Category Archives: Medicine in general

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

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

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 ( 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 —
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 —

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.

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 —   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 —

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 —

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.

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 —   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 —

Ubiquitination isn’t just for proteins

Time to look up from the plow biochemists.  Everyone knows that ubiquitin is added to proteins to destroy them.  The carboxy terminal amino acid of ubiquitin (glycine) forms an amide with the epsilon amino acid of a lysine called an isopeptide bond, and off  the protein goes to the proteasome for destruction.  This is simplistic and ubiquitination has many other other roles in the cell, but there isn’t time for it here.

I couldn’t resist putting in two interesting facts about ubiquitin.

#1. Like sharks,  evolution hasn’t changed ubiquitin much — only 3/71 amino acids differ between yeast and us.

#2 Ubiquitin is so stable that boiling water doesn’t denature it < Science vol. 365 pp. 502 – 505 ’19 >.

We have over 600 E3 enzymes (ubiquitin ligases), 40 E2 enzymes, and 8 E1 enzymes, and all 3 types are required to add ubiquitin to proteins.

Once a bacterium gets inside a cell, one of the ways the innate immune system attacks it is by ubiquitinating its proteins.  Nothing out of the ordinary there.

Salmonella (the organism responsible for most cases of food poisoning) is one such.  Our cells ubiquitinate the hell out of it.  However Nature vol. 594 pp. 28 – 29, 111 – 116 ’21 shows that, not just Salmonella proteins are the only sites of ubiquitination.  We also ubiquitinate endotoxin (lipopolysaccharide) which is a combination of sugars and lipids, with nary an amino acid in sight.  Endotoxin is a component of the outer membrane of every Gram negative bacterium, so the effect is likely not confined to Salmonella.

Even more spectacular is the enzyme adding ubiquitin.  It is called RNF213 (aka Mysterin), which looks like nothing the classic E3 enzymes we know and love.  For one thing in addition to E3 activity, it has a motor domain, a zinc binding domain and other domains of unknown function.  It’s a real monster with 5,184 amino acids and a molecular mass of 584 kiloDaltons.

There is a lot of interesting molecular biology to RNF213 — mutations cause Moya moya disease.

But the papers are particularly interesting because they show a lot of work of a new type needs to be done.

What else does Mysterin ubiquitinate?  Are there other enzymes in the cell adding ubiquitin, and if so, what do they ubiquitinate?

Definitely time to expand the well plowed field of ubiquitin.


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

l. A president in early dementia —

2. The latest in politically correct racism  —

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




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  ( 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?


Anti-vaxers, what is it that you know that we don’t ?

32 members of the University of Pennsylvania Medical School class of 1966 held a 55th reunion by Zoom a week ago.  All 32 have been (voluntarily) vaccinated.

Among the attendees were 

l. Mike Brown — Nobel Laureate whose work led to the statins —

2. Jerry Gardner — All American Basketball Player Kansas ’62  — — but far from a dumb jock — established a GastroIntestinal program at the National Institutes of Health

3. An (emeritus) professor of neurology at the University of Rochester Medical School 

4. The (emeritus) director of the radiology residency program at Yale Medical School

5. An (emeritus)  professor of medicine at Albert Einstein Medical school

6. A (retired) Rear Admiral in the US Navy

There are several more deans and professors among the 32, but you get the idea.

All classmates who spent their careers taking care of the sick (such as yours truly) were board certified in their specialties.  Some were even board examiners for certification in their specialties (such as yrs trly).

Don’t do as I do, do as I say never works.  Anyone who’s raised kids knows that.  The Penn Med class of 1966 has put its money where its mouth is.

So what is it that you know about vaccines that we don’t?  Please get vaccinated.  The new strain (B.1.1.7) is 50% more lethal and much more infectious than the original pandemic virus  [ Nature vol. 593 pp. 270 – 274 ’21 ].

Addendum 20 May:  I thought the following comment and my response were worth placing in the body of the post.

From DH :The one thing everyone in your sample has in common is old age and thus relatively high risk of death if infected with COVID. A lot of the people I argue with online are not absolute anti-vaxxers, but claim that for healthy people under 30, the risk-reward calculus favors not getting vaccinated (e.g., because the vaccines were “rushed”).

I disagree with them, but to be fair to them, your class of 1966 example is not an argument that addresses their claim.

Response:  DH — thanks for commenting: I quite agree with what you say, but there are larger issues. My sample is small but I know several antiVaxers in their 70s. The proportion of unvaccinated minorities is larger than their proportion in the population. Many of them live in multigenerational households so an infected 30 year old could kill granny. Just look at what’s going on in India.

Even worse is the fact that the newer mutations may be more virulent as well as more infectious. This has now been shown to be the case for B.1.1.7 [ Nature vol. 593 pp. 270 – 274 ’21 ]. Even if the vaccines aren’t quite as effective (in vitro) against the new strains, they still offer protection. We will inevitably continue to see new mutants. A vaccinated population is our best hope.

Ashkenazi Jews are extremely inbred

Neurologists are inherently interested in  psychosis, not least because too much dopamine in the form of L-DOPA can trigger it.  I’ve always found it remarkable that dopamine blocking agents (phenothiazines, and most antipsychotics) can attack psychotic thought itself.  This is much more impressive to me than the ability of other drugs (alcohol, coffee, marijuana, cocaine) to affect mood.

So it’s always worthwhile to read another paper about the genetics of schizophrenia, a very hereditary disease.  All the risk factors we’ve found by GWAS (Genome Wide Association Studies) account for at most of 1/3 of genetic risk in schizophrenia.  For details please see

So I was interested in another crack at finding more genetic causes of schizophrenia  [ Neuron 109, 1465–1478, May 5, 2021 ].  As often happens, the most interesting thing in the paper was something totally tangential  to my original interest in it. 

Here it is —   ”  For example, the Ashkenazi Jewish (AJ) population, currently numbering >10 million individuals world- wide, effectively derives from a mere 300 founders 750 years ago ” (Carmi et al., 2014;Nat. Commun. volume 5, 4835.).  

I find this assertion incredible.  But, as explained below, there is pretty good evidence (although subtle and quite technical) that it’s correct.

Ashkenazi Jews are those previously found only in Europe and the Americas, as opposed to Sephardic Jews, previously found only in the mideast and Africa.  Both are now found in Israel.  Ashkenazi Jews were chosen for the study because any deleterious genes producing schizophrenia  present in the original 300 wouldn’t have been washed out by natural selection in just 30 generations in 750 years. 

The Ashkenazim make the inbreeding among French Canadians look like pikers — a population of 2 million derived from a founder population of 9000 people over the next 170 years — for details please see  Note that neither population tried to inbreed, it’s just that there was no one else geographically available to breed with for the French Canadians, and no one else culturally available for the Ashkenazi’s.  

At least with the French Canadians we have immigration records to tell us how large the founder population was.  How sure are we about the 300 strong founder population of present day Ashkenazi Jews?  We’re not and I’m not even though it was published in a peer reviewed reputable journal.  There is a lot of guesswork in figuring out just how large a genetic bottleneck is.  It all depends on the model used, and I don’t trust models in general.  I’ve seen too many crash and burn. (For details —

However, the Neuron paper contains a reference to another paper which provides excellent empiric evidence for a small founder population, (PLoS Genet. 14, e1007329. 2018).  Here’s a direct quote.  It’s quite a mouthful; I’ll try to explain below the quote what the terms mean, because I think many nonscientific types are likely to be interested in the idea that Ashkenazi Jews are that inbred. 

Just skip the paragraph if it’s incomprehensible, go to *** and read the explanatory material, and then read the paragraph again. 

“We estimate that 34% of protein-coding alleles present in the Ashkenazi Jewish population at frequencies greater than 0.2% are significantly more frequent (mean 15-fold) than their maximum frequency observed in other reference populations. Arising via a well-described founder effect approximately 30 generations ago, this catalog of enriched alleles can contribute to differences in genetic risk and overall prevalence of diseases between populations.”


Explanatory material.

Our genetic material (DNA) is made of 4 different compounds A, T, G, C (called nucleotides) which are linked together in chromosomes.  The order is crucial, just as the order of letters in a word is crucial for meaning (consider united and untied).  So how many slots for the nucleotides are there in our genome ? Just 3,200,000,000.  Just as combinations of dots and dashes code for letters in Morse code, combinations of  3 nucleotides code for the 20 amino acids that make up proteins. 

Proteins are big.  For instance, the protein  (beta-globin)mutated in sickle cell anemia contains 146 amino acids, and all it takes to produce the disease is a switch from one amino acid to another at position six.  The other 145 amino acids in the chain are unchanged. So sickle cell beta globin with a change in its nucleotide sequence is an allele (alternate form) of normal beta globin.  

Every population of people contains alleles of every protein.  Some are common (over 5% of the population showing them), but most are rare.The PLoS paper looked at  73,228 alleles of all 20,000 or so proteins that we have in our genome (yes technology now can do these sorts of things) in the general population.  The authors looked at the alleles in the Ashkenazi population which were present at greater than 1/500 (.2%).  Then they looked at the frequency of the same allele in several other non-Ashkenazi population (about 5000 each of non-Finnish Europeans, African Blacks and Latinos), and found that these alleles occurred15 times less frequently (on average).   So Ashkenazi’s have alleles that are lots more common than in other populations.  Actually it’s more than some, because about 1/3 of the alleles they studied are an average of 15 times as common.

What does this mean?  It means that when a small founder population with a rare allele becomes ‘fruitful and multiplies’, the rare allele will multiply right along with it and not be lost by outbreeding (which was certainly true of the Ashkenazis for 600 of the last 750 years).

Now read the paragraph in bold above again. 

This is the evidence that current day Ashkenazi’s come from a very small founder population.  It’s pretty good.  I hope that I’ve made this somewhat comprehensible;  if not, please write a comment.

Is there anything in the cell that has just one function — more moonlighting — this time mRNA

Able was I ere I saw Elba said Napoleon. It’s called a palindrome, and can be read either way. So can DNA which brings me to antisense transcription of DNA, particularly in two famous retroviruses –the AIDS virus (HIV1) and HTLV-1.  

Proc. Natl. Acad. Sci. vol. 118 e2014783118 ’21  shows that mRNA can moonlight to do other things than code for protein.  Here’s a direct quote to set the stage.

“Retroviruses share a similar genome structure. The integrated retroviral genome, called the provirus, has two identical long terminal repeats (LTR) located at its 5′ and 3′ ends, respectively. The 5′ LTR acts as the promoter of almost all retroviral genes and thus is indispensable for viral transcription and replication. However, selective methylation of the 5′ LTR and the subsequent viral latency have been observed in HIV-1 and HTLV-1. In contrast, the 3′ LTR of HIV-1 and HTLV-1 remains nonmethylated, and recent findings have shown that novel retroviral genes are transcribed from the 3′ LTR in an antisense direction”.

The 3′ LTR of the AIDS virus enables antisense transcription for  the unimaginatively named ASP (AntiSense Protein).  So the mRNA for ASP is transcribed in the nucleus.  But it doesn’t get out as well as it might, because its 5′ end isn’t polyAdenylated.  So it sticks around in the nucleus and binds to DNA, turning off transcription of the regular HIV1 genome — e.g. helping to maintain viral latency (and preventing a true cure of HIV1 in any individual).

This is unprecedented.  Here is an mRNA with a completely different function (e.g. regulating gene expression).  This is classic moonlighting as something else and the authors call the mRNA for ASP a bifunctional mRNA. 

The other, retrovirus HTLV-1 also has an antisense transcript making a protein called HBZ (your don’t want to know what it stands for). Unlike ASP, HBZ turns on a variety of genes. 

I’ve been fascinated by moonlighting molecules, probably because they show the depths of our ignorance of the biochemical machinations inside the cell.  Even when you think you’ve got the function of a molecule tied down, it goes off and does something else. 

 Here are some links to other posts on the subject.  To get to them just click on the titles

Moonlighting molecules

More moonlighting

A moonlighting quorum sensing molecule

A moonlighting quorum sensing molecule

Bacteria talk to each other using quorum sensing molecules. Although the first one was found 50 years ago, the field really opened up with the work of Bonnie Bassler at Princeton in the 90s. These are small molecules which bacteria secrete, so that when there are a lot of bacteria around, the concentration of quorum sensors rises, allowing them to get into bacteria (by the law of mass action) changing gene expression for a variety of things, particularly virulence and biofilm formation. They have also been used by bacteria to compete with those of a different species.  There was a lot of hope, that we could control some nasty bugs (such as Pseudomonas) by messing about with their quorum sensors, but it hasn’t panned out. 

The real surprise came in a paper [ Proc. Natl. Acad. Sci. vol. 118 e2012529118  ’21 ]showing that Pseudomonas uses one of its quorum sensing molecules (C12 < N-3-oxo-dodecanoyl) homoserine lactone > ) inside the eukaryotic cells it attacks. 

What it does once inside, is to attack a cellular organelle I’ve (and probably you) never heard of called vaults.  They’s been known since ’86, and given their size (12.9 megaDaltons) I’m surprised I’d never heard of them.  The likely reason is that no one knows what their function is. 

It is made of just 3 proteins

l. MVP — Major Vault Protein, mass 100 kiloDaltons 96 copies/vault

2. VPARP — Vault poly ADP ribose polymerase 190 kiloDaltons

3. Telomerase associated protein 290 kiloDaltons.

Human vaults contain 4 different RNAs (called, naturally enough vault RNAs < vtRNAs >).  They are 88 – 100 nucleotides long.  

Vaults look like a hand grenades and are 670 Angstroms long and 400 Angstroms in maximum diameter. 

[ Cell vol. 176 pp. 1054 – 1067 ’19 ] says that there can be 10,000 to 100,000 vaults/cell.  So why haven’t I seen them?

One of the vtRNAs binds to a protein involved in autophagy inhibiting it. This is an example of an RNA binding to a protein altering its function, something unusual until you think of the ribosome or the spliceosome. Starvation decreases the number of vaults inducing autophagy.

Once pseudomonas C12 gets into a cell it binds to the Major Vault Protein, causing its translocation into lipid rafts, the net effect being attenuation of the p38 protein kinase pathway to attenuate programmed cell death (apoptosis).  

So C12 keeps the cell alive when normally it would die.  A lot of recent work has shown that bacteria infiltrate cancers.  Do they do something similar to cancer cells to keep them alive. 

It really makes you humble (or should) to realize how many separate parts of cellular and molecular biology you must understand to even hope to understand how cells (and bacteria) go about their business. 

Think of how many terms were introduced to understand what the humble quorum sensor C12 is up to. 

Welcome to the world of the physician

In a sense, the uncertainty about hematologic complications of the pandemic vaccines is good in that it is a real teaching moment for the public about what docs confront every day — balancing risk vs. reward. 

No drug is without side effects.  No surgery is without complications.  It is good to see the public  wrestle with these things.  

For a very good explanation of what those complications are and the risks and rewards of taking the vaccines please see —

Even more interesting are the 139 comments found at the end of  the article.  Some are from experts, some are from frightened lay people; as always there are people with an ax to grind.  As is usually the case in medicine, the data are not clear cut and sometimes contradictory.  As is always the case more data would be helpful, is desired and rarely available.  What is particularly interesting to me is the way some very knowledgable people wrestle with the data, interpreting the same data differently.  Welcome to the real world. 

On a more positive note, a friend who teaches at Hopkins sent me the a copy of the eMail below, with permission to share it.  This provides lots of excellent data on the protective effects of vaccination in a  group of people with a fairly high risk of exposure to the virus,  working at a major medical center where lots of very sick COVID-19 patients are being treated. 

35,000 were vaccinated.  Nonetheless 51 became infected at a time of maximum protection (5 weeks or more after the first shot), demonstrating that the vaccine isn’t 100% protective.  But no one ever claimed that it was.

 But only 2 of the 51 required hospitalization.  So the vaccine is effective in preventing serious illness from the virus (2/35,000).  So who cares if the other 49 had the symptoms of the flu.  They don’t and you shouldn’t.  The number of hematologic complications wasn’t stated. There were two at most, as they always result in hospitalization.  

To the Johns Hopkins Medicine community


Dear Colleagues,


As we continue to monitor COVID-19 infection and vaccination trends at Johns Hopkins Medicine (JHM), we want to share some data about the incidence of infection among JHM personnel following partial and full vaccination.


You are considered fully vaccinated, per the Centers for Disease Control and Prevention, two weeks or more after receiving the second dose of a two-dose COVID-19 vaccine regimen and two weeks or more after receiving a one-dose COVID-19 vaccine regimen. This is when the body has had a chance to produce the antibodies and immune response that protect against infection. Before this time, if you have started the vaccination series, you are considered partially vaccinated and you do not yet have the full amount of protection the vaccination provides against infection. While full vaccination has been found to be highly effective at preventing COVID-19, infection (the incidence is very low) is still possible even after being fully vaccinated.


We are monitoring the situation to determine how often infection seems to occur after partial or full vaccination, and the severity of those infections.


As of April 12, 2021, of the nearly 35,000 employees who were fully vaccinated (14 days or more after a second dose), 51 employees (0.14% of those who have been fully vaccinated) had tested positive for COVID-19. This demonstrates that SARS-CoV-2 infection is possible even after full vaccination, and it highlights the importance of continuing to practice basic infection prevention precautions after full vaccination. The good news is that acquiring COVID-19 after full vaccination appears to be relatively rare and, among these 51 cases, only two were severe enough to require hospitalization. This shows that the COVID-19 vaccine is highly protective against severe disease, hospitalization and death. If you have not yet been vaccinated, please schedule your appointment as soon as you can to protect yourself and others.



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 —


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 ] —, 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 —  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 —  

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.