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. 

 

 

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Comments

  • Peter Shenkin  On February 1, 2021 at 12:35 am

    Lovely. The article, that is, not the situation.

    But for clarity, there isn’t any information (or is there?) to conclude that the UK or ZA variant came from an immunocompromised patient along the way, is there?

    Nor, as far as I can see, need it have. As far as I know, it’s just the total number of generations of viral reproduction, not necessarily within the same individual, that builds up mutations (as I understand it – but I’m a simple chemist).

    I guess it would be possible to estimate how many uncompromised COVID patients would have had to be infected in sequence from the same starting point to reach that figure of 23 mutations. I suppose, if each harbored the virus for two weeks, it would have been 70/14 or about five patients who received it in sequence, each accumulating on average between 4 and 5 mutations.

    Perhaps there is something wrong with this reasoning, and indeed those surviving individuals might not have produced the same amount of virus per unit time as the immunocompromised individual. So make it 10 patients in sequence, or 20, rather than 5. It still seems to me that there are enough new cases still arising that normal transmission might well account for more mutations than production in immunocompromised COVID victims.

    Though the UK variant exhibited 23 mutations (compared to the original viral genome sequenced, I presume), I’m not sure it’s known (though it might be!) which and how many are responsible for its increased infectiousness. Presumably, most of the mutated viruses that survived, up to some critical mutation, were no more infectious than the garden-variety. It might still have been the case that only a single mutation, or a small number, were responsible for it.

    If there’s any good news, it might be that (as far as I know) a more fatal version of the virus has yet to appear. Of course, it might appear any day.

    • luysii  On February 2, 2021 at 7:57 pm

      Sorry for the delay in responding. We got vaccinated yesterday in the middle of a blizzard. The problem with sequential infection and variation from patient to patient is that the intermediate genomes should have shown up, but they haven’t.

      All I have is the well studied model cited in Cell to substantiate the idea. The highly mutant strain came out of the blue.

  • John Wayne  On February 1, 2021 at 11:38 am

    There are a lot of people getting this virus, and evolution is going to do it’s thing. The number of cases are so high we don’t need to invoke specialized patients to get to concerning endpoints (although they will certainly play a part.) I’ve started to hear more and more antivaccine rumblings from within my circle of friends; I hope this whole thing doesn’t become an exercise in self inflicted herd thinning.

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