Spiracular

• Spiracular 12 May 2020 23:49 UTC

  11 points

  in reply to: TurnTrout's comment on: Stop say­ing wrong things

  I didn’t down­vote it, but I did find the writ­ing style mildly grat­ing. (Re­lat­edly: I can­not ex­ceed your set-point of smug, it is over 9000 :) )

  To be clear: I think the un­der­ly­ing point was pretty good, and I mostly had is­sues with the de­liv­ery. I still feel it was prob­a­bly some­thing worth writ­ing, al­though I also think I’m not the tar­get au­di­ence for this par­tic­u­lar bit of ad­vice.

  Some of it was prob­a­bly a tone thing, which I won’t go into. But here are some things that seem tractable:

  My ex­pe­rience of it was a bit bet­ter as soon as I switched out al­most all the “You”s for “I”s. I have some­thing of a dis­taste for the… pup­pety-feel­ing where some­one seems to be try­ing to put words into my mouth, that don’t fit with my ac­tual ex­pe­rience. This set it off pretty badly. There are a lot of speci­fics, and it’s clearly your per­sonal ac­count; own it.*

  This got re­ally stark for me at around...

  First, you just end up be­ing an ass­hole pre­tend­ing to be honest

  ...which in­stantly broke my im­mer­sion. My ex­pe­rience of be­ing painfully hon­est with my­self, and then oth­ers, was rad­i­cally differ­ent.**

  It prob­a­bly also could have used more short para­graphs, and some va­ri­ety in pre­sen­ta­tion. Some of the goals you’ve acted on and then for­got­ten, such as Real Anal­y­sis or Man­darin, could have been bet­ter-pre­sented as sin­gle bul­let-points af­ter go­ing into only 1 of them in-depth. The Etsy sec­tion could have used a header, and been bro­ken into more than 1 para­graph. That kind of thing.

  *A lot of bad ad­vice on per­sua­sive es­say writ­ing en­courages the for­ma­tion of habits like this. One can­not list the num­ber of times one has been told to make that un­nat­u­ral sub­sti­tu­tion of “One,” where “I” would have been bet­ter, and more hon­est. Teach­ers who do this are just… wrong. Tech­ni­cal writ­ing is a real thing, but this way of teach­ing it is crap, and can ruin oth­er­wise-de­cent writ­ers.

  ** My ex­pe­rience was close to painful self-con­scious­ness (for self-hon­esty), and weird so­cial penalties (for hon­esty with oth­ers). Real hon­esty is of­ten dis­tinctly un-charm­ing, but in my case… blunt­ness leaned closer to “overly-in­vested*** ec­cen­tric” than “ass­hole.” If it had been framed as a self-ac­count, this jar­ring wouldn’t have been an is­sue.

  *** Ex­hibit A: This over­grown write-up.

• Spiracular 12 May 2020 21:48 UTC

  5 points

  on: Why don’t we tape sur­gi­cal masks to the face to seal them air­tight?

  I’ve per­son­ally found that just sta­pling shut the outer edge of the first fold on ei­ther side of a sur­gi­cal mask re­sults in a mask that mostly sucks to my face when I breathe in. It doesn’t stick well when I breathe out, though.

  This is much eas­ier to im­ple­ment than fancy ad­her­ents; all it takes is 2 sta­ples and a sta­pler, or a nee­dle and thread. It struck me as a plau­si­ble 80-20. (Well, less than 80%. Ob­vi­ously, this is no N95.)

  (It might only work for some face-shapes, though.)

  This gen­er­ates a new prob­lem, which would also ap­ply to taped/​glued solu­tions:

  The front is made of a softer fabric than N95s. After an hour of wear, it will suck to my lips if I breathe in with my mouth. And since it doesn’t stick on out-breaths, air still gets out the sides and some­times the top. I don’t know how much ad­di­tional risk this pre­sents, but I would be cu­ri­ous to hear some­one weigh in.

  (It also has un­com­fortably-high hu­midity, but that’s even more true of N95s.)

• Spiracular 9 May 2020 19:32 UTC

  3 points

  on: April Coron­avirus Open Thread

  De­spite the virus be­ing char­ac­ter­ized in pan­golins, af­ter look­ing into this, I now think it is ba­si­cally in­cor­rect to think of this as pri­mar­ily a “pan­golin virus.” The pan­golins were a dy­ing ca­nary in a coal mine, and prob­a­bly caught it from some­thing else that serves as the real reser­voir species for this nCOV pre­cur­sor*.

  Th­ese pan­golins were be­ing smug­gled when they were cap­tured by the au­thor­i­ties in Guangxi. They were dy­ing of prob­a­bly sev­eral dis­eases; they had le­sions in their skin, in­tense con­ges­tion, and were in gen­er­ally atro­cious con­di­tion when they got se­quenced for viruses. They turned up pos­i­tive for all man­ner of things (her­pes out the wa­zoo, but also a sendai virus which was most closely re­lated to the se­quence of a hu­man-taken sam­ple, a paramyx­ovirus, and yes, sev­eral coro­n­aviruses).

  Here’s the origi­nal ar­ti­cle on the pan­golins whose vi­rome they se­quenced, and the ar­ti­cle not­ing its re­lat­ed­ness to nCOV.

  Given that so many of the pan­golins died, the pan­golins look more like a highly-sus­cep­ti­ble sec­ondary species, than a mostly-asymp­tomatic pri­mary re­serve species* to me.

  * GD/​PIL or GD/​P2S is thought of as a pos­si­ble nCOV pro­gen­i­tor, alongside bat-virus RaTG13. GD/​PIL’s re­cep­tor-bind­ing mo­tif (RBM) in par­tic­u­lar is iden­ti­cal to SARS-2′s, al­though nCOV oth­er­wise ap­pears more closely re­lated to RaTG13.

  ** On ed­u­cated pri­ors, I think the true reser­voir is prob­a­bly rats, bats, or (less likely) hu­mans in the Guanxi, Hu­nan, and/​or Hubei province.

  Per­son­ally, I as­sign >90% on ei­ther rats (strong pri­ors + skin le­sions) or bats (strong pri­ors + sim­plest story). But these were ex­otic an­i­mal smug­glers; there is a small chance that the origi­nal reser­voir species could be any an­i­mal.

  What links here?

  • Spiracular's comment on Jim­ran­domh’s Shortform by jimrandomh (9 May 2020 19:28 UTC; 4 points)
  • Spiracular's comment on March Coron­avirus Open Thread by Elizabeth (1 May 2020 2:07 UTC; 1 point)

• Spiracular 9 May 2020 19:28 UTC

  4 points

  in reply to: Lukas_Gloor's comment on: Jim­ran­domh’s Short­form Posts

  I think it’s prob­a­bly a virus that was merely iden­ti­fied in pan­golins, but whose pri­mary host is prob­a­bly not pan­golins.

  The pan­golins they se­quenced weren’t asymp­tomatic car­ri­ers at all; they were sad smug­gled spec­i­mens that were dy­ing of many differ­ent dis­eases si­mul­ta­neously.

  I looked into this semi-re­cently, and wrote up some­thing here.

  ---

  The pan­golins were ap­pre­hended in Guangxi, which shares some of its bor­der with Yun­nan. Nei­ther of these provinces are di­rectly con­tigu­ous with Hubei (Wuhan’s province), fwiw. (map)

• Spiracular 7 May 2020 15:45 UTC

  2 points

  in reply to: Mary Chernyshenko's comment on: Cop­ing and Cultures

  True, and I’ve seen lab work cul­ti­vate some­thing similar.

  (I’m pretty sure this par­tic­u­lar skill is the in­verse of pro­gram­mer-style “laz­i­ness,” fun­nily enough. In one field, see­ing rep­e­ti­tion is re­as­sur­ing. In the other, it can be ev­i­dence that your code is not as el­e­gant and mod­u­larized as it could be.)

  I always thought you’d au­to­mat­i­cally learn the gait if you just did the work of­ten enough, though. It’s definitely a cop­ing skill, but I read its ori­gins as more cul­ti­vated than cul­turally-in­duced or taught.

  It mostly fol­lows the nat­u­ral in­cen­tive gra­di­ents of the work. This can be in con­trast to things like sep­a­ra­tion of self and client in psy­chol­ogy, which seems to feel ac­tively un-nat­u­ral for many peo­ple. Of course, there’s some­thing of a spec­trum here, with heavy in­di­vi­d­ual vari­a­tion.

• Spiracular 7 May 2020 6:28 UTC

  1 point

  in reply to: Ruby's comment on: Cop­ing and Cultures

  Thanks! Sounds like a promis­ing lead.

• Spiracular 7 May 2020 6:26 UTC

  3 points

  in reply to: Raemon's comment on: Cop­ing and Cultures

  It’s more “Ugh, I hate piss­ing peo­ple off on the in­ter­net” than “Oh Noes the Govern­ments.” Whether I have good or bad things to say, it’s a con­tentious and semi-poli­ti­cal topic. That said, I’m still prob­a­bly over­re­act­ing.

  (I’m more wor­ried that I’ll be wrong about some­thing, that peo­ple will badly mis­in­ter­pret me or mis­con­strue my be­liefs, or that I rub peo­ple’s per­sonal is­sues the wrong way than that I Awaken the Pow­ers That Be by… arm­chair philoso­phiz­ing about the in­fluence of cul­ture on PTSD?)

• Spiracular 7 May 2020 0:49 UTC

  11 points

  on: Cop­ing and Cultures

  The set of cul­tures I most want to poke this lens at, and yet want to write up not at all, are the var­i­ous mil­i­tary ones.

  High-stress en­vi­ron­ment, with a strong cul­ture and close-to-ex­plicit trans­mis­sion to young peo­ple. And the type of stress varies con­sid­er­ably de­pend­ing on whether you’re in the Army, Navy, Air Force… it seems like an ideal case-study. But it’s also a Whole Can of Worms. I sus­pect it’s a bad idea for me to try to pub­li­cly an­a­lyze sub­sets of Amer­i­can mil­i­tary cul­ture with thoughts that are half-cocked.

  At min­i­mum: I kinda sus­pect the style of Boy­dian thought was an ex­cel­lent fit to the challenges and cul­ture of fighter pi­lots at the time. Agile judge­ments that take un­cer­tainty into ac­count, done within a com­pet­i­tive en­vi­ron­ment where “out­ma­neu­ver­ing your op­po­nent with­out overex­tend­ing your­self” is the name of the game.

• Spiracular 7 May 2020 0:45 UTC

  11 points

  in reply to: Raemon's comment on: Cop­ing and Cultures

  I plan to flesh more ex­am­ples out, but this had lan­guished un­touched in my Drafts folder for close to a month. So I set­tled onto “pub­lish first, flesh out more later.”

  The idea mostly struck me when ex­am­in­ing differ­ences be­tween good biol­ogy cul­ture and ra­tio­nal­ist cul­ture, rather than from a par­tic­u­larly new cul­tural ex­po­sure on my part.

  (The Cat­a­lyst con­fer­ence may have high­lighted the differ­ences a bit.)

Cop­ing and Cultures

• Spiracular 1 May 2020 2:07 UTC

  1 point

  in reply to: Spiracular's comment on: Coron­avirus Open Thread

  De­spite the virus be­ing char­ac­ter­ized in pan­golins, af­ter look­ing into this, I now think it is ba­si­cally in­cor­rect to think of this as pri­mar­ily a “pan­golin virus.” The pan­golins were a dy­ing ca­nary in a coal mine, and prob­a­bly caught it from some­thing else that serves as the real reser­voir species for this nCOV pre­cur­sor*.

  See: fur­ther ex­pla­na­tion here

• Spiracular 26 Apr 2020 7:54 UTC

  1 point

  in reply to: orthonormal's comment on: Does the 14-month vac­cine safety test make sense for COVID-19?

  While we should at least ask and as­sess that ques­tion...

  Yes, it would be good to rule out those things that we do know to ex­pect. And I think an­i­mal re­sults* could check this one some­what. But cor­ners are already be­ing cut, and I still ex­pect some de­gree of sur­prises.

  I do feel like there’s a lot we don’t know with this virus. I don’t know that the prob­lems will be limited to the things we cur­rently know to look for, and I’d be a lit­tle sur­prised if timing was not at least a bit of an in­fluenc­ing fac­tor.

  * Ap­par­ently they haven’t found/​de­vel­oped an easy an­i­mal that catches the virus, but they are do­ing an­i­mal test­ing in par­allel to check the type of im­mune re­sponse? And the vac­cine test re­sult with the 4 macaques at least seemed promis­ing, now up by an­other 10 macaques tested with that same in­ac­ti­vated-virus vac­cine.

  ---

  While it definitely helps that we have some ex­pe­rience with SARS-1, we can’t to­tally rely on what we know about SARS-1 and trust that it’ll ap­ply to SARS-2.

  (I think SARS-1 and SARS-2′s ge­netic similar­ity was said to be only ~80%? This is about as much as we share in com­mon with cows. There can be mean­ingful differ­ences be­tween the two.)

  Here’s just one ex­am­ple. Did you see the “UPDATE” I added to my an­swer above? Says some­thing like “Oh hey, I guess it prob­a­bly does make im­mune cells apop­tose?” SARS-1 doesn’t do that thing. As in, the ar­ti­cle speci­fi­cally men­tions that they tried with SARS-1 and SARS-2, and only SARS-2 gets into T-cells like this. And they weren’t sure which re­cep­tor was re­spon­si­ble.

  It’s great to see a lot of sci­ence hap­pen­ing on this, but it’s also some­thing of a marker of our vast un­cer­tain­ties paired with its high pri­or­ity.

• Spiracular 24 Apr 2020 23:09 UTC

  3 points

  in reply to: Spiracular's comment on: Does the 14-month vac­cine safety test make sense for COVID-19?

  I’m nor­mally on team “the FDA is mak­ing ev­ery­thing too slow,” but in this case I ac­tu­ally think there’s good rea­son to be re­ally care­ful with those Phase-1 vac­cine de­vel­op­ment tri­als. You don’t need to be us­ing a live vac­cine to ac­tively make things worse!

  How long does test­ing for this prob­lem ac­tu­ally take? I’m not sure.

  If we were sure this was the only thing we needed to worry about (but I don’t think that it is)… get­ting a line of ev­i­dence where some vac­cine tak­ers are ex­posed de­liber­ately some time af­ter vac­ci­na­tion could maybe speed up weed­ing out vac­cines that trig­ger worse Th-2 re­ac­tions. But if it turned out that time-since-vac­ci­na­tion or cur­rent an­ti­body-titer are ma­jor fac­tors un­der­ly­ing out­come, we may gen­uinely need the full pe­riod of safety-test­ing.

  And ask­ing peo­ple to de­liber­ately ex­pose them­selves doesn’t strike me as a… safe cheap or easy thing to do.

  This looks like a com­pli­cated im­mune effect, and it seems to be un­der-char­ac­ter­ized. Over­all, it looks hard to test in-vitro or in cell cul­ture. I’m pretty sure you’d need an­i­mals or hu­mans to do it. I’m not sure which is faster.

• Spiracular 24 Apr 2020 22:26 UTC

  30 points

  on: Does the 14-month vac­cine safety test make sense for COVID-19?

  The ar­ti­cle I sum­ma­rize here goes over some of the spe­cific bad vac­cine re­ac­tions for SARS-1. I ex­pect similar challenges for SARS-2.

  Briefly:

  In situ­a­tions where some­one took the vac­cine, then gets in­fected by the con­ta­gion, they can have a bad re­ac­tion where the course of the dis­ease is more se­vere than if they had not been vac­ci­nated at all.*

  Here’s some of what we know about those bad re­ac­tions**

  • Th-2 type im­mune ac­ti­va­tion definitely hap­pens

    • This is an allergy-like im­mune response

    • Th-2 re­ac­tions hap­pen in se­vere cases of COVID-19 generally

  • There might also be a bad com­ple­ment sys­tem re­lated re­ac­tion

    • Com­ple­ment sys­tem means pro­tein com­plexes that kill cells by pok­ing holes in membranes

  • An­ti­body Depen­dent En­hance­ment (ADE) might be pos­si­ble, but is not likely

    • This is when im­perfect an­ti­bod­ies are used as an an­chor for the virus to in­fect white blood cells.

    • UPDATE: A re­lated thing now strikes me as some­what likely. It might be fus­ing with some white blood cells (at least T-cells) and or­der­ing them to apop­tose (ac­ti­vate cell-death). Ar­ti­cle, h/​t Cel­lBioGuy.

  * Go­ing off of some other bits of re­search on this, these in­di­vi­d­u­als prob­a­bly have lower virus-titer, but higher sever­ity and lethal­ity. A dam­ag­ing im­mune re­sponse, ba­si­cally.

  ** Which vac­cine types cause this bad re­ac­tion? For SARS-1, any whole-S-pro­tein vac­cines were more prone to this bad re­ac­tion. Some smaller S-pro­tein frag­ments didn’t have this is­sue, hope­fully the same fix works for SARS-2. I heard of at least one case where an N-pro­tein-only vac­cine at­tempt also re­sulted in the Th-2 re­ac­tion, though. It’s not to­tally clear how to avoid trig­ger­ing it.

  ---

  So maybe the speed-up you re­ally want is to vac­ci­nate, then de­liber­ately ex­pose to the live virus, and mon­i­tor what hap­pens?

  This is the type of test I’d rather we do on an­i­mal mod­els than hu­mans, to be frank. It seemed that you could test this phe­nomenon just fine with SARS-1 in an­i­mal mod­els.

  What links here?

  • Does the 14-month vac­cine safety test make sense for COVID-19? by orthonormal (18 Mar 2020 18:41 UTC; 56 points)

• Spiracular 23 Apr 2020 22:02 UTC

  3 points

  in reply to: Kerry's comment on: Does SARS-CoV-2 uti­lize an­ti­body-de­pen­dent en­hance­ment?

  Vac­cines are still our best shot in the long-term.

  I wouldn’t phrase it as “vac­cines do not look promis­ing,” but more as “SARS is rel­a­tively hard to vac­ci­nate well.” I do think we’ll have a vac­cine that works re­li­ably, even­tu­ally. No other an­tiviral method has their price-to-effec­tive­ness ra­tio.

  We were able to find fixes to the prob­lems with some SARS-1vac­cines, and I think we’ll be able to route around these prob­lems for SARS-2 as well.

  This just means that I don’t ex­pect vac­cine de­vel­op­ment to be quite as fast as it would be for viruses with­out these known prob­lems. Ad­di­tion­ally, I sus­pect an­i­mal-test­ing could be cru­cial to the de­vel­op­ment of a safe vac­cine, un­less we’re will­ing to risk a few hu­man lives in their stead (which, maybe we are).

  And speak­ing per­son­ally, un­til the clini­cal trial re­sults are in, I’m in­clined to be cau­tious about tak­ing vac­cines that use large swathes of the viral S-pro­tein, al­though I sus­pect some with smaller frag­ments will turn out to be fine.

• Spiracular 22 Apr 2020 2:06 UTC

  2 points

  in reply to: CellBioGuy's comment on: Coron­avirus: Jus­tified Key In­sights Thread

  As for why blood clots are a prob­lem in the first place… one of the hy­pothe­ses I’ve seen float­ing around is that it might be tied into com­ple­ment sys­tem malfunc­tion?

  Warn­ing that this is pretty spec­u­la­tive...

  The com­ple­ment sys­tem is an im­mune re­sponse that uses C-pro­tein com­plexes to poke holes in mem­branes to kill cells and fight large in­fec­tions.

  This pa­per used re­sults from 5 lung au­top­sies and tried to draw a link be­tween the pro­longed pro­co­ag­u­lant state in the lungs with ex­ces­sive ac­tivity of the com­ple­ment sys­tem. I could barely fol­low it be­yond that.

  I had also heard be­fore that com­ple­ment sys­tem malfunc­tions were thought to be con­nected to bad vac­cine re­sponse for SARS-1.

  I don’t feel cer­tainty in this at all. But it comes up semi-con­sis­tently, and I don’t have a bet­ter the­ory yet.

• Spiracular 22 Apr 2020 2:04 UTC

  4 points

  in reply to: CellBioGuy's comment on: Coron­avirus: Jus­tified Key In­sights Thread

  Here’s a pa­per that situ­a­tion­ally agrees with you on an­ti­co­ag­u­lants… An­ti­co­ag­u­lant treat­ment is as­so­ci­ated with de­creased mor­tal­ity in se­vere coro­n­avirus dis­ease 2019 pa­tients with coagulopathy

  449 peo­ple. Speci­fi­cally, they ob­served no differ­ence in sur­vival be­tween hep­arin users/​non-users over­all, but in the very-high-D-dimer sub­set (or in peo­ple with lots of sep­sis‐in­duced co­ag­u­lopa­thy), sur­vival seemed to be bet­ter with hep­arin.

  This link car­ries no new in­for­ma­tion yet, but seems to be a place­holder for a fu­ture re­view pa­per on this topic.

  The “blood co­ag­u­la­tion as a ma­jor con­trib­u­tor to death” bit gen­er­ally matches pretty well with some early re­sults where high D-dimer pre­dicted worse rates of mor­tal­ity fairly re­li­ably, since D-dimer is ba­si­cally a prob­le­matic-blood-clot in­di­ca­tor.

  There’s a po­ten­tial com­pli­cat­ing fac­tor for the el­derly, which is that many of them are already on an­ti­co­ag­u­lants (to miti­gate stroke-risk). And go­ing on some ex­pe­riences of my grand­par­ents, it seems to be hard to nav­i­gate the risks miti­gated with an­ti­co­ag­u­lants with the risk of bleed­ing out un­less you’re pretty care­ful. All the same, it looks like a promis­ing line of im­prove­ment to treat­ment of se­vere COVID-19.

  Nit­pick: __ice9 has 2 un­der­scores, not 1.

• Spiracular 21 Apr 2020 22:35 UTC

  14 points

  on: What are the costs, benefits, and lo­gis­tics of open­ing up new vac­cine fa­cil­ities?

  micpie’s an­swer here is good! I don’t have a lot to add to it.

  Here are a few re­lated refer­ence-links* and a tiny bit of com­men­tary.

  • COVID-19 vac­cine de­vel­op­ment land­scape as of April 9th (post)

  • ETA: In the Pipeline blog post pro­vid­ing com­men­tary and de­scrip­tion of the vac­cines fur­thest along in the pipeline (Apr 23)

  • Chris­ti­anKI’s LW Q for mRNA vac­cine de­vel­op­ment for COVID-19 in par­tic­u­lar (some­thing of a spin-off of the af­fore­linked thread)

    • Bit of con­text: Some of the fastest vac­cines to hit hu­man tri­als were mRNA-based vac­cines**, al­though at this point the field is more bal­anced.

  • Good ar­ti­cle on ad­di­tional vac­cine de­vel­op­ment challenges for SARS-2

    • Click­baitier take: Whole S-Protein Vac­cines Are Danger­ous (The Solu­tion May Sur­prise You!)

    • It gives a good overview of the ad­di­tional challenges to de­vel­op­ing COVID-19 vac­cines, such as Th-2 im­munopathol­ogy (allergy-like im­mune over­re­ac­tion, seen for some SARS-1 vac­cines). This doesn’t cover the de­tails of clini­cal tri­als gen­er­ally (which are hard enough on their own).

    • It’s quite read­able, but if you want bul­let-points, here

  • 2016 Re­view pa­per on the typ­i­cal vac­cine de­vel­op­ment pipeline

    • This one is tech­ni­cally-ori­ented, and about typ­i­cal vac­cine-development

    • ...as one might guess, peo­ple are Cut­ting Corners for COVID. Not all of the best-prac­tice guidelines are go­ing to be stringently ap­plied.

  *...some of which I heard about via other micpie com­ments. Go figure.

  ** 60 days from the nCOV DNA se­quence to mRNA vac­cines start­ing clini­cal tri­als! mRNA is a rel­a­tively flex­ible/​easy-to-mod­ify plat­form, but new and a bit untested.

• Spiracular 20 Apr 2020 1:58 UTC

  4 points

  in reply to: vidro3's comment on: April Coron­avirus Open Thread

  I don’t re­ally know, I wouldn’t do this. Here are a cou­ple of pos­si­bil­ities that ran through my mind.

  • COVID’s symp­toms are ba­si­cally “see: un­defined flu-like symp­toms.” This might just be an equiv­a­lent of “I looked up my symp­toms on We­bMD and it’s definitely can­cer,” only with COVID.

  • There was that rev­e­la­tion that Wash­ing­ton got it ear­lier than ex­pected. Maybe they’re pat­tern-match­ing blindly to this. It’s re­ally easy to do so, es­pe­cially if there was an­other nasty flu or cold go­ing around back then (which there prob­a­bly was).

  • Mo­ti­vated rea­son­ing

    • Peo­ple want an ex­cuse to go about their life as nor­mal (or to com­plain if they’re not)

    • Peo­ple es­pe­cially hate tak­ing the pos­si­bil­ity of their own death seriously

    • No­body wants to deal with the guilt of know­ing that their “nor­mal” ac­tions may be en­dan­ger­ing oth­ers (cough asymp­tomatic trans­mis­sion), and they would rather be­lieve some­thing po­ten­tially-false than con­tend with that

  It’s prob­a­bly a mix of all three, or even more.

  With all due af­fec­tion, I’ve heard that New York­ers as a whole are fairly prone to con­trar­i­anism. So the fre­quency with which you’re hear­ing this might also par­tially be lo­cal var­i­ance.

• Spiracular 18 Apr 2020 21:56 UTC

  10 points

  in reply to: vidro3's comment on: April Coron­avirus Open Thread

  TL;DR: No. The ear­liest I’d buy for pan­demic-track COVID is early-to-mid De­cem­ber, and in China or maybe Aus­tralia. Other­wise, it’d have to be a non-pan­demic sub­strain that died out early, and left no chil­dren be­hind ex­cept the first Wuhan strain. The the­ory loses in an Oc­cam’s Ra­zor fight with “your friends prob­a­bly had some­thing else back then.”

  ETA: This post men­tions a sec­ond in­de­pen­dent line of ev­i­dence on the mat­ter (us­ing an­ti­bod­ies), and also dates the first COVID-19 cases to no ear­lier than De­cem­ber.

  I’m go­ing to be bas­ing most of this on nextstrain’s COVID-19 phy­logeny data and their ac­com­pa­ny­ing chart.*

  The ear­liest se­quenced US case we have came from Wash­ing­ton. The Wash­ing­ton strain’s ear­liest se­quenced sam­ple was 5 weeks of mu­ta­tion out from the Wuhan strain at the time, lead­ing to the in­fer­ence that it ar­rived (or at least split off from the Wuhan gene-pool) in about mid-Jan­uary. Aus­tralia seems to have a di­ver­gent strain that might have bro­ken off even ear­lier, pos­si­bly as far back as mid-De­cem­ber.

  Go­ing on their graph, they dated the Wuhan last com­mon-an­ces­tor (LCA) strain to roughly mid-De­cem­ber, and the all-strain LCA is the same one.

  (I’m not go­ing to de­tail all of how this works, but LUCA is a similar con­cept.)

  So, cases much ear­lier than mid-De­cem­ber (and in any­place other than China or Aus­tralia) seem re­ally un­likely to me**.

  *Note that old phy­lo­ge­nies are of­ten very in­ac­cu­rate and rough, and rely heav­ily on your start­ing as­sump­tions (I’ve played around with them, and it is wild how differ­ent the trees can be). But this is a fresh phy­logeny, and should be a bit of a best-case-sce­nario. This a very re­cent se­ries of mu­ta­tions and splits, and on top of that, un­like with pa­le­on­tol­ogy we can ac­cess, date, and se­quence old blood sam­ples just fine. I ex­pect this phy­logeny to get the oc­ca­sional de­tail wrong, but to hit the broad-strokes and to be largely pretty ac­cu­rate.

  **If an ear­lier strain ex­isted, it would have had to have left no lin­ger­ing se­quenced sub-strains in the pre­sent day. If even one of those the­o­ret­i­cal highly-di­ver­gent sub-strains per­sisted, got se­quenced, and were added to the phy­logeny calcu­la­tion… it would have in­tro­duced a new early-stage split into the phy­lo­ge­netic tree that would have pushed the prob­a­ble LCA way back into the past.***

  *** I men­tion this in part be­cause… HIV did have these. A non-pan­demic an­ces­tor that we found in some very old blood sam­ples. It was nowhere near as con­ta­gious and per­sis­tent at the time, and even seemed to be a tran­sient ill­ness for those who caught it. But be­ing a pretty un­suc­cess­ful virus at the time, only a very small pool of peo­ple had it back then.