Posts

Astrobiology IV: Photosynthesis and energy 2016-10-17T00:30:46.138Z · score: 9 (11 votes)
Astrobiology III: Why Earth? 2016-10-04T21:59:57.716Z · score: 18 (18 votes)
Astrobiology, Astronomy, and the Fermi Paradox II: Space & Time Revisited 2016-03-10T05:19:29.263Z · score: 23 (24 votes)
Astronomy, Astrobiology, & The Fermi Paradox I: Introductions, and Space & Time 2015-07-26T07:38:53.498Z · score: 42 (43 votes)
Irrationality Game III 2014-03-12T13:51:00.555Z · score: 11 (18 votes)

Comments

Comment by cellbioguy on Covid-19 6/18: The Virus Goes South · 2020-06-19T13:53:01.427Z · score: 6 (3 votes) · LW · GW

I can report that at a major southern university we are starting to get plans sent out by administration for a return to in person instruction (!) in mid August (!). They are refusing to mandate masks for students and are planning for way too many in person classes. Another nearby university is forcing faculty to get medical justification for not participating in classrooms.

They've picked their priorities, they'll chew us up and spit us out.

Comment by cellbioguy on If the reproduction number is socially "controlled" to its inflection point 1, what are the ethical and predictive implications? · 2020-06-18T06:28:58.715Z · score: 3 (2 votes) · LW · GW

At first I thought that the soial system implicitly trying to control an exponential with a sensor lag longer than the doubling time would be simply impossible, and there would be wild swings between exploding cases and cratering cases. But then I realized that the dial that is being turned is the doubling time itself, such that near homeostasis the doubling/halving time is extremely long and the delays in the system don't matter as much.


That being said... South Carolina, man. They have entered a new exponential phase with a doubling time of much less than a week and we will get to see quite the excursion. These things still happen when people react faster than the delays in noticing people getting sick.

Comment by cellbioguy on Is a near-term, self-sustaining Mars colony impossible? · 2020-06-05T02:06:03.740Z · score: 5 (3 votes) · LW · GW

You drastically underestimate the difficulty of genetics.

Comment by cellbioguy on Should I self-variolate to COVID-19 · 2020-05-27T05:17:20.462Z · score: 2 (1 votes) · LW · GW

I would be worried about straight up lung, kidney, blood vessel, and heart damage in addition to the already stated chronic fatigue.

Comment by cellbioguy on What aspects of the world emotionally bothers you on an immediate personal level on a daily basis? · 2020-05-24T05:01:10.268Z · score: 6 (4 votes) · LW · GW

The huge amount of unnecessary pesticides around me and the paucity of insect life compared to my childhood. This is a disaster and won't end well.

Comment by cellbioguy on The Greatest Host · 2020-05-12T05:39:01.883Z · score: 7 (4 votes) · LW · GW

Bats sustaining viruses that rip our lungs and blood vessels apart isn't because of population structure, it's because their immune systems are tuned to produce different responses than ours in a way that causes bat viruses to frequently cause messed up responses in other mammals. For reasons that are only just starting to be figured out, their inflammatory responses are turned way the hell down and their interferon responses are turned way the hell up. This means that a virus that has evolved to replicate in them is able to basically completely silence the interferon response of other mammals, being overclocked for the job. If other factors let it actually replicate, this means the early disease goes nearly unnoticed by the innate immune system until viral replication has reached obscene levels and the adaptive immune system becomes involved, in a frequently poorly-regulated response. The viruses are also used to facing a strong innate antiviral response from the start, so they replicate much faster and with more fallout in the absence of that response than one that has reached equilibrium with us would.

---

On another note, the innate immune response of jawed vertebrates has been reshaped by interaction with the adaptive immune response over evolutionary time and cannot be considered in isolation.

Comment by cellbioguy on Nicotinamide riboside and SARS-CoV-2 · 2020-05-10T14:45:41.125Z · score: 2 (1 votes) · LW · GW

To be clear, the work I am speaking of is on enhancing the NAD salvage pathway preventing NAD depletion in stressed neurons. This treatment seems to drastically decrease neuron programmed cell death in response to brain injury, neurodegenerative diseases, and hypoxia.

The mose work showed great promise in brain injury and hypoxia and while it doesn't stop the neurodegeneration from ALS and the like (the underlying damage is being done) the threshold for individual neurons dying is raised, so the mice are healthy for a long time before suddenly falling apart rather than slowly declining.

This is work being done by Calico and by Dr. McKnight. I will provide links when I'm no longer on my phone

Comment by cellbioguy on Nicotinamide riboside and SARS-CoV-2 · 2020-05-06T01:02:15.514Z · score: 3 (2 votes) · LW · GW

There is a whole bunch of work on boosting NAD levels to suppress PARP effects on NAD depletion triggering neuron apoptosis...

Comment by cellbioguy on Nicotinamide riboside and SARS-CoV-2 · 2020-05-05T20:10:34.796Z · score: 5 (3 votes) · LW · GW

I will definitely be having my parents take it if they get sick, and this is just one of the reasons. I can't see how it would hurt acutely and there is a chance it will help acutely.

One of my parents got over cancer 10 years ago though so I am very uncertain about having them take it prophylactically on a chronic basis, especially since they are in a position to very easily nearly completely isolate. Given the biochemistry of NAD supplementation, encouraging nascent tumors to not kill themselves is one of the risks you may take with it.

Comment by cellbioguy on [Link] COVID-19 causing deadly blood clots in younger people · 2020-05-05T19:52:51.464Z · score: 3 (2 votes) · LW · GW

For the most part, all those labels are just labels for where on the tree of all sequences it falls. There is almost no evidence of widespread functional mutants. They're useful for tracking the spread of the virus around the globe.

There is one mutation in the S protein at the root of the European strains that you could *imagine* having an effect on the function of the fusion protein but there is no particularly strong evidence that it's doing much - a little equivocal difference in the measured PCR cycles required for detection from samples, but that could have to do with the fact that they happened at different times when people were getting tested at different disease stages or on different equipment. It is more common more recently relative to the other lineages in Europe and America, but that could very easily just be because it is the only lineage in Italy and once Italy exploded its shrapnel founded a lot of new transmission chains all over Europe and America. It could very easily just be a bottleneck effect having to do with breaking into a new area.

Much more interesting are a few small lineages that have actually lost whole accessory proteins involved in suppressing the innate immune response, but that's a total of like 7 patients found to have them.

Comment by cellbioguy on Should we be reassessing the argument for globalization? · 2020-04-29T16:53:15.338Z · score: 2 (1 votes) · LW · GW

I disagree profoundly with the last sentence.

The process continues when everything is perfect, but shocks undo it. If super-efficiency and super-specialization were optimal, the biosphere would have reached that point long ago.

Instead, everything is robust at the expense of efficiency at multiple levels, from individual cells to networks of ecological interactions. Super-optimized things do evolve, and sometimes spread explosively, but they are almost always shortlived and die out.

Comment by cellbioguy on Should we be reassessing the argument for globalization? · 2020-04-29T00:38:45.604Z · score: 6 (4 votes) · LW · GW

YES.

Smearing supply chains across the world and chasing them to the lowest labor costs and into very specialized locations produces a supply chain that while extremely efficient has zero surge capacity for unusual circumstances, is brittle and liable to lock up at a moment's notice, and requires far too many state actors to not be at cross purposes.

NOTHING in biology is optimized for efficiency. Everything is robust at the expense of efficiency. Everything too efficient yet brittle died off long ago. A potato manages 0.5% conversion of sunlight to starch, nowhere near the theoretical yield of its photochemistry. But if you move it from shade to sun, it doesn't burn up its electron transport chain (which is harder than you'd think for photochemistry!), and if you move it from sun to shade it gets by without starving. If a virus chews up your lungs, you have fat stores to draw on rather than only functional tissue and the capacity to get by on lower lung capacity until the crisis is dealt with and regeneration can happen.

Nothing that has stood the test of time is nearly so centralized and brittle and over optimized as the current global civilization. Regardless of the end effects, things that last will go away from that direction.

EDIT: This does not only apply to international supply chains. Over optimization and over centralization and giganticism of players of the food supply chain has resulted in a system within the US in which is untenable unless everything goes right. Closing restaurants has resulted in farms that only sell to specialized suppliers being unable to get their product into domestic supply lines leading to absurd waste and a few crowded nodes in the meatpacking industry represent both absurdly effective viral breeding grounds and critical points that are threatening to take down large fractions of the domestic meat supply. Other examples abound.

EDIT: One could make the counterargument about how everything on Earth functions as part of an ecology rather than being fully self-sufficient, but ecologies are systems with huge numbers of interacting parts that are interchangeable, not small numbers of super specialized but independent actors. Symbiosis exists but results in loss of individuation once it gets severe enough...

Comment by cellbioguy on [Link] COVID-19 causing deadly blood clots in younger people · 2020-04-28T15:59:02.534Z · score: 6 (4 votes) · LW · GW

NY is the place in America we have the most data, and are most likely to notice less common effects.


It fits with all the autopsy and clinical data that coagulation issues are a major cause of morbidity in severe cases, and the fact that children with non-severe cases are having an anomalously high rate of skin lesions in fingers and toes characteristic of circulation problems.

Comment by cellbioguy on [Link] COVID-19 causing deadly blood clots in younger people · 2020-04-28T13:26:52.038Z · score: 13 (4 votes) · LW · GW

The article seems more of a "this is a thing that's happening" article than a "this is a major cause of death" thing.

Still, it looks like it'll be important to follow recoveries for an increase in circulation issues going forward.

Comment by cellbioguy on Coronavirus: Justified Key Insights Thread · 2020-04-28T13:14:04.993Z · score: 6 (3 votes) · LW · GW

UPDATE as of 4/28/2019.

Others coming to this exact same distribution more rigorously.

https://t.co/51b3bJYg3e?amp=1

Compiling rigorous data, the compatible range is circa 0.5% to 1% with a central tendency of 0.8%.

Comment by cellbioguy on Coronavirus: Justified Key Insights Thread · 2020-04-28T13:10:23.152Z · score: 4 (2 votes) · LW · GW

The effects of measures on the spread take weeks to show up in the data.

If the doubling time hadn't cratered, the hospitalization rate would've remained exponential. At the time of posting it was comparatively flat, and I estimated.

The half came from the fact that it usually takes ~3 weeks to die, that the exponential spread had only stopped a few weeks earlier, and a drawing of a triangle and square representing a rise and flat that I drew a vertical line through.

Comment by cellbioguy on On New York’s Antibody Tests · 2020-04-26T21:13:33.001Z · score: 2 (3 votes) · LW · GW

This fits perfectly with the numbers I have been coming up with based on total deaths (~0.2% of NYC) and infection to fatality ratios that are coming out of many many MANY pieces of GOOD research (rather than the denialists and minimizers getting a LOT of airtime) - 0.5% to 1%.

Comment by cellbioguy on The Chilling Effect of Confiscation · 2020-04-26T21:12:01.504Z · score: 2 (4 votes) · LW · GW

Foolish, yes. This is what happens when parasitic short-term-focused elements take over and blow up a cooperative system. Happens all the time in symbiotic systems with parasites, cheaters, cancer.

Comment by cellbioguy on The Puzzling Linearity of COVID-19 · 2020-04-24T19:48:22.726Z · score: 2 (1 votes) · LW · GW

A constant level of testing, leading to a constant number of confirmed cases some of which die?

Comment by cellbioguy on My Covid-19 Thinking: 4/23 pre-Cuomo Data · 2020-04-24T14:55:11.890Z · score: 6 (4 votes) · LW · GW

The New York numbers are certainly interesting. I wonder if New York reached a no-longer-susceptible rate that means that it can no longer support long transmission chains in lockdown...

New study with claims of meaningful mutation in Covid-19
Claim is that European strain, which is also in New York (and I’m going to presume New Jersey and other surrounding areas as well, because physics), is deadlier than the strain elsewhere, generating orders of magnitude more viral load.

I am VERY VERY skeptical of this paper.

The mutations they show are TINY. And their methods section does not include any details at ALL of how they grew their viruses, or how they diluted them to a multiplicity of infection of 0.5. Short version, they were supposed to grow cultures of each of their 11 viral isolates, measure how infective each culture was, and then dilute them so there were 50% as many infective viruses as cells in the flasks they poured them into to make sure they all started from the same point. But they give no details of how they measured this and did the dilution.

When growing viruses, batch effects are a BITCH. Your virus culture might be a little differently diluted, they might be a different average age, or your culture might've been produced in a corner of the incubator that was a little warmer. The lines of each of the viruses bounce around over time, some higher and lower over time, and all I really see is a cloud of viral RNA levels that goes forward over time with some high and some low at any given time. They have four replicates of each virus and DO show that the replicates behave exactly like each other, but their methods section doesn't say if they took the same diluted virus stock and put it into four culture flasks, or made four separate stocks of each virus. It is QUITE QUITE possible that they are just seeing differences in the stocks they grew that have to do with their culture histories and dilution details, rather than genetic differences.

On another point, the cell line they grow them in isn't even human and doesn't really have an innate immune response, which would be by far the most important things regarding real-world infection. Their high viral replication lines were also not from their more severe cases.

They definitely did find ONE interesting thing - one of their isolates appears to have independently invented a particular missense mutation seen in another strain elsewhere in the pile of global sequences. Actually suggestive of selection. It's not in the receptor binding domain of the S protein though, so it shouldn't affect binding or immunity much.

Other papers have found MUCH more interesting mutations - there is a cluster of cases in Singapore that have up and completely lost one of the accessory proteins of the virus, which is involved in squashing the human innate immune response, and another case in Arizona has broken another such accessory protein beyond repair. This is presumably because this bugger evolved in bats, and their interferon response is on a freaking hair trigger. The anti-immune-system measures of the virus are overclocked relative to what you need to replicate in humans, and losing some of them doesn't really hurt them.

Comment by cellbioguy on Coronavirus: Justified Key Insights Thread · 2020-04-23T19:04:38.944Z · score: 12 (3 votes) · LW · GW

UPDATE as of 4/23/2020.

I'm so sick of being right.

Seroprevalence in NYC reported as 21%.

https://twitter.com/NYGovCuomo/status/1253353516803993600

There can be false negatives, but at this positive level false positives are less of an issue than at low levels. Also, they apparently specifically grabbed people out and about at grocery stores, so very sick people may have been excluded, pushing levels down. On the other hand, people shopping might be more likely to pick it up.

Pretty much right on the nose...

https://twitter.com/trvrb/status/1253398329766973441

" If we then take deaths as of today as 17,200 based on excess deaths (https://nytimes.com/interactive/2020/04/21/world/coronavirus-missing-deaths.html), we'd get an infection-to-fatality ratio of ~1%. " I suspect the true seropositivity is higher than the measured due to selection effects on the net, which would push this down a bit.


EDIT: Apparently this test also only detect IgG, which is the type of antibody that rises last and can take two weeks or more to be detectable in some people after symptoms develop.

Comment by cellbioguy on How likely is the COVID-19 apocalyptic scenario? · 2020-04-23T15:35:51.524Z · score: 3 (2 votes) · LW · GW

It is mostly just retroviruses that wind up entering the genomes of their hosts. RNA viruses leave a very different imprint: high rates of evolution of the proteins that their proteins interact with, as they race to deactivate their hosts immune responses and their hosts race to deactivate or evade the viral proteins.


There is also a constant, diversifying selection on the components of the immune system (HLA/MHC) that display viral proteins from within cells on cell surfaces for the immune system to be sensitized against. Viruses always evolve to take better advantage of the most common of these alleles, and the rarest of these genes are always selected for in populations as result. The end result is what is called 'balancing selection', where rare things become more common and common things become less common leading to the maintenance of great diversity. This is why tissue typing for transplants is so difficult - there is such immune system diversity that most people don't have the same alleles at these loci as each other. Of course, if something new enters the population that a subset of these alleles isn't great against, that set of alleles will become less common over time.

Comment by cellbioguy on Solar system colonisation might not be driven by economics · 2020-04-23T02:50:01.350Z · score: 2 (1 votes) · LW · GW

I'm still convinced that solar system colonization simply won't happen.

Comment by cellbioguy on How likely is the COVID-19 apocalyptic scenario? · 2020-04-23T02:46:57.893Z · score: 10 (6 votes) · LW · GW

Then after a few hundred years, the human population will have undergone enough selection that all the bad HLA alleles that make T-cell responses difficult are low in the population and all the formerly rare ACE2 alleles are widespread. Here, check out these papers:

https://elifesciences.org/articles/12469

https://www.biorxiv.org/content/10.1101/2020.03.18.997346v1.full

Looking at signatures of natural selection in the human population, by FAR some of the strongest signals in the past few tens of thousands of years is proteins that interact with viral proteins - the HLA alleles and all the parts of the interferon response and everything else that all those tricksy accessory proteins sequester and alter.

This is nothing new. We just have somehow decided that we expect better.

------

As for other things:

The virus apparently has a mutation rate which is on the high end, unexpectedly large rate of mutation. This makes the vaccine less probable. How much less? No idea.

This is simply not true. Coronaviruses actually proofread their polymerases unlike almost all RNA viruses. The only interesting mutations I am aware of in the current outbreak is two independent origins of a particular missense mutation away from the receptor-binding-domain of the spike protein (that thus dont affect neutralizing antibodies), and a few strains that have up and LOST whole accessory proteins that are part of how the virus evades the innate immune response (because they are so damn good at evading it in humans because the bat response is so absurdly fast that they don't need half of what they have).

Following the vaccine development scene, I am actually absurdly optimistic. All the stuff entering human studies are basically just repurposing already-researched SARS and MERS vaccines that work in monkeys, and swapping out the sequence. The preliminary data is already coming in in these animals and is good.

Comment by cellbioguy on Coronavirus: Justified Key Insights Thread · 2020-04-22T14:01:47.938Z · score: 3 (2 votes) · LW · GW

I think it's a horse, not a zebra. ACE2 is expressed on endothelial cells lining blood vessels. If you get bad viremia the inner sheath of blood vessels, especially in heavily infected organs, probably just gets all messed up.

Comment by cellbioguy on COVID-19: List of ideas to reduce the direct harm from the virus, with an emphasis on unusual ideas · 2020-04-19T02:51:42.292Z · score: 11 (4 votes) · LW · GW

See my answer of another link below. Short version:

  • Severe disease is associated with hyper-coagulation, and people experiencing breathing difficulties should be treated with anticoagulants.
  • Antivirals and anything believed to decrease viral replication should be given early, to the more moderate cases to decrease the odds of progressing to severe, rather than only to severe cases.
  • A case is likely to be followed by a period of immunosuppression, much like measles, so those who become ill should be prepared to be careful afterwards.

https://www.lesswrong.com/posts/nRX7uwT2wNvvmd2Yd/coronavirus-justified-key-insights-thread

Comment by cellbioguy on COVID-19: List of ideas to reduce the direct harm from the virus, with an emphasis on unusual ideas · 2020-04-19T02:45:07.284Z · score: 6 (4 votes) · LW · GW

There have been studies of soaking them in brine, so they have tiny salt crystals in the cloth that dessicate viruses that land on them. Had a positive effect!

Comment by cellbioguy on Coronavirus: Justified Key Insights Thread · 2020-04-19T02:43:31.562Z · score: 9 (3 votes) · LW · GW

New information. The Italian town of Vo was blanket-RNA-tested twice in late February and early March. A total of 3% of the town tested positive, and they were able to lock down this subset and shut down transmission from continuing in the town indicating they caught enough of the asymptomatic-but-transmissive carriers.

https://www.medrxiv.org/content/10.1101/2020.04.17.20053157v1

Here we have a detailed analysis of these positive-testing people.

43% asymptomatic all the way through.

~20% hospitalized. This means almost 40% hospitalization of people who were symptomatic. Critera for hospitalization is an interesting question, as is the age breakdown of the town.

One death, in a town in which a total of 82 people tested positive. That one death was what alerted authorities to the outbreak in the town, so we need to take it as a given rather than taking it as even weak evidence of an over 1% fatality rate.

No cases among hundreds of children, even in houses with symptomatic family members. Extra cases among the elderly (as in 1% of 20 year olds versus 6% of 70 year olds). Small numbers but significant. Unclear if that means they are not getting infected or are not producing long-lasting infection that is detectable or if social structure has something to do with it.

No obvious difference in symptomatic versus asymptomatic across the age distribution, subject to sample size.

More men took more than 2 weeks to clear the virus than women.

Definite confirmed asymptomatic people passing it on, and presymptomatic people passing it on.

3% of the town testing positive via PCR in the beginning of March is compatible with 15% of other towns in the area testing positive via serology a month later, as that would be less than 3 doublings. They find a 'serial interval' of only about 7 days in their contact-tracing data from before the lockdown, and 10 days after the lockdown, and a replication number before the lockdown of about 3 and 0.14 during the lockdown. That's a doubling time of well under a week before the lockdown. The rest of Italy's lockdown didn't include such good contact tracing and thus still was probably doubling a few times during that period.

Comment by cellbioguy on My Covid-19 Thinking: 4/17 · 2020-04-18T02:26:31.835Z · score: 7 (4 votes) · LW · GW

All the reports of people becoming ill (or testing positive) after only a month are almost certainly not 'reinfections', rather are some combination of false negatives and people with immune systems damaged by the infection having a bit of a relapse. There are also no documented cases of one of these relapses infecting even close family contacts. Shed viruses seem to be nonviable with much less of an immune response than is required to clear it from within the body.

It is definitely possible that the immunity could fade rapidly, but even if that is true I expect second infections to be much less severe than the first infection. Mostly because it looks like most of why this disease is so severe is that the virus escapes the interferon response allowing it to replicate up to an obscene level before the adaptive immune system notices it. Even a weak antibody response will allow the innate immune system to notice the fact that there is an infection, and it will probably have a harder time replicating up to such ridiculous levels.

This being said... we are definitely going to be living with this bastard for a while.

Comment by cellbioguy on Is this viable physics? · 2020-04-16T23:01:20.785Z · score: 2 (1 votes) · LW · GW

It appears that an implicit prediction is that at least a good fraction of dark matter would consist of almost arbitrarily low mass low interaction particles in obscene quantities, that froze out at absurd temperatures in the early universe before momentum-redshifting to near zero velocity such that they behave more like matter than radiation in gravity wells (unlike neutrinos which normally move far too fast to stay bound anywhere).

Comment by cellbioguy on Is this viable physics? · 2020-04-15T04:59:03.695Z · score: 13 (8 votes) · LW · GW

This reminds me STRIKINGLY of Sean Carrol's musings on the way to approach quantum gravity using the concept of emergent spacetime. He posits that space could emerge from the graph of all entanglements between variables, with 'more entangled' becoming 'close together' rather than the other way around. He has some very preliminary math showing similar things as here, specifically that under certain assumptions you get the equations of general relativity out of it.


See:

https://www.youtube.com/watch?v=jHLfMXvQqX8

https://www.preposterousuniverse.com/blog/2016/07/18/space-emerging-from-quantum-mechanics/

https://arxiv.org/abs/1606.08444

https://arxiv.org/abs/1712.02803


EDIT: On a sort of stylistic note... I am reminded of the way that in every epoch, whatever is hardest to understand that is newly understood is understood in terms of the most successful and powerful technology or new concept of the day. Classically, along one historical stream minds and nervous systems were talked about in hydraulic terms, then in terms of wiring diagrams, then in terms of computation. At this moment in history computation is a very powerful set of organizing metaphors and tools, and could stand to kick open new areas. That being said, I would bet that one would be able to find other formalisms that are equivalent after kicking down the door...

Comment by cellbioguy on What does the curve look like for coronavirus on a surface? · 2020-04-15T04:33:45.738Z · score: 2 (1 votes) · LW · GW

I have seen one source indicating that specifically on copper, there was a delay of half an hour or so followed by a rapid decline. I have also seen another source indicating that the effectiveness of sunlight in shortening the halflife declines with time. Wish I could find them...

Comment by cellbioguy on Coronavirus: Justified Key Insights Thread · 2020-04-14T19:04:37.449Z · score: 2 (1 votes) · LW · GW

Check all the references from https://www.nature.com/articles/d41586-020-00885-w for some data, as well as worldometer.

I am trying to find the Japanese government webpage with frequent updates as to the state of patients that were evacuated, still updating the ones that are still in the hospital (! Morbidities...)

Comment by cellbioguy on Coronavirus: Justified Key Insights Thread · 2020-04-14T18:17:41.509Z · score: 2 (1 votes) · LW · GW

Indeed! Anti-inflammatories, oxygen therapy, anticoagulants, blood pressure management, eventually invasive ventillation (though that seems less effective than was previously thought).

I suspect the United States will have a substantially higher IFR than Europe due to all the obesity and metabolic disease, and that when the ICUs pop it also rises.

Comment by cellbioguy on Coronavirus: Justified Key Insights Thread · 2020-04-14T18:07:10.542Z · score: 5 (5 votes) · LW · GW

The end data is that about 20% of the Diamond Princess was asymptomatic all the way through. They were particularly old, though.

In Iceland 50% are asymptomatic upon first test, then some progress. The data in Korea suggests 30% asymptomatic.

Small number statistics of government officials supports this too. 7 total congressmen have tested positive or been presumed positive. One or two were hospitalized, some said "it hit me hard" or "my case is mild", and 2 out of 7 (Rand Paul and Joe Cunningham) reported either zero symptoms or only loss of the sense of smell.

Comment by cellbioguy on Coronavirus: Justified Key Insights Thread · 2020-04-14T01:28:30.905Z · score: 66 (17 votes) · LW · GW

Claim: The true infection-to-fatality ratio is definitely about 0.5% to 1%, and most probably around 0.7%, with significant long term morbidity in at least several percent of survivors. Notions that this disease is already widespread or that it has flulike mortality and morbidity or most people are asymptomatic are definitively disproven.

This has been independently estimated in this range before, based on normalizing data from the Diamond Princess and areas where testing was thorough

https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30243-7/fulltext

https://www.medrxiv.org/content/10.1101/2020.03.05.20031773v2

There are a few robust new pieces of data supporting this now.

1 - Blanket RNA testing in Austria.

https://www.theguardian.com/world/2020/apr/10/less-than-1-of-austria-infected-with-coronavirus-new-study-shows

Given a 0.3% current acute infection rate and some epidemiological modeling they estimate 1% of their total population has been infected at some point, with a death rate of 0.77%. Maybe a few false negative PCRs, which would lower that number.

2 - Two serology surveys have now happened in Europe. One was in a hard-hit town in Germany, and one was in a hard-hit town in Italy at the epicenter of its outbreak. In both places, they got approximately a 15% seropositive rate. In Germany, we only have information on deaths with positive test results and it comes to 0.35%. In Italy, total excess deaths over this time last year are about 2.5x the confirmed positive deaths and account for 0.1% of the population, giving an infection fatality rate of 0.7%. It is easy to imagine that some deaths did not get positive tests in Germany which along with a less-old population could make up for the difference.

3 - New test data coming out of NYC.

https://www.nejm.org/doi/full/10.1056/NEJMc2009316

Hardly an unbiased sample, but of 200+ pregnant women coming into a hospital to give birth that were blanket-RNA-tested, 15.3% tested positive.

Of this set of positive tests, only 12% of them were symptomatic on admission, and a further 10% developed symptoms over the course of their 2-day-long stays bringing it to a total of 22% symptomatic upon discharge or transfer. Presumably already-symptomatic very-pregnant women were more likely to be in the hospital already.

Doing a little armchair epidemiology. Let's assume that half of the deaths of currently infected people have happened, due to the lockdown extending the doubling time from three days to more than a week. We get:

~8000 deaths * 2 / (15.3% of 8 million) = 1.3% infection to mortality rate.

If we assume that there were more symptomatic women who didn't show up to normal birthing due to going to the hospital for COVID symptoms, or that there is a good stock of people who have recovered in the city, we get a lower death rate. If 20% of the total population was ever infected, we get a 1% mortality rate. 30% ever infected, 0.67%.

EDIT: 4 - Apparently there is a similar maternity ward study in Stockholm, revealing 7% positive. There have been 550 deaths there, and a population of 2.3 million. If we again assume half of current cases that will die has died, we get a infection to fatality ratio of 0.68% without further corrections. I suspect they haven't crushed the doubling time as much as NYC, raising this number, which then can get lowered down again as I did above.

EDIT: 5, a meta analysis of a whole bunch of research comes to exactly my original conclusion, 0.5% to 1% with a central tendency of 0.8%.

https://t.co/51b3bJYg3e?amp=1

Comment by cellbioguy on Coronavirus: Justified Key Insights Thread · 2020-04-14T01:02:01.071Z · score: 35 (9 votes) · LW · GW

Claims:

Severe cases should be treated with anticoagulants

Inhaled interferon, antivirals, and other effective treatments are probably much more effective when taken early to prevent the first few replication rounds.

A case is probably followed by a period of immune suppression, and possibly some T-cell immunity amnesia.

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The virus may be causing abnormal inflammation and a whole-body, but especially concentrated in the lungs, hyper-coagulable state that is triggering microscopic blood clots in the lungs that are one of the main contributors to morbidity and mortality and ineffectiveness of ventilation. Effective treatment of severe cases should probably include anticoagulants unless there are contraindications, and another effective treatment has been an interleukin inhibiting antibody normally reserved for severe arthritis. See the entire recent twitter diggings of @_ice9.

There have been major reports from clinicians that the lungs of COVID patients are not responding the same way as typical ARDS. The ability to get oxygen in the blood is too low compared to the amount of air they can get into them. Autopsies are revealing lots of small clots, and blood tests are finding the most predictive measurement of outcome is an indicator of blood clot dissolution (D-dimer).

Children with non-severe cases are having anomalously high rates of sores and discoloration on fingers and toes, indicative of diffuse coagulation in small vessels causing mild tissue damage that seems to heal on its own afterwards.

This hyper-coagulable state *might* explain the reports of anomalously low oxygen measurements in people that would ordinarily indicate death or unconscoiusness. They might have small clots in the finger the sensor is on triggering temporary sporadic low blood flow. It also could explain more of the fact that ventilators are less useful than they thought - some people going on them probably didn't actually need them.

(Before anyone asks, that preprint that was making the rounds suggesting the virus was destroying hemoglobin was STUNNINGLY and EMBARRASSINGLY bad. Complete bullshit, not worth even hate-reading unless you find fantasy biochemistry from a universe in which chemical reactions have energies you normally associate with nuclear reactors and viruses do photosynthesis funny).

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Additionally, there are two bits of immunology that explain parts of this virus's behavior and suggest ways of hurting it. First, the virus evolved in bats in which the interferon response is on an absolute hair trigger, and accordingly in human cells it almost completely escapes the interferon response. This allows it to replicate to absurd viral loads before the immune system notices it, explaining the extreme infectiousness shortly before symptoms develop. Then when the immune system notices it, it goes all out on a huge viral infection, triggering an inflammatory response that is all out of whack and can do a lot of damage. This means that it is vulnerable to inhaled interferon pretreatment (https://www.biorxiv.org/content/10.1101/2020.03.07.982264v1). On top of this, it may be that anything that reduces the replication of the virus in this period before the adaptive immune system mounts a robust response could reduce the probability of progression to severe disease. If antivirals work out or if chloroquine is effective (given the biochemistry I am very hopeful!), they will probably be most effective early via reducing the fraction of patients that progress to severe disease.

Second, there is evidence that the virus is able to enter and destroy (but not replicate within) T-cells using the same receptor it uses everywhere else, triggering immune suppression and altering the inflammatory profile (https://www.nature.com/articles/s41423-020-0424-9). It lacks HIV's obscene dirty tricks and isn't actually replicating within them, so this would be a temporary thing until recovery.

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That last bit may sound bad, but it is far from unique. When looking for other examples, one should look to the Measles virus. It too basically escapes the interferon response and grows to absurd highly-communicable levels (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC112268/), and it actually infects and replicates within T-cells and B-cells which it then rides throughout the body. This causes people who get the measles to basically forget 70% of their adaptive immune responses from before they were infected, and go through a period of immune suppression afterwards. I expect the loss of immune memory to be smaller in this case because the new bug doesn't seem to infect B cells or all types of T-cells from what I have seen.

Comment by cellbioguy on Iceland's COVID-19 random sampling results: C19 similar to Influenza · 2020-04-13T23:54:35.293Z · score: 2 (1 votes) · LW · GW

Copypasting myself from another thread:


' New, amazing data from New York, as of April 13.

Hardly an unbiased sample, but of 200+ pregnant women coming into a hospital to give birth that were blanket-tested, 15.3% tested positive.

Of this set of positive tests, only 12% of them were symptomatic on admission, and a further 10% developed symptoms over the course of their 2-day-long stays bringing it to a total of 22% symptomatic upon discharge. Presumably already-symptomatic women were more likely to be in the hospital already.

Doing a little armchair epidemiology. Let's assume that half of the deaths of currently infected people have happened, due to the lockdown extending the doubling time from three days to more than a week. We get:

~8000 deaths * 2 / (15.3% of 8 million) = 1.3% infection to mortality rate.

If we assume that there were more symptomatic women who didn't show up to normal birthing due to going to the hospital for COVID symptoms, we get a lower death rate. If 20% of the total population is infected, we get a 1% mortality rate.

Compare this to what I wrote 21 hours ago, based on serology data from Italy and Germany:

'From this, I estimate that at least 10% and possibly up to 20% of New York City has been infected, given the delay between infections and deaths. (100*8000 = 800,000, out of about 8 million) '

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Adding here, that if you assume there are people who would have previously tested positive and recovered, it goes down a bit more. Most places that we get good data these days are converging on a 0.5% to a 0.7% mortality rate, so I suspect that's also a contributor.

Comment by cellbioguy on The case for C19 being widespread · 2020-04-13T23:46:10.411Z · score: 10 (3 votes) · LW · GW

New, amazing data from New York, as of April 13. https://www.nejm.org/doi/full/10.1056/NEJMc2009316


Hardly an unbiased sample, but of 200+ pregnant women coming into a hospital to give birth that were blanket-tested, 15.3% tested positive.


Of this set of positive tests, only 12% of them were symptomatic on admission, and a further 10% developed symptoms over the course of their 2-day-long stays bringing it to a total of 22% symptomatic upon discharge or transfer. Presumably already-symptomatic women were more likely to be in the hospital already.


Doing a little armchair epidemiology. Let's assume that half of the deaths of currently infected people have happened, due to the lockdown extending the doubling time from three days to more than a week. We get:


~8000 deaths * 2 / (15.3% of 8 million) = 1.3% infection to mortality rate.


If we assume that there were more symptomatic women who didn't show up to normal birthing due to going to the hospital for COVID symptoms, we get a lower death rate. If 20% of the total population is infected, we get a 1% mortality rate. Could go lower if the doubling time has slowed less than my assumption, or if people who have recovered constitute a large enough actual segment of the population. Probably can't account for more than a factor of two though, given known recovery times.


Compare this to what I wrote 21 hours ago, based on serology data from Italy and Germany:


'From this, I estimate that at least 10% and possibly up to 20% of New York City has been infected, given the delay between infections and deaths. (100*8000 = 800,000, out of about 8 million) '

Comment by cellbioguy on The case for C19 being widespread · 2020-04-13T17:45:27.795Z · score: 4 (2 votes) · LW · GW

Some non-serology blanket RNA tests coming out of Austria.

https://www.theguardian.com/world/2020/apr/10/less-than-1-of-austria-infected-with-coronavirus-new-study-shows

Given a 0.3% current acute infection rate and some epidemiological modeling they estimate 1% of their total population has been infected, with a death rate of 0.77%.

Everything seems to be converging...

Comment by cellbioguy on The case for C19 being widespread · 2020-04-13T02:24:40.910Z · score: 4 (2 votes) · LW · GW

The death rate data coming in seems to be converging on a 0.5% to 0.7% death per infection rate. Multiple sources have estimated that weeks ago based on age-normalizing the Diamond Princess, and on testing evacuees from Wuhan.

Two serology surveys have now happened in Europe. One was in a hard-hit town in Germany, and one was in a hard-hit town in Italy at the epicenter of its outbreak. In both places, they got approximately a 15% seropositive rate. In Germany, we only have information on deaths with positive test rates and it comes to 0.35%. In Italy, total excess deaths over this time last year are about 2.5x the confirmed positive deaths and account for 0.1% of the population, giving an infection fatality rate of 0.7%. It is easy to imagine that some deaths did not get positive tests in Germany which along with a less-old population could make up for the difference.

From this, I estimate that at least 10% and possibly up to 20% of New York City has been infected, given the delay between infections and deaths. (100*8000 = 800,000, out of about 8 million)

Comment by cellbioguy on The case for C19 being widespread · 2020-04-13T02:10:26.121Z · score: 4 (2 votes) · LW · GW

Boy there was a lot of desperate motivated cogniton around a few weeks ago...

Comment by cellbioguy on How credible is the theory that COVID19 escaped from a Wuhan Lab? · 2020-04-12T18:19:38.029Z · score: 2 (1 votes) · LW · GW

But there is little evidence of recent major recombination in the history of this particular virus, since its common ancestor with the 2013 virus. It looks like it has a pretty much vertical inheritance from its common ancestor with the 2013 bat sequence.

Check out the paper "Evolutionary origins of the SARS‐CoV‐2 sarbecovirus lineage responsible for the COVID-19 pandemic" (https://www.biorxiv.org/content/10.1101/2020.03.30.015008v1). They run a sliding window along the SARS-CoV-2 sequence and compare it to the sequence of many other viruses. The conservation is not constant across the genome, but different regions are under different evolutionary constraint, and the *relative* conservation across the genome looks more or less consistent rather than there being big sharp jumps in homology as you would expect from distant recombination and see in other more distantly related viruses.

Some have argued that recombination could account for the origin of the specific receptor binding domain since it seems very similar to that found in a pangolin virus. But overall there is very little recombination evidence.

The only idea that is really open at all is 'Poor procedure resulting in viral transfer from a wild lab animal', not 'recombination experiments in the lab creating something unusual'.

Comment by cellbioguy on Seemingly Popular Covid-19 Model is Obvious Nonsense · 2020-04-12T05:01:16.090Z · score: 5 (3 votes) · LW · GW

This increases my estimated odds of the federal government attempting to suppress positive test numbers via defunding and not collecting statistics.

Comment by cellbioguy on Why don't we have active human trials with inactivated SARS-COV-2? · 2020-04-10T03:56:46.947Z · score: 20 (6 votes) · LW · GW

I'm not an immunologist, I don't even play one on TV.

There are a large number of potential vaccines for the SARS-2 virus being studied, including one inactivated virus vaccine from what I have seen, but there is already a decade of work in the can on vaccines for the related SARS and MERS viruses. This work was slow compared to whats happening now due to lack of interest, eradication, or poor human to human transmission, but now can be built on very quickly. This work tells you where you should focus your effort.

It was found that several of the ways of inactivating the first SARS virus to create a vaccine caused WORSENED disease upon immunized animals later actually getting exposed to the real virus, due to a number of mechanisms including (to oversimplify) inducing the wrong kinds of antibodies that helped trigger inflammation as well as enabling non-neutralized viruses to get inside or hyperstimulate immune cells. Most work now is focusing on the types of vaccines that wound up not having that sort of problem for these related viruses, only showing the body the recombinant spike proteins or fragments of the spike protein and maybe some of the intracellular proteins. They get to be displayed either on body cells by a DNA/RNA vector or as recombinant irritating protein infusion or get displayed on a *different* modded dead virus that does not generate these problems.

The dead virus does not generate the same immune reaction as a live one since infected cells contribute signaling molecules and context, and some (but not all) dead viruses can generate immune reactions that should not happen normally.

Comment by cellbioguy on Taking Initial Viral Load Seriously · 2020-04-08T06:44:48.333Z · score: 6 (4 votes) · LW · GW

Study of symptoms in hospitalized patients: "Patients with COVID-19 who have digestive symptoms were shown to have a worse prognosis than those without."


https://www.practiceupdate.com/content/clinical-characteristics-of-covid-19-patients-with-digestive-symptoms-in-hubei-china/98000

Comment by cellbioguy on What will happen to supply chains in the era of COVID-19? · 2020-04-08T03:30:24.239Z · score: 2 (1 votes) · LW · GW

You ascribe too much agency to the great hulking amoebas that human societies are.

Comment by cellbioguy on An alarm bell for the next pandemic · 2020-04-06T14:47:58.745Z · score: 7 (4 votes) · LW · GW

There's the fact that most viral spillovers into humans don't actually transmit well, and the fact that if they do but burn out it doesn't really matter on the large scale. The latter has definitely changed.

HIV is an interesting case study. Genetically, we can tell it leaped into humans from great apes TWICE in the 1920s (HIV-1 and HIV-2) in a way that kept transmitting around the globe. This probably had to do with the urbanization of sub-Saharan Africa - the sudden sucking of huge numbers of rural people with contact with bushmeat into globally connected urban centers. Presumably it had been transmitting into people forever, just always burning out.

A few years back there was an antibody study in a village near a bat cave in China that found that 0.5% of the people that lived a few hundred meters from the cave showed antibodies against SARS-like viruses.

Comment by cellbioguy on Taking Initial Viral Load Seriously · 2020-04-06T08:16:28.504Z · score: 7 (3 votes) · LW · GW

It's a superficially plausible idea, assuming you don't always burp or vomit the virus up into your lungs anyway or get very slight viremia getting them there anyway too which is COMPLETLEY possible given what we know. And assuming you somehow get it into your gut without getting it into your throat. Huge numbers of assumptions, dosage unknown, methods unknown, effectiveness unknown. Superficially plausible and right now a very bad idea. You absolutely CANNOT assume it's safer, but it could be something to look for in case studies of natural infections, seeing if people who first manifest with intestinal issues have lower levels of pneumonia.


If you COULD somehow reliably restrict viral replication to the gut rather than the lungs... I don't think many first-world (or, to expand the sample, American) COVID patients have died of the diarrhea.


EDIT: "Patients with COVID-19 who have digestive symptoms were shown to have a worse prognosis than those without."

https://www.practiceupdate.com/content/clinical-characteristics-of-covid-19-patients-with-digestive-symptoms-in-hubei-china/98000

Comment by cellbioguy on An alarm bell for the next pandemic · 2020-04-06T02:47:10.430Z · score: 6 (4 votes) · LW · GW

I started having panic attacks and needing to find creative places to store my accumulated nonperishable supplies shortly after Valentine's day.

My attempts to warn people were primarily directed towards my university, my family and those I love. My boss had us ready for cessation of in person activity two weeks before others as a result and he may have helped convince a county to close schools earlier than otherwise. Family hasn't had to go to a grocery store for 5 weeks.

This place was a bit far from my mind due to drifting away, unfortunately.

There will be a lot more of these this century. What other possible outcome could there be to becoming 40% of mammalian biomass on the planet, with such a well-mixed system?