Was a busy day so just now getting to this article about the J&J vaccine potentially performing worse than RNA vaccines against Delta, and how a booster shot might e a good idea.

A thread on why J&J recipients may be experiencing a feeling of déja-vu...

I had predicted that, as nAbs raised against original SARSCoV2 by RNA vaccines suffered a similar loss in potency against Delta as against Beta, J&J would have similar efficacy against Delta as against Beta (relative risk ~40% vs nonvaxxed for symptoms, ~18% for severe disease)
(40% relative risk is the same as 60% relative risk reduction which is the "efficacy" number for J&J vs symptomatic disease from Beta. It's 67% vs all strains and 72% vs original strain in the US. Numbers may be off by a few % — working from memory here)
After all, antibodies are antibodies; once made and released by B cells they don't know what vaccine triggered them, if the vaccines all use the same antigen, as they did in the case of RNA vaccines and J&J. So the same hit RNA vax were seeing in nAb potency, we'd expect for J&J.
I thought the 40% relative risk of disease after J&J (compared to non-vaxxed) was high enough to be concerned about, compared to the estimates of 12% RR after Pfizer coming from the UK
As Delta is more contagious replicates to ≥4x higher levels, I'm not sure the 40% relative risk is adequate. Recall these risks are relative to unvaxxed. If unvaxxed are 2x more likely to catch COVID now per exposure, maybe we want our vax to have <20% relative risk, not 40%...
and actually now that CDC asked everyone to go without masks and party indoors and exchange aerosols, the exposures are more frequent and intense than those experienced in the trials that established the 40% RR for Beta
The exact same concerns hold for all vaccines, but J&J starts from the lower baseline of 40% RR (60% efficacy) whereas Pfizer was until recently thought to hold onto 12% RR (88% efficacy) vs Delta in the real world. (We still have no clue about J&J vs Delta in the real world)
This is why others and I have suggested that it would be prudent to give a booster to J&J recipients ahead of Delta
Anyway earlier this month we already saw that, sure enough the hit in potency of nAbs produced by J&J against Delta was similar to that against Beta, in two studies from J&J scientists and the Barouch lab
Like me, J&J extrapolated the nAb findings to argue for expected efficacy on Delta similar to previous variants. But where I saw this as a predictor of suboptimal protection, J&J saw it as good enough and most of the media just went ahead and echoed that.
However J&J and most of the media failed to address the larger concern above about whether 60% efficacy vs symptoms and 82% vs severe disease (yet to be proven) is really adequate against the higher infectivity and severity of Delta
So how about today's biorxiv paper, what does it say? It says two things we already knew (which I'll get to next). But they see the glass as half-empty, suggesting "benefit of a 2nd immunization... to increase protection against the variants."
What they showed itself is not surprising for those paying attention to the literature rather than CDC. Delta causes antibodies produced by J&J to be 7x less potent (below). This is in line with the hit taken by other vaccines, e.g. in the Lancet paper hubs.li/H0PzQ7b0
They also showed that neutralizing antibody activity on Delta was 10x lower in J&J vaccine recipients vs RNA recipients. This is also unsurprising because nAb activity against original strain was also 10x lower after J&J than after RNA vaccines, e.g.
That is, we already knew J&J was 10x weaker in antibody production than RNA vaccines, and that was indeed one of the explanations for why J&J protection was 67% vs 95% against original SARSCoV2. From that nature.com/articles/s4159… paper (purple annotation mine):
The conclusion of today’s biorxiv paper's authors is that booster shots should be considered for J&J receipients because of Delta. Yes, and we've always had the evidence to recommend them, but it's not because J&J is losing its activity worse than RNA vaccines on Delta.
J&J even seems to retain a bigger percent of its original activity on Delta than RNA vaccines are retaining theirs. But the reason to consider boosters for J&J recipients is that even that retained amount of efficacy is worse than the retained efficacy of the RNA vaccines.
The best evidence comes from J&J themselves, who tested 2 vs 1 dose, and found 2 doses to produce ~3x more antibodies in the Phase 2 trial. That's with the known issue of clearance of the second dose by antibodies made against the Ad carrier too. From nejm.org/doi/full/10.10…
And as the article says, we know from work in the UK and Europe that a single RNA boost of the AZ Ad vaccine also boosts Ab levels to that of 2x RNA. Finally there are hundreds of people on social media alone describing getting RNA boosters, so far with no safety signals reported
So today's news is nothing surprising, but it's noteworthy in bringing to light that Delta is a reason to see the glass as half-empty. But it seems that CDC is sticking to the idea that severe disease is all that matters, in which case a booster would make only a small difference
I should say J&J *may* even retain a bigger percent of its original activity on Delta than RNA vaccines are retaining of theirs. We don't know yet.

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More from @michaelzlin

9 Jul
"I am a little surprised how quickly Delta has become widespread,” said Ashish Jha, dean of Brown's School of Public Health. “We’re one week into July and it is everywhere. It suggests that it is far, far more contagious than the Alpha variant."


We knew 10 days ago Delta was 50% of sequences in the US, so that realization is both late and not surprising. The below came to me via @ScottGottliebMD on 6/28, and if Jha wasn't following Gottlieb or Delta progress by then, he should have been

We also knew Delta is far far more contagious than the Alpha variant, based on how quickly it supplanted Alpha in the UK. That happened in May.
Read 5 tweets
8 Jul
Claims of decoupling between cases, hospitalizations, and deaths in the UK have been premature.

No doubt we'll see lower death rates, but we'll also see (1) plenty of acute and likely long-term morbidity, and (2) breakthrough deaths in sick/elderly.

UK researchers weigh in...
Our sources will be two UK newspapers from opposite ends of the political spectrum: The conservative Daily Mail and the liberal Guardian. First up, the Daily Mail quotes the government for 100k daily cases and ICL epidemiologist Ferguson for a CFR of 0.1%.
100k looks plausible to me. With 50% not vaccinated, 20% of whom might be prev infected (based on total deaths so far), that makes 40% nonimmune. Half of those (20% of UK) might get Delta before herd immunity sets in. That's a similar number to all infections so far.
Read 16 tweets
7 Jul
Health officials' oversimplistic message that vaccines were perfect and treatment of breakthroughs as taboo has, predictably, led to defensiveness/apologeticness upon local breakthroughs that undermines confidence in both officials and vaccines.
Take this explanation by the CA senate secretary after a local outbreak: "Even fully vaccinated individuals can be infected with COVID-19. However, public health experts indicate that fully vaccinated individuals are less likely to suffer...
... the most serious symptoms of COVID-19, and for this reason, the Senate continues to encourage all staff to protect themselves by receiving the vaccine.”

Does one sense a little awkwardness here? Isn't the way the outbreak is discussed sound like an apology for vaccines?
Read 22 tweets
5 Jul
Must always consider mechanism and data quality in COVID19 curve. Factors Topol misses: (1) UK cases started rising early June, and deaths lag by 1mo (2) cases in the other countries cited may be underreported, increasing the death/case ratio (Russia curves esp make no sense)
Another thing to consider is if Topol included precisely those countries that have the highest death/case ratios to make a contrast with UK, then he would have filtered in exactly those countries that are underreporting their cases.
Kind of frustrating that Topol would continue to make the same mistakes in data interpretation (no mechanism, no awareness of data quality, no awareness of selection bias)
Read 7 tweets
5 Jul
Posted today: Delta evades RNA vax too

6 of 100 vaxxed attendees at open-air wedding got sick.

In 2 with Covaxin, 1 (groom) died
In 4 with RNA vax, 1 hospitalized

All expected from measured 80% efficacy, yet PH officials say we don't need to worry.

Measured efficacy of 80% for RNA vaccines on Delta variant in the below paper. That's equivalent to 20% breakthrough rate relative to unvaccinated.

Remember this next time you hear someone claim vaccinated people can't get sick from COVID-19.

CDC advice that vaccinated should feel comfortable spending all the time they want indoors and unmasked with the 50% unvaccinated population while Delta surges through their communities doesn't sound so reassuring now, does it?
Read 13 tweets
3 Jul
This thread, and probably the one it refers to by Topol, should be pulled. The study did not look at transmission from vaxxed people at all. Topol wrote "91% efficacy of blocking transmission of infection" when he should have just written "91% efficacy of blocking infection"
You can see the game of telephone going on here:
Actual results: 91% refers to the reduced infection of vaxxed people, similar to the 95% in clinical trials. All of this is pre-Delta. So kind of non-news.
Read 4 tweets

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