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Are vaccines the light at the end of the tunnel?


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58 minutes ago, PTC DAWG said:

Perfect timing, huh?  

 

image.png.7cbec368a99cf38a44123a3e11f6375f.png

Yes this is a very interesting point.  And a very critical one in assessing the number of positive cases reported.  

The number of PCR cycles are really not standardized across the industry.  PCR cycles are inversely proportional to the amount of virus in the sample.  If a patient has active infection with symptoms then the viral load can be detected in less cycles (ie, 25).   The guidelines from the FDA and CDC and WHO are all over the place if you look up specific kits and instruments.   These were all approved by EUA and careful standardization was not employed across multiple manufacturers.  Many tests are done up to 40 or more cycles.  There will be a lot of false positives in tests that stretch the cycles above a certain threshold (33-35 according to CDC).

https://www.medpagetoday.com/infectiousdisease/covid19/90508

Edited by TeeRick
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14 minutes ago, TeeRick said:

Yes this is a very interesting point.  And a very critical one in assessing the number of positive cases reported.  

The number of PCR cycles are really not standardized across the industry.  PCR cycles are inversely proportional to the amount of virus in the sample.  If a patient has active infection with symptoms then the viral load can be detected in less cycles (ie, 25).   The guidelines from the FDA and CDC and WHO are all over the place if you look up specific kits and instruments.   These were all approved by EUA and careful standardization was not employed across multiple manufacturers.  Many tests are done up to 40 or more cycles.  There will be a lot of false positives in tests that stretch the cycles above a certain threshold (33-35 according to CDC).

https://www.medpagetoday.com/infectiousdisease/covid19/90508

Good move, if aren't getting the numbers you want, change the way you calculate it until you get the results you want. It only took them ten months to lower the bar.

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On 1/20/2021 at 9:05 AM, Pinboy said:

You are correct---

To be honest, I don't care who got their vaccine, when they got it, where they got it, how long the line was, etc, etc. 

I do care what the scientific evidence is as you pointed out many times, and thank you for your clear and concise explanations.

I also care when the hell we will get more vaccine in Canada !!!

 

 

Actually, I do care.  There is so little information on the actual news about the details of these things, finding out about others experiences can be very helpful.  In fact, it's very sad that so much of the detailed information I've been able to come across has been from FB posts and CC posts, rather than from where I should be getting it - my own health department.

 

I can see the point about maybe having those conversations on another thread.  At the same time, looking at the headline of this topic, one could argue that knowing how and when the vaccine is being distributed very much follows the question of whether vaccines are the end of the tunnel.  We can't see the end of the tunnel until we know when we can get vaccinated.   Not worth arguing about, and no disrespect to either side of the question, but I think it can be looked at two ways.

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58 minutes ago, TeeRick said:

Yes this is a very interesting point.  And a very critical one in assessing the number of positive cases reported.  

The number of PCR cycles are really not standardized across the industry.  PCR cycles are inversely proportional to the amount of virus in the sample.  If a patient has active infection with symptoms then the viral load can be detected in less cycles (ie, 25).   The guidelines from the FDA and CDC and WHO are all over the place if you look up specific kits and instruments.   These were all approved by EUA and careful standardization was not employed across multiple manufacturers.  Many tests are done up to 40 or more cycles.  There will be a lot of false positives in tests that stretch the cycles above a certain threshold (33-35 according to CDC).

https://www.medpagetoday.com/infectiousdisease/covid19/90508

You guys realize when we started no one had any firm idea about how many cycles to run, right? 33-35 is the norm based on highly educated guesses, and those numbers are holding up reasonably well, although 30 might be a better cutoff.
There’s a limit technically to how much standardization can happen because the reagents are natural products with more variability than simple chemical reagents and some tests use 2 targets and others 3 targets. On the highly automated instruments like Roche, Cepheid (which are very different beasts, but both highly automated) the variation based on reagent lot is determined at the manufacturer and the end users only have to verify that they get the expected results.

To meet the demand though, labs have dusted off every thermocycler (PCR machine) that’s been tucked away in back closets and put them back into service. These older instruments are intended for both clinical and research use and allow a lot more tweaking to get an optimal result.

We just now have enough data and breathing room to make better judgments of where the false positive line lies. Remember CoV-2 has an unusually long incubation time AND onset of symptoms varies greatly from person to person - if you reduce the number of cycles you reduce false positives, but increase false negatives and narrow the window of time that a person is “positive”. Up until now this is not a disease where you want to miss any true positives and that’s what increasing false negatives means

42 minutes ago, grandgeezer said:

Good move, if aren't getting the numbers you want, change the way you calculate it until you get the results you want. It only took them ten months to lower the bar.

Actually lower the cycle count raises the bar for infection.

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37 minutes ago, cangelmd said:

You guys realize when we started no one had any firm idea about how many cycles to run, right? 33-35 is the norm based on highly educated guesses, and those numbers are holding up reasonably well, although 30 might be a better cutoff.
There’s a limit technically to how much standardization can happen because the reagents are natural products with more variability than simple chemical reagents and some tests use 2 targets and others 3 targets. On the highly automated instruments like Roche, Cepheid (which are very different beasts, but both highly automated) the variation based on reagent lot is determined at the manufacturer and the end users only have to verify that they get the expected results.

To meet the demand though, labs have dusted off every thermocycler (PCR machine) that’s been tucked away in back closets and put them back into service. These older instruments are intended for both clinical and research use and allow a lot more tweaking to get an optimal result.

We just now have enough data and breathing room to make better judgments of where the false positive line lies. Remember CoV-2 has an unusually long incubation time AND onset of symptoms varies greatly from person to person - if you reduce the number of cycles you reduce false positives, but increase false negatives and narrow the window of time that a person is “positive”. Up until now this is not a disease where you want to miss any true positives and that’s what increasing false negatives means

Actually lower the cycle count raises the bar for infection.

 

The talk of cycle numbers is rather shallow and premature.  It's far away from being something meaningful.

 

If you have institutional access: Rhoads, Daniel, et al. "College of American Pathologists (CAP) microbiology committee perspective: caution must be used in interpreting the cycle threshold (Ct) value." Clinical Infectious Diseases (2020).

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3 hours ago, UnorigionalName said:

 

The talk of cycle numbers is rather shallow and premature.  It's far away from being something meaningful.

 

If you have institutional access: Rhoads, Daniel, et al. "College of American Pathologists (CAP) microbiology committee perspective: caution must be used in interpreting the cycle threshold (Ct) value." Clinical Infectious Diseases (2020).

Caution, exactly! This summer, when we were having the hardest time getting a reliable supply of reagents, I looked deeply into comparison of tests and cycle times because we were trying to validate pooling our low risk samples to conserve reagent, and finally just said no, we can’t do it, there’s not enough solid knowledge to feel comfortable with comparing cycle time of this assay to a different assay.

I will chase down that article, thanks

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8 hours ago, grandgeezer said:

Good move, if aren't getting the numbers you want, change the way you calculate it until you get the results you want. It only took them ten months to lower the bar.

Or it only took a day, depending on how you look at it, which I think was the point being made above.  It's been a tremendously politicized disease, and the timing of an announcement of changing the rules for measuring in a way that will undoubtedly have a direct impact on lowering "official cases" is certainly suspect; especially when reports about excessive Ct were being published last summer.  

 

 

The problem with false positives is that the 'system' doesn't believe they exist (save for high profile cases).  No re-testing of asymptomatic positives is recommended, and no amount of testing will reverse the positive result.   With a false negative, symptoms are likely to develop and re-testing may be recommended. 

 

 

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On 1/17/2021 at 12:02 AM, Porky55 said:

Agree, but change ‘people’ to Media, who seem to be shaping our lives, making Leaders (and vanquished), winners & Losers, for or against at the moment with their 24/7 coverage. And not for the good I fear.

You sir, are a wise man.

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Don't mind reserving this thread for  the more " scence" oriented posts,  but hope those posting offer plain language  explantions  of what these studies and conclusions mean ...for those  of us who are not  in the know.  Thanks

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Getting a vaccine is a good start to getting back to living.  It does give some protection and alleviates stress. However, it doesn’t mean we can move about freely.  After getting my vaccine, I was told that wearing masks, distancing, etc. is still necessary.  Until most people have the vaccine, nothing changes.  Travel is not advised to many countries.  If you do travel internationally, you have to have a covid test before getting on a plane to go back to USA.  Having vaccines doesn’t exempt you from covid testing.  It seems like a real hassle.  

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9 hours ago, Redtravel said:

Getting a vaccine is a good start to getting back to living.  It does give some protection and alleviates stress. However, it doesn’t mean we can move about freely.  After getting my vaccine, I was told that wearing masks, distancing, etc. is still necessary.  Until most people have the vaccine, nothing changes.  Travel is not advised to many countries.  If you do travel internationally, you have to have a covid test before getting on a plane to go back to USA.  Having vaccines doesn’t exempt you from covid testing.  It seems like a real hassle.  

 

You are right on. Having gotten the vaccine I contacted the CDC to see if this removed the requirement to get tested prior to returning on an international flight, The came back quickly with a NO, You still must be. In addition, I contacted several of the islands to see if the vaccine negated the need to be tested prior to arrival. They all responded NO. You still must have the test. Short term, the vaccine is not the answer. Long term, I hope so but no clear answer.

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10 hours ago, hcat said:

Don't mind reserving this thread for  the more " scence" oriented posts,  but hope those posting offer plain language  explantions  of what these studies and conclusions mean ...for those  of us who are not  in the know.  Thanks

Agree. Thanks for posting this. 

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9 hours ago, Redtravel said:

Getting a vaccine is a good start to getting back to living.  It does give some protection and alleviates stress. However, it doesn’t mean we can move about freely.  After getting my vaccine, I was told that wearing masks, distancing, etc. is still necessary.  Until most people have the vaccine, nothing changes.  

 

But let's be clear.  Wearing the mask and social distancing really doesn't provide YOU or anyone else more protection.  You must continue to wear the mask because the rest of society still must wear masks and social distance.  By having you continue to follow the procedures it keeps pressure on the unvaccinated to wear their mask and social distance.

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I am among the non-vaccinated in the US amongst hundreds of millions like me waiting for my turn.  Best guess is still many months away.  Thanks to the relatively few you to date who have been fortunate enough to qualify for a vaccine to keep the rest of us in mind.  

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13 hours ago, hcat said:

Don't mind reserving this thread for  the more " scence" oriented posts,  but hope those posting offer plain language  explantions  of what these studies and conclusions mean ...for those  of us who are not  in the know.  Thanks

https://www.sciencelearn.org.nz/resources/2347-what-is-pcr

A little background that may help -

We run these tests under an EUA - Emergency Use Authroization - which means the test has been assessed for basic accuracy but doesn't hasn't had all the ancillary data submitted to the FDA that a new test would usually require. One big batch of data that we didn't have was studies to link test results with disease occurence - physicians were expected to interpret the results in the context of the patient's presentation and what we know about the disease. This is most important at the low limit of detection - is this result a true positive result or a false positive? In the case of covid, false positives can be contaminating covid genetic material from another person (yeah it does happen, even though labs take many steps to prevent this) OR it could be a true positive but a very early infection (a big issue in covid because there are so many asymptomatic or mildly symptomatic cases and the incubation time is LONG). That's what all the talk of cycle times is about - in simple words, if you let the reaction run longer you are more likely to pick up contaminants, reduce the amount of time the reaction runs, you might miss early cases or cases with low amounts of virus. Viral PCRs are reported as negative, positive and the dreaded equivocal. The equivocals are usually cases of really early infection with low viral load or maybe just poor sampling, and resolve themselves with a retest in 24-48 hours.

Normally, we would have a gold standard to compare to the new test and the clinical implications of the gold standard would be well established by years of clinical experience. With Covid not only did we not have an easily obtained gold standard lab test for the virus we also didn't have the clinical knowledge to link back to.

Where we are now is that we have gained much practical knowledge, both on the lab side and on the clinical side, and I think we will start to see "tweaking" studies coming out that will allow us to tighten up the testing and make it more clincially relevant.

More than you wanted to know.

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1 hour ago, TeeRick said:

I am among the non-vaccinated in the US amongst hundreds of millions like me waiting for my turn.  Best guess is still many months away.  Thanks to the relatively few you to date who have been fortunate enough to qualify for a vaccine to keep the rest of us in mind.  

We will know soon if it is many months or just a few. Dr. Fauci's most recent comments are encouraging. Based on his comment from yesterday, it sounds like Pfizer and Moderna are on production schedule with a big ramp-up over the next 4-6 weeks - it sounded like this was kind of the plan all along, it just wasn't well communicated. Now that we know J and J will be delayed a bit, then health depts can make plans for handling Pfizer rather than holding out for the easier to store and administer J and J. We also have had small runs all over the country with the finickier mRNA vaccines and I think more places are prepared to ramp up those.

In my place, the pharmacy had been waiting for 6 months for a -70 freezer (we had to store first doses in the lab freezer) and they got it week before last, so there is all kinds of progress going on under the surface.

Fingers crossed!

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We got lucky. We were pounding away on the internet (over and over and over) and finally hit the jackpot. We found the health department with the vaccine in a neighboring county. We never typed so fast making an appointment....the appointments were gone within an hour. We drove an hour to the health department today to get our shots. No adverse reactions so far. Our home county still does not have one injection site.

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8 hours ago, cangelmd said:

https://www.sciencelearn.org.nz/resources/2347-what-is-pcr

A little background that may help -

We run these tests under an EUA - Emergency Use Authroization - which means the test has been assessed for basic accuracy but doesn't hasn't had all the ancillary data submitted to the FDA that a new test would usually require. One big batch of data that we didn't have was studies to link test results with disease occurence - physicians were expected to interpret the results in the context of the patient's presentation and what we know about the disease. This is most important at the low limit of detection - is this result a true positive result or a false positive? In the case of covid, false positives can be contaminating covid genetic material from another person (yeah it does happen, even though labs take many steps to prevent this) OR it could be a true positive but a very early infection (a big issue in covid because there are so many asymptomatic or mildly symptomatic cases and the incubation time is LONG). That's what all the talk of cycle times is about - in simple words, if you let the reaction run longer you are more likely to pick up contaminants, reduce the amount of time the reaction runs, you might miss early cases or cases with low amounts of virus. Viral PCRs are reported as negative, positive and the dreaded equivocal. The equivocals are usually cases of really early infection with low viral load or maybe just poor sampling, and resolve themselves with a retest in 24-48 hours.

Normally, we would have a gold standard to compare to the new test and the clinical implications of the gold standard would be well established by years of clinical experience. With Covid not only did we not have an easily obtained gold standard lab test for the virus we also didn't have the clinical knowledge to link back to.

Where we are now is that we have gained much practical knowledge, both on the lab side and on the clinical side, and I think we will start to see "tweaking" studies coming out that will allow us to tighten up the testing and make it more clincially relevant.

More than you wanted to know.

But more understandable !  Thank You

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1 hour ago, TeeRick said:

There are more and more communications like this one on COVID vaccine Q&A.  I am very glad that patient education has become so important in this effort.

 

https://www.medscape.com/viewarticle/944213?src=wnl_edit_tpal&uac=370300SV&impID=3147810&faf=1#vp_1

Thanks Rick.  Unfortunately, a whole lot of people will ignore information like that. 

 

That side effect table is great to convey what to expect. 

 

 

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for those interested in updates from trials :)

My husband was officially unblinded yesterday, & as we knew, he is fully vaccinated, he will receive his card in the mail.  My Daughter will be unblinded on Jan 29th , & vaccinated on 1st if needed & my date is Feb. 4th for unblinding with first shot on 5th. (we are all Pfizer)  We will all remain in the trail with our lovely blood draws, nose swabbings, & self reporting on our apps :)

 

   From what I understand from a private vax trial group that I belong to, Moderna is setting up appointments for some early phase 1 people to come in for booster shots in May as part of the trial.  

 

another takeaway from Doctors & scientists in that group is that the mask wearing will be just for consistency....  right now when my daughter & SIL come over, it's outdoors & with masks & 6 feet...  once the 4 of us are fully vaccinated we will be free to interact with one another mask free, so for us at least, we can truly see the light :)

 

On the other hand, I am desperately trying to get appointments for elderly in laws to get vaccinated... they are in Orange County, & the system there is terrible so far :)

 

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Well here in Canada it is a bleak situation for vaccines, really there are few if any vaccines happening.

 

Essentially the Cdn federal government did the big vaccine deal (the majority of vaccine purchase) with China (CanSino) but the deal fell through and their vaccine has received no approval. China blocked shipment of vaccine samples that were to be sent to Dalhousie University (near Toronto) for trials. So the Cdn feds had to scramble for vaccine and were and will remain behind other countries in vaccine supply going forward. Canada has no vaccine production facilities. 

 

For example in Ottawa, Ontario, a city of + 1 million, there is no vaccine period. Some, but not all, people in LTC and hospital and staff in retirement homes/LTC and PSW's and first responders got a first dose of Pfizer, that is it. No date for any further vaccine.

 

Unlike the US, the limited vaccine shots are being done in public health offices - no drug stores. So very limited venues even if there was vaccine. 

 

Plenty of trying to divert the attention away from the vaccine shortage going on at the federal level. Essentially I have given up ever getting a vaccine any time soon given the incompetence at the Cdn federal level.  The CDC hopefully is paying attention to the Canadian situation and ensuring the northern border remains closed.

 

So not able to plan any trips period due to the vaccine situation in Canada.  This is one reason why numerous Canadians have flown to the US and got their vaccine shots, granted many have properties there. Not good at all.

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1 hour ago, ABoatNerd said:

 

So not able to plan any trips period due to the vaccine situation in Canada.  This is one reason why numerous Canadians have flown to the US and got their vaccine shots, granted many have properties there. Not good at all.

 

Just a heads up.  On Thursday, January 21, 2021, the state of Florida restricted vaccines to residents only.  Apparently there were a lot of fly-in's and drive-in's from other states and countries that were overwhelming the system.  Even if you own property in Florida, you have to have proof that you are a permanent resident...  

Edited by cluso
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