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.

But this is flat out wrong.  “The amino acid sequence of the FCS in SARS-CoV-2 also exists in a human protein (the ENaC α subunit)  where it is known to be functional and has been extensively studied.” Bravo to Harrison for looking further.

Even worse — “The insertion of such FCS sequences into SARS-like viruses was a specific goal of work proposed by the EHA-WIV-UNC partnership within a 2018 grant proposal (“DEFUSE”) that was submitted to the US Defense Advanced Research Projects Agency (DARPA). The 2018 proposal to DARPA was not funded, but we do not know whether some of the proposed work was subsequently carried out in 2018 or 2019, perhaps using another source of funding.”

Moreover — “The exact FCS sequence present in SARS-CoV-2 has recently been introduced into the spike protein of SARS-CoV-1 (the original SARS virus hitting Hong Kong)  in the laboratory, in an elegant series of experiments, with predictable consequences in terms of enhanced viral transmissibility and pathogenicity.”

So there you have it.   The 8 amino acid sequence (RRAR’SVAS) sticking out like a sore thumb in the genome of SARS-CoV-2  essentially saying to furin “open’here.”

The point of the paper, is that there is a lot of US work, publicly funded, yet not in the public domain which would go a long way to clear things up.

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

BMOR is a bad actor

RNA and proteins have long been known to interact, but classic molecular biology pretty much had proteins down as something that modified RNA function.   Not so for BMOR, a long nonCoding RNA (1,247 nucleotides) expressed in breast cancer cells metastatic to the brain.  BMOR binds to IRF3 (Interferon Regulatory factor 3) inhibiting its phosphorylation by TBK1 with subsequent movement to the nucleus where it stimulates interferon expression which then turns on hundreds of genes producing inflammation.  All this is described in Proc. Natl. Acad. Sci. vol. 119 e2200230119 ’22 —

May 26, 2022

119 (22) e2200230119

https://doi.org/10.1073/pnas.2200230119

Not sure if it is behind a paywall.    Definitely worth a read because knocking down BMOR in breast cancer cells prevents them from spreading to the brain (probably  by using BMOR to turni off the brain’s immune response to them).  Even more interestingly, BMOR was found to be only substantially expressed in breast cancer metastasis to brain tissue versus breast cancer metastasis to nonbrain tissues.

 

 

Teleology as always raises its head.  What in the world is the normal function of BMOR?  It can’t be what it is doing in the animal model described here.  Why would a cell make something to help it kill the organism containing it?

 

Then of course, as is typical of all interesting research, larger questions are raised.  Are there other RNAs whose function is to modify protein function?  Remember that 75% of the genome is transcribed into RNA.  Most of this has been thought of as molecular chaff, like the turnings of a lathe.   Time pick up the chaff from the factory floor and give it a look.

If the right hand don’t get you, the left hand will

Do you know the source of the title?  I found it surprising.  Answer at the end.

Some cancer cells have elevated levels of an enzyme called PHosphoGlyceride DeHydrogenase (PHGDH, others have decreased levels.  Many cancers contain both types of cells.  Neither is good news.

Those cancers  with low levels of PHGDH  have slower growth.  That’s good news isn’t it?  No.  Such cells are more likely to metastasize.

Those with high levels of PHGDH are less likely to metastasize.  That’s good news isn’t it?  No. such cells grow faster.

So cancers with both types of cells are more aggressive.

Here’s how it works [ Nature vol. 605 pp. 617 – 617, 747 – 753 ’22 ].

PHGDH is on the pathway for synthesis of serine, an amino acid required for protein synthesis (like all of them).  So low levels of the enzyme result in less protein synthesis and less tumor growth.

So how is this bad?  PHGDH binds to another enzyme PFK (PhosphoFructoKinase) stabilizing it.  When PHGDH is low PFK enzyme levels are low, so the subsrate of PFK (fructose 6 phosphate) is diverted to making sialic acid, which modifies cell surface proteins making them more likely to migrate.

So blocking sialic acid synthesis reverses the effects of low PHGDH on cancer migration and metastasis — but it does potentiate cell proliferation.

You just can’t win

Things like this may explain other paradoxic and unexpected effects of enzyme blockade.

16 Tons by Tennessee Ernie Ford

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.

But this is flat out wrong.  “The amino acid sequence of the FCS in SARS-CoV-2 also exists in a human protein (the ENaC α subunit)  where it is known to be functional and has been extensively studied.” Bravo to Harrison for looking further.

Even worse — “The insertion of such FCS sequences into SARS-like viruses was a specific goal of work proposed by the EHA-WIV-UNC partnership within a 2018 grant proposal (“DEFUSE”) that was submitted to the US Defense Advanced Research Projects Agency (DARPA). The 2018 proposal to DARPA was not funded, but we do not know whether some of the proposed work was subsequently carried out in 2018 or 2019, perhaps using another source of funding.”

Moreover — “The exact FCS sequence present in SARS-CoV-2 has recently been introduced into the spike protein of SARS-CoV-1 (the original SARS virus hitting Hong Kong)  in the laboratory, in an elegant series of experiments, with predictable consequences in terms of enhanced viral transmissibility and pathogenicity.”

So there you have it.   The 8 amino acid sequence (RRAR’SVAS) sticking out like a sore thumb in the genome of SARS-CoV-2  essentially saying to furin “open’here.”

The point of the paper, is that there is a lot of US work, publicly funded, yet not in the public domain which would go a long way to clear things up.

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

 

Another neuropharmacologic surprise.

Our genome contains 826 different genes for G Protein Coupled Receptors (GPCRs) which are targeted by at least 475 FDA approved drugs (Nature vol. 587 p. 553 ’20 ). Yet part of the fascination of reading the current literature is the surprises it brings.

Our basic understanding was that the GPCRs sit on the surface of the cell waiting for ligands outside the cell to bind to it, which produces a conformational change on the cytoplasmic side of the cell membrane, changing the way the GPCR binds to the G protein, triggering all sorts of effects inside the cell.

As far as I recall, we never thought that different GPCRs would bind to each other in the cell membrane, even though a single cell can express ‘up to’ 100 different GPCRs [ Mol. Pharm. vol. 88 pp. 181 – 187 ’15 ].  Neurons express GPCRs and some are thought to be involved in neuropathic pain

But that’s exactly what Proc. Natl. Acad. Sci. vol. 119 e2123511119  ’22  is saying.

First a few definitions, if you’re as rusty about them as I was

A cytokine is an extracellular protein or peptide  helping cells to communicate with each other.  A chemokine is an extracellular protein which attracts cells.

Our genome has over 50 chemokines.  Most are  proteins with about 70 amino acids. The are classified by where the cysteines lie in them.  We have 23 receptors for chemokines, 18 of which are GPCRs.   Binding is promiscuous — a given chemokine binds to multiple receptors, and a given receptor binds to multiple chemokines.

Clearly the chemokines and their receptors are intimately involved in inflammation which always involves cell migration.  Neurons express chemokine receptors GPCRs and some are thought to be involved in neuropathic pain.

We also know that the nervous system is involved in immune function, particularly inflammation.  One prominent neurotransmitter is norepinephrine, and a variety of receptors bind to it.  There are 3 alpha1 norepinephrine receptors (a, b and d), all of which are GPCRs.

What is so shocking is that alpha1 GPCRs bind to chemokine receptors (forming heteromers), and that this binding is required for chemokines to have any effect on cell migration.  Even more interesting is that binding of norepinephrine to the alpha1 component of the heteromer INHIBITs cell migration.

So how many of our 826 GPCRs bind to each other, and what effects do they have?

Reading the literature is like opening presents, you find new fascinating toys to play with, some of which may actually benefit humanity

 

Cassava’s Cognition Maintenance Study may prove Simufilam works

The FDA will approve less than perfect therapies if there is nothing useful for a serious condition.  Consider the following from Proc. Natl. Acad. Sci. vol. 119 e2120512119 ’22

“KRAS is the most frequently mutated oncogene in human cancer, with mutations detected across many lineages, particularly in the pancreas, colon, and lungs. Among the most commonly activating KRAS mutations at codons 12, 13, and 61, G12C occurs in ∼13% of lung and 3% of colorectal carcinomas and at lower frequencies in other tumors.

“In locally advanced or metastatic non–small-cell lung cancer (NSCLC) patients with KRAS^G12C mutations who have received at least one prior systemic therapy”  treatment with sotorasib resulted in the following “objective response  in 37.1% of the patients, with a median duration of response was 11.1 months.”   This is hardly a cure, but nonetheless “This promising anticancer activity has resulted in accelerated approval from the US Food & Drug Administration”

Which brings me to the current CMS study from Cassava Sciences.  I’ll let them speak for themselves. https://finance.yahoo.com/news/cassava-sciences-reports-first-quarter-130000375.html

“Cognition Maintenance Study (CMS) – on-going
In May 2021, we initiated a Cognition Maintenance Study (CMS). This is a double-blind, randomized, placebo-controlled study of simufilam in patients with mild-to-moderate Alzheimer’s disease. Study participants are randomized (1:1) to simufilam or placebo for six months. To enroll in the CMS, patients must have previously completed 12 months or more of open-label treatment with simufilam. The CMS is designed to evaluate simufilam’s effects on cognition and health outcomes in Alzheimer’s patients who continue with drug treatment versus patients who discontinue drug treatment. The target enrollment for the CMS is approximately 100 subjects. Over 75 subjects have been enrolled in the CMS and 35 have completed the study.”

Even though the open label study was not randomized, this one will be.

Only someone who has actually taken care of  patients would know the following.  People who are getting no benefit from a drug will soon stop taking it.  This was particularly true for my experience with Cognex for Alzheimer’s disease.

Which is exactly why the fact that 75 patients who’ve been on Simufilam have decided to continue on in the CMS study.  Presumably they feel they are getting some benefit.

There are two possible hookers to this

l. The patients are being paid to enter CMS

2. The original cohort was 200, not all of whom have finished the 1 year.  So we don’t know how many could have been in CMS but chose not to.

As I discussed in an earlier post, the most impressive thing (to me at least) was that at 9 months 5/50 had significant improvement in their cognition — here’s a link — https://luysii.wordpress.com/2021/08/25/cassava-sciences-9-month-data-is-probably-better-than-they-realize/.

The CMS study should give us an idea of how they fared at 1 year and  at 18 months.

If:

l. gains in cognition were maintained on Simufilam

2. gains in cognition were lost off Simufilam

FDA approval should follow quickly.

Results on the 75 will be available this year.   Also available this year will be 1 year results on all 200 entering the open label study.

There are two other double blind studies in progress which will provide  more definitive answers, but they are far from full and will take much longer to complete.  So stay tuned.

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 March — https://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 March — https://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.