Dec 7, 2022·edited Dec 7, 2022Liked by Brian Mowrey

Coronaviruses tend not to score aberrantly high for mutation rate in the overall roster of sequenced RNA viruses, but I understood that was because they have a fairly effective copy-correction mechanism. The 4 common human coronaviruses - as I was told - have a fairly unique protein that modulates this protection. This in essence causes significant more 'bad' (infertile/broken) copies, but allows also for faster mutation. (COVID-19 does not have this protein BTW.) Hence, why the 4 common coronaviruses could reinfect humans over and over again.

At least that was the theory as I was told.

But if not true, then how can we get reinfected? Current doctrine suggests that immunity in the humoral parts of our body is for life. For flu we know it is, so I'm skeptical our memory CD4+ and CD8+ T cells for common corona are not effective for decades too.

Then if not mutations, then either cellular immunity in the throat/mucous has weaker memory that doesn't last as long as humoral immunity, or it has perhaps a too slow response there. After all somehow we get sick again.

I also do know that a Canadian study that followed some people for 20 years showed that pretty much everybody gets reinfected again with these common cousins of COVID-19. The frequencies ranged from 3 times in these 20 years to yearly and likely depend very much on your age and lifestyle. But still some of them had a yearly re-infection. So it seems that either the mutation rate must be fast enough to throw us off, or mucous immunity is indeed very weak.

That is important, as it is a predictor for COVID-19. Its spike doesn't seem to mutate very fast and even the help it got with Omicron's release did not materially change its antibody resistance. So, as it has no animal reservoir, it will become extinct if it has to rely on that.

But if it can rely on our throat/mucous cellular immunity memory being weak enough, it can become the 5th common corona yearly sneeze.

In that sense it is surprising, so little research has been done on throat/mucous cellular immunity vs humoral immunity.

(For flu BTW I was told its mutation freedom is the result of it not targeting a large protein and hence not having a receptor binding protein but targeting an amino-acid. And hence, our antibodies must target the nucleus giving flu more freedom to make its skateboard moves. Until as you pointed out in pt 1 it runs out and runs into the wall anyway.)

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Dec 3, 2022·edited Dec 3, 2022Liked by Brian Mowrey

I don't know much about biology. Especially molecular biology. I've studied theories of evolution in kind of an outsiderish amateur way, and I know some things about dynamical systems and computer security in a more "serious" way. Squinting down through the fog from great heights of abstraction, a few rambling observations:

A virus is dependent on its host to reproduce. To even a greater extent than other (always ecologically situated) organisms, it has to co-evolve. With such a small genome, it can't hoard up a big bag of tricks allowing it to jump around on the fitness landscape, the way bacteria are known to do. Maybe a little bag of tricks. This landscape is determined by the hosts, and big lumbering multicellular guys like us change pretty slowly. On the other hand, our complex proteomes offer a vast "attack surface".

Viruses are definitely "swarms" in that they reproduce rapidly, in great numbers. Swarming doesn't, by itself, get you out of local fitness optima. You have to still do well enough in the sub-optimal valleys to survive to climb the next hill. A delicate little hopeful-mutant virus might not survive the immune onslaught.

Cultural factors (vitamin deficiencies, therapeutic fads, agricultural practices or other contacts with potential peer hosts) influence the overall landscape for human viruses. There are opportunities for "punctuated equilibria" to arise, at the decade-to-century scale. More so during periods of rapid change in material culture.

Some of this is just recapitulating your previous article. Did I get the gist? I'm enjoying these! Keep doubting the great doubts.

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