VACCINES can work!

Another #COVID19 phase 3 vaccine trial reports awesome results. This time, an estimated 94% efficacy

95 COVID19 detected: only 5! in the vaccine group and 90 in the placebo

But like Pfizer results - need to take w caution... WHY?

1/

investors.modernatx.com/news-releases/…
First, the amazing efficacy from phase 3 at this point for both @moderna_tx and @pfizer vaccines - both mRNA vaccines - is EXCEEDINGLY ENCOURAGING.

These results show that these vaccines are eliciting the correct antibody bases responses to stop symptomatic infection!

2/
What I am worried about is the time scale of the trials thus far:

The leading vaccines are presenting the spike protein to the human immune system. This makes sense! Immunize against spike and stop virus entry into the cells.

3/
But that these vaccines are designed specifically around antibody based responses suggest these early phase 3 endpoints - which are detected within a couple of months of getting the vaccine - may be enjoying a major but temporary boost from the early vaccine effects

4/
When you get an infection or a vaccine, the body makes a HUGE number of temporary antibody secreting cells called plasmablasts.

These are evolutionarily “designed” to infuse a huge and robust antibody response capable of clearing an active infection

5/
But over the month or so after the infection or vaccine, the plasmablasts have to die off - it is their fate. Over the coming weeks and months so too do the antibodies they produced.

What remains after is usually a much smaller antibody producing cellular subset

6/
So I am a bit hesitant to jump on board with the >90% efficacy results because the time scale of the phase 3 studies thus far match the time scale of the temporary plasmablast duration and the antibodies they produced...

7/
So, w these early efficacy results, we may be measuring the effects of an impressive front line army that spins up in response to the vaccine - but then we should be careful not to assume the same efficacy persists to hold that line after most of the troops disappear!

8/
That all said - what these two vaccines show is they hit the nail on the head to find the right protein to immunize against!

Only time and careful follow up will tell how much the >90% efficacy of the two vaccines holds after the early vaccine responses fade away.

9/
This is btw generally why we must monitor durability of vaccine responses over time. And why we have to always be careful to interpret efficacy within the parameters of the data we have (here - early months post vaccine)

Also - we don’t know about transmission blocking...

10/
To learn about the actual benefits long term of the vaccine reaponse - it will take continued post market analysis. The controls will likely get the vaccine - so a new type of vaccine study that is not as well controlled will ensue to measure longer term effects.

11/
Also - I’m not speaking in black and white terms here. Either way, immunity will likely persist. It’s not binary. B and T cells are produced

At population level, we must wait to see if 94% efficacy to fully block symptomatic disease becomes 90% or if it becomes 50%, or 30%

12/
And even if it becomes 50% to stop total symptomatic disease, it could remain 90% to stop severe disease. This, like testing and everything else is simply NOT a binary issue and also is NOT a simple issue meant for describing over Twitter....

13/

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More from @michaelmina_lab

15 Jan
Apparently I cannot say this loudly enough

The recent @bmj_latest articles by @deeksj et al deriding Rapid Ag Innova Tests are simply WRONG

They simply do NOT appropriately interpret Ct values & do NOT consider massive importance of how long PCR remains + post-infectiousness
Inspection of Ct values among the Asymptomatics & correlation to RNA copies / ml shows Ct values in Liverpool are ~8 lower than often seen in literature. The failure to recognize this means the estimates of Ag test sensitivity for "high virus" are totally off.

2/x
The sensitivity for "moderately high" or "high" viral loads in the Liverpool data are ~90% and ~100%.

But to know this you cannot just assume a Ct of 25 elsewhere (often described as entering "high viral load") means same thing as a Ct value in other labs.

3/x
Read 5 tweets
14 Jan
Will delaying #COVID19 vaccine doses cause vaccine immune escape?

This nice article misses an extremely important part - that unvaccinated ppl too have so called “partial immunity” while infected.

Escape from immunity isn’t same as from antibiotics

1/x

sciencemag.org/news/2021/01/c…
Unlike antibiotics where resistance happens w partial doses, to be a risk you also must be taking them in first place.

When considering escape from spike protein derived immunity - must consider everyone w/out sterilizing immunity at risk to induce a mutant upon infection.

2/x
Whether no vaccine or a single dose (or two) people create antibodies against the same part of the protein.

If discussing “partial immunity” or low affinity antibodies, must consider that a fully naive person might pose greater risk for escape than a single dose person

3/x
Read 11 tweets
13 Jan
CLARIFICATION:

Much confusion about rapid antigen tests

ALL evidence - when evaluated appropriately! - shows these are VERY good at detecting infectious virus

• ~100% if used frequently

• >95% for single samples with high, most likely contagious viral loads

The tests work
We've been evaluating rapid Ag tests on campuses. We find these tests - when used as screening w/out symptoms DO miss most PCR positives!

BUT EXPECTED! - ALL misses were previously detected and already finished isolation.

Ag is MUCH more specific than PCR for contagious virus
this is the whole point of rapid antigen tests - they find people who are currently infectious. They are fast, give crucial immediate results and unlike PCR do NOT stay positive for weeks/months after someone is no longer infectious.
Read 4 tweets
12 Jan
Dear ⁦@guardian

This article is incomplete & represents a minority view of the science.

The experts here are gravely misinterpreting the data and sowing confusion among the masses.

The rapid tests are working well!

This coverage isn’t balanced theguardian.com/world/2021/jan…
The details are difficult to describe via Twitter but I’ve tried on many occasions. The described low accuracy is false. These tests are doing very well to catch infectious people. We do NOT want to detect and isolate people who are not infectious and just have old remnant RNA.
I know people want to hate on the government for purchasing tests - but the Innova test is working entirely as expected. Very good for detecting contagious people. Which is the only goal here.

I’d be happy to write an OpEd for @guardian to explain.
Read 4 tweets
10 Jan
UK Rolling out #COVID19 Rapid Tests!

**NOTE: A quote says rapid tests missed 60% of positives in Liverpool

NOT accurate

VAST majority of MISSES were LOW PCR RNA & thus NO LONGER CONTAGIOUS.

(PCR remains Positive for a long time, rapid Ag does not)

theguardian.com/world/2021/jan…
Despite some poor messaging in UK - Rapid Ag tests work WELL to find CURRENTLY INFECTIOUS ppl

Frequent rapid Ag testing sensitivity is >95% to find infectious people.

(ppl get confused & say they're low sensitivity - but that's when compared to RNA on PCR from prior infection)
A major attribute of rapid Ag testing is they can be FREQUENT

It's not the sensitivity of a test to find virus particles that matters

It's the sensitivity of the testing program to find and isolate infectious people that matters.

For that, PCR often fails. Rapid Tests do well.
Read 6 tweets
9 Jan
Honestly @US_FDA @CDCgov

HOW have we FAILED to get frequent rapid testing out?!

•The science & plans are there

•All you've given is pushback

Almost 5 months ago I wrote:

"So we're not looking back 5 months from now wishing we acted"

PLEASE ACT NOW!

@ASMicrobiology @APHL
I know @ASMicrobiology & @APHL you do not support these tests - pity

Confounding sensitivity & specificity for EFFECTIVENESS in midst of a pandemic is a dangerous and now deadly decision

(1) Define the use
(2) Then take a stance on test effectiveness

You never really did (1)
Here is a primer for what I'm referring to.

Read 4 tweets

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