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


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.

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

In single dose vaccine, at least you are well on your way to and often able to create a strong secondary response - boost antibodies quickly upon infection. Viral replication will be diminished compared to fully naive person. We saw efficacy rose to ~90% before dose 2.

This of course has to be balanced by a natural infection eliciting antibodies across many epitopes on the whole virus - which could assist in preventing an escape mutant from getting out.

By the time antibodies arise in 1st infection, the virus is often already in decline

So it could be that the pressure induced by immunity on the virus is so overwhelmingly driven by innate immune products and not antibodies in a naive person that a 1st infection doesn’t pose a large risk of anti-Spike immune escape.

But this might be wishful thinking.

We’ve seen numerous variants arise already. At least one & likely others have already developed mutations predictable as immune escape by laboratory applied antibody pressures. This caused worry that “moderate” antibodies in ppl upon infection would breed similar effects

It could - though variants we have now arose independent of vaccines.

The question is which wins out: the more swift control of the virus after a single even if partial dose, or the viruses propensity to mutate if not immediately neutralized by low affinity antibodies.

We don’t have a clear answer, but I do think any discussion must keep front and center this idea that every fully unvaccinated person too must go through a period of “partial immunity” while battling an infection.

Also, must consider how population level effects play in

If a single dose decreases transmission enough aid herd effects (again the evidence we do have shows efficacy against disease rose to 90% in short term pre-dose 2) would this have an outsized benefit to reduce risk of escape mutants?


Should be considered.

Finally the best thing we can do to prevent rise of escape mutants is to decrease spread as much as possible without vaccines.

Rapid frequent accessible tests to everyone, masks, distancing are all helpful here.

Rapid tests might be the most, We should use them.


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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.

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.

Read 5 tweets
13 Jan

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


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

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"


@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
8 Jan
#COVID19 is overlooked by the world as as urgent a crisis in Africa as every where else

We continue to make the same mistakes of confusing a lack of testing for a lack of cases.

In this study in Zambia, ~20% of deaths were found to be COVID related!


To determine this, the researchers performed a systematic analysis of swabbing and running PCR on post-mortem individuals.

These ppl would not have been detected/confirmed as having COVID otherwise and thus not officially reported owing to a lack of testing infrastructure

As @brookenichols has discussed, rapid Ag testing isnt only a powerful tool for frequent use to slow spread (as I’ve discussed) - it is also a powerful tool for less resourced countries to access and massively scale up testing to get formal estimates of transmission/cases

Read 6 tweets

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