Category Archives: Social issues ( be civil ! )

Book Review: Proving Ground, Kathy Kleiman

Proving Ground is a fascinating book about the 6 women who programmed the first programmable computer, the ENIAC (Electronic Numerical Integrator And Computer).  Prior to this, the women were computers as the term was used in the 1940s for people who sat in front of calculating machines and performed lengthy numerical computations solving differential equations to find the path of an artillery shell one bloody addition/subtraction/multiplication/division at a time.  When World War II started and when the man were off in the army, the search was on for  women with a mathematical background who could do this.

A single trajectory took a day to calculate, and each trajectory had to be separately calculated for different wind currents, air temperature, speed and weight of the shell.  The computations were largely done at the Moore School of Engineering at Penn and were way too slow (although accurate) to produce the numbers of trajectories the army needed.

Enter Dr. John Mauchley who had an idea of how to do this using vacuum tubes, and a brilliant 23 year old engineer, J. Presper Eckert, who could instantiate it. The army committed money to building the machine, which came in 42 monster boxes 8 feet tall, 2 feet wide and what looks like 4 feet deep.

6 of the best and brightest computers of trajectories were recruited to figure out how to wire the boxes together to mimic the trajectory calculations they had already been doing.  So, if you’ve ever done any programming, you’ll know that having a definite target to mimic with software makes life much easier.

Going a bit deeper, if you’ve done any programming in machine language, you know about registers, the addition and logical unit, hard wired memory, alterable memory.

Here’s what the 6 women were given by Dr. Eckert (without ever seeing the monster boxes)

l. A circuit diagram of each box, showing how this vacuum tube activated that vacuum tube etc. etc. The 42 boxes contained 18,000 vacuum tubes.  Vacuum tubes and transistors are similar in that their utility is that they only conduct electricity in one direction and can be turned on and off.

2. A block diagram — which showed how the functions of a unit or system interrelate

3. A logical diagram — places for dials switches, plug and cables on the front of the 42 units.

So given this, the 6 had to figure out what each unit did, and how to wire them together to mimic the trajectory calculations they had been doing.

They did it, and initially without being able to enter the room with the boxes (because they didn’t have the proper security clearance).  Eventually they got it and were able to figure out how to wire the boxes together.

If that isn’t brilliant enough, because the calculations were still taking too long, they invented parallel programing.

For those of you who know computing, that should be enough to make you thirst for more detail.

The book contains a lot of sociology.  The women were treated like dirt by the higher ups (but not by Mauchley or Eckert).  When the time came to show ENIAC off to the brass (both academic and military), they were tasked with serving coffee and hanging up coats.  When Kleiman found pictures of them with ENIAC and asked who they were, she was told they were ‘refrigerator ladies’ — whose function was similar to the barely clothed models draped over high powered automobiles to sell them.

I’ll skip the book’s sociology for some sociology of my own.  The book has biographies and much fascinating detail about all 6 women.  I grew up near Philly, and know the buildings at Penn where this was done (I went to Penn Med). Two of the 6 were graduates of Chestnut Hill College, a small Catholic school west of Philly.  The girl across the street went there.  Her mother was born in County Donegal and cleaned houses.  Her father dropped out of high school at 16 to support his widowed mother.  No social services between the two world wars, wasn’t that terrible etc. etc.  Her father worked in a lumberyard, yet the two of them sent both children to college, and owned their own home (eventually free of debt).  The Chestnut Hill grad I know became an editor at Harcourt Brace, her brother became a millionaire insurance executive.  It would be impossible for two working class people to do this today where I grew up (or probably in most places).

FDA Amylyx approval 7 September implies Simufilam will be FDA approved this year

On 7 September an FDA advisory board reversed itself and recommended approval for a drug for ALS — https://www.wsj.com/articles/amylyxs-als-drug-backed-by-fda-advisers-11662590651?mod=newsviewer_click.  The head of the FDA Office of Neuroscience (Billy Dunn) gave a verbal endorsement, making it likely that Amylyx’s drug would be approved.

What does this have to do with the approval of Simufilam this year? Amylyx did a post-hoc, retrospective “responder analysis” that showed patients who did respond to drug (vs placebo) had “an usually strong response”, i.e., a bunch of non-responders in the general population masked the beneficial effects of the drug. This, after the same committee in March turned the drug down due to lack of efficacy in the studied cohort as a whole.

You may recall that I thought Cassava’s results with Simufilam were better than they realized after they released the data on the first 50 patients in the open trail reaching the 9 month endpoint. The full post published 25 August 2021 can be found below the &&&&&. 5/50 had a greater than 50% improvement in their ADAS-Cog11 score (by more than 10 points).  Data like this in Alzheimer’s has never been seen before in any study, or in my clinical experience.  So the data can not be explained by Cherry-picking.  The only other explanations are (1) Fraud (2) incompetent ADAS-Cog11 measurement (3) people without Alzheimer’s entering the study for the money, all of which I think are remote.  Also, the average decline at one year in ADAS-Cog in Alzheimer patients is 5 points.

So Cassava has data similar to Amylyx’s on the first 50 of the 200 in the open label study.  The last of the 200 will complete their full year on the drug by the end of 2022, at which point data will be released.  If the results on the 200 patients are similar to those on the first 50 (say 20/200 having significant (greater than 50% change for the better in ADAS-Cog) improvement, Cassava will have a (strong in my opinion) argument for Simufilam approval.

Clinicians know that patients always respond variably to any sort of therapy. We now know why.  Given that the human genome contains 3,200,000,000 positions.  Full genome sequencing of well over 100,000 people has shown that any two people will differ at one position in a thousand — that’s 3,200,000 differences  — source   https://www.ncbi.nlm.nih.gov/books/NBK20363/

 

Gentlemen start your engines

&&&&&

Cassava Sciences 9 month data is probably better than they realize

My own analysis of the Cassava Sciences 9 month data shows that it is probably even better than they realize.

Here is a link to what they released — keep it handy https://www.cassavasciences.com/static-files/13794384-53b3-452c-ae6c-7a09828ad389.

I was unable to listen to Lindsay Burn’s presentation at the Alzheimer Association International Conference in July as I wasn’t signed up.  I have been unable to find either a video or a transcript, so perhaps Lindsay did realize what I’m about to say.

Apparently today 25 August there was another bear attack on the company and its data.  I’ve not read it or even seen what the stock did.  In what follows I am assuming that everything they’ve said about their data is true and that their data is what they say it is.

So the other day I had a look at what Cassava released at the time of Lindsay’s talk.

First some background on their study.  It is a report on the first 50 patients who had received Simulfilam for 9 months.  It is very important to understand how they were measuring cognition.  It is something called ADAS-Cog11

Here it is and how it is scored and my source — https://www.verywellhealth.com/alzheimers-disease-assessment-scale-98625

The original version of the ADAS-Cog consists of 11 items, including:1

1. Word Recall Task: You are given three chances to recall as many words as possible from a list of 10 words that you were shown. This tests short-term memory.

2. Naming Objects and Fingers: Several real objects are shown to you, such as a flower, pencil and a comb, and you are asked to name them. You then have to state the name of each of the fingers on the hand, such as pinky, thumb, etc. This is similar to the Boston Naming Test in that it tests for naming ability, although the BNT uses pictures instead of real objects, to prompt a reply.

3. Following Commands: You are asked to follow a series of simple but sometimes multi-step directions, such as, “Make a fist” and “Place the pencil on top of the card.”

4. Constructional Praxis: This task involves showing you four different shapes, progressively more difficult such as overlapping rectangles, and then you will be asked to draw each one. Visuospatial abilities become impaired as dementia progresses and this task can help measure these skills.

5. Ideational Praxis: In this section, the test administrator asks you to pretend you have written a letter to yourself, fold it, place it in the envelope, seal the envelope, address it and demonstrate where to place the stamp. (While this task is still appropriate now, this could become less relevant as people write and send fewer letters through the mail.)

6. Orientation: Your orientation is measured by asking you what your first and last name are, the day of the week, date, month, year, season, time of day, and location. This will determine whether you are oriented x 1, 2, 3 or 4.

7. Word Recognition Task: In this section, you are asked to read and try to remember a list of twelve words. You are then presented with those words along with several other words and asked if each word is one that you saw earlier or not. This task is similar to the first task, with the exception that it measures your ability to recognize information, instead of recall it.

8. Remembering Test Directions: Your ability to remember directions without reminders or with a limited amount of reminders is assessed.

9. Spoken Language: The ability to use language to make yourself understood is evaluated throughout the duration of the test.

10. Comprehension: Your ability to understand the meaning of words and language over the course of the test is assessed by the test administrator.

11. Word-Finding Difficulty: Throughout the test, the test administrator assesses your word-finding ability throughout spontaneous conversation.

What the ADAS-Cog Assesses

The ADAS-Cog helps evaluate cognition and differentiates between normal cognitive functioning and impaired cognitive functioning. It is especially useful for determining the extent of cognitive decline and can help evaluate which stage of Alzheimer’s disease a person is in, based on his answers and score. The ADAS-Cog is often used in clinical trials because it can determine incremental improvements or declines in cognitive functioning.2

Scoring

The test administrator adds up points for the errors in each task of the ADAS-Cog for a total score ranging from 0 to 70. The greater the dysfunction, the greater the score. A score of 70 represents the most severe impairment and 0 represents the least impairment.

The average score of the 50 individuals entering was 17 with a standard deviation of 8, meaning that about 2/3 of the group entering had scores of 9 to 25 and that 96% had scores of 1 to 32 (but I doubt that anyone would have entered the study with a score of 1 — so I’m assuming that the lowest score on entry was 9 and the highest was 25).  Cassava Sciences has this data but I don’t know what it is.

Now follow the link to Individual Patient Changes in ADAS-Cog (N = 50) and you will see 50 dots, some red, some yellow, some green.

Look at the 5 individuals who fall between -10 and – 15 and think about what this means.  -10 means that an individual made 10 fewer errors at 9 months than on entry into the study.  Again, I have no idea what the scores of the 5 were on entry.

So assume the worst and that the 5 all had scores of 25 on entry.  The group still showed a 50% improvement from baseline as they look like they either made 12, 13, or 14 fewer errors.  If you assume that the 5 had the average impairment of 17 on entry, they were nearly normal after 9 months of treatment.  That doesn’t happen in Alzheimer’s and is a tremendous result.   Lindsay may have pointed this out in her talk, but I don’t know although I’ve tried to find out.

Is there another neurologic disease with responses like this.  Yes there is, and I’ve seen it.

I was one of the first neurologists in the USA to use L-DOPA for Parkinsonism.  All patients improved, and I actually saw one or two wheelchair bound Parkinsonians walk again (without going to Lourdes).  They were far from normal, but ever so much better.

However,  treated mildly impaired Parkinsonians became indistinguishable from normal, to the extent that I wondered if I’d misdiagnosed them.

12 to 14 fewer errors is a big deal, an average decrease of 3 errors, not so much, but still unprecedented in Alzheimer’s disease.   Whether this is clinically meaningful is hard to tell.  However, 12 month data on the 50 will be available in the fourth quarter of ’21, and if the group as a whole continues to improve over baseline it will be a very big deal as it will tell us a lot about Alzheimer’s.

Cassava Sciences has all sorts of data we’ve not seen (not that they are hiding it).  Each of the 50 has 4 data points (entry, 3, 6 and 9 months) and it would be interesting to see the actual scores rather than the changes between them in all 50.  Were the 5 patients with the 12 – 14 fewer errors more impaired (high ADAS-Cog11 score in entry) or less.

Was the marked improvement in the 5 slow and steady or sudden?   Ditto for the ones who deteriorated or who got much worse or who slightly improved.

Even if such dramatic improvement is confined to 10% of those receiving therapy it is worth a shot to give it to all.  Immune checkpoint blockade has dramatically helped some patients with cancer  (far from all), yet it is tried in many.

Disclaimer:  My wife and I have known Lindsay since she was a teenager and we were friendly with her parents.  However, everything in this post is on the basis of public information available to anyone (and of course my decades of experience as a clinical neurologist)

 

When to get your booster — a possibly useful post

I thought everyone knew that vaccines and boosters against the pandemic flu reach maximum protection against infection in a week or two, and then start declining.  Each of the zillions of papers on the subject say exactly this.

So if you’ve been isolating yourselves, as my wife and I have because of our age, the time to get that booster is a week or so before a time of likely exposure — in our case a visiting grandchild.

I thought everyone knew this, but maybe not.  My wife got an eMail today from her  85 year old cello teacher.   She summers on an island off the Maine coast near Mt. Desert Island (the home of Acadia National Park)

 

“We’re so far well, thanks to xxxx, I took his advice and got 2nd booster just before leaving middle of June. The whole island was shut down, the  only grocery store had signs SHUT TODAY, NO STAFF, went to Kneisel Hall in Blue Hill, people had not been able to rehearse together because they were actively sick, and so on. He and news are proving to be a blessing!

For this, we all thank you.”

The silence is deafening

3 weeks ago I published a post about a paper that I thought would be a real bombshell, in effect contradicting a paper in a prestigious journal, and strongly arguing from real data that the pandemic virus could have been made in a lab, quite possibly Wuhan.  .

Absolutely nothing has happened. No letters to PNAS (the source of the article) to Cell (the source of the criticized study).  With a question of this magnitude and importance  you’d think Nature or Science would weigh in about it.  The origin of the pandemic virus is certainly they’ve covered extensively.

So I’m going to send this to all concerned and see if I get any feedback.

Here is the original post.

Evidence that the pandemic virus was made in a lab

 

Everyone knows that the Chinese have been less than forthcoming about the origin of the pandemic virus (SARS-CoV-2).  An article in the current Proceedings of the National Academy of Sciences — https://doi.org/10.1073/pnas.2202769119 arguesthat US data, which hasn’t been released, and some 290 pages of which has been redacted could shed a good deal of light on the subject (without any help from China).  One of the authors is an economist, but the other has serious biochemical chops — https://www.pharmacology.cuimc.columbia.edu/profile/neil-l-harrison-phd.

Basically a variety of US institutions (see the paper — it’s freely available) have been working with the lab at Wuhan for years modifying the virus, long before the pandemic.  The paper names the names etc. etc. and is quite detailed, but I want to explain the evidence that the virus could have been produced (by human modification) at the Wuhan lab.  It has to do with a site in a viral protein which says ‘cut here’.

Here is more background than many readers will need, but the virus has affected us all and I want to make it accessible to as many as possible.

Proteins are linear strings of amino acids, just as this post is a linear sequence of letters, spaces and punctuation.

We have fewer amino acids (20 to be exact) than letters  and to save space each one has a one letter abbreviation (A for alanine V for valine, etc. etc.).  The spike protein (the SARS-CoV-2 protein binding to the receptor  for it on our cells) is quite long (1,273 amino acids all in a row).

Our genome codes for 588  proteins (called proteases) whose job it is to cut up other proteins. Obviously, it would be a disaster if they worked indiscriminately.  So each cuts at a particular sequence of amino acids. Think of the protease as a key and the sequence as a lock.  One protease called furin cuts in the middle of an 8 amino acid sequence RRAR’SVAS (R stands for aRginine and S for Serine).  This is called the furin cleavage site (FCS)

A paper (The origins of SARS-CoV-2: A critical review. Cell 184, 4848–4856 (2021) argued that the amino acid sequence of the FCS in SARS-CoV-2 is an unusual, nonstandard sequence for an FCS and that nobody in a laboratory would design such a novel FCS.  So, like many, I skimmed the paper and accepted its conclusions, as Cell is one of the premier molecular biology journals.

One final quote “The NIH has resisted the release of important evidence, such as the grant proposals and project reports of EHA, and has continued to redact materials released under FOIA, including a remarkable 290-page redaction in a recent FOIA release.”

Sounds like Watergate doesn’t it?

 

Watch this space

Evidence that the pandemic virus was made in a lab

 

Everyone knows that the Chinese have been less than forthcoming about the origin of the pandemic virus (SARS-CoV-2).  An article in the current Proceedings of the National Academy of Sciences — https://doi.org/10.1073/pnas.2202769119 argues that US data, which hasn’t been released, and some 290 pages of which has been redacted could shed a good deal of light on the subject (without any help from China).  One of the authors is an economist, but the other has serious biochemical chops — https://www.pharmacology.cuimc.columbia.edu/profile/neil-l-harrison-phd.

Basically a variety of US institutions (see the paper — it’s freely available) have been working with the lab at Wuhan for years modifying the virus, long before the pandemic.  The paper names the names etc. etc. and is quite detailed, but I want to explain the evidence that the virus could have been produced (by human modification) at the Wuhan lab.  It has to do with a site in a viral protein which says ‘cut here’.

Here is more background than many readers will need, but the virus has affected us all and I want to make it accessible to as many as possible.

Proteins are linear strings of amino acids, just as this post is a linear sequence of letters, spaces and punctuation.

We have fewer amino acids (20 to be exact) than letters  and to save space each one has a one letter abbreviation (A for alanine V for valine, etc. etc.).  The spike protein (the SARS-CoV-2 protein binding to the receptor  for it on our cells) is quite long (1,273 amino acids all in a row).

Our genome codes for 588  proteins (called proteases) whose job it is to cut up other proteins. Obviously, it would be a disaster if they worked indiscriminately.  So each cuts at a particular sequence of amino acids. Think of the protease as a key and the sequence as a lock.  One protease called furin cuts in the middle of an 8 amino acid sequence RRAR’SVAS (R stands for aRginine and S for Serine).  This is called the furin cleavage site (FCS)

A paper (The origins of SARS-CoV-2: A critical review. Cell 184, 4848–4856 (2021) argued that the amino acid sequence of the FCS in SARS-CoV-2 is an unusual, nonstandard sequence for an FCS and that nobody in a laboratory would design such a novel FCS.  So, like many, I skimmed the paper and accepted its conclusions, as Cell is one of the premier molecular biology journals.

One final quote “The NIH has resisted the release of important evidence, such as the grant proposals and project reports of EHA, and has continued to redact materials released under FOIA, including a remarkable 290-page redaction in a recent FOIA release.”

Sounds like Watergate doesn’t it?

 

Watch this space

 

A touching Mother’s day story — with an untouching addenum

Yes, a touching mother’s day story for you all. It was 55 years ago (yes over half a century ago ! ! ), and I was an intern at a big city hospital on rotation in their emergency room in a rough neighborhood. The ER entrance was half a block from an intersection with a bar on each corner. On a Saturday night, we knew better than to try to get some sleep before 2AM or until we’d put in 2 chest tubes (to drain blood from the lungs, which had been shot or stabbed). The bartenders were an intelligent lot — they had to be quick thinking to defuse situations, and we came to know them by name. So it was 3AM 55 years ago and Tyrone was trudging past on his way home, and I was just outside the ER getting some cool night air, things having quieted down.

“Happy Mother’s day, Tyrone” sayeth I

“Thanks Doc, but every day is Mother’s day with me”

“Why, Tyrone?”

“Because every day I get called a mother— “

Untouching Addendum

Well, it’s 55 years later and the terrible violence in the Black community continues unabated.  Nothing has changed from 1967.  Fifty percent of the murdered in the USA are blacks, with only 13-14% of the population.

My white neighbors drench themselves in holiness, displaying their virtue for all to see with signs on their lawns saying Black Lives Matter.  This neatly avoids facing the real problem — Black Lives Matter except to other Blacks.  

Any solution must come from within the Black community itself, not from outsiders, however well-motivated like my neighbors.

Does getting COVID19 shrink your brain?

Does getting COVID19 shrink your brain?  A paper from last Thursday’s Nature says yes.  Not only that, but it slows you mentally. Here’s a link: https://www.nature.com/articles/s41586-022-04569-5.pdf.   and a reference: Nature vol. 604 pp. 697 – 707 ’22.

Here’s what they did.  Take 785 people over 50 from England. Have 401 get infected with the pandemic virus, after obtaining MRI scans, all sorts of data including mental function about them.   Then repeat the MRI and mental tests  4 – 5 months after the infection.  Compare the two groups and there’s your answer.

The moral among you must be wondering how they ever got this past an Institutional review board.  It didn’t.  This was an experiment of nature on participants in the UK Biobank — https://en.wikipedia.org/wiki/UK_Biobank.  Starting in 2006 and ending in 2010 some 100,000 people (ages 40 – 69 on entry) from the United Kingdom (UK) were intensively studied (they donated urine, saliva and blood, filled out questionnaires, and consented to access to their electronic health records).   Planned follow up is 30 years.  All this before we had any idea about the pandemic to hit us in 2020.

Obviously the control group without infection, must be as similar as possible to the infected group and I think the authors tried their hardest.  Even so the control group was a bit older, and the infected group had slightly lower cognitive abilities.

The average time between the two scans was 3 years.  The average time from COVID19 to the second scan was 141 days.  The scans were done before Omicron hit.  Even so only 15/401 had to be hospitalized.  This is consistent with the mildness of the pandemic presently.  On 9 April 22 Shanghai reported some 23,000 positive PCR tests (for Omicron), but only one thousand or so were symptomatic.   Excluding the 15 from analysis didn’t change the result.  I’ve heard from clinicians, that the severely ill are usually obese.  This is partly true for the 15 hospitalized (average Body Mass Index 29.3) vs. the 386 not hospitalized (BMI – 26.6).

So the clickbait is that being infected with the virus shrinks your brain. But does it? It is stated that there was a decrease in thickness of the cerebral cortex (the gray matter on the surface of the brain) concerned with smell and taste.

The decreases were minimal.  Have a look at figure 1a p. 701.  The changes between scans are plotted vs. age, and separately for cases and controls. As we get older the brain shrinks.  This was true for both patients and the controls, but the patients showed more shrinkage (measured by the change between successive MRIs).

What sort of shrinkage in the thickness of he cerebral cortex are we talking about here?  At most 3% and usually under 2%.  But 3% of what?  Most estimates of the thickness of the human cerebral cortex place it around 2 – 3 millimeters (range 1 to 5 millimeters).  So I got out a clear plastic ruler and found that 1 milliMeter is about the thickness of a penny?  Are they really saying that the MRI can measure thickness differences of 2 – 3% of something only 2 – 3 millimeters.

It gets worse.  Most of us have seen MRI pictures by now.  If you look closely, you’ll see that they are slices made of pixels.  These are computed slices of 3 dimensional cubes (voxels).  And what dear reader is the size of an MRI voxel — around 1 x 1 x 1 milliMeters.  So they are measuring cortical thickness with a rather blunt instrument which is 30 – 50% the size of cortical thickness.  Do you think, even with averaging of hundreds of people, that they can pick up a change in cortical thickness of several percent in something so small.

I don’t, and am amazed that the reviewers let them get away with this.

The cognitive changes are on much better ground.  But that’s for the next post.  This post is long enough.

Local transmission in Beijing, the avalanche continues

The pandemic has now come to Beijing with its 21 million people.

From CNN: https://www.cnn.com/2022/04/24/china/beijing-covid-outbreak-lockdown-fears-intl-hnk/index.html”More than 20 cases were detected in the capital over a period from midnight Friday morning (22 April ’22) to 4 p.m. Saturday afternoon, officials said. One middle school where multiple cases were detected was shuttered on Friday, with students and teachers in the district required to take several Covid-19 tests over the coming week. more than 20 cases were detected in the capital over a period from midnight Friday morning to 4 p.m. Saturday afternoon, officials said. One middle school where multiple cases were detected was shuttered on Friday, with students and teachers in the district required to take several Covid-19 tests over the coming week.”

Other sources think the pandemic has been silently spreading in the city for a week.  If present policies continue and the if rapid spread shown in Hong Kong and Shanghai happens in Beijing, we are likely to see lockdown of the political capital.  Unfortunately I was worried about something like this last December, and by 15 March I thought China would be brought to its knees.  All this can be found in the series of posts recopied verbatim after the ***

As of 21 April Mainland China had 2,971 symptomatic cases and 21,335 asymptomatic, most of which were in Shanghai.  As of 23 April it was in 17 of 31 Chinese provinces.

Very sad.  At some point, attempting to control the pandemic by lockdown will cause more harm than good.   Events are proving the zero-Covid policy isn’t working.  Unfortunately, I don’t have any brilliant suggestions for them.

Basically this is happening because the zero-Covid policy produced a set of immunologic virgins to the Pandemic virus.

***

There’s a lot here.  If you are new to the Chinese pandemic

First scroll down to (and read) the following post written 12 December ’21

Is China following a Smokey the Bear policy on the pandemic?

Then look at (and read) the following — written 15 Jan ’22

I hope to Hell I was wrong about China

Then look at (and read) — written 25 March

China will be near collapse due to COVID19 — here’s why

Lastly look at the one just below — written 10 April

It’s a long sad story

China is closer to near collapse

26 days ago on 15 March ’22  I wrote a post beginning “Here is why I think China will be near collapse due to COVID19 in the next few months.”  At that time there were essentially no symptomatic cases in Shanghai and 1,000 locally transmitted cases.  At the end of 9 April there were 1,006 symptomatic cases and 23,937 asymptomatic ones, essentially all locally transmitted.  The city of 27 million people is now locked down.  The epidemic in Hong Kong has calmed down and the number of new locally transmitted is down to 2,000.

However the new organism (BA.2) is very infectious, and the fact that it is in all 31 Chinese provinces does not bode well.  Mainland China (excludes Hong Kong) has 1,318 symptomatic and 25,111 asymptomatic cases, essentially all locally transmitted.

We have to be impressed by the fact that 25,000,000 PCR tests for the virus were performed in Shanghai the past week, with roughly one in every thousand people carrying the virus.  It’s great to have data showing just how asymptomatic most cases are (96%).  We owe Shanghai and its people a great debt for this.

Xi reminds me of King Canute.  I think BA.2 will pop up again and again until it runs through the population.  Clearly full  vaccination with boosters  is not protective against infection here in the USA (witness Pelosi, Vilsack, Garland and Collins) although in the past  COVID19 was stated to be a disease of the unvaccinated.   The ‘fully vaccinated’ rate this year in Massachusetts for those in the hospital with COVID has ranged from 37 %  to 64% (currently 54%).  I think the USA is doing better, because given that 96% of cases (in Shanghai) are asymptomatic, almost everyone in the states has been infected with one or another strain of the pandemic virus, so there is some degree of immunity in the population.  Not so for China.  They are immunologic virgins for the pandemic virus (SARS-CoV-2)

Due to stringent criteria for who can bring in supplies to Shanghai there are problems with supplying food for the population.

Here is the post of 15 March — it’s long but has a lot more evidence to back up what I’m saying here

China will be near collapse due to COVID19 — here’s why

Here is why I think China will be near collapse due to COVID19 in the next few months.

Due to a strict containment policy, the only experience the Chinese population (excepting Wuhan) has had with the pandemic virus has been by vaccination, mostly with Sinopharm and Coronavac.  These are known to be less effective against the Omicron variant than the western mRNA vaccines (Pfizer, etc.) which themselves are not terribly effective against infection.  So most Chinese are immunologic virgins for exposure to the variants of the pandemic virus and the omicron variant of the virus is incredibly infectious.

In contrast, western populations have been exposed to variant after variant of the pandemic virus, building up immunity to coronaviruses.  The vast majority of cases are mild not requiring hospitalization, and many are completely asymptomatic.

One small piece of evidence for this — there are many more —

The following is from a post July/2020.

https://www.nytimes.com/2020/07/09/nyregion/nyc-coronavirus-antibodies.html–https://www.cnbc.com/2020/04/23/new-york-antibody-study-estimates-13point9percent-of-residents-have-had-the-coronavirus-cuomo-says.html.

New York State  randomly tested 3,000 people at grocery stores and shopping locations across 19 counties in 40 localities to see if they had the antibodies to fight the coronavirus, indicating they have had the virus and recovered from it. With more than 19.4 million people residents, according to U.S. Census data, the preliminary results imply that at least 2.7 million New Yorkers have been infected with Covid-19.They weren’t all hospitalized.

If you’re into authoritative statements, here is Dr. Fauci 3 months ago –Source — https://nypost.com/2021/12/12/omicron-appears-to-evade-some-protection-from-covid-vaccines/

“We’re getting anecdotal information … not necessarily confirmed yet, that the level of severity appears to be maybe a bit less than in the Delta. But there are a lot of confounding issues that it may be due to the underlying protection in the community due to prior infections,”

Omicron spreads like wildfire.  For example, we had to call our plumber a week ago.  He has trained his teenage daughter to enter the trade.  We talked about the pandemic.  Teenagers love crowded parties (well I did, and so did our kids). His daughter  told us that apparently one irresponsible kid came to a party while sick in the early stages of what turned out to COVID19 and transmitted the virus to NINETEEN people.

Here is the Hong Kong experience.  It began with an aircrew member from Cathay Pacific Airways Ltd., who was subsequently found to be infected with omicron.  He ate lunch at a restaurant 27 December ’21 with his family. . Five other customers later tested positive.   By the first week in March there were over 50,000 new cases each day.  Fortunately Hong Kong appears to have passed the peak with ‘only’ 20 – 30 thousand new cases each day.

The South China Morning Post of 16 March notes that 90% of Hong Kong residents have received one dose of a vaccine.  This hardly speaks well for the efficacy of whatever they received.

The Hong Kong experience has been rationalized by several reasons perhaps peculiar to Hong Kong:

l. A very low vaccination rate among the most vulnerable (e.g. over 80)

2. Very high population density — 50% of the population in Hong Kong live in public housing which is mostly very tall, very skinny high rises, due to the lack of buildable land in Hong Kong.  The elevators are a perfect way to transmit the virus.

I can’t speak to how common this is elsewhere in China.

5 days ago the number of cases in China was 1,000.  Today (16 March) I read that there were 5,100 on 15 March — https://www.scmp.com/news/china/science/article/3170631/china-reports-another-3000-covid-19-cases-latest-surge-continues?module=lead_hero_story&pgtype=homepage

So the elevator pitch is — a highly infectious virus is loose in a huge, previously uninfected population with minimal vaccine protection.

I was very worried that something like this could happen all over China in posts  written 2 and 3months ago, long before the number of cases in Hong Kong took off.  You can find my reasoning in the following post — https://luysii.wordpress.com/2022/01/15/i-hope-to-hell-i-was-wrong-about-china/   It was published 15 January ’22, and can be found below and it contains the 12 December ’21 post:

Addendum 16 Marchhttps://www.shine.cn/news/nation/2203163160/–MainlandChina now has 1,860 locally transmitted cases — with most in the province next to North, but in 20 other locations all over China including Shanghai and Beijing. This is is not good news given how infectious Omicron is.

 

I hope to Hell I was wrong about China

From the South China Morning Post — 9:52pm, 15 Jan, 2022

“The Chinese capital reported its first community case of the Omicron coronavirus variant on Saturday, with local and imported infections of the strain now detected in about half of the country’s provinces and municipalities.”

https://www.scmp.com/news/china/politics/article/3163525/china-braces-omicron-variant-extends-its-reach-and-lunar-new-

If true, containment, quarantine, lockdowns and isolation are hopeless.  The quote implies that they’ve already failed.

I find this very worrisome for reasons listed in a post 12 December 2021, a copy of which is below.

The short answer is that the mainland Chinese are immunologic virgins to exposure to the variants of the pandemic virus.  Hopefully their vaccines will work better against omicron than those of the west, but there is no reason to think they will.

Is China following a Smokey the Bear policy on the pandemic?

China is following a prevent pandemic virus infection policy, just as Smokey the Bear followed a prevent forrest fires policy.  The latter didn’t work out well, as although fires were prevented for a while. However, when fires did occur, they were much much worse than the smaller ones Smokey prevented.  There was much more tinder and stuff to burn.

Actually Smokey has changed his tune slightly.

https://en.wikipedia.org/wiki/Smokey_Bear  SmokeyBear.com’s current site has a section on “Benefits of Fire” that includes this information: “Fire managers can reintroduce fire into fire-dependent ecosystems with prescribed fire. Under specific, controlled conditions, the beneficial effects of natural fire can be recreated, fuel buildup can be reduced, and we can prevent the catastrophic losses of uncontrolled, unwanted wildfire.”

Revision 14 December 2021 — China’s policy of prevention has resulted in a Chinese population which has been vaccinated using two killed virus vaccines (Sinopharm, Coronavac).  They have not had any natural infections with the virus (aside from the original cases) as far as we know given what China has allowed out.

Infection with the virus itself exposes you to all its proteins, with your immune system responding to all of them.   Western vaccines are just to the spike protein.

It tends to be forgotten that moist cases of pandemic viral infection are asymptomatic.

Given 800K deaths  from COVID19  in the USA, how can I possibly say this is good. Here’s how :>

If you had an infection with the virus, you develop antibodies.  Nowadays, everyone who is vaccinated has antibodies so there is no point in testing for them, but what were things like in the days before vaccines?

The following is from a post July/2020.

https://www.nytimes.com/2020/07/09/nyregion/nyc-coronavirus-antibodies.html–https://www.cnbc.com/2020/04/23/new-york-antibody-study-estimates-13point9percent-of-residents-have-had-the-coronavirus-cuomo-says.html.

New York State  randomly tested 3,000 people at grocery stores and shopping locations across 19 counties in 40 localities to see if they had the antibodies to fight the coronavirus, indicating they have had the virus and recovered from it. With more than 19.4 million people residents, according to U.S. Census data, the preliminary results imply that at least 2.7 million New Yorkers have been infected with Covid-19.They weren’t all hospitalized.

Here’s some work the same month from Queens — https://www.nytimes.com/2020/07/09/nyregion/nyc-coronavirus-antibodies.html

At a clinic in Corona, a working-class neighborhood in Queens, more than 68 percent of people tested positive for antibodies to the new coronavirus. At another clinic in Jackson Heights, Queens, that number was 56 percent. But at a clinic in Cobble Hill, a mostly white and wealthy neighborhood in Brooklyn, only 13 percent of people tested positive for antibodies.

So the disease has already to spread to half the population in some neighborhoods in Queens. If even 10% of them were sick that would have been 140,000 hospitalizations.  They didn’t happen.

OK, so a lot more people were infected than got sick.  Why is this good?

Enter the omicron variant of the pandemic virus.  It can evade the antibodies produced by all the current vaccines (in the West — protection against the Chinese killed viral vaccines CoronaVac and Sinopharm isn’t known yet).   Yet omicron doesn’t appear to produce severe disease. Thus far…

 

The CDC in the past week said of the 40+ omicron cases it knows about (there certainly are more out there, and more to come), there was one hospitalization (for two days) and no deaths.

Here is Dr. Fauci 12 December 2021 — “We’re getting anecdotal information … not necessarily confirmed yet, that the level of severity appears to be maybe a bit less than in the Delta. But there are a lot of confounding issues that it may be due to the underlying protection in the community due to prior infections,”

Source — https://nypost.com/2021/12/12/omicron-appears-to-evade-some-protection-from-covid-vaccines/

So the Chinese population may be sitting ducks for omicron having been given vaccines (Sinopharm, Coronavac) of unknown potency against omicron.  If their statistics are true there has been little or no natural infection with the pandemic virus in the Chinese population (which Fauci has just implicated is protective),.  Given that I have a son, daughter in law and two grandkids living in Hong Kong, I find this extremely disconcerting.

Should you get a second booster of the Pfizer vaccine?

Should you get a second booster of the Pfizer vaccine?  As usual, with medical questions the answer is “it depends”.  Fortunately we now have excellent data on this point for those over 60.  As usual the best data is from Israel, with a mere 623,335 people over 60 getting the fourth shot and 628,976 not getting it.

The short answer is that the booster will give you some protection (compared to not getting the 4th shot)  against getting infected for a few weeks, but essentially no protection from infection at 6 weeks.

The headline news is that for 6 weeks the 2nd booster cuts your chance of  severe COVID19 by a factor of 3.  The protection against severe infection didn’t wane at 6 weeks.

The numbers in a minute, but I’m sure you’re wondering why such a short study?  Because infections with the B.1.1.529 variant of omicron started surging in Israel in December.  So with that in mind  the Israelis began vaccinating people over 60 in January of 2022. You don’t just go and vaccinate over half a million people for fun.   They had to balance the hunger for data about the help a fourth dose would give with the time needed to pass to get a meaningful study.  The longer the study, the better the data, but the longer to remain in the dark.

I’m certain the study will be updated with the passage of time, but likely the number of people with only 3 doses will shrink.  Also almost certainly more people in both groups will get severe COVID19

Now for the numbers: there were 355 severe cases of COVID19 in the 623,335 getting 4 doses and 1,210 cases in the 628,976 getting only 3 doses of the Pfizer vaccine.  So the protection from severe illness by the fourth dose was a decrease in  risk by greater than 2/3.

That’s the headline, but there is more to think about. 1/500 people getting 3 doses had severe COVID vs. 1/1500 people getting 4 doses.  Neither risk is very high.

Although there was no decline in severe COVID19 protection at 6 weeks, some decline at 6 months and a year is likely (if it’s like every other vaccine that’s been studied).  Even more to the point, if the first booster had not declined in protection we wouldn’t need a second.  I don’t see any reason the second booster should act differently. Remember both boosters are to a virus which is no longer circulating.

So should you rush out and get that 4th shot?  Again it depends.  You want maximum protection when cases are surging in your area.  That’s when you get the most bang for your buck.

Here in the USA, statistics are good.   What you are interested in, is people admitted to hospital because of COVID19.  To avoid spreading the virus, everyone admitted gets tested for the virus even if they got run over by a truck..  In this regard Massachusetts’s reporting is quite good — on  14 April ’22 there were 343 COVID19 patients in hospital statewide, but only 113 were hospitalized because of COVID19.   Hopefully, your local statistics are that good.

One of the (few) benefits of the pandemic is the fact that articles about the virus and COVID19 are not behind paywalls, but freely available to all (which is good because we’re all in the same boat, and we need all the brainpower we have to evaluate the latest data).

So here’s a link to the article discussed above — https://www.nejm.org/doi/pdf/10.1056/NEJMoa2201570?articleTools=true

China is closer to near collapse

26 days ago on 15 March ’22  I wrote a post beginning “Here is why I think China will be near collapse due to COVID19 in the next few months.”  At that time there were essentially no symptomatic cases in Shanghai and 1,000 locally transmitted cases.  At the end of 9 April there were 1,006 symptomatic cases and 23,937 asymptomatic ones, essentially all locally transmitted.  The city of 27 million people is now locked down.  The epidemic in Hong Kong has calmed down and the number of new locally transmitted is down to 2,000.

However the new organism (BA.2) is very infectious, and the fact that it is in all 31 Chinese provinces does not bode well.  Mainland China (excludes Hong Kong) has 1,318 symptomatic and 25,111 asymptomatic cases, essentially all locally transmitted.

We have to be impressed by the fact that 25,000,000 PCR tests for the virus were performed in Shanghai the past week, with roughly one in every thousand people carrying the virus.  It’s great to have data showing just how asymptomatic most cases are (96%).  We owe Shanghai and its people a great debt for this.

Xi reminds me of King Canute.  I think BA.2 will pop up again and again until it runs through the population.  Clearly full  vaccination with boosters  is not protective against infection here in the USA (witness Pelosi, Vilsack, Garland and Collins) although in the past  COVID19 was stated to be a disease of the unvaccinated.   The ‘fully vaccinated’ rate this year in Massachusetts for those in the hospital with COVID has ranged from 37 %  to 64% (currently 54%).  I think the USA is doing better, because given that 96% of cases (in Shanghai) are asymptomatic, almost everyone in the states has been infected with one or another strain of the pandemic virus, so there is some degree of immunity in the population.  Not so for China.  They are immunologic virgins for the pandemic virus (SARS-CoV-2)

Due to stringent criteria for who can bring in supplies to Shanghai there are problems with supplying food for the population.

Here is the post of 15 March — it’s long but has a lot more evidence to back up what I’m saying here

China will be near collapse due to COVID19 — here’s why

Here is why I think China will be near collapse due to COVID19 in the next few months.

Due to a strict containment policy, the only experience the Chinese population (excepting Wuhan) has had with the pandemic virus has been by vaccination, mostly with Sinopharm and Coronavac.  These are known to be less effective against the Omicron variant than the western mRNA vaccines (Pfizer, etc.) which themselves are not terribly effective against infection.  So most Chinese are immunologic virgins for exposure to the variants of the pandemic virus and the omicron variant of the virus is incredibly infectious.

In contrast, western populations have been exposed to variant after variant of the pandemic virus, building up immunity to coronaviruses.  The vast majority of cases are mild not requiring hospitalization, and many are completely asymptomatic.

One small piece of evidence for this — there are many more —

The following is from a post July/2020.

https://www.nytimes.com/2020/07/09/nyregion/nyc-coronavirus-antibodies.html–https://www.cnbc.com/2020/04/23/new-york-antibody-study-estimates-13point9percent-of-residents-have-had-the-coronavirus-cuomo-says.html.

New York State  randomly tested 3,000 people at grocery stores and shopping locations across 19 counties in 40 localities to see if they had the antibodies to fight the coronavirus, indicating they have had the virus and recovered from it. With more than 19.4 million people residents, according to U.S. Census data, the preliminary results imply that at least 2.7 million New Yorkers have been infected with Covid-19.They weren’t all hospitalized.

If you’re into authoritative statements, here is Dr. Fauci 3 months ago –Source — https://nypost.com/2021/12/12/omicron-appears-to-evade-some-protection-from-covid-vaccines/

“We’re getting anecdotal information … not necessarily confirmed yet, that the level of severity appears to be maybe a bit less than in the Delta. But there are a lot of confounding issues that it may be due to the underlying protection in the community due to prior infections,”

Omicron spreads like wildfire.  For example, we had to call our plumber a week ago.  He has trained his teenage daughter to enter the trade.  We talked about the pandemic.  Teenagers love crowded parties (well I did, and so did our kids). His daughter  told us that apparently one irresponsible kid came to a party while sick in the early stages of what turned out to COVID19 and transmitted the virus to NINETEEN people.

Here is the Hong Kong experience.  It began with an aircrew member from Cathay Pacific Airways Ltd., who was subsequently found to be infected with omicron.  He ate lunch at a restaurant 27 December ’21 with his family. . Five other customers later tested positive.   By the first week in March there were over 50,000 new cases each day.  Fortunately Hong Kong appears to have passed the peak with ‘only’ 20 – 30 thousand new cases each day.

The South China Morning Post of 16 March notes that 90% of Hong Kong residents have received one dose of a vaccine.  This hardly speaks well for the efficacy of whatever they received.

The Hong Kong experience has been rationalized by several reasons perhaps peculiar to Hong Kong:

l. A very low vaccination rate among the most vulnerable (e.g. over 80)

2. Very high population density — 50% of the population in Hong Kong live in public housing which is mostly very tall, very skinny high rises, due to the lack of buildable land in Hong Kong.  The elevators are a perfect way to transmit the virus.

I can’t speak to how common this is elsewhere in China.

5 days ago the number of cases in China was 1,000.  Today (16 March) I read that there were 5,100 on 15 March — https://www.scmp.com/news/china/science/article/3170631/china-reports-another-3000-covid-19-cases-latest-surge-continues?module=lead_hero_story&pgtype=homepage

So the elevator pitch is — a highly infectious virus is loose in a huge, previously uninfected population with minimal vaccine protection.

I was very worried that something like this could happen all over China in posts  written 2 and 3months ago, long before the number of cases in Hong Kong took off.  You can find my reasoning in the following post — https://luysii.wordpress.com/2022/01/15/i-hope-to-hell-i-was-wrong-about-china/   It was published 15 January ’22, and can be found below and it contains the 12 December ’21 post:

Addendum 16 Marchhttps://www.shine.cn/news/nation/2203163160/–MainlandChina now has 1,860 locally transmitted cases — with most in the province next to North, but in 20 other locations all over China including Shanghai and Beijing. This is is not good news given how infectious Omicron is.

 

I hope to Hell I was wrong about China

From the South China Morning Post — 9:52pm, 15 Jan, 2022

“The Chinese capital reported its first community case of the Omicron coronavirus variant on Saturday, with local and imported infections of the strain now detected in about half of the country’s provinces and municipalities.”

https://www.scmp.com/news/china/politics/article/3163525/china-braces-omicron-variant-extends-its-reach-and-lunar-new-

If true, containment, quarantine, lockdowns and isolation are hopeless.  The quote implies that they’ve already failed.

I find this very worrisome for reasons listed in a post 12 December 2021, a copy of which is below.

The short answer is that the mainland Chinese are immunologic virgins to exposure to the variants of the pandemic virus.  Hopefully their vaccines will work better against omicron than those of the west, but there is no reason to think they will.

Is China following a Smokey the Bear policy on the pandemic?

China is following a prevent pandemic virus infection policy, just as Smokey the Bear followed a prevent forrest fires policy.  The latter didn’t work out well, as although fires were prevented for a while. However, when fires did occur, they were much much worse than the smaller ones Smokey prevented.  There was much more tinder and stuff to burn.

Actually Smokey has changed his tune slightly.

https://en.wikipedia.org/wiki/Smokey_Bear  SmokeyBear.com’s current site has a section on “Benefits of Fire” that includes this information: “Fire managers can reintroduce fire into fire-dependent ecosystems with prescribed fire. Under specific, controlled conditions, the beneficial effects of natural fire can be recreated, fuel buildup can be reduced, and we can prevent the catastrophic losses of uncontrolled, unwanted wildfire.”

Revision 14 December 2021 — China’s policy of prevention has resulted in a Chinese population which has been vaccinated using two killed virus vaccines (Sinopharm, Coronavac).  They have not had any natural infections with the virus (aside from the original cases) as far as we know given what China has allowed out.

Infection with the virus itself exposes you to all its proteins, with your immune system responding to all of them.   Western vaccines are just to the spike protein.

It tends to be forgotten that moist cases of pandemic viral infection are asymptomatic.

Given 800K deaths  from COVID19  in the USA, how can I possibly say this is good. Here’s how :>

If you had an infection with the virus, you develop antibodies.  Nowadays, everyone who is vaccinated has antibodies so there is no point in testing for them, but what were things like in the days before vaccines?

The following is from a post July/2020.

https://www.nytimes.com/2020/07/09/nyregion/nyc-coronavirus-antibodies.html–https://www.cnbc.com/2020/04/23/new-york-antibody-study-estimates-13point9percent-of-residents-have-had-the-coronavirus-cuomo-says.html.

New York State  randomly tested 3,000 people at grocery stores and shopping locations across 19 counties in 40 localities to see if they had the antibodies to fight the coronavirus, indicating they have had the virus and recovered from it. With more than 19.4 million people residents, according to U.S. Census data, the preliminary results imply that at least 2.7 million New Yorkers have been infected with Covid-19.They weren’t all hospitalized.

Here’s some work the same month from Queens — https://www.nytimes.com/2020/07/09/nyregion/nyc-coronavirus-antibodies.html

At a clinic in Corona, a working-class neighborhood in Queens, more than 68 percent of people tested positive for antibodies to the new coronavirus. At another clinic in Jackson Heights, Queens, that number was 56 percent. But at a clinic in Cobble Hill, a mostly white and wealthy neighborhood in Brooklyn, only 13 percent of people tested positive for antibodies.

So the disease has already to spread to half the population in some neighborhoods in Queens. If even 10% of them were sick that would have been 140,000 hospitalizations.  They didn’t happen.

OK, so a lot more people were infected than got sick.  Why is this good?

Enter the omicron variant of the pandemic virus.  It can evade the antibodies produced by all the current vaccines (in the West — protection against the Chinese killed viral vaccines CoronaVac and Sinopharm isn’t known yet).   Yet omicron doesn’t appear to produce severe disease. Thus far…

 

The CDC in the past week said of the 40+ omicron cases it knows about (there certainly are more out there, and more to come), there was one hospitalization (for two days) and no deaths.

Here is Dr. Fauci 12 December 2021 — “We’re getting anecdotal information … not necessarily confirmed yet, that the level of severity appears to be maybe a bit less than in the Delta. But there are a lot of confounding issues that it may be due to the underlying protection in the community due to prior infections,”

Source — https://nypost.com/2021/12/12/omicron-appears-to-evade-some-protection-from-covid-vaccines/

So the Chinese population may be sitting ducks for omicron having been given vaccines (Sinopharm, Coronavac) of unknown potency against omicron.  If their statistics are true there has been little or no natural infection with the pandemic virus in the Chinese population (which Fauci has just implicated is protective),.  Given that I have a son, daughter in law and two grandkids living in Hong Kong, I find this extremely disconcerting.