Greetings from Palmia Observatory
Well this week has been clouded out, and I had hoped to report more data points for our tracking of Titan's orbit around Saturn, so we have to resort to other topics and can report on our ongoing armchair study of computer deep learning systems with detour into armchair study of virology.
I have been following Lex Fridman's podcast for sometime now and he always has discussions on artificial intelligence, lasting sometimes over three hours, with interesting scientists. Fridman emigrated from Russia and is now a professor at MIT. This time his conversions was with Michael Mina, MD and Harvard professor.
Mina has been a fulltime advocate of changes to the COVID-19 testing approach and methods. He argues that the current situation has testing being controlled as a medical device, which means that the need for testing as a public health issue does not get adequately addressed. The current testing, based mainly on PCR, is very accurate and meets the needs of the medical community to diagnose illness, but the delay time, up to five days in getting results, makes prevention of the public health issues problematic.
Fast, at home test methods, are available that provide test results, positive or negative for COVID-19, in under 15 minutes, and only cost about $1, instead of a $100 or so for the medical tests. For mitigating the public health issue, you want rapid testing, but these rapid tests do not meet medical profession dictated FDA requirements and cannot be made available for public use.
Mina argues that there is a lot of resistance from the whole medical products industry and regulators who don't like the $1 test and argue that it is not accurate enough. Mina counters this argument saying that the accuracy is sufficient for public health. If a person were to test at home, they would know immediately if there were contagious or not. The more expensive test will show positive results weeks after the inception of disease, even when the person is no longer infectious.
His argument is not against the use of the PCR test for medical use, but that a different kind of test, essentially an at home or quick response type of test, is what is needed to stem the public health menace of the COVID-19 pandemic. The FDA regulations are not responsive to this type of need.
|Michael Mina opens one of the low cost home test kits (Source: Lex Fridman, Dec 18, 2020 podcast)|
So, Lex agrees to try the test out and here we see him using the less invasive nasal sampling tool. The sample was mixed with a few drops of reagents and a strip display shows a color change to indicate that the sample size was sufficient and also indicates positive or negative for the disease.
|Lex Fridman gets a nasal swab sample for self test (Source: Lex Fridman, Dec 18, 2020 podcast)|
If you want to hear the original, 3 hour podcast with Dr. Michael Mina, or follow up with other podcasts on artificial intelligence, check out the video at: https://www.youtube.com/watch?v=L-RuvUkcyJI&feature=youtu.be
Ok, so wow, why have we not heard more about this need for fast, at home type of testing and why is it not being officially promoted by the FDA or other authorities? My online search found that Mina had appeared on another of my favorite podcasts, This Week in Virology (TWIV) with Professor Vincent Racaniello, Columbia University. I have been sporadically following TWIV ever since last March when I sat in on his online virology class, but missed this July 15 podcast.
|Michael Mina appears in discussion with TWIV experts ( TWIV, Jul 15, 2020)|
The TWIV discussion agreed with the importance of low cost, rapid testing. It seems the FDA requirements are not geared to public pandemic health issues and this is a roadblock that should be changed. TWIV also discussed why the higher accuracy of PCR testing is not needed for public health. The issue is that PCR is much more accurate, but that since the detection of viral RNA can be found weeks after the time when the person could be infective and contagious, it doesn't really help to know that the person tests positive.
This brought up another issue for me, not specifically addressed during this TWIV podcast, but touched on in an earlier podcast, and that was why the new vaccines are 95% effective at preventing disease, but only 65% percent effective in preventing a person from being contagious. I don't know for sure, but my conjecture is that the vaccine prevents the buildup of viral particles so as to prevent disease, but enough particles are present that they could still be shed and make someone else sick.
To that end, I copied one of the TWIV slides and modified it to show this proposed effect. Note how it takes many days from first infection until the person has symptoms because the viral load has increased exponentially. Now suppose that the inoculated person's immune system responds much faster and so limits the exponential increase below the threshold of causing symptoms, but still enough viral particles are present to present a contagious risk. It seems plausible to me, but I wait for other information.
|TWIV slide, modified with effect of vaccine conjecture (in yellow)|
If you want to check out the other details with the TWIV #640 discussion with the gang and Dr. Mina, check out the video at: https://www.youtube.com/watch?v=L-RuvUkcyJI&feature=youtu.be
You can always scan the Center for Disease Control (CDC) website for more details on viral transmission and contagiousness. Note particularly how detection of the RNA, weeks after the disease has run its course and that the person is not contagious is a key finding.
|Transmission of virus (Source: www.cdc.gov)|
Another interesting confirmation of what Dr. Mina and experts on the TWIV podcast was how the current FDA approved test method will give positive results weeks after your infection even though you are no longer contagious. The risk of infecting others is the excuse that is used to lock down the society and destroy the economic lives of millions. We definitely have shot ourselves in the foot by not working to more quickly approve the at home, rapid virus test!
|Getting tested again can show positive, even though you are not contagious (Source: www.cdc.gov)|
The discussion about the higher accuracy of the PCR test requires us to delve a little more and do some "homework" in that area too. Recall from previous posts, way back in March timeframe, we described how PCR is used to amplify the amount of viral particles present in a sample by duplicating and cloning the RNA or DNA present in the sample. Each time the PCR machine cycles though a cloning step, the amount of RNA doubles. This doubling is measured by the "threshold cycle or "CT value", which tells us the total number of doubling cycles. For instance if CT = 3, then the amount of RNA is increased 8 times. A CT difference of 6 means an increase of 64 times, so CT is a logarithmic measure of the amount of virus initially present.
Check out the chart below where we see for a CT = 21 means a very high amount of virus was present in the sample compared to a sample where a value of CT = 39 was required to amplify the sample to the same level of virus.
Now we can get back to the issue we talked about earlier. If your sample tests positive with CT=39, you have very, very little virus in you. So, the test can be surprisingly accurate and sensitive, but as noted in the CDC paragraphs, some viral RNA can be detected in you even if you are no longer sick or contagious. So, the higher accuracy of the approved test, gives you a positive result even when you are not contagious anymore. This is also why the at home, fast test for contagiousness is of so much importance.
|CT Values (Source: www.wvdl.wisc.edu)|
Another topic of much interest is how long it takes for a population to become immune to the virous. An interesting article on this topic of herd immunity and how effective a strategy can be to achieve it, is "The False Promise of Herd-Immunity for COVID-19", by Christie Aschwanden, Nature, October 20, 2020.
It turns out that an interesting experiment has already been conducted, not actually planned, in Brazil. The government of Brazil did not take any extraordinary measures to lockdown the society and somewhat just let everyone go about their business. So many people will become infected, many will die, and overtime may reach herd immunity and the disease will just die out and end. The following extracts from the paper are pasted below.
|The herd immunity situation in Brazil (Source: Christie Aschwanden, Nature, Oct 21, 2020)|
The article discussed the situation in Manaus, which is a city on the Amazon and has a population of about 2 million. The article caught my attention because we were scheduled to be on a cruise through the Caribbean and up the Amazon to Manaus in January. Well, as you already know the cruise was cancelled and Manaus was known to be a terrible hotspot of COVID-19. Anyway, here is a map of Manaus on the Amazon.
|Location of Manaus on the Amazon River (Source: iPhone Map App)|
This might be the right time to digress and make sure our homework about calculating herd immunity is up to par. Remember we start with R0, pronounced "R-naught", which is defined as the average number of persons that become infected by that one typical person. For measles, if can be very high, something like 18. For flu, it is much lower, around 1.3. For COVID-19, R0 is thought to be about 3, which means one infected person on average infects three other people.
Any R0 greater than 1.0 means the spread will be exponential. So, mitigation strategies are used to reduce the R0 value to less than one. When this happens the contagion will just die out; it can't infect enough people to keep going.
You can also ask the related question: How many people have to have been infected, and thereby show some immunity, so that the contagion just dies out and can't keep going? This number is what sets the herd immunity and is calculated as equal to 1 - 1/R0. So, for unmitigated COVID-19 R0 = 3, this means that herd immunity is reached with 67% of the population have already been infected or otherwise immune. For more infectious diseases, with higher values of R0, the percentage of the population increases much higher. This calculation ad definitions are summarized in this slide below.
|Definition of herd immunity (Source: www.Slideshare.net)|
So, what was the outcome of this unplanned experiment?
|Achieving herd immunity can carry heavy cost (Source: Christie Aschwanden, Nature, Oct 21, 2020)|
So, what data can we find about how the herd immunity approach played out in the "experiment" going on in Brazil. Here are the number of cases and deaths for Brazil and the World.
|Achieving herd immunity can carry heavy cost (Source: )|
So, in Brazil the percentage of deaths per number of cases is 189k / 7.37 M = 2.6%. The percentage of deaths world wide per number of cases is 1.73 M / 78.7 M = 2.2%.
The death rate is higher in the Brazil experiment and we can't know or examine any of the other factors that go into this condition, but it doesn't seem that just aiming for herd immunity and not locking down the economy resulted in a catastrophe? We can wonder what would have happened if Brazil had maybe done more to mainly protect the super vulnerable population while leaving most everyone else free to go about their business. Even if they had instituted a use of mask policy without shutting everything down. So, with just this one data point it is not clear that the lockdown was all that more effective, in preventing deaths, given the high cost to people from the lockdown itself.
I can't help but want to advocate for more freedom, for each person to make their own risk assessment, but we need the data to be truly informed. In California we are ordered not to have a sitdown meal inside or on a restaurant patio, while at the same time the chief health officer admits that there is no scientific evidence supporting such a lockdown, or we can drive to neighboring states, like Utah, and continue enjoying an inside restaurant meal.
So in summary, my conjecture based on my desire for freedom and my armchair study of virology is:
- Low cost, at home tests are available and can meet the public health issues of the pandemic
- Low cost, at home tests could cost about $1 and results available in less than 15 minutes
- The low cost test allows everyone more freedom to go about their business and not worry if you might be contagious. Still wear a mask to prevent yourself from getting the virus
- The standard FDA mandated PCR test takes days to get a result and costs $100 of dollars
- The FDA has no authority to approve the at home test because it is not a medical device
- The FDA regulatory structure is shooting our country in the foot in the middle of a public heath pandemic. By not approving the at home test, we have caused mass damage to our society
- The standard test can be obtained for free, but the cost to society is $100
- The standard test can be positive weeks after you are symptom free and not contagious
- I agree with the experts and the CDC webpages, and yet we need to argue for the home test
We also see that we are very close to the vaccine flowing down to the rest of us, "the non-essential", which we hope gets us on the way to herd immunity, even at the risk of still being contagious during our first encounter with the virus.
See you next time, here from our burrow, stay safe, as we recover more of our freedom,