Ryan Hisner Profile picture
May 26, 2021 7 tweets 2 min read Read on X
1/7 Satan is trending on Twitter. I recall what Mark Twain said about him.
"I am quite sure that I have no race prejudices, and I think I have no color prejudices nor caste prejudices nor creed prejudices. Indeed, I know it..."
2/7 "I can stand any society. All that I care to know is that a man is a human being—that is enough for me; he can't be any worse."
3/7 "I have no special regard for Satan; but I can at least claim that I have no prejudice against him. It may even be that I lean a little his way, on account of his not having a fair show."
4/ "All religions issue bibles against him & say the most injurious things about him,but we never hear his side. We have none but the evidence for the prosecution, yet we have rendered the verdict. To my mind, this is irregular. It is un-English; it is un-American; it is French."
5/7 "We may not pay [Satan] reverence, for that would be indiscreet, but we can at least respect his talents."
6/7 "A person who has for untold centuries maintained the imposing position of spiritual head of four-fifths of the human race, and political head of the whole of it, must be granted the possession of executive abilities of the loftiest order."
7/7 "In [Satan's] large presence the other popes and politicians shrink to midges for the microscope. I would like to see him. I would rather see him and shake him by the tail than any other member of the European Concert."

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More from @LongDesertTrain

Jan 2
Two quick notes on the state of chronic-infection SARS-CoV-2 seqs

#1) ~3 years after its peak, BA.1 is still showing up in nasal swab seqs—despite reduced surveillance—most recently a mid-late Dec BA.1 from Nebraska.

#2) Chronic JN.1 seqs now more common, w/1 peculiarity

1/12
While BA.1 still show up semi-regularly, pre-Omicron seqs are much rarer. Why? I think there are four major reasons, two obvious & two less obvious.

A) Time.
This one’s obvious: Over time, some chronic infections are cleared, while in other cases, the host dies.

2/12
B) Number of infections.

BA.1 infected more people, more quickly than any previous variant. More infections = more chances to establish long-term infection.
3/12 Image
Read 12 tweets
Dec 23, 2024
Fantastic review on chronic SARS-CoV-2 infections by virological superstars Richard Neher & Alex Sigal in Nature Microbiology. I’ll do a short overview, outline a couple minor quibbles, & defend the honor of ORF9b w/some stats & 3 striking sequences from the past week.
1/64 Image
First, let me say that this is well-written, extremely readable, and accessible to non-experts, so you should go read the full paper yourself, if you can find a way to access it. (Just realized it’s paywalled, ugh.) 2/64nature.com/articles/s4157…
Neher & Sigal focus on the 2 most important aspects of SARS-CoV-2 persistence: its relationship to Long Covid (including increased risk of adverse health events) & its vital importance to the evolution of SARS-CoV-2 variants. I’ll focus on the evolutionary aspects.
3/64 Image
Read 64 tweets
Dec 6, 2024
In SARS-2 evolution, amino acid (AA) mutations get the lion’s share of attention—& rightfully so, as noncoding & synonymous nucleotide muts—which cause no AA change‚ are mostly inconsequential. But there are many exceptions, including a possible new one I find intriguing. 1/30
I’ll discuss four categories of such “silent” mutations, two of which might be involved in the recent growth of one synonymous mutation.

#1. Kozak sequence changes
#2. Secondary RNA structure
#3. TRS destruction/improvement
#4. TRS creation 2/30
Maybe the single most remarkable example of convergent evolution in SARS-CoV-2 involves noncoding mutations: the multitude of muts in major variants that have pulverized the nucleocapsid (N) Kozak sequence.
I wrote about this below & a few other 🧵s 3/
Read 33 tweets
Nov 24, 2024
@SolidEvidence There was yet another paper this week describing someone chronically infected, with serious symptoms, but who repeatedly tested negative for everything with nasopharyngeal swabs. On bronchoalveolar lavage (BAL), they were Covid-positive. 1/ ijidonline.com/article/S1201-…Image
@SolidEvidence BAL is very rarely performed, yet there must be dozens of documented cases now where NP-swab PRC-negative patients who were very ill tested positive by BAL. This has to be way more common than we realize.

If we had a similar GI test, I imagine we'd find something similar. 2/
@SolidEvidence Importantly, the patient was treated and improved, likely clearing the virus for good. Many, maybe most, chronic infections could be treated and cleared. But they have to know they're infected for that to happen. 3/
Read 4 tweets
Nov 22, 2024
Superb thread here by @jbloom_lab that meshes well with what we've seen over the last few months in SARS-CoV-2 spike evolution: not much.

IMO, nothing significant has happened since the NTD-glycan-adding muts (T22N, ∆S31) & Q493E appeared. This 🧵 explains why. 1/6
Read full 🧵for explanation, but the short story is that the best apparent escape mutations all interact w/something else—like a nearby spike protomer or other important AA—making mutations there prohibitively costly.

In short, the virus has mutated itself into a corner. 2/6
It's very hard to effectively mutate out such a local fitness peak via stepwise mutation in circulation since multiple simultaneous muts might be required to reach a higher fitness peak. 3/6

Read 6 tweets
Nov 10, 2024
It's an interesting thought. I think the evidence is strong that all new, divergent variants have derived from chronic infections. The first wave of such variants—Alpha, Beta, Gamma—IMO involved chronic infections lasting probably ~5-7 months. It's controversial to say.... 1/15
…that Delta originated in a chronic infection, but I think the evidence that it did is strong. One characteristic of chronic-infection branches is a high rate of non-synonymous nucleotide (nuc) substitutions (subs)—i.e. ones that result in an amino acid (AA) change. 2/15 Image
For example, if 80% of nuc subs in coding regions cause an AA change, that’s a very high nonsynonymous rate. The branch leading to Delta has 17 AA changes—from just *15* nuc subs! That’s over 100%. How is this possible? 3/15
Read 15 tweets

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