libera/##covid-19/ Friday, 2021-09-10

nixonix	.title https://twitter.com/kallmemeg/status/1435954475567566852 read the comments a bit lower on VE vs identified infection...	00:00
Brainstorm	nixonix: From twitter.com: Meaghan Kall (@kallmemeg): "NEW: From today, PHE will publish vaccination status of COVID-19 cases, deaths and hospitalisations over the past 4 weeks in the weekly Vaccination Surveillance Report [...]	00:00
nixonix	.title https://twitter.com/JamesWard73/status/1436017485262823424 so it was incorrect? or isnt?	00:02
Brainstorm	nixonix: From twitter.com: James Ward (@JamesWard73): "…estimates of population in each age group to estimate the number of unvaccinated (this is a bit rough & ready, because I can’t match the dates precisely, but it’s close [...]	00:02
LjL	wow, from today, PHE will publish vaccination status? GROUNDBREAKING	00:03
nixonix	"I’m not saying the ONS numbers are definitively right either, they will also be distorted by other effects, but in this case I suspect this is a bit closer to the truth"	00:03
LjL	sorry for the sarcasm but my question is why the fuck was it not being published before	00:03
nixonix	whats all this trickery here now? brits come and explain	00:03
LjL	there is... practically no difference in rates between vaccinated people and unvaccinated ones, at least in some age groups?	00:05
LjL	so basically we can simplify things and say efficacy against infection and getting a positive PCR is roughly 0?	00:05
nixonix	yeah but its still unadjusted. and it isnt likely that protection waning with time wouldnt show up, like younger got 2nd dose later etc. its bad raw data, but it proves protection vs infection is waning in uk with their intervals too quite fast	00:06
nixonix	which might explain that finnish hc official quote above. he knew, and now they somehow have to tell it in finland too, sooner or later. unless the press helps again to cover up things from people	00:07
nixonix	most of media here stopped publishing daily case numbers couple of days ago. almost like they all had common agreement (actually i know the platform they use for stuff like that)	00:11
lastshell	I saw some news about fauci wuhab lab gain of function	00:12
lastshell	not sure what is true and what is false anymore	00:12
nixonix	its all gray area now	00:13
ublx	i'm impressed you once found it possible to be sure	00:13
nixonix	ljl did you read about israel, hospitalization 80% etc, from above?	00:16
LjL	ublx, to be honest, "sure" would be an overstatement, but i definitely felt like i had some more things to be like "we must do this! we must do that! it's like this! it's like that!" in the early months... let's say during the first half of this so far	00:16
LjL	now i'm more like "why are people even debating, we're all doomed anyway" ;(	00:16
LjL	nixonix, i read the times of israel article	00:16
nixonix	hosp data isnt nearly as messy, since those needing hospital usually also go there. when cases, those vaccinated may not bother to go tested, when they think its prob something else, or wont be bad. etc effects	00:17
nixonix	but waning shows up later, so we dont have much yet, exp israel	00:17
LjL	yeah 80% is a glass more than half full to many people i guess, but to me, 80% against hospitalization when at least Italy is very far from boosters for regular people is... way underwhelming	00:18
LjL	these vaccines seemed to be so great at first (at least the mRNA ones), then the combination of getting worse because of Delta and getting worse because they just quickly get worse with time... ugh	00:19
lastshell	do we need booster every N period ?	00:20
nixonix	maybe az on top of 2 mrna doses would wane slower, since dna degrades slowly. and there is no antibodies vs chimp virus from previous doses	00:20
lastshell	so a mix ?	00:21
LjL	so far, it seems... probably? but i have some hope that variant-specific vaccines and/or "universal" vaccines will improve the situation (although those things aren't intrinsically related to duration)	00:21
LjL	but i mean, at least once a year or two, it will always be likely	00:21
nixonix	and match (i hate those type of expressions, which are repeated ad naseum in media)	00:21
LjL	just i think if it needs to be every 6 months, we won't be able to do it	00:21
ublx	haven't seen much comment on mu variant go past in the scroll. LjL, much in the way of mu related link yet?	00:22
nixonix	for hospitalization, it looks like 4.5-5 months would be good. not perfect. for infections, well it helps a bit. a lot during the first couple months	00:22
nixonix	but moderna, maybe 2 months longer. not confirmed	00:23
nixonix	with longer intervals. idk, brits should publish their data	00:23
nixonix	.title https://twitter.com/TWenseleers/status/1435020716341084163	00:24
Brainstorm	nixonix: From twitter.com: Tom Wenseleers (@TWenseleers): "Updated fits on GISAID lineage freqs for Colombia & Ecuador. Delta taking over with Mu (B.1.621) having growth rate disadvantage rel to Delta in both countries of 6% [...]	00:24
LjL	ublx, i added one study to Zotero, that nixonix linked probably, but barely read it, the abstract said it elicit less antibody response than any of the other variants of concerns, so that's nice	00:25
LjL	but that's about all i know	00:25
nixonix	no i just read it yesterday myself. great evasion, not that good transmission it looks	00:26
nixonix	south american sequence data is probably pretty spotty	00:27
LjL	nixonix, makes sense given it's not spreading much yet (?) but you're right to say we should consider this kind of thing a serious threat when most everyone is vaccinated, and it has the advantage of evasion	00:27
nixonix	luckily these wane so fast, that day may never come	00:28
LjL	that's what you call luck ;(	00:28
nixonix	you take what you get	00:28
LjL	maybe i'll make a voice chat where we can optionally join and just scream	00:29
LjL	therapeutically	00:29
nixonix	either those hc officials dont pay attention to latest research, like those i think 7 preprints showing delta 2x or more lethal than alpha (which prob 60% more than previous), or they are just hiding everything they can	00:31
nixonix	vs 1 norwegian (theres critique on that one), that found it the same	00:31
nixonix	and the same about waning. israel, qatar, and now uk	00:32
Brainstorm	New from CIDRAP: Biden details new plan of attack for COVID-19: Stephanie Soucheray \| News Reporter \| CIDRAP News Sep 09, 2021 Biden's goals are to keep schools open, mandate vaccines for all federal workers, and increase testing. → https://is.gd/6o4KHP	00:32
nixonix	saying things in media, that are very unlikely to be true. like that increased infectivity was only in mucosa (meaning not more lethal). thats just a hypothesis, with no evidence supporting	00:33
de-facto	.title https://www.biorxiv.org/content/10.1101/2021.09.06.459005v1.full	00:38
Brainstorm	de-facto: From www.biorxiv.org: Ineffective neutralization of the SARS-CoV-2 Mu variant by convalescent and vaccine sera \| bioRxiv	00:38
de-facto	ublx, ^^	00:38
ublx	looking	00:38
nixonix	.title https://twitter.com/TWenseleers/status/1435382772034637826 i have thought the same. self-replicating vaccine with no furin site, that was more transmissive somehow. maybe too late with delta	00:39
Brainstorm	nixonix: From twitter.com: Tom Wenseleers (@TWenseleers): "As a thought experiment I sometimes wonder how many lives we would have saved if we would have gone for deliberate mass infection with a nonpathogenic FCS deletion [...]	00:39
nixonix	...ssible	00:39
ublx	de-facto: wonder how this pseudovirus investigation compares to the viral isolate of https://onlinelibrary.wiley.com/doi/10.1002/jmv.27247	00:46
ublx	^ from July, "A cluster of the new SARS-CoV-2 B.1.621 lineage in Italy and sensitivity of the viral isolate to the BNT162b2 vaccine"	00:46
ublx	they found it possible to conclude, "All sera (after BNT162b2 vaccine) efficiently neutralized the SARS-CoV-2 B.1.621 isolate (Figure 1C), demonstrating that this VOI is not a concern for vaccine efficacy."	00:49
ublx	these two results seem incompatible	00:49
de-facto	Neutralization titer B.1 against Mu in the later paper is 95÷197=0,48	00:54
de-facto	in the first paper from Japan its 76÷497 = 0,15	00:55
de-facto	so yeah 3,2-fold difference	00:56
de-facto	in the japan paper it looks like Mu and Beta seem pretty similar in their evasive potentia	00:57
Brainstorm	New from WebMD: Sweeping New Vaccine Mandates Will Impact Most U.S. Workers: President Joe Biden on Thursday announced a host of new plans to rein in COVID-19’s runaway transmission in the U.S., including sweeping vaccine mandates that will affect 100 million American workers, nearly two-thirds of the country’s workforce. → https://is.gd/rzoWVM	01:05
nixonix	*self-spreading vaccines (i wrote self-replicating above). aka self-disseminating, self-propagating. i think all those terms are in use	01:15
LjL	controvurshal	01:18
LjL	maybe a country that gives no fucks will do it eventually	01:18
de-facto	https://covid19.trackvaccines.org/vaccines/ <-- there are some replicating vaccines in the pipeline	01:21
de-facto	title	01:21
de-facto	.title	01:21
Brainstorm	de-facto: From covid19.trackvaccines.org: Vaccines – COVID19 Vaccine Tracker	01:21
de-facto	but i dont think those would spread, probably using some harmless viral vector that easily gets killed off by the immune sytem	01:26
LjL	de-facto, uhm, but what's the scope exactly? we talked about a "self-propagating" vaccine a few days ago but i think we weren't clear on whether maybe it only reproduced itself for one iteration, or it was actually meant to spread to other people	01:27
nixonix	replicating like one cycle only?	01:28
de-facto	yeah LjL that is probably something different you discussed about there then	01:28
nixonix	i think there are some animal vaccines that are multi-cycle or something	01:28
nixonix	id like to design one that works for insects	01:29
LjL	right	01:29
LjL	maybe they could spread, like accidentally to a limited extent	01:29
LjL	but making a vaccine intended to spread would be different	01:29
LjL	nixonix, wasn't it you saying that as a plausible thing?	01:29
LjL	that it would one cycle	01:29
nixonix	how is it different than plan to infect unvaccinated kids	01:29
nixonix	yeah, its possible, and i think they do stuff like that with pseudoviruses used in reasearch	01:30
de-facto	LjL, maybe if one could delete some of the properties from the SARS-COV-2 genome itself but who knows it that is possible	01:30
de-facto	we dont even really know all those other functions yet, only a few of them	01:30
LjL	i think the major danger if you designed a "weak" version of SARS-COV-2 that spreads a lot but kills no one and protects everyone would be recombination, then it could combine with a variant that kills a lot, and it would also spread a lot	01:30
de-facto	as the one i linked above with the host cell mRNA blocking etc	01:31
LjL	but if it's another virus, a known-harmless one, unrelated to coronaviruses, that just happens to show/produce the spike protein, maybe that wouldn't be an issue	01:31
nixonix	what, just eliminate furin cleaving. and its way less pathogenic	01:31
de-facto	yeah it cant contain something that would give it an advantage over the wild type, hence also would not spread more than it	01:31
nixonix	that would affect infectivity though	01:32
de-facto	so it would not outcompete in in real life	01:32
nixonix	yeah. it should have been done with ancient variant. and letting it gain more fitness with serial passage	01:33
de-facto	decimation of wild type functions would be ok to attenuate it, but not gain of other functions, because it would, as you said, impose the danger of recombination with the wild type then	01:33
nixonix	checking it doesnt get fcs back ofc	01:33
LjL	de-facto, but if it were another virus type entirely? then it wouldn't be a matter of competition with SARS-COV-2. it would just need to be "pretty infectious" so it spreads to everyone reasonably quickly	01:33
LjL	the one we were looking at the other day, that one i remember, used some kind of animal virus... don't remember which, just, unrelated to coronaviruses, but presenting a spike protein	01:34
de-facto	it would compete with it in everyday life about infection pathways in its transmission	01:34
de-facto	those are not specific to genetic variants but to types of viruses, such as respiratory etc	01:34
LjL	also maybe it would make some people take risks in order to "catch" the vaccine	01:34
LjL	although i find that unlikely	01:34
de-facto	yeah you can implant the spike protein to other viruses, wasnt that what Baric did develop?	01:35
LjL	noooo idea, but let me see what that one we were discussing was	01:36
de-facto	but what would be the purpose? we would need a harmless virus that spreads with much higher reproduction number and annoys the immune system with blooming with sars-cov-2 spikes	01:36
de-facto	i dont think that is possible without creating a monster	01:36
LjL	why much much higher? only much much higher if you wanted to blitz-vaccinate everybody. but just the fact it spreads (sure, it needs to spread a fair amount) would give a logistic advantage, and vaccinate also some people who normally wouldn't get a vaccine (because they can't, or won't)	01:37
nixonix	the key would be similar neutralizing antibodies, so those that get our liberavirus infection, will be protected vs delta. just similar enough spike, with modified fcs, would do. if more transmissible somehow	01:37
LjL	i'm not thinking "just vaccinate one person and then wait"	01:37
LjL	i'd still be vaccinating lots of people, but it would add an advantage	01:37
de-facto	because we need to maintain SARS-CoV-2 containment and stll would want such a thing to be able to spread if that is the idea	01:37
de-facto	i dont think its possible and tbh sounds quite insane to me	01:37
LjL	de-facto, in your world we have containment, but in my world there is currently virtually no containment :P	01:38
de-facto	in contrast to controlled vaccination e.g. by spraying it into the nose or such	01:38
LjL	i mean, maybe Australia, NZ and China wouldn't like a vaccine like that, because they have containment	01:38
LjL	but we don't, even though you'd like us to, we just don't, not even close	01:38
de-facto	we are all wearing masks here	01:38
de-facto	the whole day in work or stores etc	01:39
LjL	well, yeah, okay	01:39
LjL	do you have an FFP2 mandate yet?	01:39
LjL	or was that just Austria	01:39
nixonix	.title https://www.nature.com/articles/s41559-020-1254-y	01:39
Brainstorm	nixonix: From www.nature.com: Self-disseminating vaccines to suppress zoonoses \| Nature Ecology & Evolution	01:39
de-facto	medical masks are also ok here	01:39
nixonix	.title https://www.nature.com/articles/s41586-021-03237-4	01:39
Brainstorm	nixonix: From www.nature.com: Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis \| Nature	01:39
LjL	nixonix, hmm, that's interesting, but you need to identify zoonoses that are very likely to spillover to humans (i.e. still dangerous work with bats), because... you certainly aren't going to create self-disseminating vaccines for all zoonoses	01:40
nixonix	the difference might be even bigger in humans, if its true that fcs has a superantigen for t-cells	01:41
LjL	but it does mention that in the abstract so maybe they have A Plan	01:41
LjL	they being... two people :P	01:41
nixonix	and losing that itself increases fitness, it seems. in murines	01:41
nixonix	but why hasnt it lost it then? so maybe not in humans	01:42
LjL	anyway i keep forgetting what i was doing, namely finding that "self-propagating" vaccine in the logs, so nixonix, de-facto, i don't remember which one of you i was talking about this one with, but anyway it was https://www.nrxpharma.com/nrx-pharmaceuticals-announces-partnership-with-the-israel-institute-for-biological-research-to-complete-development-and-commercialization-of-brilife-covid-vaccine/	01:42
LjL	nixonix, "mice are not little humans" :P	01:42
nixonix	lets try them on insects anyway. ill take the responsibility if something awkward happens	01:42
LjL	↑ remember everyone, this is publicly logged	01:43
LjL	he said it	01:43
nixonix	find "self-replicating" from summer 2020. it was me	01:44
LjL	freenode/##covid-19/2020-03-03.log:[04:21:51] <LjL> yuriwho, that measure of success is decent and i assume the one actually used in biology, but i think other metrics could be used too. it's all complicated by the fact that the self-replicating system doesn't actually replicate itself but often/sometimes a modified copy of itself... which if you see as an individual occurrence, is just a failure to replicate, but when you have many of those things, it's	01:44
LjL	actually an asset because it can undergo evolution.	01:44
LjL	freenode/##covid-19/2020-12-14.log:[06:44:07] <ryouma> line-1 segments are iirc self-replicating stretches of dna that comprise a big proportion of your genome. the hypothesis also says could come from rt from hiv.	01:44
LjL	that didn't work!	01:44
nixonix	the other chan	01:45
LjL	oh, right	01:45
nixonix	sorry "self-spreading"	01:45
LjL	freenode/##coronavirus/2020-07-21.log:[19:41:55] <nixonix> another 2017 paper: combining self-amplifying replicon RNA (RepRNA) technology with nanotechnology. RepRNA are large self-replicating RNA molecules (12-15 kb) derived from viral genomes defective in at least one structural protein gene. They provide sustained antigen production, effectively increasing vaccine antigen payloads over time, without the risk of producing infectious progeny	01:45
LjL	well there is this also	01:45
LjL	looks like sorcery	01:45
nixonix	sorry "self-spreading", i repeated the typo	01:46
LjL	freenode/##coronavirus/2020-07-12.log:[02:04:27] <nixonix> you can call it self-spreading vaccine, so it will sound better for public	01:46
LjL	freenode/##coronavirus/2020-07-21.log:[20:01:59] <nixonix> but should be called self-spreading vaccine, not a weakened strain of virus :)	01:46
de-facto	hmm is that a rabies like virus they are using there?	01:46
LjL	nixonix for WHO PR	01:46
LjL	de-facto, the nrxpharma?	01:46
de-facto	https://en.wikipedia.org/wiki/Indiana_vesiculovirus	01:47
LjL	uhm, okay, i hadn't noticed that	01:47
LjL	that looks a little scary	01:48
nixonix	i thought at time that my idea was original, but found it wasnt (and accidentally happened once, with polio vax or something)	01:48
de-facto	sounds pretty similar to VSV-EBOV	01:48
nixonix	and even the name was used (along those other names)	01:48
de-facto	https://clinicaltrials.gov/ct2/show/NCT04608305	01:48
LjL	well in theory it could happen with any attenuated-virus vaccine, no? just, not at scale	01:49
de-facto	https://www.precisionvaccinations.com/vaccines/brilife-vaccine	01:49
LjL	"The spike protein was replaced with that of SARS-CoV-2" so the virus itself already had a spike protein of its own?	01:50
LjL	also we were a bit confused by "The vaccine differs from other COVID-19 vaccines by presenting the entire COVID-19 spike protein to the body's immune system." because, like, the other vaccines, most of them, also present "the entire COVID-19 spike protein"	01:50
de-facto	well the original virus had to enter cells somehow	01:50
LjL	they could only present the RBD maybe, but that's not what they do	01:50
LjL	sure but i assume the means to do so are not all called "spike proteins"	01:51
LjL	like you could have messengers that tell the cells to open up its cytowhatsitcalled for instance	01:51
nixonix	not a modified virus as a vaccine - or as a way to finally get rid of insects - but close to topic anyway:	01:51
LjL	i'm sure there are quite a few ways viruses enter cells	01:51
nixonix	.title https://www.science.org/news/2020/01/genetically-engineered-mosquitoes-resist-spreading-any-form-dengue	01:51
Brainstorm	nixonix: From www.science.org: Genetically engineered mosquitoes resist spreading any form of dengue \| Science \| AAAS	01:51
LjL	please don't get rid of insects even though they scare/annoy me	01:52
LjL	we need them ;(	01:52
nixonix	maybe they could engineer other viruses too, make them green and to escape humans	01:52
nixonix	i mean insects	01:52
de-facto	nixonix, we cant do such things, wipe out whole species, that would be of consequences we cant even fully understand yet	01:52
nixonix	yeah, not other species	01:53
de-facto	deal with the insects even if they are annoying	01:53
nixonix	they did that for mosquitoes. why stop now	01:53
de-facto	huh? mosquitoes are still quite annoying here	01:54
nixonix	some sub-specie anyway, maybe just locally	01:54
de-facto	nope, we cant do that	01:54
de-facto	individuals, fine, but not whole species	01:55
de-facto	we would not even know what we would loose by doing such things	01:55
nixonix	lets keep a few in zoo, so its not a genocide	01:55
nixonix	anyways, it would be just modifying those species a bit, not a genocide	01:56
LjL	de-facto, he's right though, they did that, at least in a limited area, i think with the mosquito species that carried Zika although i'm not sure	01:56
LjL	i'm not saying whether it's right or wrong, just that they did it	01:56
de-facto	yeah they sprayed it with insecticides and put something in the water where they breed or such	01:57
nixonix	dengue, linked above. maybe its not the only one, but i remembered there was at least one like that, and googled it	01:57
de-facto	i mean where is the limit then?	01:57
de-facto	Bats carry many viruses with pandemic potential	01:57
de-facto	let wipe them all out, shall we?	01:58
de-facto	what else?	01:58
de-facto	hmm monkeys?	01:58
de-facto	they are just too close to humans	01:58
de-facto	we cant start doing such things, the consequences would be catastrophic	01:59
de-facto	i get it, i hate mosquitoes with passion and yes they are a problem with spreading viruses and parasites	02:00
pwr22	Kill all the things!	02:00
de-facto	but we dont know the full role they play in the ecosystem	02:00
de-facto	its all interdependent on many timescales	02:00
pwr22	I'm pretty sure we're onboard globally with wiping out mosquitos	02:01
pwr22	There seem to be a bunch of different initiatives	02:01
ublx	anyone fancy engineering ACE2?	02:01
de-facto	what if they drive evolution with spreading a certain amount of viruses in the wild?	02:01
ublx	thought i was having an original idea, but no. ancient history: https://www.science.org/doi/full/10.1126/science.abc0870	02:01
pwr22	One of them seems to be gene modification that makes them sterile down the line in the female line	02:01
pwr22	ublx: I'm wary of the idea of people just trying to make or inhibit ACE2. It's part of our normal metabolism to have it behave as it does	02:02
pwr22	it might stop covid but it might also mess people up	02:02
ublx	indeed	02:02
pwr22	I mean, it's related to kidney stuff, it can protect kidneys	02:02
pwr22	It can also cause blood vessels to grow in parts of the kidney they should not	02:03
pwr22	and it's irreversible	02:03
pwr22	Leads to kidney failure	02:03
ublx	it's all over the place	02:03
pwr22	It can raise / lower blood pressure	02:03
pwr22	ACE1 can cause cold and flu symptoms	02:04
pwr22	when I was on 10mg of ramipril I was "ill" for like 6+ months	02:04
ublx	just learned that circulating ACE2 is a thing (and is more pronounced in presence of various diseases like kidney and heart disease, and in smokers)	02:04
pwr22	Felt terrible	02:04
pwr22	Went away when when I stopped it	02:04
LjL	i think maybe inhibiting ACE2 could be useful as a treatment in bad cases	02:04
pwr22	Replaced with candasarten that was gradually increased to the max dose and that doesn't give me those side effects	02:04
LjL	but you wouldn't just do prophylaxis with it	02:04
ublx	LjL: ACE2 blockade by SARS2 is part of the story of inflammation though	02:05
pwr22	LjL: we already have a lot of ACE2 inhibitors and I'm not sure we ever worked out if they made covid symptoms better / worse?	02:05
LjL	pwr22, hmm someone (presumably nixonix) posted something about kidneys being the <i don't remember what, but something important> of COVID	02:05
ublx	you'd be screwed if you ran out of ACE2	02:05
nixonix	oh yeah, we had discussion on those decoy ace2 long time ago. i thought it wouldnt be very efficient as an antiviral. i think defacto liked the idea	02:05
LjL	pwr22, yeah that was unclear, but there was some study where they engineered things that looked like ACE2 receptors instead, so that most of the virus would bind to those, which leads to nothing, instead of to actual ACE2	02:06
LjL	yes the decoy ACE2	02:06
nixonix	what ublx just linked above	02:06
* pwr22 goes back to sipping on the bleach		02:07
* pwr22 slurps		02:07
de-facto	.title https://www.biorxiv.org/content/10.1101/2021.03.12.435191v2.full	02:07
Brainstorm	de-facto: From www.biorxiv.org: A novel soluble ACE2 protein totally protects from lethal disease caused by SARS-CoV-2 infection \| bioRxiv	02:07
de-facto	ublx, ^^	02:07
pwr22	Is ACE2 involved in the inflammatory response or how covid infiltrates our cells?	02:08
pwr22	I kind of recall it being the latter but that is from a long time ago	02:09
pwr22	Maybe we found more stuff?	02:09
ublx	pwr22: yes, it is critical in the regulation of inflammation	02:09
pwr22	But is it also critical for covid to infect cells?	02:09
pwr22	Or does it do that by other means?	02:09
LjL	wow, i don't have the decoy ACE2 thing in the github	02:10
LjL	i'm such a failure	02:10
pwr22	You're too hard on yourself 🙂	02:10
ublx	ACE2 is the cellular entry point for SARS2, yes, pwr22	02:10
pwr22	Brainstorm: Wouldn't this thing end up inhibiting our things that need to bind ACE2 or the opposite	02:12
pwr22	I'm never sure which way these things go from some of these papers	02:12
ublx	anyway. but if ACE2 is exaggerated in circulation in presence of various disease states and insults such as smoking, presumably this is because the body is producing vast excess to ameliorate disease. presumably for it to move and fuse where required? if this is so, in what ways are these decoy ACE2s engineering to prevent them falling out of circulation and replacing natural ACE2	02:12
ublx	s/engineering/engineered/	02:12
pwr22	ublx: a lot of "healthy" people seem to benefit from ACE2 inhibitors so I don't think it's that cut and dry	02:12
pwr22	Well, ACE then ACE2 depending on tolerance of the ACE inhibitors	02:13
ublx	still, according to de-facto's link, it has already shown promise	02:13
pwr22	ACE inhibitors give me persistent flu symptoms	02:13
pwr22	Also, deploying something like that is great but it's like a monoclonal antibody (that potentially fucks shit up without the bodies safety checks that usually stop auto-immune) and covid mutations that reduce binding affinity will rapidly proliferate and soon it doesn't give any fucks about the novel protein?	02:15
pwr22	The novel protein from september 2020 so it doesn't seem to have gone anywhere?	02:15
ublx	maybe it went too far and there are now zombies running around they desperately don't want us to know about	02:16
nixonix	ACE2 is a part of renin-angiotensin homeostasis, which sars2 infection messes up. but i remember there was a study where they thought that the actual spike binding to cells surface ace2 caused some inflammatory cascade	02:16
pwr22	ublx: I think ACE / ACE2 are the enzymes that bind other things in our bodies (angiotensins maybe?)	02:16
pwr22	ublx: 🧟	02:17
LjL	ublx, well the paper says that they did things to these "decoy" receptors to make them bind more tightly to SARS-COV-2 than normal human ACE2 does	02:17
* pwr22 has flashbacks of renin-aldosterone ratio tests		02:17
pwr22	Gotta collect all your pee for 24 hours	02:18
LjL	"Chan et al. used deep mutagenesis to identify ACE2 mutants that bind more tightly to the spike protein and combined mutations to further increase binding affinity"	02:18
nixonix	then if theres superantigen in spikes fcs, probably some number of t-cells can get crazy from vaccination too. does it matter? population studies show, that not much. maybe those myocarditeses, but if, then prob also some of the vaccine must go to vein	02:18
pwr22	Oh wait, was the the metanephrines... 🤔	02:18
Brainstorm	New from https://covid19.specops.network : Add long-overdue link to "decoy ACE2" paper: It was probably a preprint when we looked at it, now it's right on Science... → https://is.gd/nf9ory	02:19
ublx	LjL: i was wondering what prevented them from replacing natural ACE2 but i suppose the dosing, were it ever implemented, would be infinitesimal compared to natural, and that the body would only ever manufacture the natural	02:19
pwr22	LjL: Sure that's a good start but the virus binds to these receptors because it looks like our stuff right? Flooding my body with enough stuff to stop up all the covid, even if it only has lower binding affinity for that stuff, it's probably gonna have side effects	02:20
LjL	<pwr22> But is it also critical for covid to infect cells? <pwr22> Or does it do that by other means? ← there are some indications that it might do so by other means as well, but they are probably secondary means and by far the primary one is ACE2	02:20
pwr22	It's a fairly critical system	02:20
-RSSBot[LjLmatrix- Zotero / COVID links Group / Top-Level Items: Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2 ( https://www.zotero.org/groups/covid_links/items/N6AHRFI7 )		02:20
pwr22	ublx: How would you replace the natural ACE2? It's in our cells in the membranes and manufactured inside the cell	02:21
pwr22	You can only inject something else into our blood to soak up the covid	02:21
pwr22	Also wouldn't replacing the natural ACE2 with our version that binds better to covid be the opposite of what you want to do?	02:23
LjL	pwr22, but our version doesn't lead to entry into cells!	02:23
LjL	it's just "floating" receptors that recept nothing	02:24
nixonix	there are hACE2 mice. so its doable	02:24
LjL	yes, but i think we're confusing a few things together here	02:24
LjL	one thing is genetically engineering mice to have human ACE2 receptors (or humans to have murine ACE2 receptors i suppose)	02:24
LjL	that's about changing the ACE2 receptors on the actual cells	02:25
LjL	then you could have another two things	02:25
nixonix	K18 mice	02:25
pwr22	"it's just "floating" receptors that recept nothing" sure but I was meaning the "replace natural ACE2"	02:25
LjL	1) inject a lot of whatever normally binds to ACE2 (it has a name, maybe it is ACE2, i also keep getting confused about this), and this is basically ACE2 inhibitors, and it's not been shown to be useful, i think, or at least it's dubious, and it may have side effects	02:25
LjL	this would stop the virus from binding because they're all already bound	02:26
LjL	2) inject a lot of "fake" ACE2 receptors that don't lead to cells, and ideally, that bind to the COVID virus more tightly than real ones	02:26
LjL	2 is what that study does	02:26
de-facto	but with all that, what happens with the virions that are cluttered with the artificial ACE2 or nanobodies or such?	02:26
LjL	pwr22, yes alright, i'm trying to untangle the various things we're all meaning now because i'm not sure we mean the same :P	02:26
de-facto	are they marked for trash by that?	02:26
nixonix	surface proteins get recycled every now and then. so its doable. maybe a nanoparticle with mrna for it, and another for reverse transcriptase, and there you go, a human with new ace2 that sars2 doesnt like	02:26
pwr22	LjL: 1) ACE2 inhibitors stop angiotensin binding to ACE2 without activating ACE2	02:26
de-facto	do they get digested by macrophages or such?	02:27
nixonix	needs to get it distributed wide enough	02:27
pwr22	Injecting a bunch of angiotensin would do the opposite	02:27
pwr22	But yeah, I do wonder if they competitively inhibit and then you'd think they'd prevent covid	02:27
LjL	pwr22, okay. and it also sounds like a terribad idea unless maybe as a very last extreme meaasure	02:27
pwr22	Which I would have thought we would have figured out by now, i.e. do BP drugs stop covid?	02:27
de-facto	antibodies have a "flag" on the other side that marks the virion to be get disposed of by the immune system	02:27
pwr22	Probably a better avenue than ivermectin	02:27
pwr22	To research I mean	02:27
nixonix	ace2 on surface, depends whats on the other side if immune cells are interested or not	02:28
pwr22	Doh, probably should ignore me	02:28
ublx	pwr22: right. having just learned that ACE2 circulates in plasma (in addition to being in practically every tissue everywhere), and does so in higher levels in diseased individuals (including during covid infection, where circulating ACE2 is apparently a good predictor of severity and outcome), i supposed that this circulating material must be.. is recombinant the right word here? ... thusly	02:28
ublx	introducing the possibility of engineered decoy ACE2 replacing natural type as long as dosing continued. i was just wondering how concerning that would be	02:28
pwr22	"activating ACE2" would mean converting antiotensin somehow so what I said isn't super accurate but yeah more angiotensins probably not great	02:28
nixonix	you could add something like Fc end of IgA and see if those ab mediated effector functions would get macrophages interested	02:28
nixonix	or nk cells etc	02:28
LjL	pwr22, i don't know, it's... puzzling... because very early on, everyone was talking about BP drugs of various kinds helping against COVID, potentially, but then it all died down, and i never really quite got an "it died down because we've unequivocally established it doesn't work, period" message. instead it was like, telling people not to take ACE2 inhibitors (and there was something else related too that escapes me now) because it wasn't proven to help and	02:29
LjL	might be dangerous, but... why did the research on this die down? i don't know	02:29
nixonix	i mean IgG (no such functions assumed with IgA, but not confirmed i think)	02:29
pwr22	ublx: I suppose it depends on whether it is "there is more ACE2 because it is causing problems" or "there is more ACE2 because of problems and they are attenuating them"	02:29
pwr22	I'm not sure we really have that level of understanding of things at this level in general ☹️	02:29
pwr22	We are probably learning a lot because of covid that might reap benefits down the line	02:30
LjL	pwr22, i actually remember that was one of the earliest things on which i was confused, because at first i was glad of the ACE2 news because my parents were taking this kind of medications, but then some other study or something said they may make COVID worse. it would be nice if such "early" things were now clearly established	02:30
ublx	smoking causes proliferation of ACE2, so i wager the latter	02:30
nixonix	they would go to liver anyway, for enzymes to break, after awhile	02:30
pwr22	ublx: I bet a bunch of people with essential hypertension also have elevated ACE2 that are otherwise healthy?	02:30
ublx	yes	02:31
LjL	(maybe they are clearly established, just quietly, and they don't make news when it's "well, they do nothing")	02:31
pwr22	You can't pick one thing in a vacuum and draw a definitive conclusion 🤦‍♂️	02:31
pwr22	Doh, I misunderstood you I think ublx sorry	02:31
pwr22	But I still dunno	02:32
ublx	you can suppose that disease states go hand in hand with oxidative stress, which ACE2 is involved in regulating	02:32
pwr22	Smoking causes a lot of stuff - there's like a billion compounds in it	02:32
LjL	sometimes taking something that binds to something makes you feel better about your something, but then your body sees there is a lot of binding, so it makes more of the something to be bound to, and then the something that binds to it cease having its beneficial effect, unless you take more of it	02:32
LjL	i'm sure you know what i mean	02:32
ublx	i offered smoking as a very obvious example of such a stress	02:32
pwr22	Smoking also raises BP, which is associated with ACE2 inhibitors reducing it	02:33
nixonix	ace inhibitors prob, or ARB, not ace2. they found they didnt make symptoms worse	02:33
pwr22	So does more ACE2 / angiotensin increase BP / does it decrease it / is it caused by BP / smoking / something else?	02:33
nixonix	and might even be beneficial as a treatment	02:33
nixonix	.title https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00303-5/fulltext	02:33
Brainstorm	nixonix: From www.thelancet.com: The Lancet \| The best science for better lives	02:33
pwr22	We don't know, we only have correlative data	02:33
LjL	nixonix, ARB, right, ARB was the other thing often being discussed "at first" together with ACE2 inhibitors, i think	02:33
LjL	%links ARB	02:33
Brainstorm	LjL, https://survstat.rki.de/Content/Query/Create.aspx (SurvStat@RKI 2.0) lets you create arbitrary queries on official German case data, with the query format described https://survstat.rki.de/Content/Query/Main.aspx (here)	02:33
LjL	clearly not zat	02:34
pwr22	ARBs block the stuff that angiotensin bind to or something?	02:34
ublx	ACE2 is a vasodilator. it's not going to increase blood pressure	02:34
nixonix	there was stuff in media they might be bad, but it was quickly corrected (or found out, they werent)	02:34
LjL	pwr22, i have Absolutely No Idea	02:34
LjL	but they were being discussed	02:34
pwr22	ublx: Why does blocking it decrease blood pressure then?	02:34
ublx	it doesn't?	02:34
pwr22	It does	02:34
pwr22	I take ACE 2 inhibitors	02:34
pwr22	for my blood pressure	02:34
nixonix	wiki for renin-angiotensin system	02:34
pwr22	it makes it lower	02:34
LjL	nixonix, oh it's nice that this starts with "Early in the Covid-19 pandemic, concern abounded..." so it's recent and goes back to the old concerns, for once	02:35
ublx	pwr22: not ACE inhibitors?	02:35
pwr22	ACE and ACE2 inhibitors both are used	02:36
pwr22	I took an ACE inhibitor, it game me flu symptoms for 6 months	02:36
pwr22	With a cough	02:36
LjL	sounds ncie	02:36
pwr22	So when I came off that I went onto a ACE2 inhibitor	02:36
LjL	and ARBs... whatever they do, are they used more or less for the same stuff?	02:37
ublx	pwr22 must be captured and studied for science	02:37
ublx	:p	02:37
nixonix	they block a receptor for ang-II	02:38
nixonix	but the effect is similar to balance i think. used more nowdays i read	02:38
pwr22	ublx: they've already tried	02:38
pwr22	Ah, I am wrong in my understanding then?	02:38
pwr22	I vaguely recall coming to that conclusion before but helpfully not actually changing my knowledge 🤦‍♂️	02:39
pwr22	In which case sorry ublx	02:39
ublx	well it's my understanding that ACE2 UPregulation is contemplated for the treatment of various disease including hypertension	02:41
nixonix	i dont really find ace2 inhibitors used for some medical issue. as a research tool, and potentially tested for sars2, but with quick googling i think thats it	02:41
nixonix	can you give the name of the drug?	02:41
pwr22	What I called ACE2 blockers are ARBs	02:41
pwr22	For a start	02:41
pwr22	And ACE inhibitors block ACE, not ACE 2	02:41
pwr22	So I'm learning something (again) 😛	02:41
LjL	aaaaah right now i'm also getting vague memories of someone telling me that "ACE2 blockers" and "ACE2 inhibitors" were not the same thing	02:42
LjL	make of that what you will	02:42
nixonix	i dont think thats accurate. but since i read about those over a year ago, maybe my memory doesnt serve	02:42
LjL	lol freenode/##covid-19/2020-03-28.log:[04:35:06] <LjL> ryouma, i'm really confused about the various ACE2-like receptors, and difference between inhibitors and blockers	02:43
LjL	this is all 2020 in a loop	02:43
pwr22	Seems angiotensin 2 is a vasocontrictor, so my ARBs are vasodilators	02:43
LjL	freenode/##covid-19/2020-04-19.log:[04:13:15] <LjL> Toadisattva, some of the ACE2 "stuff", and i specifically refrain from calling them inhibitors, blockers or ARBs or something else because at this point i've completely lost track, were tentatively shown to be good, then tentatively shown to be actually quite bad	02:43
pwr22	LjL: yeah I hoped this stuff would get made clearer but I'm convinced there's like 6 people in the world who understand it	02:44
pwr22	Like how only like 6 people understand how X11 works	02:44
pwr22	I recall those quotes 😛	02:44
LjL	and yuriwho probably understood a fair bit but he had the bright idea to die :(	02:45
LjL	pwr22, i don't, which is a bit depressing	02:45
pwr22	nixonix: ACE inhibitors block conversion of Angiotensin 1 to Angiotensin 2. ARBs block Angiotensin 2 from binding to one of it's receptors	02:45
ublx	probably ACE2 and AT-II both having 2 in their name doesn't help with confusion	02:45
pwr22	AT-I + ACE2 = ACE2 + AT-II	02:46
nixonix	yeah, but you didnt say that above	02:46
pwr22	> And ACE inhibitors block ACE, not ACE 2	02:46
pwr22	That wasn't wrong though, or inaccurate	02:46
pwr22	and what I was calling ACE 2 inhibitors are actually ARBs	02:46
pwr22	So it is what I said above unless I was misunderstood	02:47
pwr22	In which case, whatever	02:47
pwr22	Above above above I was wrong yeah, I already said that	02:47
pwr22	<ublx> "well it's my understanding..." <- Wouldn't more ACE2 mean more AT-2 which would be bad for hypertension?	02:48
ublx	i swear i'm not getting paid by medcram, but go to 7min49secs for diagram and commentary which struck me as excellent intro survey of ACE2's place in this corner of inflammation network: https://www.youtube.com/watch?v=1vZDVbqRhyM	02:48
Brainstorm	New from r/WorldNews: worldnews: France awards citizenship to 12,000 health workers battling country's Covid crisis → https://is.gd/wXpPfG	02:51
pwr22	> AT-I + ACE2 = ACE2 + AT-II	02:53
pwr22	Oh ffs I wrote the wrong thing again	02:53
pwr22	That should have been ACE not ACE2	02:53
pwr22	ffs	02:53
nixonix	no, it goes the other way, it converts ang-2 to ang-1.7, and the effect is vasodilating	02:53
nixonix	ang-II	02:53
pwr22	%tell nixonix I was going from https://en.wikipedia.org/wiki/ACE_inhibitor which says "Therefore, ACE inhibitors decrease the formation of angiotensin II, a vasoconstrictor, and increase the level of bradykinin, a peptide vasodilator."	03:00
Brainstorm	pwr22, I'll pass nixonix your message when they are around.	03:00
pwr22	yay I did it right	03:00
pwr22	%tell nixonix This would also seem to fit with the vasoconstriction / bp increasing from it https://en.wikipedia.org/wiki/Vasopressin	03:05
Brainstorm	pwr22, I'll pass nixonix your message when they are around.	03:05
pwr22	%tell nixonix And this page too "Angiotensin II acts on the central nervous system to increase vasopressin production, and also acts on venous and arterial smooth muscle to cause vasoconstriction." https://en.wikipedia.org/wiki/Angiotensin#Angiotensin_II	03:05
Brainstorm	pwr22, I'll pass nixonix your message when they are around.	03:05
pwr22	%tell nixonix Before that sentence we have "Angiotensin I is converted to angiotensin II (AII) through removal of two C-terminal residues by the enzyme angiotensin-converting enzyme (ACE), primarily through ACE within the lung (but also present in endothelial cells, kidney epithelial cells, and the brain). "	03:06
Brainstorm	pwr22, I'll pass nixonix your message when they are around.	03:06
pwr22	I dunno what to say, its vasoconstrictive man	03:07
ublx	what is, AT-II?	03:08
Aidhan	Med nerds! Yay	03:12
pwr22	ublx: I mean angiotensin-2 https://en.wikipedia.org/wiki/Angiotensin#Angiotensin_II	03:26
pwr22	I think AT-2 may actually be the receptor for it	03:26
pwr22	%tell nixonix I don't disagree with anything you said about Ang(1-7) btw, was just talking about angiotensin 2 instead 😛	03:27
Brainstorm	pwr22, I'll pass nixonix your message when they are around.	03:27
ublx	i think the three of us were talking at crossed purposes the entire time	03:28
pwr22	Yes I also think that 😛	03:36
pwr22	I also was talking at crossed purposes from my self	03:36
pwr22	Which doesn't help 😀	03:36
Aidhan	Where’s my aldosterone lovers at	03:36
Brainstorm	New from Eric Topol: @EricTopol: At the US pandemic peak, when there were no vaccines, we averaged 3,300 deaths per day. Somehow, with a Florida backlog, we managed to reach that unthinkable level again today.At a time when nearly all deaths are preventable. → https://is.gd/nWhULY	03:43
Brainstorm	New from r/WorldNews: worldnews: Cuba begins vaccinating children as young as two for Covid-19 → https://is.gd/3CdNQY	03:54
chile09[m]	yikes	03:56
chile09[m]	2 years old	03:56
Brainstorm	New from Politico: Declassified: How to fool anti-vaxxers into getting the coronavirus jab → https://is.gd/oUEbaZ	04:36
de-facto	.title http://biorxiv.org/content/10.1101/2021.09.09.459577v1	04:48
Brainstorm	de-facto: From biorxiv.org: A virus-encoded microRNA contributes to evade innate immune response during SARS-CoV-2 infection \| bioRxiv	04:48
de-facto	.tell nixonix http://biorxiv.org/content/10.1101/2021.09.09.459577v1 "A virus-encoded microRNA contributes to evade innate immune response during SARS-CoV-2 infection"	04:49
Brainstorm	de-facto, I'll pass nixonix your message when they are around.	04:49
Brainstorm	New from r/WorldNews: worldnews: India evicted 21 people every hour during COVID between March '20 and July '21: Advocacy group → https://is.gd/Jbj1Jp	05:28
Al2O3	http://reisenweber.net/irclogs/freenode/__covid-19/	05:47
foo	Has anyone seen any reports/studies on long-covid being more of an issue with the Alpha variant and less so with the Delta variant?	05:51
Brainstorm	New from r/WorldNews: worldnews: 74% Of Fully Vaccinated COVID-19 Cases In Philippines Received SinoVac Vaccine → https://is.gd/jX82Oo	06:10
Brainstorm	New from The Indian Express: World: Popular vaccination minister Kono to enter race for Japan’s next leader → https://is.gd/MUjxFI	07:02
Brainstorm	New from r/WorldNews: worldnews: Data shows the U.S. is the world’s largest Covid vaccine donor → https://is.gd/q0Xt8g	07:23
Brainstorm	New from r/WorldNews: worldnews: Ardern secures 250,000 Pfizer doses from Spain as New Zealand records 13 new cases → https://is.gd/FHuCY1	07:54
Brainstorm	New from The Lancet (Online): [Comment] A new strategy for health and sustainable development in the light of the COVID-19 pandemic: To build a post-pandemic future, in which everyone's health is protected and promoted, what can we learn from the events of the COVID-19 pandemic and previous crises? The Pan-European Commission on Health and Sustainable [... want %more?] → https://is.gd/HrEVPw	08:04
Brainstorm	New from WHO Euro: The COVID-19 pandemic calls for urgent reform of health care, surveillance and governance in the WHO European Region and beyond: "We can’t allow another pandemic to bring the world to its knees and must do everything in our power to prevent a catastrophe on the same scale from happening again. That’s why I have convened the [... want %more?] → https://is.gd/Ep3fkq	08:25
Brainstorm	New from The Indian Express (Health): Health: Covid vaccine potentially benefits mental health, a study finds → https://is.gd/j1weyB	09:07
Brainstorm	New from EMA: What's new: Medicine: Veterinary medicines European public assessment report (EPAR): Vectormune FP ILT, Fowlpox and avian infectious laryngotracheitis vaccine (live, recombinant), Date of authorisation: 09/12/2020, Status: Authorised → https://is.gd/ZoJhjT	09:17
Brainstorm	New from Science-Based Medicine: The Pro-Vaccine Test: When it comes to children and COVID-19, certain doctors seem unwilling to acknowledge negative information about the virus and positive information about the vaccine. Can they pass the pro-vaccine test? The post first appeared on Science-Based Medicine . → https://is.gd/VwWhXc	09:39
Brainstorm	New from r/WorldNews: worldnews: Denmark lifts all covid restrictions, with 73% of the population fully vaccinated → https://is.gd/vyuR2g	10:34
Brainstorm	New from StatNews: Any qualms about an extra Covid vaccine dose? STAT readers respond: We asked STAT readers if they had qualms about getting an extra Covid vaccine dose before many in the world had their first. Here’s what they had to say. → https://is.gd/jwIl5g	10:45
Brainstorm	New from StatNews: Opinion: Covid-19 trauma complicates the 9/11 ‘anniversary effect’: Just as people had to process trauma following 9/11, they will need to work toward recovery and resilience in the wake of the Covid-19 pandemic. → https://is.gd/Y0oFjx	10:56
jokoon	question: cant the mRNA vaccine work on animals?	11:13
gry	jokoon: probably yes	11:20
jokoon	I've read that deers carry the virus	11:21
Brainstorm	New from r/WorldNews: worldnews: Daily Covid-19 cases likely to soon exceed 1,000, next 2-4 weeks crucial for Singapore → https://is.gd/QwfcXw	11:50
Brainstorm	New from r/WorldNews: worldnews: Ivermectin: Australian regulator bans drug as Covid treatment after sharp rise in prescriptions → https://is.gd/hXOBsn	12:00
Aidhan	People will find a way	12:18
Brainstorm	New from Reddit (test): China_Flu: Health Ministry releases portion of vaccine data shared with Pfizer → https://is.gd/9Xj3JN	12:44
Brainstorm	New from ECDC: Data on country response measures to COVID-19: This downloadable data file contains information on non-pharmaceutical interventions (or response measures) that countries in the EU/EEA have reported to date. → https://is.gd/6BvFYG	13:16
Brainstorm	New from Shane Crotty: @profshanecrotty: Topics we chat on the latest TWiV w/@profvrr:🔵 Hybrid immunity = infected + vaccinated. Why so great? 🔵 Best time interval for vaccination?🔵 Why germinal centers and memory B cells?🔵 Types of protective immunity to COVID🔵 What about boosters?https://www.youtube.com/watch?v=nEB4oxO9F1A → https://is.gd/jR9y8w	14:18
Brainstorm	New from Eric Topol: @EricTopol: Why Biden's 6-point covid plan is "a tepid half measure," missing critical componentshttps://www.washingtonpost.com/opinions/2021/09/09/bidens-six-step-covid-strategy-does-not-go-far-enough-compel-vaccinations/ by @DrLeanaWen @PostOpinions → https://is.gd/RnTVCF	14:50
specing	does any country have mandatory vaccination, yet?	14:55
dTal	as far as I am aware there are no countries which make vaccination unconditionally compulsory for all citizens	15:04
dTal	there are plenty of places where you need to be vaccinated to do certain things	15:05
de-facto	afaik some have it mandatory for healthcare workers etc	15:06
Brainstorm	New from Derek Lowe: @angie_rasmussen: RT by @Dereklowe: Co-sign Dr. Kamil’s take here. The vaccines are not selecting for immune-evasive variants and that’s abundantly clear. Ignore anyone who says otherwise, particularly those who lead consulting groups who profit from this misinformation. → https://is.gd/NytnIA	15:11
Brainstorm	New from Eric Topol: @EricTopol: The UK's mix and match booster programhttps://www.ft.com/content/a03b8c21-7412-460f-9196-8c41ac80c6eb @SebastianEPayne @SarahNev @HannahKuchler @mroliverbarnes The data are clear for an enhanced immune response for AZ first, then Pfizer/mRNA (cf 2 doses of either). I haven't seen data to support the reverse sequence. → https://is.gd/Z6UN1C	15:22
Brainstorm	New from FDA Press Releases: FDA Will Follow The Science On COVID-19 Vaccines For Young Children: FDA leadership outlines steps the FDA will take to ensure the safety and efficacy of COVID-19 vaccines for young children → https://is.gd/HCqyH9	15:33
Brainstorm	New from Eric Topol: @EricTopol: How to reduce covid in kids?State data on adult vaccinationhttps://nytimes.com/interactive/2021/09/09/us/covid-children-cases-icu.html… by @LaurenLeatherby@amyswalk @nytgraphics San Francisco data via @AnaCabrera: NO outbreaks → https://is.gd/QTcjxe	15:54
Brainstorm	New from r/WorldNews: worldnews: Teenage boys more at risk from vaccines than Covid → https://is.gd/8KKPAC	16:05
specing	I've read somewhere that *carditis is 25/1e6 for 18-25 male age group	16:14
Brainstorm	New from Eric Topol: @EricTopol: R to @EricTopol: More exhibits, based on latest @PHE_uk report data for unvaccinated and fully vaccinatedLog-plot of case fatality rate by @EdConwaySky Cases, hospitalizations and deaths by @PaulMainwood Latter shows some vulnerability to breakthrough disease for 60+ age → https://is.gd/TMPIVM	16:26
ELEPICNoob[m]	Which is the safest vaccine?	16:32
Raf[m]	which ones are you talking about?	16:36
Raf[m]	J&J/BioNtech/Moderna? or others?	16:36
Brainstorm	New from Virological.org: Latest posts: High rate of mutational events in SARS-CoV-2 genomes across Brazilian: See this study revised and published in Viruses Journal: Viruses \| Free Full-Text \| High Rate of Mutational Events in SARS-CoV-2 Genomes across Brazilian Geographical Regions, February 2020 to June 2021 . → https://is.gd/QcCoX3	16:37
Brainstorm	New from Eric Topol: @EricTopol: “For the first time since the Delta variant, the reproduction rate is dropping. The percentage of positive tests is also declining. The morbidity rate has shifted from spreading to stopping.”—@NitzanHorowitz@IsraelMOH 👍 → https://is.gd/8IhOyU	16:58
Raf[m]	the 3 major vaccines in the US are mostly safe. Jansen had some bad press about several clotting cases. mRNA vaccines in general had some cases of heart inflammation. incidence of either of those reports is very low	16:59
Raf[m]	moderna has the "COVID arm", but it's also probably the most effective of the 3	17:00
Brainstorm	New from ClinicalTrials.gov: (news): PMMA vs Polysulfone in SARS-CoV-2 Infection Hemodialysis Patients → https://is.gd/mooIom	17:08
Brainstorm	New from ClinicalTrials.gov: (news): Evaluation of the Impact of the Administration of Single Dose of Ivermectin in the Early Phase of COVID-19 → https://is.gd/LKDBAW	17:19
Raf[m]	Brainstorm: darn no results posted	17:21
Brainstorm	New from ClinicalTrials.gov: (news): EP-7041 for Treatment of Thromboprophylaxis in Patients Managed in Intensive Care Settings for COVID-19 Syndrome → https://is.gd/KeVwnS	17:40
purplesail[m]	%cases World	17:49
Brainstorm	purplesail[m]: Sorry, World not found. Either there aren't cases, or it's under a different name.	17:49
purplesail[m]	%cases planet	17:49
Brainstorm	purplesail[m]: Sorry, planet not found. Either there aren't cases, or it's under a different name.	17:49
purplesail[m]	%cases world	17:50
Brainstorm	purplesail[m]: Sorry, world not found. Either there aren't cases, or it's under a different name.	17:50
Brainstorm	New from ClinicalTrials.gov: (news): A Pilot Study of a PhysiOthErapy-based Tailored Intervention for Long Covid → https://is.gd/6MSKXs	17:51
purplesail[m]	%cases Germany	17:58
Brainstorm	purplesail[m]: Germany has had 4.0 million confirmed cases (4.8% of all people) and 92641 deaths (2.3% of cases) as of 6 days ago. 68.3 million tests were done (5.8% positive). 54.5 million were vaccinated (65.6%). +11377 cases since 23 hours ago. See https://corona.rki.de/ or https://corona-data.eu/en/	17:58
Brainstorm	New from ClinicalTrials.gov: Abbott ID NOW COVID-19: Conditions : Covid19; SARS-CoV-2 Infection → https://is.gd/AeMMr4	18:23
Brainstorm	New from r/WorldNews: worldnews: Cuba begins vaccinating children as young as two for Covid-19 → https://is.gd/U5Espd	19:06
Klinda	is this channel pro vaccine or against	19:20
ecks	this generally believes in science	19:24
ecks	this channel*	19:24
Brainstorm	New from r/WorldNews: worldnews: Unvaccinated people were 11 times more likely to die of covid-19, CDC report finds → https://is.gd/hotkVj	19:27
nixonix	^ that tells nothing. need to know used vaccine, dose interval, time from the last dose etc	19:28
specing	Just 11 times more likely, huh?	19:32
nixonix	it would be over 90% on average. i didnt check the article, did it say if it was from the last few weeks, or over the whole year?	19:35
nixonix	but that ONS report, which showed no VE vs identified infection for 40-79 yo, and very little for 80+ yo. something was obviously wrong, because ofc there is some protection. raw unadjusted data can show strange things	19:37
Brainstorm	New from Eric Topol: @EricTopol: 3 new @CDCMMWR reports today provide very strong reassurance of vaccination benefits vs Delta and point toward a potential edge of @Moderna_tx for real-world effectiveness [... want %more?] → https://is.gd/a0EYXz	19:37
nixonix	sorry, it was PHE report	19:38
nixonix	couple people then questioned PHE's age group sizes as denominators and calculated their own diagrams using ONS data on them. but which one is correct, or neither?	19:39
nixonix	anyways, both were wrong. and i wasnt smart enough to notice the big bias, because i was involved here, trying to find some brit to take responsibility of PHE hiding that waning information...	19:40
nixonix	the problem with age groups 18-69 was, they contained lots of hcw and social care workers, that were vaccinated among the first ones. so waned because of that	19:41
nixonix	so we can only look at 70+ yo with any accuracy on VE, from that raw data	19:42
nixonix	using PHE's denominator, the VE vs identified infection would be zero for 70-79	19:43
nixonix	but using ONS's age group information as a denominator, there's a tweet:	19:44
nixonix	.title https://twitter.com/PaulMainwood/status/1436073744590639105 theres a diagram with numbers	19:45
Brainstorm	nixonix: From twitter.com: Paul Mainwood (@PaulMainwood): "Cases, hospitalisations, death PHE graphs redone with ONS 2020 denominators. Implicit VEs for death and hospitalisation coming out at similar (90%) levels to the PHE [...]	19:45
nixonix	VE for identified infections for 70-79 would be 26.2%. i checked when they got the 2nd dose, and it was in april, around 4 months before those weeks 32-35	19:48
nixonix	so for that age group, mostly with 12 week interval, lots of them apparently got AZ in that age group, VE left was that. or less, if PHE's denominator was closer to right	19:49
nixonix	but with pfizer its prob a bit better, because higher IgG. and with moderna, possibly way better	19:50
nixonix	pfizer's 3rd dose gives 4x higher neut titers for 99.5%, which means around two months more time than the 2nd dose for infection. for severe, ICU and deaths, who knows	19:52
Klinda	all are you saying you are a medic or just a normal guy as me?	19:56
nixonix	sorry, 4x68 days would mean around 5 months more time than after 2nd, yay! pfizer	19:56
nixonix	just a nerd	19:56
nixonix	closer to 4.5 months, if pfizers information is correct, and it mostly depends on IgG titers	19:58
Brainstorm	New from WebMD: New Tally Adds 16,000 Nursing Home Residents Lost to COVID: A new study suggests COVID-19 in U.S. nursing homes appears grossly underestimated because federal guidelines did not require nursing homes to report cases and deaths until May 24, 2020 -- months after the pandemic began. → https://is.gd/qO3EDZ	19:59
nixonix	according to IHME's estimate, they still miss close to 400k deaths or something, in usa. unless they have updated their estimate	20:03
anniea	nixonix: can one do 1st 2 jabs BNT, and booster Moderna?	20:06
nixonix	depends on country i guess. but modernas booster is only 50 mcg. and since pfizer has better codone optimization, maybe that booster is on par with pfizer then	20:08
nixonix	.title https://twitter.com/EricTopol/status/1436385801852506113 if this was adjusted right, it looks like moderna is double potent compared to pfizer, and didnt it have double neut titers, if i recall (but using 4 weeks vs 3 in pfizer)	20:09
Brainstorm	nixonix: From twitter.com: Eric Topol (@EricTopol): "The Table from 5 @DeptVetAffairs medical centers report which replicates the above for the potential Moderna advantage [...]	20:09
nixonix	when looking at (1 - VE)	20:09
imaginary	.title https://twitter.com/michaelzlin/status/1436393327604105218	20:23
Brainstorm	imaginary: From twitter.com: Michael Lin, PhD-MD (@michaelzlin): "And there you go New CDC stuy shows best estimate of J&J efficacy vs Delta hospitalization is 60% This is worse than 80% for Pfizer and 95% for Moderna [...]	20:23
imaginary	yikes that CI	20:23
imaginary	this is more inline with what iw as expecting of the j&j vaccine	20:23
nixonix	.title https://twitter.com/EricTopol/status/1436384706849697795 seems similar as in israel, pfizer waning vs hospitalization to 80% in 4 months or maybe a bit over (i checked from owid their 2nd dose times, as i did for uk for above results)	20:29
Brainstorm	nixonix: From twitter.com: Eric Topol (@EricTopol): "The Table from the report on vaccine effectiveness from 9 state analysis for reduction in emergency department, urgent care, and hospitalizations [...]	20:29
nixonix	moderna was slower in the beginning, if i recall, so if they didnt consider it and adjusted for that, maybe moderna's result would be slightly closer to pfizer, than in the table	20:30
nixonix	but still looking way stronger vs hosp too	20:31
anniea	nixonix: so you would take a booster if offered? of pfizer	20:31
nixonix	because moderna is only 50 mcg, prob not much difference	20:31
Klinda	I did pfizer two doses, in 30 days interval, kinda	20:32
Raf[m]	nixonix: I thought moderna was 100 mcg	20:33
nixonix	ah, booster, yeah sure. in 4 months from the 2nd if they just let me. i thought you asked moderna or pfizer	20:33
Raf[m]	oh I don't know anything about boosters	20:33
nixonix	"Moderna said it submitted initial data for the use of a 50-microgram booster dose of its two-shot vaccine	20:33
Raf[m]	i think the original shots were 30 mcg for pfizer and 100 mcg for moderna	20:33
Raf[m]	gotcha	20:33
nixonix	first two were those. booster just 50	20:34
anniea	nixonix: I was , but then just in general, I've heard some talk that booster isn't going to add much	20:35
Klinda	the third dose only to over 80 and compromised immune system	20:35
Klinda	in my country	20:35
anniea	I'm already about 7 months post 2nd pfizer	20:35
nixonix	it does 4-fold your neut ab titers compared to 2nd. (and way more compared to what you have left when its offered)	20:36
nixonix	pfizer. moderna, prob something similar, who knows	20:36
nixonix	since there seems to be some booster hesitancy, maybe a bit shilling is allowed:	20:38
nixonix	.title https://twitter.com/ChristosArgyrop/status/1426894575252037632	20:38
Brainstorm	nixonix: From twitter.com: ChristosArgyropoulos MD, PhD (Green Chili Check) (@ChristosArgyrop): "Mild memory loss, mild spongiform changes... stop inhaling PCR cycler fume without being one of the Gigavaxxed" \| nitter	20:38
nixonix	check the meme below that too (carl barks, i think)	20:40
Brainstorm	New from Politico: Coronavirus: Ex-French health minister under investigation over handling of coronavirus → https://is.gd/IS6Rg1	20:41
nixonix	"Early onset dementia is a feature not a bug. You will forgot all the stupid shit they told you before getting sick"	20:42
nixonix	^^ i think they started in italy even earlier	20:42
specing	Klinda: in my it seems to be available to everyone	20:48
nixonix	.title https://www.cdc.gov/mmwr/volumes/70/wr/mm7037e1.htm?s_cid=mm7037e1_w check graphs from page 5 of the pdf	21:00
Brainstorm	nixonix: From www.cdc.gov: Monitoring Incidence of COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Status â 13 U.S. Jurisdictions, April 4âJuly 17, 2021 \| MMWR	21:00
nixonix	but it stops till 3 weeks ago. and the earliest vaccinees include all above 65 yo, some of them got the 2nd dose just 2-3 months before that date, so for some of them didnt wane so much yet	21:01
nixonix	hospitalization curves for over 65 yo	21:01
nixonix	the right end means the latest date, 3 weeks ago	21:01
nixonix	death curve doesnt look much better. small sample, so needs more confirmation. but hospitalizations looks similar waning than in israel and in uk	21:03
nixonix	breakthrough case data from usa is unreliable, because they are not registered usually, and many ppl with mild symptom breakthroughs (or asymptomatic) are not registered or even tested	21:05
nixonix	not all delta prob yet, on week ending july 17	21:06
Brainstorm	New from r/WorldNews: worldnews: France's new travel restriction bans unvaccinated US tourists → https://is.gd/b8NGvn	21:13
nixonix	.title https://www.cdc.gov/mmwr/volumes/70/wr/mm7037e3.htm?s_cid=mm7037e3_w	21:15
Brainstorm	nixonix: From www.cdc.gov: Effectiveness of COVID-19 mRNA Vaccines Against COVID-19âAssociated Hospitalization â Five Veterans Affairs Medical Centers, United States, February 1âAugust 6, 2021 \| MMWR	21:15
nixonix	VE for hospitalizations on later periods: "The estimated vaccine effectiveness among persons aged ≥65 years (79.8%; 95% CI = 67.7%–87.4%) was lower than among persons aged 18–64 years (95.1%; 95% CI = 89.1%–97.8%)"	21:16
nixonix	which is no wonder, since >65 yo got their vax earlier	21:16
anniea	nixonix: I'm hearing >10% of hospitalizations are vaccinated in some form	21:21
nixonix	that ratio alone doesnt necessarily tell anything, since if everybody was vaccinated, 100% of cases, hospitalizations and deaths would be among vaccinated	21:23
Brainstorm	New from COVID19 Vaccine Tracker: Andy Becker: Altimmune Inc: AdCOVID → https://is.gd/bnKPpU	21:24
nixonix	.title https://www.medrxiv.org/content/10.1101/2021.08.06.21261707v2 this is v2	21:33
Brainstorm	nixonix: From www.medrxiv.org: Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence \| medRxiv	21:33
Brainstorm	New from COVID19 Vaccine Tracker: Andy Becker: AnGes: AG0302-COVID19 → https://is.gd/vxnUZO	21:35
nixonix	.title https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3874014	21:38
Brainstorm	nixonix: From papers.ssrn.com: Safety and Immunogenicity Report from the Com-COV Study – a Single-Blind Randomised Non-Inferiority Trial Comparing Heterologous And Homologous Prime-Boost Schedules with An Adenoviral Vectored and [...]	21:38
nixonix	i dont think that proves, 2*mrna and then az or jnj as a third would be worse than mrna as a third, since that chinese vector vaccine in that study is so weak	21:39
nixonix	or is that ChAd AZ? yet another name...	21:40
nixonix	just 10% neut titers, 2ChAd (AZ) vs 2pfizer, in their assay! is that real?	21:45
Brainstorm	New from Eric Topol: @EricTopol: More on the 3 CDC reports Benefit data are summarized in🧵👇They converged on reduced vaccine effectiveness vs hospitalization in people over age 65 (10-15% points). And fairly early into the Delta wave + time from vaxx These findings provide support for a 3rd shot in ≥ 65 yrs → https://is.gd/b8X51D	21:45
nixonix	and that was in shorter time than 4 months	21:48
nixonix	if its confirmed that 2*az has only 10% of neut IgG compared to pfizer, it prob gets more protection from killer t-cells then. maybe they wane slower with az's dna vaccine	21:51
de-facto	nixonix, i found http://biorxiv.org/content/10.1101/2021.09.09.459577v1 "A virus-encoded microRNA contributes to evade innate immune response during SARS-CoV-2 infection" related to https://www.biorxiv.org/content/10.1101/2021.09.08.459464v1 "SARS-CoV-2 expresses a microRNA-like small RNA able to selectively repress host genes"	21:54
de-facto	not sure if Brainstorm delivered the links to you	21:54
nixonix	yeah, i got 1 link from you. and then some other stuff, i thought ill look at them a bit later when you are around	21:55
nixonix	so much new epidemiological stuff, that i wouldnt even like to follow much, but i guess we need to find out the waning rates	21:56
de-facto	yeah	21:56
nixonix	link me if you remember which papers had neut titer fold reductions, esp for moderna and az (and jnj)	21:57
nixonix	especially at the same paper, more than one brand	21:58
nixonix	but anything goes for moderna, az, jnj	21:58
de-facto	well i already linked a few	21:58
de-facto	!title https://www.nejm.org/doi/full/10.1056/nejmc2103916	21:59
de-facto	.title https://www.nejm.org/doi/full/10.1056/nejmc2103916	21:59
Brainstorm	de-facto: From www.nejm.org: Antibody Persistence through 6 Months after the Second Dose of mRNA-1273 Vaccine for Covid-19 \| NEJM	21:59
de-facto	.title https://www.science.org/doi/10.1126/science.abf4063	21:59
Brainstorm	de-facto: From www.science.org: Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection	21:59
nixonix	in that nejm, live neut is more like 1000 or so, if thats comparable to other papers results, would be similar to pfizer i think	22:01
nixonix	so maybe not that comparable, depends on cells etc	22:01
nixonix	just the waning rates might be	22:02
Brainstorm	New from CIDRAP: US COVID-19 vaccine mandates met with mixed response: Stephanie Soucheray \| News Reporter \| CIDRAP News Sep 10, 2021 In the coming months, two thirds of the US workforce will be mandated to get vaccinated. → https://is.gd/8GfMHk	22:28
Brainstorm	New from Contagion Live: us: Pfizer-BioNTech Expects to Seek Approval for Vaccine for Younger Pediatric Population → https://is.gd/3KRD5f	22:38
Brainstorm	New from Eric Topol: @MCSlab_uiuc: RT by @EricTopol: CDC released a report today on monitoring COVID-19 cases and severity. Vaccines do work! However, once infected, analysis of CDC numbers suggest that the difference in Case hospitalization ratio or case fatality ratio between V and U is not big. @EricTopol @NigelGoldenfeld → https://is.gd/GsFAEB	22:49
nixonix	.title https://www.telegraph.co.uk/business/2021/09/07/covid-booster-jab-campaign-may-not-needed-says-astra-boss/	22:55
Brainstorm	nixonix: From www.telegraph.co.uk: Covid booster jab campaign may not be needed, says Astra boss	22:55
grys	nixonix: it is paywalled.	22:56
nixonix	it works for me. solutions: turn of javascript, if it doesnt help, maybe max article amount or something (remove cookies for the site and/or local storage). or user web archives	22:58
nixonix	.title https://news.sky.com/story/covid-19-astrazeneca-boss-says-booster-jabs-may-not-be-needed-for-everyone-and-widespread-rollout-could-put-extra-pressure-on-nhs-12401704	22:59
Brainstorm	nixonix: From news.sky.com: COVID-19: AstraZeneca boss says booster jabs may not be needed for everyone and widespread rollout could put extra pressure on NHS \| UK News \| Sky News	22:59
nixonix	*user=use	22:59
nixonix	.title https://www.biorxiv.org/content/10.1101/2021.09.09.459634v1 why M does seem to make a big difference?	23:10
Brainstorm	nixonix: From www.biorxiv.org: A thermostable oral SARS-CoV-2 vaccine induces mucosal and protective immunity \| bioRxiv	23:10
nixonix	this is what i call a 2nd gen	23:11
de-facto	.title https://www.cdc.gov/mmwr/volumes/70/wr/mm7037e3.htm	23:11
Brainstorm	de-facto: From www.cdc.gov: Effectiveness of COVID-19 mRNA Vaccines Against COVID-19âAssociated Hospitalization â Five Veterans Affairs Medical Centers, United States, February 1âAugust 6, 2021 \| MMWR	23:11
nixonix	and they deleted the furin site, which is great. we dont like that...	23:13
nixonix	i quoted a piece and commented that above, 2h ago. that veteran hosp paper	23:15
Brainstorm	New from Contagion Live: CDC: Vaccinated People Reduce Risk of COVID-19 Mortality by More Than 10 Times: In a large study looking at incidence rates for hospitalization and mortality, results changed relatively little in terms of vaccine effectiveness, even after the Delta variant became the dominant strain. → https://is.gd/0xqSwp	23:20
nixonix	anybody knows about these: "Additional mutations were inserted in specific variant: Sst1: K986P/V987P; Sst2: T791C/A879C; Sst3: S884C/A893C; Sst4: G885C/Q913C; Sst5: S884C/Q913C	23:26
nixonix	sst1 perhaps proline subs for open confirmation	23:27
nixonix	here is a typo, its 614G. but they use it, which is interesting: wild type strain Swt (NC_045512, original Wuhan variant) all having the D615G and the 682RRAR-685GSAS (modFurinCS) mutations	23:28
Brainstorm	New from CIDRAP: COVID-19 vaccines protect against severe illness during Delta: Lianna Matt McLernon \| News Writer \| CIDRAP News Sep 10, 2021 In the Delta era, unvaccinated people have 10 times the risk of severe COVID-19 than vaccinated people do. → https://is.gd/cXxpPf	23:31
nixonix	.title https://www.pnas.org/content/117/41/25254 one of problens with furin site, perhaps	23:34
Brainstorm	nixonix: From www.pnas.org: Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation \| PNAS	23:34
nixonix	.title https://www.eurekalert.org/news-releases/674497	23:36
Brainstorm	nixonix: From www.eurekalert.org: Antibodies that enhance SARS-CoV-2 infection \| EurekAlert!	23:36
nixonix	that can be called another type of ADE, i think	23:37
LjL	"It is important to analyze not only neutralizing antibodies but also infection-enhancing antibodies. In the future, it may be necessary to develop vaccines that do not induce the production of infection-enhancing antibodies, because infection-enhancing antibodies may be more effective against mutant strains in which neutralizing antibodies are not sufficiently effective," says Professor Hisashi Arase.	23:39
LjL	what does this even mean	23:39
LjL	we don't want to induce them because they are... more effective?	23:39
nixonix	effective in a negative way, when some of the abs are ineffective against more evasive variants	23:40
nixonix	different ADEs might be happening all the time, but prob not very much the way it would mean much	23:41
nixonix	oh yeah, it was adjuvanted too, that oral vax above. and they did animal tests using both oral and iv doses	23:46
LjL	well let's hope current vaccines aren't making subtle ADE-ing antibodies because i'll stop having good arguments against the vaccine skeptics then	23:47
nixonix	like all the VLP vaccines are likely to be. adjuvanted	23:47
nixonix	and killed whole virus vaxes	23:48
nixonix	why vector and mrna vaxes are not? it could improve memory b-cell maturating. the problem is, that adjuvant should last for days somehow probably, even longer with vector vaxes i think. maybe there are solutions, slow releasing capsule or something	23:50
Brainstorm	New from WebMD: Public Reaction to Biden Vaccine Push Varied but Strong: Across social media, supporters and critics of President Joe Biden's new plan to boost American vaccine rates offered sharp opinions. → https://is.gd/fwVudV	23:52
nixonix	.title https://www.science.org/doi/10.1126/sciimmunol.abj2901 OC43	23:56
Brainstorm	nixonix: From www.science.org: Early cross-coronavirus reactive signatures of humoral immunity against COVID-19	23:56

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