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.
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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
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.
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.
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