To Vaccinate or Not---The Rat Flu Odyssey Continues

[summit]

Summit is also currently, actively, (professionally - it appears ) involved in this, and may be seeing Information. . .

and I have not seen anything "official" about alternative testing procedue(s)...

I occasionally check in on the thread. What is the question?

Is there even a standard yet for cycle thresholds or is that still being decided locally? Seems like if you want a standard test with more sensitivity (say, to account for more contagious variants) that might be a good starting point. My googler machine is not showing me very current stuff on that.

It should not be decided locally. Follow the IFU from the manufacturer. A particular assay on a particular analyzer will have instructions for use determined by the manufacturers testing as part of the approval process for that assay. CLIA is pretty strict about following instructions. I am not a laboratorian.

And the more contagious variants have typically replicated more easily and so you really don't need a more sensitive naat (includes pcr) because the viral load (and thus probe targets) are equal or higher sooner than Wuhan-1.

[skiJ]

I'd still like to know what was the final expert opinion regarding the notion that swabbing the throat could give a better sample than swabbing the nose. The discussion seems to have just fizzled out without any official CDC or NIH opinion given. @SkiJ, MoForo Trackhead, did any of you see anything official about that theory before it just kind of quietly went away.. Or did the experts determine for sure that the nose is still the better sample source for rapid tests?

swabbing the throat v/ swabbing the sinus...

[summit]

Oh. I have him on ignore to avoid wasting brain cells.

In the beginning, we collected everything, saliva, OP (throat), NP (deeeeeep nose brain tickler), blood, bronchial lavage, urine... there were even fecal studies... obviously we also indirectly now test feces through wastewater.

It was found that NP was the most sensitive. Later data showed that AN (nose, but not deep), though it lowered sensitivity over NP, was sufficient for symptomatic diagnostics (high suspicion) or for screening/clearance (low suspicion).

With Omicron we saw some anecdotes of antigen OP swabs being positive while AN was negative. I never saw any literature here. I suspected this had more to do with (poor) AN collection technique.

[skiJ]

Thank you... skiJ

[RShea]

^^^^
I ordered last round that promised 8 tests... probably about 6 weeks ago. It took almost a month but they sent 10, 2 packs of 5. It definitely took more than 2 weeks though. First time they came really quick. Your experience this round seems similar to mine. I did get notices with tracking when they shipped. I'm guessing you didn't get that yet..

Thanks for the update with your experience. I saw some tests at stores before and just after they announced the government program. Not as many other there now- but I did not go to every pharmacy in town. And have not seen any on shelves recently, so stores must have figured they would be hard to complete with free.

As for what updates I got. I received the 2 emails (stating 4 kits in each) the day after I did the order back in May. It had a "tracking" number, but was not anything that USPS or other shipping carrier that I see regularly for stuff. So I guess they will arrive sometime next few weeks or more from the sounds of it.

[SumJongGuy]

Oh. I have him on ignore to avoid wasting brain cells.

In the beginning, we collected everything, saliva, OP (throat), NP (deeeeeep nose brain tickler), blood, bronchial lavage, urine... there were even fecal studies... obviously we also indirectly now test feces through wastewater.

It was found that NP was the most sensitive. Later data showed that AN (nose, but not deep), though it lowered sensitivity over NP, was sufficient for symptomatic diagnostics (high suspicion) or for screening/clearance (low suspicion).

With Omicron we saw some anecdotes of antigen OP swabs being positive while AN was negative. I never saw any literature here. I suspected this had more to do with (poor) AN collection technique.

So the answer is nobody has any idea and aren't actively really trying to find out. After all, why waste brain cells on something like that eh?

Let's see, I was right about masks (to prevent the spread to others, not to protect ourselves) right after this shit started, when the CDC was telling everyone NOT to wear them..

I was right about Uvalde cops saying "NOPE" to going in because they knew their protective gear was worthless against AR fire (even though protocol was go go in anyway).

We may find out eventually that different variants test differently based on the sample source.. FWIW, a clue may have been that Omicron no longer impacts sense of smell, so perhaps the nasal cavity isn't the best source for that? Ya conjecture, but whatever..

[skiJ]

Summit, thank you for your insight.

SJG, Summit's post addresses your question -
NP and AN sampling are current protocols.
your claim about Omicron and sense of smell and testing protocols is Two big leaps
( Omicron's impact on sense of smell may have nothing to do with testing, And if you want to revise testing protocols based on some hypothesis ,,, well that certainly might happen.
If you want to promote OP testing while efforts are to create a nasal vaccine that would be more effective at limiting transmission. - Go For It. ! !!


I appreciate Summit's professional insight -

Thank you. skiJ

[SumJongGuy]

Summit, thank you for your insight.

SJG, Summit's post addresses your question -

Not really. He said he heard something to that effect but suspects it was poor collection. No formal info seen about it on his end.. AKA maybe but probably not.. but nobody's really studying it to find out for sure at this point. Earlier variants the shallow nose worked fine..

With Omicron we saw some anecdotes of antigen OP swabs being positive while AN was negative. I never saw any literature here. I suspected this had more to do with (poor) AN collection technique.

I appreciate Summit's professional insight -

Thank you. skiJ

I do too but he's really kind of a dick about it sometimes..

Too busy looking down his nose to see other valuable insights..

[jono]

I occasionally check in on the thread. What is the question?



It should not be decided locally. Follow the IFU from the manufacturer. A particular assay on a particular analyzer will have instructions for use determined by the manufacturers testing as part of the approval process for that assay. CLIA is pretty strict about following instructions. I am not a laboratorian.

And the more contagious variants have typically replicated more easily and so you really don't need a more sensitive naat (includes pcr) because the viral load (and thus probe targets) are equal or higher sooner than Wuhan-1.

The question I was thinking about was more public health related (and maybe clinical norms make it moot, IDK): at various points it has been postulated that contagiousness was at least somewhat correlated with positive tests and also with viral load. It would be convenient if a negative test could at least give some indication of a person being less contagious (for public health purposes, aside from treatment plans). But if newer variants require a lower infectious dose then it stands to reason that a lower threshold for test positivity would be needed to achieve that result, as compared to Wuhan classic.

Couple that with lots of symptomatic negatives simultaneous with family members testing positive. It seems like everyone I know has been a negative/presumed positive at some point. Knowing how much weight to give a negative result (or two or three) in that scenario would be helpful, if it's possible.

I realize that locally changing the procedure isn't kosher, and as I'm thinking about it I don't know if I've seen that referenced since some kerfuffle in 2020, so hopefully it's not a thing. But manufacturers could adjust this for more sensitivity, right? On the other hand, if the RNA has changed a little anyway (and will again...) maybe there's no will for it?

[bobz]

Ugh, I'm in the same boat. My elderly mom caught Covid a few days ago (from a caregiver; amazing that this never happened up until recently). I ended up having to take her to the ER for antibodies infusion, and was stuck sitting in a small hospital room with her for a couple of hours while she complained pretty much constantly. I was wearing a good fitting 3M N95, but still... I'm isolating, more or less, masking etc... and waiting nervously. Glad my booster is nice and fresh. (And, incredibly, it's looking like mom will survive; yes, she's vaxed.)

Well, looks like Mom's surviving Covid; she's still pretty drained, but she's also finally testing negative. And I never caught it, no symptoms, and negative tests; amazing, good fitting N95 for the win.

In the meantime, my wife got cast in a show, and she went for it; outdoor stage, at least. 20 rehearsals, and I went to opening night day before yesterday. Singing, dancing, tapping, comedy... all good. Yesterday morning, the lead actor tested positive. They did last night's performance using an understudy in his role. This morning, a bunch of cast members (not my wife) tested positive, and they canceled the show for tonight and next weekend (the rest of its run). Sigh. So we're once again watching and waiting; my wife's not out of the woods on this one at all, and of course I could catch it if she comes down with it.

Anyway, yeah, it's really going around. In the Bay Area, I can't recall another time when I'd known and heard of nearly as many people having Covid; it's just not even close to previous Covid blooms. And the statistics aren't showing that. Because most people (and probably a much larger percentage outside the somewhat affluent Bay Area, "WTF, a $65 co-pay and who knows what other charges they'll come up with? I'll pass on that, thanks") are just self-testing, self-diagnosing, and self-dealing with it these days. But at least we're all vaxxed in this region, so hospitalizations aren't actually all that high, my mom's visit notwithstanding.

[summit]

The question I was thinking about was more public health related (and maybe clinical norms make it moot, IDK): at various points it has been postulated that contagiousness was at least somewhat correlated with positive tests and also with viral load. It would be convenient if a negative test could at least give some indication of a person being less contagious (for public health purposes, aside from treatment plans). But if newer variants require a lower infectious dose then it stands to reason that a lower threshold for test positivity would be needed to achieve that result, as compared to Wuhan classic.

Couple that with lots of symptomatic negatives simultaneous with family members testing positive. It seems like everyone I know has been a negative/presumed positive at some point. Knowing how much weight to give a negative result (or two or three) in that scenario would be helpful, if it's possible.

I realize that locally changing the procedure isn't kosher, and as I'm thinking about it I don't know if I've seen that referenced since some kerfuffle in 2020, so hopefully it's not a thing. But manufacturers could adjust this for more sensitivity, right? On the other hand, if the RNA has changed a little anyway (and will again...) maybe there's no will for it?

Ah. OK. Now I'm picking up what you are putting down. Your reasoning is good in that viral load has correlation to cT and that ID50 has decreased as the variants have evolved. But I think there are some details that would help clarify the situation:

In general PCR was set to a ct for positive that was, and I believe still is, sensitive enough to capture most cases who are contagious but asymptomatic and even PREsymptomatic.

Lower ID50 doesn't mean that a person is necessarily contagious much sooner nor for longer. Replication cycles in the body due to reproductive fitness boost viral load quickly. I think incubation has shortened due to viral reproductive fitness: loads rise above threshold sooner. When people stop being contagious has more to do, in my understanding, with the lack of replication competent virus which wouldn't correlate as well with cT because the probes have lots to bind to (fragments and neutralized virus).

This presence of gene targets while no longer being contagious is the problem with positive tests persisting more frequently and longer with PCRs after a person is no longer contagious and why we in mid 2020 moved away from PCR clearance to time based clearance from isolation (and now we have the combo option of negative antigen and time). It was also the hazard of PCR screening/surveillance being prone to a technically correct positive but a clinically false positive result in the case of recent infection. So are you finding people who are asymptomatic transmitters earlier or are you finding people who already had they asymptomatic disease and are not contagious?

If you raise cT you increase the risk of these technically correct (target is present) but clinically false positive results AND you also raise the risk of technical false positives. Testing is always a balance between variables because there are hazards to a false negative but also to a (clinically) falsie positive.

I suppose my thought is that even if you took all that I said above and had a good argument for adjusting cT values, most testing in my state has shifted to antigen while most NAAT is being used clinically: diagnostic testing on high suspicion patients. This is most appropriate because we want the better sensitivity and specificity of the PCR in these patients: high PPV and NPV augmented by high pretest probably.

The public is using antigen with its lower sensitivity and specificity which is offset by the ability to do serial testing and have instant feedback. So in general, serial antigen testing freely available with instant results is going to inform more people what protective measures they should take than fewer more sensitive PCRs with delayed resulting.

Testing is hard.

[Tri-Ungulate]

Testing is hard.

To add to the confusion, there is inter-assay variability for cT (between companies) in re: what constitutes a positive PCR result - noting the type of machine used along with the cT is really important but often overlooked. Usually not an issue with a hospital or system that unites around a single assay, but if comparing between, this needs to be taken into account.

With what Summit mentions above re: differences in LD50, as well as our estimates of contagiousness between variants, the difficulty in drawing conclusions is compounded.

Most people have no inkling how difficult it is to assess the problem. Kudos to those who are making the effort.

[summit]

Each of the two health systems I work for has at least 4 in house NAAT assays for COVID, as was necessary for POC (Abbot IDNow) and multiple PCRs to handle volume and supply chain issues. On top of this we send out other tests to reference labs (sendout in normal talk).

One thing we don't do is even look at, much less compare, is cT values at the patient or population level. It is set and tested by the labs as per manufacturer. We have internally studied cT values between assays as part of our validation process for new assays.

As TriU mentions, there is variations in performance between tests, but it is mostly subtle (unless you have S dropout, but none of ours did) except for the difference between single target NAAT like IDNow and multitarget PCRs. It only matters when you get a negative with high pretest probability, no alternative explanatory dx, and continued clinical suspicion. Then we may retest if it will change the clinical course (qualify for treatment) but usually we just isolate.

[mb6f50]

If people are sick they should stay home regardless if its covid, the flu, a cold, etc.

Period. End of subject.

A positive covid test really should be to notify close contacts and to be aware of potential serious or life threatening symptoms.

[Cisco Kid]

Right, good luck with you relying on me to keep you healthy.

[Mofro261]

The question I was thinking about was more public health related (and maybe clinical norms make it moot, IDK): at various points it has been postulated that contagiousness was at least somewhat correlated with positive tests and also with viral load. It would be convenient if a negative test could at least give some indication of a person being less contagious (for public health purposes, aside from treatment plans). But if newer variants require a lower infectious dose then it stands to reason that a lower threshold for test positivity would be needed to achieve that result, as compared to Wuhan classic.

Couple that with lots of symptomatic negatives simultaneous with family members testing positive. It seems like everyone I know has been a negative/presumed positive at some point. Knowing how much weight to give a negative result (or two or three) in that scenario would be helpful, if it's possible.

I realize that locally changing the procedure isn't kosher, and as I'm thinking about it I don't know if I've seen that referenced since some kerfuffle in 2020, so hopefully it's not a thing. But manufacturers could adjust this for more sensitivity, right? On the other hand, if the RNA has changed a little anyway (and will again...) maybe there's no will for it?

First, excellent summaries by Summit.

Re: cT thresholds. Yes, they do vary by the low end cut-off across various manufacturer's tests and different machine set-ups, but largely speaking these cutoffs are ~38-42 and significantly below the cutoffs for recovery of live virus.

Regardless of the strain variant, the ability to culture live virus in parallel from a NP or AN remains almost constant- between cT 30-32. Repeating that this is significantly less than the assay cut off value ( 1 log = 3.2 cycles) for all of the assays.

What has changed via the variants and now onward thru Omicron, is the % of those testing postive with low cT's less than 30 (higher viral burdens, more contagious). Like from a 20% superspreader capacity to >80% now capable of onward transmission. Part of this may be Omicron has an easier time estabilishing infection in the Upper RT and nasal tissues, less virus needed to initiate/more chances to set up infection.

In the early stages of infection it is possible to be PCR+ and still Ag neg- as it takes time for the viral replication to make enough to the Nucleoprotein antigen that is the basis for every Ag detection assay, usually Ag+ will lag by 1-1.5 days. Most Ag assays have a sensitivity falling somewhere between cT 28-33, and generally >90% for below 30, so Ag+ does have a good correlate with contagiousness still.

But PCR type assays also cost 5-10X more than a Ag assay to run, and the actual cT isn't part of a consideration for +/-; one can have lingering RNA that will still amplify long after the ability to culture live virus is gone.

And the virus while not neccessarily topping out at a much higher viral burden, is achieving max viral load at least 1.5-2 days earlier (day 4 vs 5.5) in the infection cycle than the WU-1 did.

[mb6f50]

Right, good luck with you relying on me to keep you healthy.

Exactly. If I can't rely on you to stay home when you have a cold or a flu why would I rely on you to stay home when you have covid?

I stay home when I'm sick, though.

If everyone did so less people would get sick and there would be more sick leave available.

Well for skiers and dentists and stuff, anyways.

'Merica doesn't give a fuck about low wage workers.

[summit]

In the early stages of infection it is possible to be PCR+ and still Ag neg- as it takes time for the viral replication to make enough to the Nucleoprotein antigen that is the basis for every Ag detection assay, usually Ag+ will lag by 1-1.5 days. Most Ag assays have a sensitivity falling somewhere between cT 28-33, and generally >90% for below 30, so Ag+ does have a good correlate with contagiousness still.

But PCR type assays also cost 5-10X more than a Ag assay to run, and the actual cT isn't part of a consideration for +/-; one can have lingering RNA that will still amplify long after the ability to culture live virus is gone.

Great post Mofro.

I think the issue for most people is that they won't get in for a PCR and get results for 1-3 days so doing two antigens in that time period is both cheaper, more timely, and nearly as clinically sensitive.

I think most folks don't get the messaging that antigens should be done in twos.

[bodywhomper]

So is it possible for pcr+ and Ag - the same day, followed by ag - for every two days afterwards over a week, no symptoms, ag- every other day for two weeks prior to the pcr +, and fully vaxed/boosted mean that person was infected and fought off the infection due to vax and was not infectious? Nobody else in the household was pcr or ag + with testing almost every other day for a month.

Also, stay at home when you’re sick is great and should happen, but it’s tricky when people have allergies

[summit]

So is it possible for pcr+ and Ag - the same day, followed by ag - for every two days afterwards over a week, no symptoms, ag- every other day for two weeks prior to the pcr +, and fully vaxed/boosted mean that person was infected and fought off the infection due to vax and was not infectious? Nobody else in the household was pcr or ag + with testing almost every other day for a month.

Also, stay at home when you’re sick is great and should happen, but it’s tricky when people have allergies

or they didn't have COVID at the time...

1. The PCR+ Ag- person's peri-PCR symptoms were incidental (they had something else like rhinovirus... or a hangover and allergies... or whatever) AND
2. PCR was false positive: either technically, or more likely clinically because they had COVID sometime within the previous ~90 days, perhaps asymptomatically, and still had enough genetic targets floating about to be PCR+

This scenario is more common given that unbelievably large proportion of the population that had COVID this year

[Cono Este]

My 33 yr old cousin was buried today. Got Covid, got cleared then went to hospital on day 14 complaining of an ear ache. They sent her home and she Died in her sleep.

33, with a 2 yr old.


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[bodywhomper]

Cono este, really sorry to hear about your cousin. That’s horrible and sad. Another motherless child

or they didn't have COVID at the time...

1. The PCR+ Ag- person's peri-PCR symptoms were incidental (they had something else like rhinovirus... or a hangover and allergies... or whatever) AND
2. PCR was false positive: either technically, or more likely clinically because they had COVID sometime within the previous ~90 days, perhaps asymptomatically, and still had enough genetic targets floating about to be PCR+

This scenario is more common given that unbelievably large proportion of the population that had COVID this year

Thx. Having covid previously was our other main thought except nobody in the household were symptomatic during that time period. For all of May, we were under nearly daily exposures, but my household was always masked (kn95) during indoor exposures and all testing negative with Ag tests.

Incidentally, the long timeframe of testing positive on pcr tests with not a lot of other good information available was a main reason the US swim team pulled out of the olympics in 2020.

[jono]

Condolences to you and yours Cono, that's gut wrenching.

Thanks for the discussion Summit, Tri-U and Mofro. Feels repetitive now (probably moreso to you guys) but that helps.

I'm gathering that the situation for late testing (Ag and PCR) is about what it's been for a while but a PCR may show positive sooner than was common previously (and at or near symptom onset?) due to quicker rise in viral load. Am I reading that right?

Similar to bodywhomper, I'm looking at my recent experience of a probably very mild but non-zero infection/invasion* (with lucky timing on a booster) and wondering how common it might be to have a good immune response, minimal symptoms and never test positive. Maybe it's super unusual, or it just goes unreported, written off as a cold/allergies etc. Perhaps moot clinically, but it feels like the weird stuff is part of the picture for understanding collective immunity and evolution etc. because there seem to be a lot of these just judging from people I know.

*over in 3 days, 95% sinus, 2 negative PCRs @ days 1 and 3 of symptoms, known exposure to PCR+ for a couple days before symptoms (she seems almost better now, occasional coughing at day 23, still some fatogue, but good clinical confidence of +), and no other exposures on a likely timeframe (contact tracing was pretty easy for the 5 days prior). Call that ~95% confident?

[The SnowShow]

My 33 yr old cousin was buried today. Got Covid, got cleared then went to hospital on day 14 complaining of an ear ache. They sent her home and she Died in her sleep.

33, with a 2 yr old.


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OMG, so sorry to hear. Brutal.

[Dantheman]

My 33 yr old cousin was buried today. Got Covid, got cleared then went to hospital on day 14 complaining of an ear ache. They sent her home and she Died in her sleep.

33, with a 2 yr old.


Sent from my iPhone using TGR Forums

Jesus. "Ear ache" was some kind cerebral embolism due to a covid blood clot?