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Re:Scientists create antibody that defeats coronavirus in lab by joubert on Monday May 04, 2020 @08:34PM (#23075038)
I've also wondered about the end game and so far concluded that most societies (including the US) would go the vaccine route (which confers herd immunity) as opposed to natural immunity (what I think you mean by "herd immunity"), but I would love to hear what you think.

The reason why I doubt the end game is herd immunity via natural infection is:

* millions would die

* health systems would get crushed

* the virus is unlikely to disappear entirely, so would simmer around the world, triggering epidemics every few years or so.

What do you think?

Re:Scientists create antibody that defeats coronavirus in lab by rpiguy on Saturday May 09, 2020 @01:05PM (#23126405)
I do think a vaccine will be made available and likely sooner than anyone is predicting, but it will not be mandatory and if states or employers try to make it mandatory they will held up in lawsuits for years.

I could see a future where, like the flu vaccine, everyone is encouraged to get a SARS COV2 vaccine and there will be reasonable compliance.

Hospital systems were only really crushed in there places, Lombardi, NYC, and Spain. Only in Lombardi Italy did hospitals actually run out of beds (go over capacity). Even in London today the hospitals are under capacity. I am not saying this is a good yard stick to go by, I am pointing out that outside of three locations most hospitals are sitting virtually empty. Therefore it is unlikely health systems would be crushed.

As far as millions would die, again I would say look to the mortality rates outside of the three outlier areas (Lombardi, Spain, and NYC) and the mortality is far below 1%. I can see a future where COVID kills as many people as the flu. I don't see a future with a crushing mortality rate.

Viruses rarely disappear entirely, but the mortality rate is not high enough to be so afraid of it. It spreads fast, but not as fast as measles, whooping cough, or TB, which spread faster, kill more people, and also kill children. We try to eradicate those diseases for a reason. Covid is nowhere near their level. If we set the bar this low, we will be stopping the world economy every decade to fight viruses that bubble up and kill comparatively few people.

Re:Scientists create antibody that defeats coronavirus in lab by mlyle on Monday May 04, 2020 @09:41PM (#23075479)
We may not have a choice, in that we're not guaranteed to have a useful vaccine in massive doses anytime soon.

But rebutting your individual points:

> millions would die

Unlikely. Improved estimates (thanks to serological data) for infection fatality rate range from 0.3% to 0.5%. If we can protect the most vulnerable populations, we can have a lower death rate than this-- e.g. in the under-30 crowd, the risk of hospitalization is 1 in 500 and the risk of death a tiny fraction of this (1 in 5000 or less).

Further, any variance of susceptibility or contact density means you don't need to reach 60% for herd immunity. Some estimates say that the real threshold may likely be 25% or less: e.g. https://www.medrxiv.org/content/10.1101/2020.04.27.20081893v... Further, lighter weight social distancing measures can further reduce Rt and attain herd immunity at a lower percentage.

If you assume we need 40%, and 0.25% IFR from protecting the most vulnerable-- you come up with 328k deaths. This is bad, but less bad than many alternatives. Note that the shorter lived the controls protecting the elderly and other vulnerable people, the more effectively we can protect them, too.

> health systems would get crushed

We'd not want to do what New York did, but let's look at it as an example. New York's health care system (barely) sustained the load. Now they're very possibly most of the way to herd immunity in NYC. Yes, we'd like to flatten the curve a bit from this and be better prepared.

> the virus is unlikely to disappear entirely, so would simmer around the world, triggering epidemics every few years or so.

The long term immunity question is interesting. Of course, vaccines could help improve this picture even if one ends up with disease-spread based herd immunity.

My personal belief is that A) total antibody-based immunity will last a few years, based on our experience with SARS-CoV-1; B) partial antibody-based immunity will likely last longer than that; C) memory B cell / T cell based immunity is likely lifelong and makes any subsequent course of disease less severe.

That is, I think it's likely that the current human coronaviruses that cause the common cold might very well cause a high death rate and be very transmissable if exposed to an immunologically naive population.

Of course, your third point holds even more true when it comes to interim suppression and containment efforts while we isolate and wait for a vaccine. It's an even more intractable issue to try and maintain suppression when the vast majority of the population is still susceptible.

Re:Scientists create antibody that defeats coronavirus in lab by ekidd on Monday May 04, 2020 @10:54PM (#23075932)
> Unlikely. Improved estimates (thanks to serological data) for infection fatality rate range from 0.3% to 0.5%.

This seems optimistic. I did the math last week, and 0.2% of New York City had died either from the coronavirus, or from something that was probably the coronavirus. About 21% percent of New York City was testing positive for antibodies. (Both deaths and antibodies are lagging indicators of infection, although a noticeable fraction of the deaths lag by quite a bit.)

That would give us an IFR around 1%. If we needed to have two-thirds of Americans catch the virus to reach herd immunity, that would be about 2 million dead. With any luck, some people are already immune. And as you point out, variation in susceptibility may stop things earlier than that.

The are some nasty side-effects in some percentage of survivors: Impaired breathing and damage from blood clots seem to be two of the most frequently mentioned, and Wuhan is apparently seeing a spike in dialysis patients.

The CDC is predicting 3,000 deaths/day in the US by June 1st. This seems plausible: We'd only need a few other metro areas to have a NYC-style spike.

So far, several countries do seem to be able to control the virus. But at this point, I increasingly fear that the US will not be able to do the same. We don't seem to be able to ramp up testing, and we haven't gotten the infection rate down to the point where contact tracing would work. And significant portions of the US seem to be giving up on control and going for a herd immunity strategy.

Re:Scientists create antibody that defeats coronavirus in lab by bobf on Tuesday May 05, 2020 @03:49AM (#23077538)
The study that showed 21% positive antibody results came from self-selected testing of people physically shopping at grocery and big-box stores. Unfortunately, that ultimately doesn't effectively represent the overall population of NYC at all. This was posted by the Head of Decision Intelligence at Google about the study a day after the "21%" headline was published: https://towardsdatascience.com/were-21-of-new-york-city-resi...
Re:Scientists create antibody that defeats coronavirus in lab by ekidd on Tuesday May 05, 2020 @05:42AM (#23078187)
> Unfortunately, that ultimately doesn't effectively represent the overall population of NYC at all.

Yes, as the Google article points out, the study is probably an undercount. IIRC, the samples were taken from mid-day grocery shoppers. If so, this would push the real NYC IFR higher, possibly into the 2% range. And as the Diamond Princess has shown, the real IFR continues to climb for weeks, as the final ICU patients succumb.

This would make the ultimate costs of herd immunity higher.

Re:Scientists create antibody that defeats coronavirus in lab by steveeq1 on Tuesday May 05, 2020 @12:31AM (#23076508)
> I did the math last week, and 0.2% of New York City had died either from the coronavirus, or from something that was probably the coronavirus

"Something PROBABLY was the coronavirus?". So you're from the camp of "someone was shot 9 times, so he died from corona virus". I question the way you calculate the numbers.

Re:Scientists create antibody that defeats coronavirus in lab by ekidd on Tuesday May 05, 2020 @05:38AM (#23078156)
> "Something PROBABLY was the coronavirus?". So you're from the camp of "someone was shot 9 times, so he died from corona virus".

Specifically, I counted COVID-19 "confirmed deaths" plus "probable deaths" from https://www1.nyc.gov/site/doh/covid/covid-19-data.page. The probable deaths are defined as:

> People who did not have a positive COVID-19 laboratory test, but their death certificate lists as the cause of death "COVID-19" or an equivalent.

Since tests are scarce, they're not necessarily being used to confirm people who died at home or who died during triage. But COVID-19 is pretty distinctive, and in any case, the COVID-19 deaths are only a portion of the excess mortality.

Re:Scientists create antibody that defeats coronavirus in lab by rallison on Tuesday May 05, 2020 @12:41AM (#23076572)
That's not how that works.

It's also most likely still an undercount. Confirmed plus probable cases are thousands short of total excess deaths for that period for New York City.

Re:Scientists create antibody that defeats coronavirus in lab by mlyle on Tuesday May 05, 2020 @02:06AM (#23076990)
Ascribing all excess deaths to coronavirus is a mistake. People are avoiding ERs and doctors; the incidence of typical CVA, MI, etc, in hospitals is way down. Not because we're having fewer CVAs and MIs, but because people are dying at home instead of being treated.

(Prolonging the epidemic increases the number of people who will die this way, too).

Re:Scientists create antibody that defeats coronavirus in lab by rallison on Tuesday May 05, 2020 @02:27AM (#23077109)
> Ascribing all excess deaths to coronavirus is a mistake.

I worded my statement intentionally.

> It's also most likely still an undercount

Some of the excess deaths will be other things. It will take more careful analysis to come up with reasonable breakdowns, and what percentage is likely covid-19 deaths.

Basically, as this article mentions - https://www.washingtonpost.com/investigations/2020/05/02/exc...

> “I think people need to be aware that the data they’re seeing on deaths is very incomplete,” said Dan Weinberger, a Yale professor of epidemiology who led the analysis for The Post.

> Those excess deaths — the number beyond what would normally be expected for that time of year — are not necessarily attributable directly to covid-19, the disease caused by the coronavirus. They could include people with unrelated maladies who avoided hospitals for fear of being exposed or who couldn’t get the care they needed from overwhelmed health systems, as well as some number of deaths that are part of the ordinary variation in the death rate. The number is affected by increases or decreases in other categories of deaths, such as traffic fatalities and homicides.

> But excess deaths are a starting point for scientists to assess the overall impact of the pandemic.

Re:Scientists create antibody that defeats coronavirus in lab by mlyle on Monday May 04, 2020 @11:16PM (#23076095)
> About 21% percent of New York City was testing positive for antibodies.

From samples returned 10 days ago, so add a bit more lag.

It's not beyond the realm of possibility that New York City has reached the herd immunity threshold. The biggest estimates of variance in contact networks and susceptibility (from fitting to case count data) predict a herd immunity threshold of ~15%. (Cited above).

> We don't seem to be able to ramp up testing

Testing, shmesting. It only provides a minimal adjustment to Rt; sensitivity isn't great, and you can't test everyone every day.

> we haven't gotten the infection rate down to the point where contact tracing would work

Nor will we. The most aggressive lockdowns produce case count decays of 40% or so per week-- possibly less. The suggested threshold for where contact tracing can work well is 1 infection per million population. The SF Bay Area probably has about 3500x that. -ln(3500)/ln(0.6) =~ 16 weeks.

IHME was predicting the virus would magically go away in California with continued shelter in place in the next 3 weeks. They just backed away from this crazy prediction that the data has never fit. However, policymakers depended upon it in making the tradeoff: aggressive policies aimed at control could be justified if they'd really get us to a sustainable containment regime in a couple months.

> And significant portions of the US seem to be giving up on control and going for a herd immunity strategy.

In the end, the only long term paths are to radically change our way of life forever, or herd immunity. There's only really one vaccine effort that could deliver tens of millions of doses to North America by mid-2021, and that's the Johnson & Johnson program. Odds of that program's success are 50-50 at best.

Re:Scientists create antibody that defeats coronavirus in lab by 100ideas on Tuesday May 05, 2020 @12:02AM (#23076357)
Your personal belief about medium-to-long-term immunity is contradicted by research on same with SARS; see “Lack of Peripheral Memory B Cell Responses in Recovered Patients with Severe Acute Respiratory Syndrome: A Six-Year Follow-Up Study" [pdf] https://www.jimmunol.org/content/jimmunol/186/12/7264.full.p...
Re:Scientists create antibody that defeats coronavirus in lab by mlyle on Tuesday May 05, 2020 @02:07AM (#23077010)
From the abstract of your source: "Memory T cell responses to a pool of SARS-CoV S peptides were identified in 14 of 23 (60.9%) recovered SARS patients, whereas there was no such specific response in either close contacts or healthy controls."
Re:Scientists create antibody that defeats coronavirus in lab by 100ideas on Tuesday May 05, 2020 @02:51PM (#23083409)
Correct - there was a long-term memory T cell response. However, see sentance immediately preceeding the one you quoted - basically SARS-CoV IgG antibodies ("IgG Ab" below) were totally absent 6 years after infection. So, antibodies against SARS are not produced long-term, unlike many other types of viral infections, and unlike the desired mechanism of most vaccines.

"Six years postinfection, specific IgG Ab to SARS-CoV became undetectable in 21 of the 23 former patients. No SARS-CoV Ag-specific memory B cell response was detected in either 23 former SARS patients or 22 close contacts of SARS patients."

here is HTML version of article https://www.jimmunol.org/content/186/12/7264.long (DOI 10.4049/jimmunol.0903490)

Re:Scientists create antibody that defeats coronavirus in lab by mlyle on Tuesday May 05, 2020 @04:12PM (#23084424)
K. Thanks for "refuting" a comment where I said "total antibody-based immunity will last a few years, based on our experience with SARS-CoV-1" with evidence that antibodies are gone several years later. :P
Re:Scientists create antibody that defeats coronavirus in lab by 100ideas on Thursday May 07, 2020 @03:32PM (#23107187)
No no, thank YOU for "refuting" my "refutation"! I do stand corrected, I did not internalize your "total antibody-based immunity will last a few years" sentance, and was focused on the following "memory B cell / T cell based immunity is likely lifelong".
Re:Scientists create antibody that defeats coronavirus in lab by mlyle on Sunday May 10, 2020 @11:04PM (#23138523)
Your study leans against the memory B cell part, but found strong memory T cell response, so...
Re:Scientists create antibody that defeats coronavirus in lab by 100ideas on Tuesday May 05, 2020 @12:15AM (#23076426)
Furthermore it seems as if mutations to the spike gene unique to hCov-2019 somehow is involved in suppression of immune systems’ ability to properly regulate its inflammation response; specifically, it seems to mess with the correct functioning of “M2” macrophages that act in a wound-healing mode to regulate the activity of proinflammatory “M1” macrophages. This leads to a runaway inflammation response.

The antibodies described here need to be tested en vivo (monkeys perhaps) to make sure they don’t actually lead to worse pathology (which for hCov-2019 seems to be immune mediated rather than directly caused by virus)

See my Twitter feed for references, I’ve been tweeting an immuno lit review (@100ideas).

Re:Scientists create antibody that defeats coronavirus in lab by 100ideas on Tuesday May 05, 2020 @02:54PM (#23083446)
Here's the reference: Liu 2020 "Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection." https://doi.org/10.1172/jci.insight.123158

here are my highlights of the article and other articles I cited https://twitter.com/100ideas/status/1255671725112659969

Re:Scientists create antibody that defeats coronavirus in lab by rallison on Monday May 04, 2020 @11:45PM (#23076274)
> Further, any variance of susceptibility or contact density means you don't need to reach 60% for herd immunity. Some estimates say that the real threshold may likely be 25% or less: e.g. https://www.medrxiv.org/content/10.1101/2020.04.27.20081893v.... Further, lighter weight social distancing measures can further reduce Rt and attain herd immunity at a lower percentage.

Not surprisingly, that paper has had some discussion: https://twitter.com/CT_Bergstrom/status/1257452758376091648

> It is true that if you could somehow pick and choose who became immune — the way you can in principle with vaccination — you might be able to do pretty well, vaccinating the high-contact individuals only and reaching herd immunity at low levels of vaccination.

> But natural infections don't spread like this. High-contact individuals are connected to low contact individuals. An epidemic spreads organically through the population, infecting who it happens to, not who you want it to.

> IF high contact individuals were only connected to other high contact individuals with high probability, you still might make some headway with nature disease progression. This sort of thing can matter for STD transmission.

> Respiratory viruses tend to be different. You have household transmission, cohort-based (school/work) transmission, and incidental transmission (subway/supermarket). These render the transmission network quite well-connected.

Additionally, if we're talking natural infection to get to herd immunity, you have the issue of overshoot, so unless you're very precise on measures to tamp down on transmission before you get to herd immunity levels, you easily overshoot the herd immunity threshold by quite a bit.

Re:Scientists create antibody that defeats coronavirus in lab by mlyle on Tuesday May 05, 2020 @02:12AM (#23077034)
> > But natural infections don't spread like this. High-contact individuals are connected to low contact individuals. An epidemic spreads organically through the population, infecting who it happens to, not who you want it to.

Surely high contact people are infected -more-, though, no?

In many ways, R0 is a "somewhat worst case number", in that it's something you observe in a population where the virus propagates well. There are likely to be other populations that it doesn't spread quite so well in-- either because of innate susceptibility or behavior differences.

> Additionally, if we're talking natural infection to get to herd immunity, you have the issue of overshoot, so unless you're very precise on measures to tamp down on transmission before you get to herd immunity levels, you easily overshoot the herd immunity threshold by quite a bit.

Exponential processes with a lot of delay and noise are a difficult controls problem, but it wouldn't be hard for jurisdictions that are doing well to target Rt=~ 0.95 .. 1.1 with interventions instead of trying to maintain Rt =~ 0.8. Of course, you need to be prepared to react quickly if things look like they are getting out of hand. And, thankfully, as the susceptible population drops the control problem gets a lot easier, because there's a ceiling of how high Rt can get...