Thread by @profshanecrotty

The J&J COVID-19 1-dose vaccine data have been filed with the FDA and are under review there (probably final decision tomorrow).
Here are my thoughts on the J&J 1-dose COVID-19 vaccine, now that the data are public.🧵

(Janssen=J&J = Johnson & Johnson) Vaccine name: Ad26.COV2.S

Executive summary:
🔵 1-dose. Very convenient! And easy to store.
🔵 Essentially 100% protective against death or hospitalization. Very good!
🔵 69% protection against symptomatic COVID-19. Just ok.
🔵 Similar protection against the South Africa variant (72%-->64%). Very good!

The FDA EUA package data are consistent with the statements in the J&J vaccine press release several weeks ago.

Here's my tweet thread from then:

https://twitter.com/profshanecrotty/status/1355294402755739650?s=20

The J&J vaccine EUA documents for the USA FDA:
main = fda.gov/media/146219/d…
addendum = fda.gov/media/146218/d…

Let's start out strong.
_Hospitalizations_
100% protection against hospitalizations starting at 1 month after immunization.
93% protection by day 14.

I like the larger data set in the addendum. The case # available for consideration increased 50% (that's a lot!), and the conclusions were identical. That's a sign of the robustness of the data. Very nice.
fda.gov/media/146218/d…

_Deaths_
100% protection against death.
All 5 COVID-19 deaths were in the placebo group.
(8 COVID-19 deaths, by casting a wider net. Still all in the placebo group).
Very good to see.

So, that's very good protection about hospitalizations and death, what about broader protection against COVID-19?

The primary conclusion is that the J&J 1-dose vaccine provides 72% protection against moderate to severe COVID-19.

What does that mean?

In this particular vaccine trial there was a really generous definition of "moderate". There is nothing inherently wrong with that, it just makes it a bit confusing because, in contrast, in most of the clinical literature, "moderate" COVID-19 are hospitalized cases,

and "mild" incorporates all non-hospitalized disease. Instead, in the J&J trial, almost all of the symptomatic cases reached their definition of "moderate" instead of "mild".

They also define severe independently of hospitalized. Quite a few of the 'severe' cases were not hospitalized, so I focused more on the metrics above.

Still, they observed 85% protection against severe disease by 28 days after vaccination, which is in line with the rest of the data. That is to say, very good protection against hospitalizations or death.

Getting past confusion about the names used for COVID disease severity....protection against all symptomatic disease:
69%.
That reflects the addition of 'mild' cases.

There is also evidence that the J&J vaccine reduces symptoms. People who do get sick are sick for a shorter period of time.

Protection against Asymptomatic SARS-CoV-2 infections
74% protection against asymptomatic infections. (VE [95% CI]: 74.2% [47.13; 88.57]).
That's a bit perplexing, because it basically matched the symptomatic numbers, or is 5% better.

Nevertheless, evidence of protection against asymptomatic infection is a good thing, because if asymptomatic infections are prevented that also prevents SARS2 transmission.

Altogether, excellent protection against death and hospitalization-level COVID-19, and good protection from average cases of COVID-19 (cold or flu-like symptoms)

Next:
Notably, the 1-dose J&J vaccine had almost equal efficacy against the parental SARS2 strain and the variant dominant in South Africa (B.1351, 501Y2). 72% in the USA and 64%. That is very good!

The vaccine works in a wide range of people and is safe.
Vaccinated: A total of 43,783 participants (21,895 in the Ad26.COV2.S group and 21,888 in the placebo group)
That is a lot of people! And good representation of different populations: age groups, races, ethnicities.

From that:
- Very good safety profile for the J&J COVID-19 vaccine.
- Vaccine efficacy was similar in all subgroups. Except people over 60 who also had comorbidities. There appears to be a substantial drop in protection for that group. But not all people with comorbidities.

Were there disappointments in the J&J data package to the FDA?
a) There was no T cell data past day 29. Thus, we don't know how good the T cell memory is.

b) Over, the follow up time was rather short. Predominantly 60 day follow up. A lot more time folllow up is needed to get a sense of durability of protection with 1-dose.

c) No neutralizing antibody data were provided against the SA variant (B1351 / 501Y.2), which is the most worrisome variant of concern.

Comparison to other vaccines:

Pfizer and Moderna RNA vaccines have 95% protection against symptomatic cases of COVID-19, after 2-doses. AstraZeneca adeno vaccine has ~75% after 1-dose and ~85% after 2-doses. All have very good protection against deaths and hospitalizations.

At face value, protection by the J&J 1-dose vaccine is comparable to the AstraZeneca vaccine with 1-dose (both are adeno vector based). And J&J 1-dose is less good that 2-doses of the two RNA vaccines.

At face value, protection by the J&J 1-dose vaccine is comparable to the AstraZeneca vaccine with 1-dose (both are adeno vector based). And J&J 1-dose is less good that 2-doses of the two RNA vaccines.

But:
(i) these are not perfect comparisons.

(ii) The J&J trials were during periods of a lot of viral transmission, and so it may be harder to prevent COVID-19 cases during surges than outside of surges. (discussed in previous threads)

https://twitter.com/profshanecrotty/status/1355920669750435841?s=20

(iii) The J&J 1-dose vaccine only requires one dose, and easier freezing/ handling than the RNA vaccines.

(iv) Durability of immunological protection against COVID-19 is still unknown for each of these vaccines.

(v) The J&J 1-dose does quite well against the SA variant. That's a big deal! In contrast, the AstraZeneca vaccine appears to have almost no efficacy against that variant (~10% efficacy in confirmed cases).

https://twitter.com/profshanecrotty/status/1358836370404352003?s=20

(vi) Lastly, the J&J vaccine had substantial increases in neutralizing antibodies after two doses (T cells were not reported post-boost).
nejm.org/doi/full/10.10…

J&J has an ongoing 2-dose COVID-19 vaccine clinical trial, and it is therefore reasonable to expect very high protective immunity in that 2-dose J&J trial.

https://twitter.com/profshanecrotty/status/1356692102113976320?s=20

So, no perfect interpretation. Well, it's not a perfect world. The new J&J vaccine definitely works, and my advice is that you take whichever of these three vaccines you are offered in America (Pfizer, Moderna, or J&J). It is WAY better than not being vaccinated!

Protection against hospitalization-level COVID-19 disease, and SARS-CoV-2 variants of concern, are both a big deal.

Also, some people keep complaining about the FDA being slow. The FDA is NOT being slow!  A company has to submit an EUA package to start the process, and the FDA has responded VERY quickly to those EUA packages. Also, as a practical matter, there isn't a backlog of J&J vaccine

there isn't a backlog of J&J vaccine sitting around. There are a couple million doses right now. There will be more by the end of March, and 100 million or more in a few months, but the FDA is definitely not slowing this vaccine rollout. Also,

the FDA requires all of the data to be public, and have a public hearing, all of which is fantastic for pubic trust. That is an American openness medicine-approval policy that is not the case in many other countries.

Completely separately, for the antibody aficianados: In the EUA package, evidence of vaccine-elicited antibody affinity maturation!
Nice to see. 😁