Are vaccines the light at the end of the tunnel?

[K.T.B.]

46 minutes ago, Porky55 said:

Apologies - wasn’t trying to offend anyone - obviously wrong 🙄 

 

YOU did not, that article is offensive, IMO.  I didn't mean to "shoot the messenger".

[nocl]

deleted

Edited October 31, 2020 by nocl

[Porky55]

3 hours ago, K.T.B. said:

 

YOU did not, that article is offensive, IMO.  I didn't mean to "shoot the messenger".

Fair enough 👍

Edited October 31, 2020 by Porky55

[TeeRick]

18 hours ago, Porky55 said:

This is exactly why the ten minute tongue swab being developed here NOW is imperative. A test that can scan for coronavirus with near immediate results in a hand held unit - just imagine 🤔 And before you ask - 

 

“In an Australian first, UTS scientists have used novel optical technology to design a highly sensitive saliva test for the SARS-CoV-2 virus antigens, or viral protein fragments. The test can deliver a positive result in under 15 minutes.

The rapid antigen test collects saliva in a cartridge placed in an existing hand-held device, first developed by Perth company Alcolizer for illicit drug testing. Customised iStrip technology measures the viral load in the saliva sample, even at very low levels, and displays the result on the instrument’s small screen.” 

 

Source: https://www.uts.edu.au/news/health-science/spot-coronavirus-test-within-spitting-distance

 

I would like to see evidence that this "Spit" antigen detection test is more sensitive than the current rapid antigen tests or the RNA RT-PCR test.  

[nocl]

49 minutes ago, TeeRick said:

I would like to see evidence that this "Spit" antigen detection test is more sensitive than the current rapid antigen tests or the RNA RT-PCR test.  

one comment about spit tests. I have seen a couple of studies that show that using a spit sample is as good as, and maybe better than the nasal swabs with pcr.  It is beyond me why the focus is still on the nasal swabs with require more complex kits, trained personnel, and are uncomfortable.

[TeeRick]

20 minutes ago, nocl said:

one comment about spit tests. I have seen a couple of studies that show that using a spit sample is as good as, and maybe better than the nasal swabs with pcr.  It is beyond me why the focus is still on the nasal swabs with require more complex kits, trained personnel, and are uncomfortable.

Yes I agree with you.  I think the at-home Covid tests in the near future will be Spit Tests.  

[Porky55]

5 hours ago, TeeRick said:

I would like to see evidence that this "Spit" antigen detection test is more sensitive than the current rapid antigen tests or the RNA RT-PCR test.  

I agree totally. I presume this is what they are currently working on.

 

 

Edited October 31, 2020 by Porky55

[mimbecky]

My understanding is that the vaccines won’t keep you from getting the disease but rather just the severity. Doesn’t that just mean we’re going to have a lot more people out there who are asymptomatic and passing the virus?

In other words if everyone is vaccinated in order to go on a cruise, it seems it will still be possible to contract it and pass it to other passengers. Does that mean there is no end to masks in sight? Ugggg

Appreciate feedback from those in the know.

M

 

[Fouremco]

3 minutes ago, mimbecky said:

My understanding is that the vaccines won’t keep you from getting the disease but rather just the severity. Doesn’t that just mean we’re going to have a lot more people out there who are asymptomatic and passing the virus?

In other words if everyone is vaccinated in order to go on a cruise, it seems it will still be possible to contract it and pass it to other passengers. Does that mean there is no end to masks in sight? Ugggg

Appreciate feedback from those in the know.

M

 

While the efficacy of the numerous vaccines currently under development won't be known for some time, the objective is definitely to prevent the disease, not just to lessen the severity. Like many existing vaccines, it is unlikely to be 100% effective, but it is highly unlikely that any vaccine would be brought to market if it didn't offer substantial prevention.

[markeb]

16 minutes ago, mimbecky said:

My understanding is that the vaccines won’t keep you from getting the disease but rather just the severity. Doesn’t that just mean we’re going to have a lot more people out there who are asymptomatic and passing the virus?

In other words if everyone is vaccinated in order to go on a cruise, it seems it will still be possible to contract it and pass it to other passengers. Does that mean there is no end to masks in sight? Ugggg

Appreciate feedback from those in the know.

M

 

 

The goal of the vaccines under development is essentially to stop the virus from entering cells, which stops or significantly reduces viral load and  and therefore transmission, and should also decrease disease severity. It's been awhile since I looked at clinicaltrials.gov, but pretty much all the trials had an endpoint measuring recovery of virus from vaccinated versus unvaccinated participants, which would be a surrogate of the vaccines ability to block transmission.

 

The nature of the vaccine target(s) (so far all are going after the same viral surface protein, but probably different segments) means immunity should block the first step in the virus' replication and the pathogenesis of the disease, so it "should" accomplish all the desired endpoints if it accomplishes any of them. But only time and the clinical trials will tell...

[cangelmd]

On 10/31/2020 at 9:46 AM, nocl said:

one comment about spit tests. I have seen a couple of studies that show that using a spit sample is as good as, and maybe better than the nasal swabs with pcr.  It is beyond me why the focus is still on the nasal swabs with require more complex kits, trained personnel, and are uncomfortable.

Two reasons - one is that to validate existing kits, especially those that are under an FDA EUA, for a different sample type is a total PIT*, we looked into that early on for a change in sample type and later to try to pool presumed negative samples. So most hospitals outside of large teaching institutions simply don't have the resources to do the study, and so the manufacturer has to submit that data to make the change. Second, when you are talking outside the healthcare setting, you cynically have to wonder why is the person being tested - can you trust them to not adulterate the sample, or get a buddy to spit in the cup? There is a downside to unobserved sample collection, depending on the circumstances.

When our commercial kits are released for saliva or when saliva adapted kits become commercially available, there will be a rapid switch I would guess.

[cangelmd]

12 minutes ago, Fouremco said:

While the efficacy of the numerous vaccines currently under development won't be known for some time, the objective is definitely to prevent the disease, not just to lessen the severity. Like many existing vaccines, it is unlikely to be 100% effective, but it is highly unlikely that any vaccine would be brought to market if it didn't offer substantial prevention.

Isn't there also a good possibility that later generations of a given vaccine may be more effective as the vaccines are refined - more accurate targets producing more neutralizing antibodies or more specific immunity? Does that apply to the new technology vaccines?

[nocl]

3 minutes ago, cangelmd said:

Two reasons - one is that to validate existing kits, especially those that are under an FDA EUA, for a different sample type is a total PIT*, we looked into that early on for a change in sample type and later to try to pool presumed negative samples. So most hospitals outside of large teaching institutions simply don't have the resources to do the study, and so the manufacturer has to submit that data to make the change. Second, when you are talking outside the healthcare setting, you cynically have to wonder why is the person being tested - can you trust them to not adulterate the sample, or get a buddy to spit in the cup? There is a downside to unobserved sample collection, depending on the circumstances.

When our commercial kits are released for saliva or when saliva adapted kits become commercially available, there will be a rapid switch I would guess.

The way China is running so many tests is because they group test on the first pass 100 to 1.  Then if a group test positive they retest the group in smaller lots. So one positive case in a 100 can be identified with no more than 21 tests.  If all negative it takes only 1.

[nocl]

2 minutes ago, cangelmd said:

Isn't there also a good possibility that later generations of a given vaccine may be more effective as the vaccines are refined - more accurate targets producing more neutralizing antibodies or more specific immunity? Does that apply to the new technology vaccines?

If nothing else later generation will probably be tested using infection as the criteria, not just preventing symptoms.

[cangelmd]

1 minute ago, nocl said:

The way China is running so many tests is because they group test on the first pass 100 to 1.  Then if a group test positive they retest the group in smaller lots. So one positive case in a 100 can be identified with no more than 21 tests.  If all negative it takes only 1.

Exactly, pooling. The military (sorry don't remember which branch) did the study here and have the green light to do pooling. I wouldn't be surprised if LabCorp and/or Quest are pooling. The problem for them with samples coming in from all over the country is that the optimum size of your pool is dependent on the prevalence of virus in the population. The algorithm and the procedure approved by the FDA for the military does not even allow pooling when prevalence gets over a certain level.

[Fouremco]

3 minutes ago, cangelmd said:

Isn't there also a good possibility that later generations of a given vaccine may be more effective as the vaccines are refined - more accurate targets producing more neutralizing antibodies or more specific immunity? Does that apply to the new technology vaccines?

One would certainly hope that this would be the case.

[hcat]

On 10/30/2020 at 10:05 PM, K.T.B. said:

 

YOU did not, that article is offensive, IMO.  I didn't mean to "shoot the messenger".

Last para is a political pitch

[TeeRick]

16 hours ago, mimbecky said:

My understanding is that the vaccines won’t keep you from getting the disease but rather just the severity. Doesn’t that just mean we’re going to have a lot more people out there who are asymptomatic and passing the virus?

In other words if everyone is vaccinated in order to go on a cruise, it seems it will still be possible to contract it and pass it to other passengers. Does that mean there is no end to masks in sight? Ugggg

Appreciate feedback from those in the know.

M

 

The short answer is that true vaccines are for prevention of infection.  It is more complex depending how they prevent infection.  For those seeking a longer but very general answer see below:

 

Vaccines against most bacterial diseases give you protective antibody responses which neutralize the bacteria in the blood and tissue.  Some bacteria can bind to cells but still can be neutralized by antibodies and antibiotics.  Most bacteria do not replicate inside your host cells with a few exceptions (like tuberculosis).

 

Vaccines against viruses are different since viruses replicate inside the host cells.  Vaccines which induce strong neutralizing anti-body responses will prevent viruses from binding to and infecting cells.  But the best anti-viral vaccines will also produce protective T-Cell responses.  These specialized T-Cells eliminate the virus replicating in the host cell after infection.

 

So yes a vaccine can reduce the severity of disease or infection if the virus has initially evaded the neutralizing antibodies and the TCell response takes over.  Many believe that this Tcell response is the basis for asymptomatic individuals with COVID, or individuals with just mild COVID symptoms.  Or the basis to control re-infection.  A recent study just published out of the UK shows effective Tcell responses 6 months after infection with COVID.  So a vaccine approach developing robust Tcell responses should be a very good approach. 

 

https://www.cnbc.com/2020/11/03/t-cells-responding-to-covid-19-six-months-after-infection-study-finds.html

 

https://www.uk-cic.org/news/cellular-immunity-sars-cov-2-found-six-months-non-hospitalised-individuals

[Arizona Wildcat]

22 hours ago, cangelmd said:

Exactly, pooling. The military (sorry don't remember which branch) did the study here and have the green light to do pooling. I wouldn't be surprised if LabCorp and/or Quest are pooling. The problem for them with samples coming in from all over the country is that the optimum size of your pool is dependent on the prevalence of virus in the population. The algorithm and the procedure approved by the FDA for the military does not even allow pooling when prevalence gets over a certain level.

The University of Arizona is doing pooling testing.  Working well.  Also testing sewage from dorms.  If a dorm tests negative then all in the dorm are negative.  Sounds crazy but working.

[nocl]

22 hours ago, Fouremco said:

While the efficacy of the numerous vaccines currently under development won't be known for some time, the objective is definitely to prevent the disease, not just to lessen the severity. Like many existing vaccines, it is unlikely to be 100% effective, but it is highly unlikely that any vaccine would be brought to market if it didn't offer substantial prevention.

  The current vaccine trials for Pfizer and AstraZeneca are using symptoms to determine efficacy, not infection prevention.

 

As far as these trials go, the data will not reveal if they prevent asymptomatic infection, only the number of symptomatic cases in each arm.  It was one of the issues discussed by the vaccine advisory committee during their October 22 meeting. Then did indicate while they considered to basing efficacy on symptoms to be a weakness, and is somewhat subject, compared to the objective measure of infection, they still consider the vaccine to provide medical benefit.

 

So if the results of these trials show efficacy, the trials will not answer the question if the vaccine is effective at reducing asymptomatic infection, if any asymptomatic cases are infectious. Not saying that they will be, only that it will not be known.

 

Covid, with its large numbers of asymptomatic infections is a bit more difficult, than most where asymptomatic cases are rare.

 

For them to use infection as the criteria, then they would need to test all participants periodically, which would between the need to report for testing and the discomfort involved with testing, would result in higher drop out rates.  it would also have a substantial cost.  Since even with grouping (100 to 1)  a periodic sample requirement would mean that 30,000 + samples would have to be taken and 3000+ analysis run (the exact number with the + would depend upon how many positives  turn up).

 

Oxford did run a primate challenge test with their vaccine candidate. The primates did not develop symptoms, but virus was detected in the nasal passages.  Unclear if that virus was residue from the initial doing, or if the virus was replicating.

 

Unfortunately without capturing asymptomatic cases they have no way to check for virus shedding, or to check if any asymptomatic cases result in any of the secondary impacts such as the cardiac damage that has been shown to occur in even some asymptomatic cases.  No way to test if no way to detect asymptomatic cases.

 

Hopefully they will start a follow up trial looking for asymptomatic cases once they have the data from the existing trials.

[Ken the cruiser]

1 hour ago, nocl said:

The current vaccine trials for Pfizer and AstraZeneca are using symptoms to determine efficacy, not infection prevention.

Which begs the question, are they taking the volunteers "word" that they have/don't have any symptoms via periodic phone surveys or are they required (and paid) to come in for periodic visits/checkups? If they come in, aren't they at least given a COVID test and their blood drawn to record their health status or do they just fill out a form? If the latter, that doesn't sound very scientific. 

[markeb]

17 minutes ago, Ken the cruiser said:

Which begs the question, are they taking the volunteers "word" that they have/don't have any symptoms via periodic phone surveys or are they required (and paid) to come in for periodic visits/checkups? If they come in, aren't they at least given a COVID test and their blood drawn to record their health status or do they just fill out a form? If the latter, that doesn't sound very scientific. 

 

At least for AZ, no.

 

 

Secondary Outcome Measures  :

1. The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of SARS-CoV-2 infection [ Time Frame: 1 year ]
   The proportion of participants who have a post-treatment response (negative at baseline to positive post treatment with study intervention) for SARS-CoV-2 Nucleocapsid antibodies over time.

Haven't looked at Pfizer.

 

I'm torn here. The practitioner says preventing disease (symptoms) is a perfectly acceptable endpoint for the individual (and not unusual, BTW). The public health guy says preventing infection (and therefore transmission) is the more important endpoint for the population as a whole. Reality is I don't think you get an take rate on the vaccine if it doesn't reduce symptoms in individuals...

Edited November 3, 2020 by markeb

[Ken the cruiser]

6 minutes ago, markeb said:

At least for AZ, no.

No to which part of my question?

[nocl]

1 hour ago, Ken the cruiser said:

Which begs the question, are they taking the volunteers "word" that they have/don't have any symptoms via periodic phone surveys or are they required (and paid) to come in for periodic visits/checkups? If they come in, aren't they at least given a COVID test and their blood drawn to record their health status or do they just fill out a form? If the latter, that doesn't sound very scientific. 

I do not know. One would think that if they reported Covid like symptoms they would need to get those confirmed in some fashion to make sure that it is not flu or some other illness that generates similar symptoms.  The ones that do not report symptoms do not get tested.

 

Hopefully Cruise Kitty is still checking this stream and will comment further.  She is in one of the trials

Edited November 4, 2020 by nocl

[nocl]

59 minutes ago, markeb said:

 

At least for AZ, no.

 

 

Secondary Outcome Measures  :

1. The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of SARS-CoV-2 infection [ Time Frame: 1 year ]
   The proportion of participants who have a post-treatment response (negative at baseline to positive post treatment with study intervention) for SARS-CoV-2 Nucleocapsid antibodies over time.

Haven't looked at Pfizer.

 

I'm torn here. The practitioner says preventing disease (symptoms) is a perfectly acceptable endpoint for the individual (and not unusual, BTW). The public health guy says preventing infection (and therefore transmission) is the more important endpoint for the population as a whole. Reality is I don't think you get an take rate on the vaccine if it doesn't reduce symptoms in individuals...

There was certainly some discussion on this by the Vaccine Advisory Committee meeting  after the 7 hour point.

 

It sounded like they there were two issues 1. symptoms are subjective, a test for infection is objective and therefore a better measure  2. The inability to determine impact of asymptomatic cases and all that implies.

 

Of course if you prevent infection you also eliminate symptomatic as well as asymptomatic cases.

 

I can understand why they designed the protocol this way because using infection means frequent tests with the cost and drop out rate that such a protocol would have.  I can also understand why they have not started a smaller test just to collect data on infection (do not what to potentially cause confusion that could delay or prevent approval if there is some conflicting data. To keep it clean you keep and such trials until after approval and run them as single arm not double blinded, placebo.