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
In the Liverpool data, a Ct value <18 or so should be considered similar to Ct ~25 in many other papers. This is reflected across numerous data streams when you do the right analysis.

@deeksj et al entirely missed this and instead have spewed misinformation to the globe.

4/x
Where @deeksj suggested incorrectly that the Innova test had a 66% sensitivity for "higher viral loads" what they would have found, given correct analysis, is the sensitivity was >90% for higher viral loads, and in that study, found to be 100% in the highest viral loads.

5/x
Further, the analyses fail to properly account for long duration of PCR post contagiousness

When evaluated correctly, a priori we EXPECT a test for infectiousness to have a Max sensitivity of ~40% among Asymptomatics (20% - 60% depending on if outbreaks going down or up)

6/x
This is bc average duration of PCR + is approximately ~20 days or so and average duration of culture positivity (i.e. best proxy for infectiousness) only 4-7 days average. So, ~70% or so of the time you are PCR positive you are EXPECTED to be Ag test negative.

7/x
This cannot be overstated

A public health test for contagiousness does NOT want to detect ppl after no longer infectious

PCR is simply NOT the right gold-standard... *IF* used as a comparator, the Cts must be interpreted correctly

The BMJ reports by Deeks are simply wrong here
Unfortunately, the series of letters by @deeksj, some which use wholly inappropriate extrapolations to contort a warped view of reality, is harming global fight against SARS-CoV-2

All Eyes are on UK experience and @deeksj misinformation campaign is confusing governments.

END

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More from @michaelmina_lab

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
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!

1/

medrxiv.org/content/10.110…
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

2/x
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

3/x
Read 6 tweets

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