Tag Archives: SARS-CoV-2

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

 

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.

These are the people who ‘believe in Science’

It certainly passeth my understanding why the travel ban on flights from Africa to the USA is to begin 2 days from (27 November)  now on Monday (29 November) rather than immediately.   This is from the ‘adults in the room’ running our country who supposedly ‘believe in science’.

Sixty-one people who arrived in Amsterdam on two flights from South Africa have tested positive for Covid-19, Dutch officials say.

They have been placed in isolation at a hotel near Schiphol airport.

They were among some 600 passengers held for several hours after arrival while they were tested for the virus.”  — source — https://www.bbc.com/news/world-europe-59442149.

The new bug (omicron variant to avoid using nu for confusion with new and xi for confusion with you know who (these were the next letters in the Greek alphabet)) is clearly incredibly infectious, based on 10% of the passengers in two flights being positive for a coronavirus.

The time to ban flights from southern Africa is now, not two days from now as have the European Union and many other countries have done.   Perhaps the President didn’t want to be accused of racism, the way he accused President Trump when he did the same thing in 2020.

Now a bit abut the omicron virus itself and why it is of such concern.  The protein of the virus which gloms on to our cells is the spike protein which is large (over 1,000 amino acids).  300 of them are involved is actually binding to a receptor (ACE2) on our cells.

Omicron has changed (mutated) some 30 of them, many more mutations than most viral variants contain.  Remember it just took one mutation of one amino acid  of beta globin to cause Sickle Cell Anemia.  Some of these mutations have been found in other SARS-CoV-2 variants, and these were associated with (1) increased infectivity (2) ability to evade existing antibodies to the virus.   So far there is no evidence that the omicron variant is associated with more lethal disease, but absence of evidence is not evidence of absence.

It is important to remember that all information about omicron does not come from peer – reviewed journal articles — it’s just too early, as the first mention of the virus was 14 November, so all of this may change.  Reports from the battlefield are always fragmentary and inaccurate.

 

 

Is the end of the pandemic at hand?

6 days ago I published my brother’s idea, that the pandemic may be nearing an end.  That post can be found below the ****

Here is some startling evidence that he might be right.  Today’s (12 August) Nature pp. 175 – 176, notes that new ‘cases’ in the UK defined as a positive test for the viral genome dropped in half from 17 July to 2 August 54,674 to 22,287. That could just be due to fewer people being tested (the total number tested isn’t given in the article).  More to the point, hospitalizations dropped from 836 25 July to 645 1 August.  It isn’t clear if all these numbers are daily or weekly.  Regardless, it is worth noting just how few cases are actually hospitalized ( 836/54674 = 1.5%)

These numbers are those persons deciding or required to be tested.  A random population survey is in order to see how many people now have antibodies to the virus.  Clearly SARS-Cov-2 can spread widely without making most people sick.

It is worth noting that the article doesn’t consider my brother’s idea as a possibility, so it likely originated with him.  If so, Bravo ! ! !

Addendum 19 August — from Nature vol. 596 p. 326 “In a nationwide survey of about 28,000 people (two-thirds of whom were unvaccinated and had therefore acquired immunity from infection) in June and July this year, researchers found that 68% had SARS-CoV-2 antibodies in their blood. This represented a huge increase from the 21% with antibodies, recorded in a similar survey in December 2020 to January 2021, before the second wave.”  This is exactly what my brother was talking about — vaccination by infection. It shows that most infections are survivable — with a population of 1.3 billion, the vast majority of those coming in contact with the pandemic virus are still here.

****

Sibling rivalry aside, my younger brother thinks that we’re currently in a mass vaccination situation with the pandemic virus.  He does not mean that people are willingly signing up for vaccinations. He says that the Delta virus is so infectious and spreading so quickly, and that most cases are asymptomatic that  the populace is being vaccinated by infection.  If so, those who will die because they weren’t vaccinated will die and those unvaccinated who have been infected but not sick will be immune, so that the populace will achieve herd immunity in a month or two and the pandemic will be over.Fantastic if true.

My kid brother’s brilliant idea

Sibling rivalry aside, my younger brother thinks that we’re currently in a mass vaccination situation with the pandemic virus.  He does not mean that people are willingly signing up for vaccinations. He says that the Delta virus is so infectious and spreading so quickly, and that most cases are asymptomatic that  the populace is being vaccinated by infection.  If so, those who will die because they weren’t vaccinated will die and those unvaccinated who have been infected but not sick will be immune, so that the populace will achieve herd immunity in a month or two and the pandemic will be over.Fantastic if true.

How a doctor must learn to think

The previous post (found just below) is a textbook example of how a doctor (e.g. me) thinks about medical issues.

“A steady rise in COVID-19 is continuing this week as the state reported 208 new cases Wednesday.

Updated data from the Massachusetts Department of Public Health shows that new cases last week rose 46% over the previous week. The updated percentage includes cases from last week that were reported Wednesday. It’s the second week in a row that cases rose after more than two months of decline that hit a pandemic low the week of June 20.”

Well those are the first two paragraphs of https://www.masslive.com/coronavirus/2021/07/just-one-month-aver-hitting-pandemic-lows-new-covid-cases-in-massachusetts-continue-to-rise-as-delta-variant-spreads.html

Which led to the post

Here are the next two paragraphs

“Deaths continue to remain low, however, with one new COVID death being reported on Wednesday. A total of 17,648 Massachusetts residents have died from the virus since the start of the pandemic.

Hospitalizations ticked back up to 102 after hitting a low of 80 on July 4. They have slowly been trending back up since then. Of the hospitalizations, 37 are in intensive care and 17 are intubated.”

 

If they led with the second two paragraphs no one would have read the article.
This is typical in several ways of the medical literature

 

l. Make the most spectacular claim you can first off to grab the readers attention — we’re in another wave of the epidemic

2. The actual data don’t seem to support the lead (things just aren’t that bad).

Eventually I’d read each medical paper wondering how the authors were lying to me — for a horrible example (from Johns Hopkins yet — please see   https://luysii.wordpress.com/2009/10/05/low-socioeconomic-status-in-the-first-5-years-of-life-doubles-your-chance-of-coronary-artery-disease-at-50-even-if-you-became-a-doc-or-why-i-hated-reading-the-medical-literature-when-i-had-to/

So now the doc has to deal with two conflicting pieces of information.  This never happens in math (which is why I love reading it in retirement).  You can prove anything from assuming a statement and its negation are both true.  Here’s how Bertrand Russell proved that he was the Pope starting with 1 = 2. “Either the Pope and I are one person or we are two people. If 1=21=2 then in either case we are one person. Therefore, I am the Pope.”

 

So the doc has to reach into his/her store of knowledge to figure it out.  Well, he/she knows that most COVID-19 stay in the hospital for longer than a day.  Clearly not all the 208 cases wound up in the hospital as there were only 102 COVID-19 cases in the hospital.  I’m guessing that the median (not average) length of hospital stay for COVID-19 is two weeks.

 

But it’s more complicated than that (https://www.nuffieldtrust.org.uk/resource/chart-of-the-week-how-long-do-covid-19-patients-spend-in-hospital) as in England the median length of stay ranged from 5 to 10 in the past year.

 

So how many ‘cases’ of COVID-19 were there in Massachusetts — the excellent statistics of the Department of Health says about 1,000 in the past two weeks.
So if there are only 100 in hospital and the average stay is 10 days (I couldn’t find data for Massachusetts — again this is typical of medical practice — you can’t find the data you really want), 90% of the COVID-19 cases aren’t severe enough to be hospitalized.

 

This led to the conclusion in the first part of the post “What does the rise in COVID-19 cases mean?  NOT MUCH.”

 

The data is quite similar to that from Los Angeles — http://publichealth.lacounty.gov/media/coronavirus/data/index.html
1,827 cases on the 17th, 500 COVID-19 cases in the hospital.  Assume that cases are rising and figure 1,000 cases/day over the past 10 days, and you get to 95% of ‘cases’ not sick enough to be hospitalized.

 

When the normal person thinks of a ‘case’ of a disease, they think of someone who is physically ill.  Not so with COVID-19, and this is incredibly dishonest reporting by the press, various health departments etc. etc.

 

My post ends with “Presently nearly all the deaths from COVID-19 are in people who were not vaccinated, so to lower your odds further please get vaccinated.”

I couldn’t track this down to any sort of hard data.  It certainly is plausible, but how may plausible medical ideas have I seen crash and burn.  The Associated Press quotes a former official in the Obama administration making this claim.  At least they identify him Andrew Slavitt — a former investment banker — rather than an anonymous source.

Addendum 21 July

“There’s a common theme among those behind the worsening COVID-19 numbers, said Dr. Rochelle Walensky, director of the US Centers for Disease Control and Prevention:

“This is becoming a pandemic of the unvaccinated,” Walensky said at a COVID-19 briefing Friday.”

More than 97% of people getting hospitalized with COVID-19 now are unvaccinated, Walensky said. And 99.5% of deaths are among the unvaccinated, US Surgeon General Dr. Vivek Murthy said Sunday.”

Even more reason to get vaccinated.

*****

What is a ‘case’ of COVID-19

What does the rise in COVID-19 cases mean?  NOT MUCH.  Here’s how the local paper played it — https://www.masslive.com/coronavirus/2021/07/just-one-month-aver-hitting-pandemic-lows-new-covid-cases-in-massachusetts-continue-to-rise-as-delta-variant-spreads.html

There were 208 ‘cases’ today 14 July 2021   in Massachusetts, which is a rate 46% higher than last week. In the past two weeks there have been about 1,000 cases according to the Massachusetts department of health. https://www.mass.gov/info-details/covid-19-response-reporting#covid-19-interactive-data-dashboard-

So the hospitals must be packed and deaths must be soaring.  Right?

Wrong — the same article tells us that there are currently 100 people in Massachusetts hospitals with COVID-19 and that there was one death today

This means that what they are calling a case of COVID-19 is not enough to put 90% of people with it in the hospital.  Most of the ‘cases’ of COVID-19 in Massachusetts are either asymptomatic or mild.

It’s hard to find comparable statistics from states with lower vaccination rates (e.g. the south) but deaths are also lower there.

Well what about the Delta variant?  It is definitely more infectious, and the disease it causes is more severe.  We should be in big trouble if Delta takes over in the USA.  Right?

Wrong.  Delta has taken over.  According to the CDC, Delta accounts for 58% of all new cases of COVID-19 in the USA — https://abcnews.go.com/Health/delta-variant-now-accounts-58-covid-19-cases/story?id=78834579.   Deaths have not spiked.  The vaccines are working.

Presently nearly all the deaths from COVID-19 are in people who were not vaccinated, so to lower your odds further please get vaccinated.

My friends and I did — https://luysii.wordpress.com/2021/05/19/anti-vaxers-what-is-it-that-you-know-that-we-dont/

Frameshifting

It is a pleasure to get back to the science after the ugly real world intruded with

l. A president in early dementia — https://luysii.wordpress.com/2021/06/30/biden-is-in-early-dementia-the-evidence/

2. The latest in politically correct racism  — https://luysii.wordpress.com/2021/07/03/hitler-would-have-loved-it/

but these things needed to be addressed.

I was very pessimistic about the chance of a vaccine for the pandemic based on my experience with AIDS/HIV1.  Why? Because no vaccine for HIV1 has been forthcoming despite 40 years of intense effort.  I am delighted to be wrong about pandemic vaccines.

But AIDS isn’t the kiss of death it was when I was in practice back in the 80s.  Why?  Because we know so much about what happens after the virus infects cells.  We attack all it’s weak points, from its genome, its reverse transcriptase.  So AIDs is now a chronic manageable disease.

So the more we know about SARS-Cov-2 the more ways we’ll find to attack it.   Which brings me to Science vol. 372 pp. 1306 – 1313 ’21.

The pandemic virus SARS-CoV-2 (and all coronaviruses) use something called frameshifting.

Here is a brief tutorial

Her fox and dog ate our pet rat

H erf oxa ndd oga teo urp etr at

He rfo xan ddo gat eou rpe tra t

The last two lines make no sense at all, but (neglecting the spaces) they have identical letter sequences.

Here are similar sequences of nucleotides making up the genetic code as transcribed into RNA

ATG CAT TAG CCG TAA GCC GTA GGA

TGC ATT AGC CGT AAG CCG TAG GA.

GCA TTA GCC TAA GCC GTA GGA ..

Again, in our genome there are no spaces between the triplets. But all the triplets you see are meaningful in the sense that they each code for one of the twenty amino acids (except for TAA which says stop). ATG codes for methionine (the purists will note that all the T’s should be U). I’m too lazy to look the rest up, but the ribosome doesn’t care, and will happily translate all 3 sequences into the sequential amino acids of a protein.

Both sets of sequences have undergone (reading) frame shifts. The examples are of +1 and +2 frameshifts.

SARS-CoV-2 uses a -1 frameshift.  this is necessary for the synthesis of nonstructural protein 12 (nsp12), crucially important to the virus as it codes for the viral RNA dependent RNA polymerase.

To produce the frameshift, the virus actually throws a monkey wrench at the ribosome.  At the site of the future frameshift the viral genome forms a pseudoknot  (https://en.wikipedia.org/wiki/Pseudoknot) which blocks the smooth translation of the ribosome along the viral genome, then it backs up by 1 (the -1 frameshift) and chugs on.

So PNAS vol. 118 32023051118 ’21 threw the kitchen sink (e.g. every compound they could think of) at the virus to find one which stopped the frameshift and they found one: merafloxacin a fluoroquinolone.  There are all sorts of fluoroquinolones in use as antibodies, so it’s time to try the others out.

This is unlikely to be a general approach to coronavirus therapy, as the RNA sequence at the frameshift site is likely to be different in each coronavirus.

I don’t think frameshifting occurs in eukaryotic cells, but I’m not sure.  Does anyone out there know?

 

Another virus escapes from a lab

Given the excitement over the possibility that the pandemic virus (SARS-CoV-2) escaped from a lab in Wuhan, it’s time to shamelessly republish a clairvoyant science fiction story of mine first published 19 November 2019.

A science fiction story (for the cognoscenti) — answer to the puzzle and a bit more

Comrade Chen we have a serious problem.

Don’t tell me one of our bugs escaped confinement.

Worse.  One of theirs did.  And it’s affecting the PLA (People’s Liberation Army).  Some are turning into pacifists.

It doesn’t kill them?

No. But for our purposes it might as well.

It’s a typical adenoassociated virus (AAV) like we use.

Well, what does the genome look like?

We’ve sequenced it and among other things, it codes for a protein which enters the brain and alters behavior.

What?

Well, the enemy has some excellent biologists, one of whom works on Wolbachia.

What’s that?

It’s a rickettsial organism which changes the sex life of some insects.

I don’t believe that.

Do you have a cat?

Yes.

Well many cats contain another organism (toxoplasma gondi).

So what.

Rats infected by the organism become less afraid of cats.

Another example please.

A fungus infecting carpenter ants causes the ant to leave its colony, climb a tree, chomp down on the underside of a leaf and die, freeing fungal spores to fall on the ground where they can reinfect new ants.

Well what is the genome of the virus?

It has some very unusual sequences, and one which proves that the Wolbachia biologist on the other side has a very large ego.

How so.

Well in addition to the brain infecting protein, there is a very unusual triplet of peptides all in a row.

Methionine Alanine Aspartic Acid Glutamic acid, then a stop codon, then Isoleucine Asparagine, than a stop codon, then Threonine Alanine Isoleucine Tryptophan Alanine Asparagine.  We think that the first two in some way cause readthrough of the stop codons so the protein following the short peptides is made.

Where does the big ego come in?

Sir, proteins can have hundreds and hundreds of amino acids.  People got tired of writing their full names out, so each of the 20 amino acids was given a single letter to stand for it.

M – Methionine

A – Alanine

D – Aspartic acid

What does D have to do with Aspartic acid?

Nothing sir, look on the letters as Chinese characters.

E -Glutamic Acid

I – isoleucine

What about the stop codon between Glutamic acid and Isoleucine

Just regard it as a space.

N – Asparagine

Nooo! ! ! I I’m beginning to get the picture.

Yes sir, it stands for MADE IN TAIWAN

—-

A few years later

Well the Taiwanese biologist outsmarted himself (or herself).   The Taiwanese soldiers wouldn’t fight either as the virus spread.  Most conflicts between nation states pretty much ended (Russia/Ukraine, North Korea/South Korea) etc. etc.  The Taiwanese biologist was nominated for the Nobel Peace Prize, and did receive it in absentia, as every military type in the world was looking for him (or  her), so he (or she) went into hiding, and is believed to be living in an Ashram near Boulder, Colorado.

Unfortunately, the idea of using viruses to change human behavior spread past nation states, and private groups with their own agendas began using it.

The ‘new soviet man’ of the previous century looked rather benign compared to what subsequently happened.

The next story for the scientific cognoscenti will describe the events leading up to the impeachment trial of President Jon Tester in 2028.

Some very disturbing pictures

Granted that these pictures look like microscope slides containing colored blobs, but once you understand what they show, the implications are quite frightening.

These images are biopsies of various portions of the gastrointestinal tract in a person who had become  symptomatic  three months earlier with COVID-19 from which the person  has now recovered).The green blobs represent fluorescent antibodies binding to the nucleocapsid protein of the pandemic virus (SARS-CoV-2).  They are found in the enterocyte cells which line the inside of the gut.  These are the enterocyte which live for just 5 days before they are shed.  

This is my first shot at getting pictures into my blog, and they do appear blurry (apologies !).  I will try to correct this. All you need view is in the first and second columns of rows a, c, and e as most  of the rest are controls. The pictures are from a Nature paper — here’s a link — https://www.nature.com/articles/s41586-021-03207-w.pdf

 

Why is this disturbing?  Because their presence implies that they have been made continually for the whole three months, as enterocytes are born and die. 

Well maybe it’s an artifact confined to one patient.  Unfortunately similar findings were present in 5/14 cases recovered COVID-19 patients who received GI tract biopsies for clinical reasons unrelated to COVID-19.  The 14 are from a larger series of recovered COVID19 patients (see the copy of the previous post below). Like Reverend Paley’s found watch, the presence of the viral nucleocapsid protein demands an explanation of what had to be present to put it there.

There are a series of requirement for this to happen.  The messenger RNA for the protein had to be made and present, which, in turn means at the least that the viral gene from which the mRNA for the nucleocapsid protein was made must also be present.  What mades nucleocapsid mRNA? The viral RNA dependent polymerase. So the polymerase must be present as well, along with the 3 genes coding for the 3 proteins making up the polymerase.  Not only that but all of the above must have been present in longer lived cells  than the enterocytes.

Defective viruses certainly appear during the course of viral infection (particularly as in AIDS), but it is very scary to realize just how much of the virus must be present and functioning to produce just these findings. Perhaps the fluorescent antibody was really binding to another protein, not from the virus at all.  After all, antibodies aren’t always as specific as we’d like them to be.  

However, the authors did something else which makes this much less likely. They wrote, “In addition, viral RNA was detected by in situ hybridization in biopsy samples from the two participants who were tested for it”

Further scariness:  Pictures e and f show the nucleocapsid protein is present at the far end of the terminal ileum (small intestine) a part of our GI tract which is 22 feet long

So this person although well, was literally crawling with both the viral protein and the machinery necessary to make it. 

Are many more, or all such people who are clinically recovered from clinical COVID-19 excreting infectious virus?  I’m sure people have looked, and if they haven’t they should be. 

I’m going to now insert the previous post on the subject.  It contains a link to the Nature paper, so feel free to follow it and look for yourself.  It contains a lot more detail. 

Is the virus still within you? Will it cause trouble?

Let’s say you’ve recovered from a bout with COVID-19. Is the virus still with you? Could it come back and cause trouble? Given the data in a recent paper [ Nature vol. 591 pp. 639 – 644 ’21 ] — https://www.nature.com/articles/s41586-021-03207-w.pdf, it’s quite possible.

But first a story about my grandmother.  She was born somewhere around the Baltic Sea in 1880 and came to America in 1893.  She died of undiagnosed (hence untreated) miliary Tuberculosis in a University Hospital in 1967.  Just about everyone in Europe in the 1880s was exposed to TB and just like SARS-CoV-2 many if not most were asymptomatic.  Their lungs walled off the organism in something called a Gohn complex — https://en.wikipedia.org/wiki/Ghon%27s_complex.  The organism didn’t die — and probably broke out of the complex as my grandmother aged and her immune system got weaker and weaker.  It is very unlikely that she picked it up by exposure in the 1960’s.  As they say TB is forgotten but not gone.  

Which brings me to the Nature paper.  At first I thought it was great and very optimistic.  Some 87 people from New York City who had symptomatic SARS-CoV-2 infection (proven by finding the viral genome using RT-PCR technique).  The authors studied the antibody responses at an average of 1.3 and 6.2 months after infection.  Although the antibody levels dropped (which always happens) they changed so they bound the virus more tightly.  This is called affinity maturation — https://en.wikipedia.org/wiki/Affinity_maturation.  

So that’s good? 

No that’s bad because it implies that the protein stimulating affinity maturation is still around. The authors note the persistent antigenic stimulation of the immune system is possible because an “antigen trapped in the form of immune complexes on follicular dendritic cells .. . . . can be long-lived, because follicular dendritic cells do not internalize immune complexes”.  

Well maybe, but the paper gives evidence for another mechanism of antigen persistence (which I find more persuasive). 14 of the people had intestinal biopsies for appropriate clinical indications (see Table 7 in the supplementary information of the article). In some of the biopsies they detect viral antigen in some of the enterocytes (cells which line the inside of the gut) — I’m assuming the antigen is the viral spike protein, but it’s hard to find exactly what it is. 

This is quite bad, as the lifetime of the enterocyte is 5 days.  This means that the antigen is being continually produced, which means that the mRNA for the antigen is being continually produced, which in turn means that the viral genome is still around.  The mean lifetime of cellular mRNAs is 10 hours although some hang around for days, however I doubt that the mRNA responsible for the viral antigen had lasted for 2.8 to 5.7 months which is the time after clinical infection when the biopsies were done. 

So it is possible, that like TB in the Gohn complex, the immune system has fought the virus to a draw, but that the intact organism could be still present.  As in my grandmother, it is possible that the virus will reappear as the immune system weakens with age (something that happens in all of us). 

In that case we wouldl have recrudescence not reinfection. 

PS:  My grandmother came to this country at age 13 alone and speaking no English.  Every time I feel sad at what the pandemic has put us all through, I think of that generation.  

PPS: When she got sick, I wanted to put her in the hospital where I was an intern, but our family GP (Dr. Richard A. Gove) told me taking care of my own family was a very bad idea and put her elsewhere.  I doubt that I’d have made the diagnosis, or that anyone at our hospital would have. 

PPPS:  I don’t know if they still do autopsies, but I was always able to get one after I’d tell families of the deceased about my grandmother.  It meant that my wife and I and our two little kids were all screened for TB. 

PPPPS — a friend brought up the following — Eleanor Roosevelt, who was thought to have aplastic anemia, was treated with prednisone and later found to have died of military tuberculous, probably the recurrence of tb acquired some 4 decades earlier.