dljones

Not what it says.

Immunocompromised people, in order for their "omicron" to develop resistance to the various treatments available (the monoclonal antibodies) must have been exposed to those treatments. If they were exposed to those treatments, they were being followed medically. If they were being followed medically, and receiving long-term treatments, it's then odd that they didn't infect a single other person in a year and a half.

On the other hand, there's the somewhat bigoted implication that "oh there are a lot of remote people in Africa that don't come in contact with anyone else." Well, then how did their omicron develop resistance to all the fancy treatments?

Either it's an immune compromised patient who never came in contact with anyone else, and the specific resistance to monoclonal antibodies, which they never received, is not explained.

Or it's an immune compromised patient who received intensive treatments for a long time, in which case the lack of any intermediate variants ever being documented is not explained.

S/he didn't say immunocompromised people don't have antibodies.

S/he says mice don't have human antibodies, so if the "mouse hypothesis" is correct, how did the mice, unless they were lab mice, get the immunity to all these human treatments?

Neither one of those hypotheses accounts for the four weirdnesses described in the article. So they don't seem like very good hypotheses.

Similarly "it came from an animal" that we've never found two years later is not a hypothesis that accounts for the information we have about the first COVID-19 outbreak either.

To me that sounds very much like OJ vowing to find the real killer, but somehow he never did.

So, you take on faith that the s/ns ratio as described by "Eigenrobot" who is quoting "Brett" (who are they?) is correct, and the s/ns ratio described by many microbiologists and genome experts, identifiable on their Twitter accounts, is wrong?

I mean, we can find anyone on Twitter saying anything. I could create an account right now that says I'm an expert on time travel and tweet about it.

And of course now that omicron is circulating widely in humans, its pattern and ratio of mutations is occurring as one would expect. I wonder why something we know is a natural occurrence (mutation as it infects humans worldwide) looks natural. It makes me wonder why the original omicron looked so weird.

To me this is not a conversation about whether a lab leak occurred. It's a conversation about why the experts are not ruling out hypotheses that explain the information so they can (if necessary) move on to other hypotheses. Just dismissing hypotheses that explain the existing information is not very scientific, unless the hypotheses are untestable or are truly off the wall. This hypothesis is not truly off the wall.

The ratio is one of four "weirdnesses" laid out by the author, which a lab leak might parsimoniously explain, and which, so far, other hypotheses do not neatly or parsimoniously explain.

So for you to jump to "no predictive value" is a little odd.

Since you feel well-equipped to judge the validity of the various hypotheses for the origin of omicron, which hypothesis do you think explains the information and why?

Thanks.

Yes, s/he clarified it. "[Edited, 5 Jan 2021, to add: Many people have been confused about the statement about delta, so I must have worded it poorly. I’m not saying delta originated in a lab leak. I’m saying delta escaped from a lab late in 2021 where it was being used in research. It’s an example of a research-related lab leak.]"

S/he clarified the delta thing:

"[Edited, 5 Jan 2021, to add: Many people have been confused about the statement about delta, so I must have worded it poorly. I’m not saying delta originated in a lab leak. I’m saying delta escaped from a lab late in 2021 where it was being used in research. It’s an example of a research-related lab leak.]"

S/he clarified it now.

"[Edited, 5 Jan 2021, to add: Many people have been confused about the statement about delta, so I must have worded it poorly. I’m not saying delta originated in a lab leak. I’m saying delta escaped from a lab late in 2021 where it was being used in research. It’s an example of a research-related lab leak.]"

"poorly monitored infections of the immunocompromised can easily explain this. It hardly seems necessary to posit nefarious secret labs when COVID is constantly spreading among billions of people, a significant fraction of whom are immunocompromised and chronically infected in minimally monitored areas."

How do "poorly monitored infections of the immunocompromised" explain weirdnesses 2 and 4? (Referring to the blog post under discussion)

Did the blog author "posit nefarious secret labs"? Not that I'm seeing. There are labs all over the world doing things with SARS-CoV-2, probably for what they believe to be legitimate reasons. "Nefariousness" and "secrecy" is not in the article. "Nefariousness" and "secrecy" are not part of the hypothesis.

"a significant fraction of whom are immunocompromised and chronically infected in minimally monitored areas": Contrary to people's seeming stereotypes about "Africa," South Africa monitors SARS-CoV-2 really well. The hypothetical immunocompromised person in Alina's discussion would not be someone untreated in some remote village, unnoticed for a year and a half. No, to get that level of immune evasion, Alina must be talking about someone who was being treated medically, with fancy treatments, and being monitored for a very long time.

Well, for one thing: My first question is "Who is it? Who is this person who received all the convalescent plasma and all the different monoclonal antibodies for a year and half, in well-monitored South Africa?"

But even if we don't know who this hypothetical person is, there are other problems:

That person apparently never infected anyone else. And...that person in a year and a half never had any _intermediate_ viruses that infected anyone else either, to account for the gaps in the phylogenetic tree. And...that person had a set of mutations that you might expect to see in a humanized mouse (Weirdness 4).

You see, then, that while this is all "possible" it's not very parsimonious. I think we do better to begin with parsimonious hypotheses and try to test those and rule those out.

The lab leak is a parsimonious hypothesis -- but instead, mainstream people, for whatever reason, are portraying it as so far-fetched as not to merit consideration -- they would dismiss it, rather unscientifically, as if the hypothesis were really wild and not meriting consideration, like "Space aliens from planet X did it." Then, instead, they put forward hypotheses that are in fact way more far-fetched because they don't account for the data neatly, like "it was an immune compromised person" -- but the set of circumstances in which that would be true, while kinda-sorta possible, is much more unlikely than the circumstances of "lab leak."

The failure of the scientific community to address this really makes no sense to me.

Absence of evidence is not evidence of absence, yes. But take another look at the phylogenetic tree. Those are huge gaps. See also this article describing how good South Africa is at spotting and sequencing variants."The reality is that southern Africa is a top international powerhouse of COVID-19 surveillance." https://www.businessinsider.com/how-southern-africa-detected...

The Nature article you mention says, "These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals."

Fair enough. So is the hypothesis that this immune compromised person in SA was given a lot of antibodies over a long period of time, creating enough evolutionary pressure to create highly mutated forms of the virus? Such a person might end up with a highly mutated virus that is resistant to existing antibodies. Fair enough.

That explains one of the four weirdnesses, and leaves three unexplained. Where are all the missing silent mutations (Weirdness 2)? If someone is followed medically and receiving all these treatments, did no one around them ever get sick with an intermediate variant? (Weirdness 1)? And what about the mouse-related mutations? (Weirdness 4) Did the viruses in the immune compromised person develop those mouse-related mutations independently?

I find the "immune compromised person" hypothesis not a very parsimonious or compelling one, although if you can steelman it further, I'm all ears.