If you see papers/media that show very low sensitivity for rapid Ag tests (i.e. 30%-60% sensitivity) the report is most likely making a common mistake:
Comparing a test meant to detect viable virus to a test that can detect minuscule amounts of RNA is a mistake.
1/x
PCR RNA stays around long after live virus is cleared
So if you see a paper that shows very low sensitivity, ask:
"Are they comparing rapid antigen tests to "anytime" PCR RNA positivity? (Especially studies asking about sensitivity among asymptomatics)
2/x
To interpret this, you should know that only 25%-40% of the time someone is PCR positive are they infectious w live virus.
So... even a test that is 100% sensitive for live virus should only show a 25%-40% sensitivity against PCR among asymptomatic people.
3/x
(For various more epidemiologically complicated reasons having to do with the growth or decay rate of the epidemic, the sensitivity range is actually more like 30% - 60%... but that's for another tweet sometime)...
But to interpret studies of rapid antigen tests...
4/x
Simply put... If you see reports of rapid antigen tests "only" 30% - 60% sensitivity in asymptomatics (vs PCR) - you should think:
"Great! That could well be an exceptional test with sensitivity as high ~905-100% sensitive for likely contagious virus - and its rapid!"
5/x
This is too important to allow yourself to be misguided.
So, unfortunately here, don't always believe scientific papers
You have to ask "Why is the test being done?"
If it is to detect asymptomatic contagious people, then know that comparing vs. PCR is misleading.
6/6
Also, PLEASE don't look only at Ct values against Rapid Ag tests. Need a way to understand what each Ct represents. Some platforms run ~8 Cts lower than CDC / WHO assays. This means that every platform needs to be considered individually. Can Not just say "Ct < 30" = "live virus"
We are finding that whole platforms consistently run low. TaqPath it seems runs low for instance.
So in that case, a Ct of 23 may be more like a Ct of 29/30. This was the case in Liverpool and I believe recently a JCM paper looking at BinaxNOW among asymptomatics in Utah.
Waning immunity is likely as a component. The immune system memory is just like real memory. I needs to be exercised w repetition - like studying for a test. A single event will not likely offer life long immunity.
2/x
My real concern is mutation that will evade, even If partial our immune responses to earlier versions of the virus or to vaccines being made (which are directed specifically towards mimicking earlier versions)
We have to act now on slowing spread in this case w/out immunity
3/x
It’s a new virus - not in an optimal state upon “birth” as it leaped into humans.
Has so much room to grow and ‘learn’
Increases in transmission rates and evasion of immunity should be expected.
We can anticipate and act accordingly.
1/x
We can start now to think through new vaccine designs that are not all narrow number of epitopes (in this case single [important] protein) and essentially identical to each other.
We can start “future proofing” our vaccine design choices to reduce immense risk of escape.
2/x
We can also immediately start building an Arsenal of contingency plans.
Tools that will not be susceptible to the same risk of mutants escaping immunity that arise from the ecological pressures from vaccines and infections....
3/x
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
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.