I’ve spoken on sensitivity and why rapid Ag tests shouldn’t be compared to PCR
Nevertheless, we’re stuck comparing to PCR. So, to deal w this, “we” have taken to comparing rapid antigen tests to PCR results below specific Ct values that may represent contagious virus loads
2/x
In many studies, Ct of <30 or <25 are considered to be likely contagious or “high virus”, respectively
HOWEVER this is bad. We must stop assuming this
Not all labs are the same
A Ct 25 in many labs may = a Ct of 18 elsewhere
This happened in Liverpool w Innova evaluation
3/x
In Liverpool, one scientist made a huge deal of saying that Innova was not performing well at a Ct of 25 - which he considered as “high” virus load.
But it turns out that that lab uses a particularly efficient PCR assay and a 25 is actually “low”. In that lab <18 is “high”
4/x
When evaluated against the correct cutoff for moderate/high virus load (likely contagious virus) the Innova test performed extremely well (>90% overall sensitivity in that range).
So it is SO important for scientists to take the variation in CT values across labs seriously
5/x
The simple failure to accurately translate Ct values to viral RNA load has unfortunately led governments to question certain rapid tests & delay rapid Ag test use... all bc a scientist made a mistake and went to the media before correcting that mistake
(Still hasn’t)
6/x
Thanks @GiorgiaWithAnI for doing such a thorough reporting on the myriad issues of rapid tests. Wonderful write up (see top of thread 👆)
It covers much of the controversy. The issue I discuss here starts halfway down at: “But differently calibrated PCR systems...”
7/7
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Good thing is the mRNA vaccines provided exceptional efficacy. But that was also when plasmablasts (temporary antibody producing cells) were fully abundant. We don’t know the efficacy after a few months after they all die off. Hopefully will remain very high and protect. But..???
We also do not know (or at least so far I haven’t heard) whether people are getting severely ill or not. If the AZ vaccine prevents severe disease w the new variant, then that can be good enough. I wish this part was reported so far.
Possible we may be starting see a combination of seasonality on our side and likely seeing herd effects kick in.
1/x
On seasonality:
We knew in the summer that this virus was going to roar back in the fall. It did!
While coronaviruses collectively have a broad window each year, We can see that each individual coronavirus in the graph 👆has only a few months when it peaks. And then drops
2/x
This virus started really hitting us hard a second time in November. Oct-Jan may well be this viruses peak transmission window. We could be entering a reprieve from its grasp, at least for a while. If so, could help us get vaccines out and control spread quickly.
3/x
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
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