Tag Archives: SARS-CoV-2

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.

 

 

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.

 

 

 

600,000 Pandemic deaths in the United Kingdom ! ! !

Yes, 600,000 pandemic deaths in the UK given their attack rate of 182/100,000 and a population the size of the USA (328 million) actually it’s even worse than that because their case fatality rate is 2.9 % and ours is 1.8% — so multiply the 600,000 deaths by 1.6 and you get a million deaths in the UK given their attack rate and case fatality rate (and scaling their population to match ours).

Where are these numbers coming from — the same place that those in the previous post came from — https://coronavirus.jhu.edu/data/mortality, Johns Hopkins. 

Here are the top ten attack rates per 100,000 population from the previous post

181.70, 180.83, 158.39, 155.25, 152.49, 143.61. 142.73, 140.98, 124.72, 118.50

You were asked to guess where the USA, and the UK were.  No the USA is not at the top, but in the middle (hardly great but not as bad as the 500,000 headline would imply).  The UK is at the top. 

Here are the 10 countries (alphabetized) from which these rates were drawn

Czech Republic, France, Italy, Mexico, Peru, Portugal, Slovakia, Spain, United Kingdom, USA

Here are the case fatality rates (in percent) from the same 10 countries

8.8, 3.5, 3.4, 2.9, 2.3, 2.2, 2.1, 2.0, 1.8, 1.7

The UK is 2.9 and the US among the lowest at 1.8  

Not what you’ve likely been led to believe.  

There are worse problems afoot for the USA.  Granted the following  are 3 small and nonrandomized samples, but the minorities who need it the most aren’t getting the vaccine (and not because it is being withheld from them).

Sample #1 Yrs Trly and wife second shot yesterday —

My wife and I received the booster dose of the Pfizer vaccine today. We live in a town that is 45% Latino (mostly Puerto Rican). Both times we were there, the vaccinees were almost all Caucasian, a disaster in the making. The nurse I spoke with said that what we’d seen about Latinos not getting vaccinated was typical in her experience. She also noted misinformation going around among them, such that vaccination would make you sterile.

Sample #2 a friend who was vaccinated elsewhere (but in the same metro area)- “That was my experience at the State Curative site at XXXXXXX. Large African-American population in that area; however, only caucasians getting the vaccines on both occasions. Puzzling.”

Sample #3 a college classmate and friend –Welcome to the club. I received my vaccine through Hopkins as a practicing clinician. My wife received hers as a DC resident through the DC Government in a Black neighborhood; all of the vaccinees there were whites from Foggy Bottom and Georgetown. the DC Government then got smart and has been allocating vaccine by specific neighborhood.

Now there was a giant article in the 4 January New Yorker by Lawrence Wright blaming the magnitude of the pandemic on Trump’s not pushing mask wearing. 

Well here’s our Vice President — https://abc7ny.com/vice-presidential-debate-vp-2020-kamala-harris/6852144/

Harris was asked if Americans should take the vaccine and if she would. Harris says that if doctors “tells us that we should take it, I’ll be the first in line to take it, absolutely. But if Donald Trump tells us that we should take it, I’m not taking it.”  Well he did tell us exactly that. 

Is it her fault that minorities aren’t taking the vaccine?  Don’t wait for the New Yorker to take up the issue. 

 

Virus 1 Astra Zenica vaccine 0

It’s already happened. A mutated pandemic virus has rendered a vaccine useless. This is serious — the game of cat and mouse with the mutating pandemic virus (otherwise known as natural selection) has begun. You can read all about it here

For a leisurely stroll through the background needed to understand the Science and Nature articles I’m going to essentially republish (and refurbish) a very recent  post — trying to make things as accessible as possible. 

The human species as a culture medium for the pandemic virus

Creationists or not, we are all about to get an unwanted lesson in natural selection and evolution, courtesy of the current pandemic virus (SARS-CoV-2).  This is going to be a long post, which will contain an incredible case of meningitis, thoughts on selfish genes in viruses, evolution, natural selection and why we’re in for a very, very long haul with the pandemic virus.

As you probably know, mutant pandemic viruses (all different) have emerged (in England, South Africa, Brazil).  Even worse they appear to be more infectious, and some are more resistant to our vaccines (all of which were made before they appeared).  

Here is lesson #1 in natural selection.  Viruses have no brains, they barely have a genome.  The human genome contains 3 billion positions, the pandemic virus 30,000.  So we have 100,000 times more information in our genome than the virus does. 100,000 is about the number of inches in a mile and half.  

So how is the virus outsmarting us?  Simply by reproducing like mad.  The molecular machines that copy our genome are very accurate, making about 1 mistake per 100,000,000 positions copied — that’s still enough for the average newborn to have 30 new mutations (more if the parents are older).  The viral machine is much less accurate.  So lots of genome mutations are made (meaning that the viral proteins made from the genome change slightly).  Those that elude the vaccines and antibodies we’re throwing at them survive and reproduce, most don’t.  This is natural selection in action. Survival of the fittest.  Darwin wasn’t kidding.

What is so remarkable about the British and the South African variants, is that they contain multiple mutations (23 in the British variant, at least 3 in the South African variant).  Usually its just one or two.

 You’ve probably heard about the mutation changing just one of the 147 amino acids  in hemoglobin to cause sickle cell anemia. Here’s another.  APOE is a 299 amino acid protein.  It comes in 3 variants  — due to changes at 2 positions.  One variant greatly increases the risk of Alzheimer’s disease, another decreases it.  So even single mutations can be quite powerful. 

So how did these multiple mutations come about?  We likely now have an answer due to one very well studied case [ Cell vol. 183 pp. 1901 – 1912 ’20 ] in an immunocompromised patient with chronic lymphatic leukemia (CLL). She shed the virus for 70 days.  Even so, she wasn’t symptomatic, but because the patient had enough immune system to fight the virus to a draw, it persisted, and so its genome was always changing.  The authors were smart enough to continually sequence the viral genome throughout the clinical course and watch it change.  So that’s very likely how the virus accumulates mutations, it lived for a long time in a patient who lived a long time with a weakened immune system allowing the virus to merrily mutate without being killed and allowing the weakened immune system to effectively select viruses it can’t kill. 

Could this happen again? Of course.   There are some 60,000 new cases of CLL each year in the USA.  Many of them have abnormal immune systems even before chemotherapy begins.

Here is an example from my own practice. The patient was a 40 year old high school teacher who presented with severe headache, stiff neck and drowsiness.  I did a spinal tap to get cerebrospinal fluid (CSF) for culture so we could find the best possible antibiotic to treat the organism.  This was 30+ years ago, and we had no DNA testing to tell us immediately what to do.  We had to wait 24 hours  while the bugs grew in culture to form enough that we could identify the species and determine  the antibiotics it was sensitive to. . 

As the fluid came out, I had a sinking feeling; as it was cloudy, implying lots of white cells fighting the infection. Enough white cells to make CSF cloudy (it normally looks like water) is a very bad sign. So after starting the standard antibiotic to be used in the first 24 hours before the cultures came back, I called the lab for the cell count.  They said there weren’t any.  I thought they’d seriously screwed up maybe losing what I’d sent or mislabeling it and looking at the wrong sample, and I unpleasantly stormed down to the lab (as only an angry physician can do) to see the spinal fluid.  They were right.  The cloudiness of the CSF was produced by hordes of bacteria not white cells.  This was even worse as clearly the bacteria were winning and the patient’s immune system was losing, and I never expected the patient to survive.  But survive he did and even left the hospital.  

Unfortunately, the meningitis turned out to be  the first symptom of an abnormal immune system due to a blood malignancy — multiple myeloma. 

****

Addendum 2 February — I sent this post to an old friend and college classmate who is now a hematology professor at a major med school.  He saw a similar case —

“When I was a medical student I saw a pediatric sickle anemia patient (asplenic) with fever and obtundation. When I looked at the methylene-blue stained CSF, I thought that stain had precipitated. So I obtained a fresh bottle of stain and it looked the same. Only this time, I looked more closely and what I thought was precipitated stain were TNTC pneumococci.

I urge all my immunosuppressed patient to get vaccinated for covid-19. I worry that if many people don’t get vaccinated,  those who do will not be that better off.”

Addendum 3 February– I asked him if his patient had survived like mine —

answer 

“Unfortunately, no. With the pneumococcus, If antibiotics are not started within 4 hours after recognition, the train has left the station.”

 

****

So there are millions of active cases of the pandemic, and tons of people with medical conditions (leukemia, multiple myeloma, chemotherapy for other cancer) with abnormal immune systems, just waiting for the pandemic virus to find a home and proliferate for days to weeks.  Literally these people are culture media for the virus. Not all of them have been identified, so don’t try to prevent this by withholding vaccination from the immunocompromised — they’re the ones who need it the most. 

I think we’re in for a very long haul with the pandemic.  We’re just gearing up to stay on top of the viral sequence du jour.   Genome sequencing is not routine (it should be).  The South African and British mutations were picked up because a spike in cases led people to sequence the virus from these patients.  Viral genome sequencing and surveillance should be routine in most countries and should not wait for an infection spike to occur. 

You may come across the terms B.1.351 and  507Y.V2 — they are different names for the South African virus which beat Astra Zenica.  The British variant is also called B.1.1.7

The human species as a culture medium for the pandemic virus

Creationists or not, we are all about to get an unwanted lesson in natural selection and evolution, courtesy of the current pandemic virus (SARS-CoV-2).  This is going to be a long post, which will contain an incredible case of meningitis, thoughts on selfish genes in viruses, evolution, natural selection and why we’re in for a very, very long haul with the pandemic virus.

As you probably know, mutant pandemic viruses (all different) have emerged (in England, South Africa, Brazil).  Even worse they appear to be more infectious, and some are more resistant to our vaccines (all of which were made before they appeared).  

Here is lesson #1 in natural selection.  Viruses have no brains, they barely have a genome.  The human genome contains 3 billion positions, the pandemic virus 30,000.  So we have 100,000 times more information in our genome than the virus does. 100,000 is about the number of inches in a mile and half.  

So how is the virus outsmarting us?  Simply by reproducing like mad.  The molecular machines that copy our genome are very accurate, making about 1 mistake per 100,000,000 positions copied — that’s still enough for the average newborn to have 30 new mutations (more if the parents are older).  The viral machine is much less accurate.  So lots of genome mutations are made (meaning that the viral proteins made from the genome change slightly).  Those that elude the vaccines and antibodies we’re throwing at them survive and reproduce, most don’t.  This is natural selection in action. Survival of the fittest.  Darwin wasn’t kidding.

What is so remarkable about the British and the South African variants, is that they contain multiple mutations (23 in the British variant).  Usually its just one or two.

 You’ve probably heard about the mutation changing just one of the 147 amino acids  in hemoglobin to cause sickle cell anemia. Here’s another.  APOE is a 299 amino acid protein.  It comes in 3 variants  — due to changes at 2 positions.  One variant greatly increases the risk of Alzheimer’s disease, another decreases it.  So even single mutations can be quite powerful. 

So how did these multiple mutations come about?  We likely now have an answer due to one very well studied case [ Cell vol. 183 pp. 1901 – 1912 ’20 ] in an immunocompromised patient with chronic lymphatic leukemia (CLL). She shed the virus for 70 days.  Even so, she wasn’t symptomatic, but because the patient had enough immune system to fight the virus to a draw, it persisted, and so its genome was always changing.  The authors were smart enough to continually sequence the viral genome throughout the clinical course and watch it change. 

Could this happen again.  Of course?   There are some 60,000 new cases of CLL each year in the USA.  Many of them have abnormal immune systems even before chemotherapy begins.

Here is an example from my own practice. The patient was a 40 year old high school teacher who presented with severe headache, stiff neck and drowsiness.  I did a spinal tap to get cerebrospinal fluid (CSF) for culture so we could find the best possible antibiotic to treat the organism.  This was 30+ years ago, and we had no DNA testing to tell us immediately what to do.  We had to wait 24 hours  while the bugs grew in culture to form enough that we could identify the species and determine  the antibiotics it was sensitive to. . 

As the fluid came out, I had a sinking feeling; as it was cloudy, implying lots of white cells fighting the infection. Enough white cells to make CSF cloudy (it normally looks like water) is a very bad sign. So after starting the standard antibiotic to be used in the first 24 hours before the cultures came back, I called the lab for the cell count.  They said there weren’t any.  I thought they’d seriously screwed up maybe losing what I’d sent or mislabeling it and looking at the wrong sample, and I unpleasantly stormed down to the lab (as only an angry physician can do) to see the spinal fluid.  They were right.  The cloudiness of the CSF was produced by hordes of bacteria not white cells.  This was even worse as clearly the bacteria were winning and the patient’s immune system was losing, and I never expected the patient to survive.  But survive he did and even left the hospital.  

Unfortunately, the meningitis turned out to be  the first symptom of an abnormal immune system due to a blood malignancy — multiple myeloma. 

****

Addendum 2 February — I sent this post to an old friend and college classmate who is now a hematology professor at a major med school.  He saw a similar case —

“When I was a medical student I saw a pediatric sickle anemia patient (asplenic) with fever and obtundation. When I looked at the methylene-blue stained CSF, I thought that stain had precipitated. So I obtained a fresh bottle of stain and it looked the same. Only this time, I looked more closely and what I thought was precipitated stain were TNTC pneumococci.

I urge all my immunosuppressed patient to get vaccinated for covid-19. I worry that if many people don’t get vaccinated,  those who do will not be that better off.”

Addendum 3 February– I asked him if his patient had survived like mine —

answer 

“Unfortunately, no. With the pneumococcus, If antibiotics are not started within 4 hours after recognition, the train has left the station.”

 

****

So there are millions of active cases of the pandemic, and tons of people with medical conditions (leukemia, multiple myeloma, chemotherapy for other cancer) with abnormal immune systems, just waiting for the pandemic virus to find a home and proliferate for days to weeks.  Literally these people are culture media for the virus. Not all of them have been identified, so don’t try to prevent this by withholding vaccination from the immunocompromised — they’re the ones who need it the most. 

I think we’re in for a very long haul with the pandemic.  We’re just gearing up to stay on top of the viral sequence du jour.   Genome sequencing is not routine (it should be).  The South African and British mutations were picked up because a spike in cases led people to sequence the virus from these patients.  Viral genome sequencing and surveillance should be routine in most countries  — not waiting on an infection spike.