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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A fascinating SARS-CoV-2 sequence was recently uploaded—collected from a dog in Kazakhstan in July 2022.
Usher places the seq 1 nuc mut from the Wuhan ref seq—C21846T/S:T95I—i.e. pre-D614G. Could this seq somehow have a close connection to the first days of the pandemic?
1/19
Of the sequences near this one on the tree, all are low-quality & clearly bad BA.1 or Delta sequences. The only genuine one is from the UK, collected April 2020. So it's likely even S:T95I was not inherited.
This sequence has several fascinating aspects. 2/
(This all assumes the sequence is accurate and that C241T & C14408T (ORF1b:P314L) are genuinely absent. Its mutational characteristics make me certain this is a good sequence, though it's not impossible there's dropout not indicated hiding C241T and/or C14408T.) 3/
Do you remember BA.3—the weakling cousin of BA.1 & BA.2 that seemed to take the worst from each & had weaker ACE2 binding than even the ancestral Wuhan Virus?
After 3 years, BA.3 is back.
And it is transmitting.
Who saw this coming?
1/13
While the full extent of the new BA.3’s spread is not known, it’s been detected in 2 different South African regions through regular (not targeted) surveillance by @Dikeled61970012, @Tuliodna, & the invaluable South African virology community.
2/13 github.com/cov-lineages/p…
After nearly 3 years of intrahost evolution in a chronically infected person, the new BA.3 is almost unrecognizable. It has ~41 spike AA substitutions (4 of which are 2-nuc muts) to go with 14 AA deletions (∆136-147+∆243-244). We’ve seen nothing like this since 2023.
3/13
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
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
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.
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/
@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-…
@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/