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  Rapid antigen tests
Posted by: M_T - 12-24-2021, 11:56 AM - Forum: COVID-19 - Replies (1)

People still use the term "COVID test" without specifying what kind of a test it is.   Those that want results to be negative (regardless of infection) say they want positive confirmation.   To me, for PCR tests, that seems unwarranted.   I suspect some may use techniques to interfere with this testing.

If you acquire a rapid antigen test (BinaxNOW was $14 at Walmart when I bought some last week), you will see that it is actually two tests in a box.  The tests are to be taken 1.5 to 3 days apart.  If EITHER test is positive, then you almost definitely have COVID.  If BOTH tests are negative, then likely you don't have COVID. (What does "likely" mean? See below)

While the test has an EUA only for symptomatic individuals, the disease has a high percentage of asymptomatic infections.  So it is being used to detect those people.

Here are a couple of studies comparing the results of simultaneous testing by BinaxNOW and PCR-RT.
 1. "Performance characteristics of a rapid SARS-CoV-2 antigen detection assay at a public plaza testing site in San Francisco"
 2. "Effectiveness of Abbott BinaxNOW Rapid Antigen Test for Detection of SARS-CoV-2 Infections in Outbreak among Horse Racetrack Workers, California, USA"

First, a bit about PCR tests.   While most people just see a thumbs-up or thumbs-down result for PCR tests (yep, you have COVID; nope, you don't), the PCR test actually can give a Ct (cycle threshold) score that basically gives a measure of the amount of virus in the sample  (note that the process of taking the sample may impact whether that sample is indicative of the virus in the body).   The higher the Ct score, the less virus.  

As I understand it, no one knows how much virus it takes to infect others around you, or (more probably) the amount of time for you to infect someone around you. However, study 1 asserts without reference "we defined a threshold for high virus levels corresponding to the range thought to be the most transmissible: a cycle threshold of 30".

The first study (in SF) has images showing BinaxNOW results on lab-grown samples (Figure 1) at various levels of virus. The also have an image (Figure 2) showing the positive/negative results on 26 people who tested positive by PCR-RT ranked by Ct values. These show the BinaxNOW test always (N=10) negative for Ct>34 and always (N=13) positive for Ct<27.

One could say that the BinaxNOW properly indicated an infection in 16 of 27 (59%) people with PCR-RT confirmed COVID. But I now see that as too simplistic. The positive predictive agreement (59%) will vary depending on the distribution of the levels of virus in the tested population. IF (and I'm not sure it is correct) the apparently less-severe nature of Omicron in the vaccinated population means that people have lower levels of virus, then BinaxNOW probably will have a much lower agreement with PCR-RT testing.

The second study (Racetrack) had more disagreement when comparing BinaxNOW vs Ct. See their Figure 1. One test with a Ct score of 17 was a negative BinaxNOW results.

In both studies, two samples (for BinaxNOW and PCR) were taken by the same person, so that shouldn't matter. Perhaps which sample was taken first might matter. So, why the difference? One might be in the interpretation of the resultant BinaxNOW test. The first study established a standard for reading the results that is more formal than what is in the test kit. The first study also took images of the results and used a colorimeter to evaluate the result.

I'll also mention that when I was looking for instructions on how to perform the BinaxNOW test, I first found some training video produced by some firefighters. I figured they would be good. Well, no. They inserted the swabs deeper than recommended, and then failed to run the swabs around the inside of the nose but instead just twirled the stick. Sigh...

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  Pfizer vs Moderna boosters vs Omicron
Posted by: M_T - 12-21-2021, 12:07 AM - Forum: Vaccine - Replies (3)

We now have data from Pfizer & Moderna on how their boosters do against Omicron. (See other posts (P, M) I just made)

Warning:  I have previously seen warnings to not take the neutralizing antibody titers from different studies and compare them.  I am not qualified to say whether the raw numbers from the two studies are equivalent.  For instance, I haven't compared the subjects in the two studies.

I believe, but am not certain, that the ratio of increase by the booster may be comparable across studies.  Moderna seemed better at 37x (EUA 50ug booster for >= 18yo)  or 83x (EUA 100ug booster for immune-compromised people)  versus 25x for Pfizer.

However, should the numbers be on the same scale, it looks like Moderna is doing better against Omicron than Pfizer.  Pre-boost titers were 25 vs 6.  Post-boost were 850 (Moderna 50 ug booster) or 2228 (Moderna 100 ug booster) vs 155.

Pfizer says they are working on an Omicron-specific formulation.  Moderna indicated they were going to concentrate in the short-term on the current formulation.  I take this to mean that Moderna thinks their booster is the best currently and will be working on getting more doses out for people in the short run.  I think Pfizer wants to improve their situation.

What we haven't seen here are heterologous effect of mixing Moderna and Pfizer (2 shots of one, a booster of the other).  I previously posted one study that showed
  1. AZ + b. Pfizer > 1. Pfizer + 2. Pfizer > 1. Moderna + 2. Moderna > 1. AZ + 2. AZ
Note that in that study, it seemed that Pfizer+Pfizer was better than Moderna+Moderna.

I got my booster as soon as it was available. But if I were considering getting my booster at this point,
  1)  DON'T WAIT.  Whether I had contracted COVID (any variant) or not, I'd get a Pfizer or Moderna booster today.   I wouldn't even think about waiting months for an Omicron-specific booster.  That may be too late as the infections are going to peak very soon.
  2)  I'd probably get a Moderna booster, no matter what initial formulation I had.
  3)  If I could get a Moderna full-dose third shot (rather than the half dose EUA booster), I'd think that's best.
PLEASE NOTE:  I am not a physician. I know nothing about other people's health status.  This is my opinion for me.  Consult a physician for your situation.

People far more knowledgable than me will be comparing the vaccines after this report.  Pay attention to them.

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  Reproduction numbers of different variants in US
Posted by: M_T - 12-12-2021, 04:51 PM - Forum: Research - No Replies

(This does not include Omicron)
SARS-CoV-2 variant dynamics across US states show consistent differences in effective reproduction numbers

Quote:Here, we extend methods for inferring the effective reproduction number of an epidemic using confirmed case data to jointly estimate variant-specific effective reproduction numbers and frequencies of co-circulating variants using case data and genetic sequences across states in the US from January to October 2021. 



The reproductive number is affected by numerous factors: variant, population density, size of families, steps taken to reduce spread, adherence to those steps, completeness of infection numbers.  This group tries to compute this and to pull out the reproduction number for each variant, and then to compute a fixed growth advantage for each variant.   I'm trying to understand the state-to-state differences.

In other (colorful!) graphs in the paper they show the time-varying R for the variants.

[Image: COVID-R-by-Variant.png]

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  Estimates of Vaccine Effectiveness against Omicron hospitalization, etc.
Posted by: M_T - 12-12-2021, 04:33 PM - Forum: Research - No Replies

Estimates of reduced vaccine effectiveness against hospitalization, infection, 
transmission and symptomatic disease of a new SARS-CoV-2 variant, Omicron 
(B.1.1.529), using neutralizing antibody 
titers


Quote:Omicron increased the risk of hospitalization four to five-fold and increased the risk of symptomatic disease seven to ten-fold for mRNA vaccinees, with similar relative effects for recently vaccinated, or individuals with waned antibody titers. Third doses restored titers and protection to levels similar to waned immunity against Delta. Overall, these analyses indicate that vaccine effectiveness against severe disease is significantly diminished for waned individuals, and protection against infection, symptomatic disease and transmission is nearly eliminated. However, third doses significantly ameliorate these reductions but only restore protection to levels equivalent to waned protection against the Delta variant. The invasion of Omicron is likely to result in widespread infection, and substantial hospitalizations unless widespread boosting of immunity occurs.
(bold and italics are mine)

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  Natural&Vaccine-produced Antibodies against variants including Omicron
Posted by: M_T - 12-12-2021, 04:25 PM - Forum: Research - No Replies

SARS-CoV-2 B.1.1.529 variant (Omicron) evades neutralization by sera from vaccinated and convalescent individuals

Quote:Neutralization capacity against B.1.1.529 [Omicron] was maintained best against sera from super immune individuals (infected and vaccinated or vaccinated and infected).


Vaccines & natural immunity versus Alpha, Beta, Delta, Omicron.  This shows the neutralization for various vaccines or prior infections against Alpha, Beta, or  Delta.   It doesn't look great.  Best was for people that got sick & then vaccinated; followed by those that got sick after vaccination.

Spikevax = Moderna
ChAdOx1 = AstraZeneca
BNT162b2 = Pfizer
ChAdOx1/BNT162b2  means full vaccination with AZ and a Pfizer booster.
B.1.1.7 = Alpha (UK variant)
B.1.351 = Beta (South Africa)
B.1.617.2 = Delta
B.1.1.529 = Omicron

Higher numbers indicate better immunity.


[Image: COVIDab-Rossler.png]

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  Antibodies for vaccinated with/without natural infection
Posted by: M_T - 12-12-2021, 04:04 PM - Forum: Research - Replies (5)

Delta breakthrough infections elicit potent, broad and durable neutralizing antibody responses

Quote:However,  we  show  that  Delta  breakthrough  cases,  subjects  who  were  vaccinated  after  
SARS-CoV-2  infection  and  individuals  vaccinated  three  times  (without  infection)  have  
serum  neutralizing  activity  of  comparable  magnitude  and  breadth  indicate  that  multiple  
types of exposure or increased number of exposures to SARS-CoV-2 antigen(s) enhance 
spike-specific antibody responses.

Graph A shows the  level of antibodies over time (30, 60, ... days)
B, C, and D show different kinds antibodies at the same time (shortly after infection or vaccination)

A thru D are measures of how effective the antibodies were against one particular culture of COVID.
E and F are the same  graph as D but against two other cultures of COVID.

In each graph are different groups of people.  Purple triangles are vaccinated people that got Delta (so probably recently).
The cyan diamonds are people who were infected with COVID (original or other) and then got vaccinated.
The orange circles are people who have been vaccinated but not had COVID.
The gray squares are people that were infected (in WA in 2020) but not vaccinated.
The white circles are people that were not vaccinated and not had COVID.
2X means two vaccinations.  3X means three vaccinations

[Image: COVIDab-Walls.png]


Quote:Figure 1: Repeated exposures to  SARS-CoV-2 antigens through  vaccination  or infection enhance S-specific serum IgG and IgA binding titers. 

(A) Serum IgG binding titers at 30 or 60 days post infection or 10, 112, or 180 days post second or third vaccine dose were evaluated
for longitudinal samples by ELISA using prefusion-stabilized SARS-CoV-2 S Hexapro as
antigen. Serum samples were obtained from  individuals who had a Delta breakthrough infection
(n=15, magenta triangle), were previously infected then vaccinated (n=15, teal diamond), have
only  been  vaccinated  (n=15,  orange circle),  were  infected in  2020 in Washington  State  (n=15,
gray  square),  or  were  SARS-CoV-2  naive  (samples  taken  prior  to  vaccination,  n=15,  open
hexagon).  

(B)  Serum  IgA  binding  titers  at  30  days  post  infection  or  10  days  post  second
vaccine  dose  were  evaluated  by  ELISA  using  prefusion-stabilized  SARS-CoV-2  S  Hexapro  as
antigen. 

© Serum IgM binding titers at 30 days post infection or 10 days post second vaccine
dose  were evaluated by ELISA using prefusion-stabilized SARS-CoV-2 S Hexapro as antigen. 

(D) Serum  IgG binding titers were evaluated by ELISA at 30 days post infection, 10 days post 
second  or  third    vaccine  dose  or  prior  to  SARS-CoV-2  exposure  (SARS-CoV-2  naive)  using  
prefusion-stabilized SARS-CoV 2P S as antigen. 

(E-F) Serum IgG binding titers were evaluated 
at 30 days post infection,  10 days post second or third vaccine dose, or prior to SARS-CoV-2 
exposure (SARS-CoV-2 naive) by ELISA using OC43 S (E) or HKU1 2P S (F) as antigen. # of 
doses:  number  of  vaccine  doses  received. 

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  Your brain on COVID-19
Posted by: M_T - 12-06-2021, 01:14 PM - Forum: COVID-19 - Replies (2)

A couple of not-yet-reviewed studies on effects on the brain related to COVID-19 infection.
  "Brain imaging before and after COVID-19 in UK Biobank"
    Posted in August.  Comparison of brain scans of 401 patients (and 384 controls) where brain scans had been done before infection.
    Post-COVID, there was a reduction in grey matter thickness in some areas, markers of tissue damage, decrease in brain size.

Quote:These brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease — or of the virus itself — via olfactory pathways (a possible entry point of the virus to the central nervous system being via the olfactory mucosa), or of neuroinflammatory events due to the infection, or of the loss of sensory input due to anosmia. 


"Brain Injury in COVID-19 is Associated with Autoinflammation and Autoimmunity"

Quote:During hospitalisation, patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependant manner, and there was evidence of ongoing active brain injury at follow-up 4 months later. Raised NfL and GFAP were associated with both elevations of pro-inflammatory cytokines and the presence of autoantibodies; autoantibodies were commonly seen against lung surfactant proteins as well as brain proteins such as myelin associated glycoprotein, but reactivity was seen to a large number of different antigens. Furthermore, a distinct process characterised by elevation of serum total Tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses in the same manner as NfL and GFAP.



Stay well.

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  Weather & COVID
Posted by: M_T - 12-04-2021, 03:37 AM - Forum: COVID-19 - Replies (1)

New Hampshire is #1 in cases/100K in the last week at 539.5.
New Hampshire is #1 in vaccination rate at 88.5% of the total population having had at least one vaccination.

Cases/100K population in last 7 days
[Image: COVIDcase-Rate20211203.png]
To me, this looks like the weather map, showing a cold front coming down from the north.  Maybe the outdoor temperature or the side-effects of cold weather (indoors; heating with little recycling of air; wood smoke somehow helping the virus to get into airways) are contributing to this.


Vaccination rate:[Image: COVIDvac-Rate20211203.png]

ME, NH, VT, MA, CT, RI, PA are the states with > 80% vaccination (of total population)
NJ is 79.7%, CA is 79.3%, NY is 78.8%  Every other state is lower.

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  Booster Hesitancy
Posted by: ChrisGreene - 12-03-2021, 08:37 AM - Forum: Vaccine - Replies (1)

My wife, 58, did not want to get the booster because she felt extremely sick for two days after the second dose. The symptoms were all extreme and included nausea and weakness. Only at the end of the second day could she hold down water, in the form of ice chips that I would feed to her every few minutes. (Doctor's recommendation).

After the Omicron thing I asked her to speak to her doctor about the booster. The doctor recommended it and also prescribed anti-nausea medicine. It made my wife say she will schedule a shot. So if you know someone who is hesitant to get a booster due to a previous reaction, a conversation with their physician may be helpful. 

Are there cases where boosters are contra indicated?

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  It ain't over
Posted by: M_T - 11-28-2021, 04:17 AM - Forum: COVID-19 - Replies (2)

We grow tired of a constant fight.  However,  ....

As of November 2021, Europe's number one cause of death is COVID.

Here are the current world and US levels of COVID weekly cases and deaths. 
I wouldn't count on the cases being actual, but the deaths are probably closer.
The fact that the number of cases in the US is on the rise means that deaths will
soon be on the rise.  But for now, there are just over 50,000 COVID deaths a week in the
world, with approximately 8,000 COVID deaths a week in the US (out of a normal 60K deaths).

[Image: Covid20211128.png]
(Sorry, the right-hand side of the thumbnail is truncated.  Click on it to see the full image.)

Approximately the middle of each graph is where vaccines first came available.

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