ScottGottliebMD estimates the same

https://twitter.com/michaelzlin/status/1403071331554381827

The most important PH measure of course is to keep on pushing for vaccination as quickly as possible. But can we do something easy for the already immunized at the same time to further protect them?

There is a clinical trial studying boosters for the already "fully" immunized which is defined as 2 shots of RNA (Pfizer/Moderna) or the 1 shot of J&J. The trial will look at neutralizing antibody titers and safety.
clinicaltrials.gov/ct2/show/NCT04…

The CDC might be waiting for the outcome before making any recommendations. But safety for J&J is almost certainly assured. UK and EU have already shown the safety of 1 shot of AZ adenovirus vaccine then RNA.
nature.com/articles/d4158…

Efficacy in terms of neutralizing antibodies is also assured for J&J recipients. They have lower antibodies than the 2-dose RNA recipients, so there's room for improvement. Also AZ+Pfizer trial showed increased antibodies by after the Pfizer boost
nature.com/articles/s4159…

So really there's not much mystery to the "delayed heterologous boost" trial (NCT04889209) for J&J recipients. It will confirm what the European data have shown already after 1 shot of the similar AZ vaccine.

At the same time, for J&J we have the largest need in terms of boosting efficacy against the upcoming Delta wave, or even further variants. The 40% of exposed people getting sick and being able to pass on to others is worth preventing if we can.

The 40% expected breakthrough in J&J recipients exposed to Delta is a big contrast to the 12% expected for RNA recipients. And recall J&J recipients can and should be going about their daily business the same as RNA recipients, e.g. dining in restaurants
medrxiv.org/content/10.110…

Why not bump the protection against illness from (and tranmission of) Delta from 60% for J&J recipients to ~90% like the RNA recipients have? This can be easily accomplished with a RNA booster for existing J&J recipients.

On top of that, increasing protection against disease will reduce the probability of getting hospitalized (and dying, for the unfortunate) further. It might make a small difference to the numbers, but a big difference to individuals.

All it would take is a recommendation from the CDC that J&J recipients be allowed to receive boosters. If CDC wants to be cautious, they can suggest that doctors consider prescribing a booster on a case-by-case basis. It would then be allowable off-label use of an approved drug.

Thus with a glut of soon-to-expire RNA doses, no lines at vaccination locations, Delta surging, J&J not fully protected against disease, and overwhelming evidence for safety and efficacy of RNA boosters, allowing J&J recipients a RNA booster is a no-brainer.

In conclusion, CDC issuing guidance allowing RNA boosters for J&J recipients would be a proper application of the principle of "identifying the worst-case scenario using the most up-to-date science and recommending easy things that can mitigate that".

Sorry meant "The prediction of partial disease protection". What happens when auditory cortex is linked to language output through Broca's area