April 25, 2020
Saturday
I have been thinking about the patterns of news, data reporting, and the minimum time it takes to arrive at a reasonable consensus on known knowns. How long should developing new testing, treatments, and vaccines take? Two months seem too long, but in the context of typical scientific advancement, this is nothing. There is a mad rush of work and a ton of data daily. If you can step back for a moment, the pace and volume of published material are remarkable. The amount of information is enough to write a daily email about just the new stuff.
----
Latest data
FT data (No change in the presentation)
https://www.ft.com/coronavirus-latest
Death vs. Cases in the US.
https://ourworldindata.org/grapher/daily-covid-cases-deaths?country=US
remember the reasons for variable daily reporting, look for the trends.
An estimate of the effective reproduction number by state (not updated daily)
https://rt.live/
What is this analysis about? http://systrom.com/topic/coronavirus/
Nature published a pointed editorial on the consequences of having so much focus on HCQ, with the notion that it is diverting resources and attention.
https://www.nature.com/articles/d41586-020-01165-3
I have been asked repeatedly about visuals on per capita death by US state. Here is a YouTube video animating this over the 1st three months of the pandemic. It is 2:46.
https://seedatavisually.com/news/coronavirus-deaths-per-capita-by-us-state-first-3-months/
There has been press about Remdesivir. Last week, trial data was leaked, with some speculating the data leak was a stock manipulation effort. In the previous 72 hours, the Chinese arm of the Remdesivir trial was being characterized as a failure. Gilead reported that they stopped the trial due to low enrollment. Given the hopes riding on this drug, I suspect drama is inevitable.
Biotech investment newsletter: https://www.fiercebiotech.com/biotech/remdisivir-flop-china-analysts
Overview of ongoing Remdesivir trials:
https://www.clinicaloncology.com/COVID-19/Article/05-20/Early-Data-on-Remdesivir-for-COVID-19-Cause-Guarded-Optimism/58086?ses=ogst
Here is an interesting look at places the virus is hiding in the body. It is an example of reasonable medical investigation - correlate symptoms with lab-proven PCR findings. However, when you see a derivative of this report in the lay press, be skeptical. This was one patient, and it is unclear what viral RNA in ocular swabs means on day 45 of illness - is it infectious or merely viral RNA left on the mucosa? The authors rightly conclude, "These findings highlight the importance of control measures, such as avoiding touching the nose, mouth, and eyes and frequent hand washing. A related implication is the importance of appropriate use of personal protective equipment for ophthalmologists during clinical examination because ocular mucosa may not be only a site of virus entry but also a source of contagion." Adam's read - the virus can infect someone through any mucosa, including the eyes. And, if you are infected, you could spread the virus by touching your eyes and then touching other surfaces. However, it is unclear how long one is truly contagious.
https://annals.org/aim/fullarticle/2764963/sars-cov-2-isolation-from-ocular-secretions-patient-covid-19
Home mid-turbinate PCR testing is now FDA-approved for use. LabCorp is the vendor. I imagine consumer-collected tests have a higher false-negative rate and there will be a delay between testing and the results, but it is a step in the right direction.
https://www.nytimes.com/2020/04/21/health/fda-in-home-test-coronavirus.html
Siemens Healthineers is reporting they will have new immunoassay for COVID antibodies for lab-based analysis in late May. The article reports 99% sensitivity AND specificity with a 14 min run time. Thoughts:
too good to be true?
not point of care
Who came up with the name "Healthineer"?!? It sounds like a Disney brand.
This article strikes me as something Siemens paid for placement. It is little more than a press release.
Show me the real-world data.
Still, I suspect we will be seeing a lot of entrants into the testing, vaccine, and treatment markets. Even a small piece of the COVID pie is going to be worth billions.
https://interestingengineering.com/siemens-healthineers-significantly-expanding-covid-19-testing-including-antibody-test
infographics of the day
Apples!
https://i.redd.it/o2ypbjd9fru41.png
The psychology of color!
https://i.redd.it/0xbns801nxu41.jpg
----Bonus Round - A Saturday with smallpox edition
I was reading about Edward Jenner, the British physician who studied, popularized, and published about vaccination with Cowpox as prevention of smallpox. Until you read about this story, it is hard to appreciate how big of a deal eradicating smallpox is. Smallpox was responsible for 4000+ years of human misery marked by outbreaks, physical deformities, and 60-80% case fatality rates in children. Here is the part that I think is most interesting- it took 3-4 years, between 1798 and 1801, for Jenner's work to become "standard of care." All in a world before speedy communication, before standardized scientific journal articles, and before they understood why vaccination with one disease might mitigate another, albeit similar disease. (Even Jenner's original 1798 pamphlet was wrong in many ways and met with skepticism in the medical community.) The number of cases Jenner used in demonstrating the value of cowpox inoculation was small. The long history of prior attempts at inoculation with actual smallpox was marred by initiating outbreaks and had a high conversion rate to full-bore smallpox infection. But, the hunger for treatment was so great that many scientists of the day, and even Thomas Jefferson, became early adopters of Jenner's vaccination. So, my read is that this was a large bet that paid off. It turned out vaccination helped mitigate smallpox for many and without much downside. Pretty amazing.
I would not, however, conclude from this story that we should apply equally lax scientific rigor to our coronavirus efforts. The fact is, Jenner had been making observations for years amongst milkmaids, and efforts at inoculation with smallpox had been going on for centuries in other areas of the world. He was building on lots of data that was not well categorized or understood. I do advise all of us to be observant, curious, and lucky.
Here is a brief, readable, and detailed overview:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200696/#B18
Clean hands and sharp minds,
AW
I have been thinking about the patterns of news, data reporting, and the minimum time it takes to arrive at a reasonable consensus on known knowns. How long should developing new testing, treatments, and vaccines take? Two months seem too long, but in the context of typical scientific advancement, this is nothing. There is a mad rush of work and a ton of data daily. If you can step back for a moment, the pace and volume of published material are remarkable. The amount of information is enough to write a daily email about just the new stuff.
----
Latest data
FT data (No change in the presentation)
https://www.ft.com/coronavirus-latest
Death vs. Cases in the US.
https://ourworldindata.org/grapher/daily-covid-cases-deaths?country=US
remember the reasons for variable daily reporting, look for the trends.
An estimate of the effective reproduction number by state (not updated daily)
https://rt.live/
What is this analysis about? http://systrom.com/topic/coronavirus/
Nature published a pointed editorial on the consequences of having so much focus on HCQ, with the notion that it is diverting resources and attention.
https://www.nature.com/articles/d41586-020-01165-3
I have been asked repeatedly about visuals on per capita death by US state. Here is a YouTube video animating this over the 1st three months of the pandemic. It is 2:46.
https://seedatavisually.com/news/coronavirus-deaths-per-capita-by-us-state-first-3-months/
There has been press about Remdesivir. Last week, trial data was leaked, with some speculating the data leak was a stock manipulation effort. In the previous 72 hours, the Chinese arm of the Remdesivir trial was being characterized as a failure. Gilead reported that they stopped the trial due to low enrollment. Given the hopes riding on this drug, I suspect drama is inevitable.
Biotech investment newsletter: https://www.fiercebiotech.com/biotech/remdisivir-flop-china-analysts
Overview of ongoing Remdesivir trials:
https://www.clinicaloncology.com/COVID-19/Article/05-20/Early-Data-on-Remdesivir-for-COVID-19-Cause-Guarded-Optimism/58086?ses=ogst
Here is an interesting look at places the virus is hiding in the body. It is an example of reasonable medical investigation - correlate symptoms with lab-proven PCR findings. However, when you see a derivative of this report in the lay press, be skeptical. This was one patient, and it is unclear what viral RNA in ocular swabs means on day 45 of illness - is it infectious or merely viral RNA left on the mucosa? The authors rightly conclude, "These findings highlight the importance of control measures, such as avoiding touching the nose, mouth, and eyes and frequent hand washing. A related implication is the importance of appropriate use of personal protective equipment for ophthalmologists during clinical examination because ocular mucosa may not be only a site of virus entry but also a source of contagion." Adam's read - the virus can infect someone through any mucosa, including the eyes. And, if you are infected, you could spread the virus by touching your eyes and then touching other surfaces. However, it is unclear how long one is truly contagious.
https://annals.org/aim/fullarticle/2764963/sars-cov-2-isolation-from-ocular-secretions-patient-covid-19
Home mid-turbinate PCR testing is now FDA-approved for use. LabCorp is the vendor. I imagine consumer-collected tests have a higher false-negative rate and there will be a delay between testing and the results, but it is a step in the right direction.
https://www.nytimes.com/2020/04/21/health/fda-in-home-test-coronavirus.html
Siemens Healthineers is reporting they will have new immunoassay for COVID antibodies for lab-based analysis in late May. The article reports 99% sensitivity AND specificity with a 14 min run time. Thoughts:
too good to be true?
not point of care
Who came up with the name "Healthineer"?!? It sounds like a Disney brand.
This article strikes me as something Siemens paid for placement. It is little more than a press release.
Show me the real-world data.
Still, I suspect we will be seeing a lot of entrants into the testing, vaccine, and treatment markets. Even a small piece of the COVID pie is going to be worth billions.
https://interestingengineering.com/siemens-healthineers-significantly-expanding-covid-19-testing-including-antibody-test
infographics of the day
Apples!
https://i.redd.it/o2ypbjd9fru41.png
The psychology of color!
https://i.redd.it/0xbns801nxu41.jpg
----Bonus Round - A Saturday with smallpox edition
I was reading about Edward Jenner, the British physician who studied, popularized, and published about vaccination with Cowpox as prevention of smallpox. Until you read about this story, it is hard to appreciate how big of a deal eradicating smallpox is. Smallpox was responsible for 4000+ years of human misery marked by outbreaks, physical deformities, and 60-80% case fatality rates in children. Here is the part that I think is most interesting- it took 3-4 years, between 1798 and 1801, for Jenner's work to become "standard of care." All in a world before speedy communication, before standardized scientific journal articles, and before they understood why vaccination with one disease might mitigate another, albeit similar disease. (Even Jenner's original 1798 pamphlet was wrong in many ways and met with skepticism in the medical community.) The number of cases Jenner used in demonstrating the value of cowpox inoculation was small. The long history of prior attempts at inoculation with actual smallpox was marred by initiating outbreaks and had a high conversion rate to full-bore smallpox infection. But, the hunger for treatment was so great that many scientists of the day, and even Thomas Jefferson, became early adopters of Jenner's vaccination. So, my read is that this was a large bet that paid off. It turned out vaccination helped mitigate smallpox for many and without much downside. Pretty amazing.
I would not, however, conclude from this story that we should apply equally lax scientific rigor to our coronavirus efforts. The fact is, Jenner had been making observations for years amongst milkmaids, and efforts at inoculation with smallpox had been going on for centuries in other areas of the world. He was building on lots of data that was not well categorized or understood. I do advise all of us to be observant, curious, and lucky.
Here is a brief, readable, and detailed overview:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200696/#B18
Clean hands and sharp minds,
AW
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