SARS-CoV-2 testing

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Pucksoppet
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Re: SARS-CoV-2 testing

Post by Pucksoppet » Fri Mar 20, 2020 9:02 am

EACLucifer wrote:
Fri Mar 20, 2020 8:43 am
A lot of people I respect are treating this like a big deal, and it looks to be one to me. However, I don't know enough about this field to know for definite. Thoughts?

A serological assay to detect SARS-CoV-2 seroconversion in humans
I don't know either, but it passes my first sniff test, and has a lot of truthiness.

- Researchers from a set of well-known institutions who have reputations to preserve
- Reasonable looking set of references (no obvious woo-journals, Internet woo-website sources)
- Academic language feels right.

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Re: SARS-CoV-2 testing

Post by shpalman » Fri Mar 20, 2020 2:13 pm

A twitter thread discussing covid immunity in those who recover from the infection:

https://twitter.com/NAChristakis/status ... 65472?s=09

(more specifically, the relevant tests for it)
molto tricky

AMS
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Re: SARS-CoV-2 testing

Post by AMS » Fri Mar 20, 2020 5:55 pm

shpalman wrote:
Fri Mar 20, 2020 2:13 pm
A twitter thread discussing covid immunity in those who recover from the infection:

https://twitter.com/NAChristakis/status ... 65472?s=09

(more specifically, the relevant tests for it)
It says a couple of things I've been saying too. We need to be able to identify those who've developed immunity, because they can safely go out and be economically active, and also be the front line of support for the elderly and vulnerable.

Also, antibodies can be manufactured as a therapeutic. We can determine the sequences of antibodies that "work", make these at large scale and inject them intravenously. Typically an i.v. IgG will have a half-life of a few weeks in your bloodstream, so it will buy a window of protection for the vulnerable. People are definitely working on this already...

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Re: SARS-CoV-2 testing

Post by Pucksoppet » Fri Mar 20, 2020 8:13 pm

AMS wrote:
Fri Mar 20, 2020 5:55 pm
Also, antibodies can be manufactured as a therapeutic. We can determine the sequences of antibodies that "work", make these at large scale and inject them intravenously. Typically an i.v. IgG will have a half-life of a few weeks in your bloodstream, so it will buy a window of protection for the vulnerable. People are definitely working on this already...
It's impressive what modern medical/microbiological technology can do.

I know this won't happen, but just imagine scaling up production so that 'all' you had to do was to go to your doctor and be injected every 4 weeks while waiting for the research to find vaccine to bear fruit. It's the kind of thing 'big pharma' would like, as it could be an impressive revenue stream so long as no vaccine appeared.

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Re: SARS-CoV-2 testing

Post by shpalman » Sat Mar 21, 2020 6:02 pm

AMS wrote:
Fri Mar 20, 2020 5:55 pm
shpalman wrote:
Fri Mar 20, 2020 2:13 pm
A twitter thread discussing covid immunity in those who recover from the infection:

https://twitter.com/NAChristakis/status ... 65472?s=09

(more specifically, the relevant tests for it)
It says a couple of things I've been saying too. We need to be able to identify those who've developed immunity, because they can safely go out and be economically active, and also be the front line of support for the elderly and vulnerable.

Also, antibodies can be manufactured as a therapeutic. We can determine the sequences of antibodies that "work", make these at large scale and inject them intravenously. Typically an i.v. IgG will have a half-life of a few weeks in your bloodstream, so it will buy a window of protection for the vulnerable. People are definitely working on this already...
And of course there isn't an answer to the question of how long-term immunity might work out, because we're not yet in the long term of this virus outbreak.

So is that really a decline in immunity to exactly the same virus, rather than the virus mutating to get around immunity? (I was assuming that we don't have a vaccine for the common cold because it's actually caused by a whole range of different viruses.)
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Re: SARS-CoV-2 testing

Post by Pucksoppet » Sat Mar 21, 2020 6:38 pm

shpalman wrote:
Sat Mar 21, 2020 6:02 pm
AMS wrote:
Fri Mar 20, 2020 5:55 pm
shpalman wrote:
Fri Mar 20, 2020 2:13 pm
A twitter thread discussing covid immunity in those who recover from the infection:

https://twitter.com/NAChristakis/status ... 65472?s=09

(more specifically, the relevant tests for it)
It says a couple of things I've been saying too. We need to be able to identify those who've developed immunity, because they can safely go out and be economically active, and also be the front line of support for the elderly and vulnerable.

Also, antibodies can be manufactured as a therapeutic. We can determine the sequences of antibodies that "work", make these at large scale and inject them intravenously. Typically an i.v. IgG will have a half-life of a few weeks in your bloodstream, so it will buy a window of protection for the vulnerable. People are definitely working on this already...
And of course there isn't an answer to the question of how long-term immunity might work out, because we're not yet in the long term of this virus outbreak.

So is that really a decline in immunity to exactly the same virus, rather than the virus mutating to get around immunity? (I was assuming that we don't have a vaccine for the common cold because it's actually caused by a whole range of different viruses.)
The number of antibody molecules in blood and intracellular fluids declines due to pinocytosis. Different types of antibodies have different half lives: IgG have a half-life of 14 - 21 days due to mechanisms that allow them to avoid pinocytosis, others are shorter lived. If you have an active infection some, of course, will be used up attaching to the antigen on the foreign bodies surface, but even when no active infection is occurring, the antibodies get taken out of circulation by pinocytosis, so the level of protection declines, and you'll need a top up. No mutations necessary.

For example, if I remember correctly, travellers used to be given Anti-Hepatitis-A Immunoglobulin vaccinations*, which gave protection for 1 or two months; but now Hepatitis-A attenuated virus vaccines are available (e.g. Havrix) which give (hopefully) life-long protection.

See also
Wikilite.com: Half-life of IgG, IgA and IgM
Arthritis Research » Molecular Immunology: Halflife of Antibodies
Immunoglobulin Therapy & Other Medical Therapies for Antibody Deficiencies

*Which was a ruddy big vaccination in the thigh. Ouch.

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Re: SARS-CoV-2 testing

Post by AMS » Sat Mar 21, 2020 6:56 pm

shpalman wrote:
Sat Mar 21, 2020 6:02 pm
(I was assuming that we don't have a vaccine for the common cold because it's actually caused by a whole range of different viruses.)
Indeed:

Image

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Re: SARS-CoV-2 testing

Post by AMS » Sat Mar 21, 2020 7:20 pm

I think I've heard the UK's chief science advisor comment that viruses tend to evolve to become less virulent over time, and I've been wondering about this. SARS-cov-2 certainly has its opportunity to evolve in the coming millions of cases.

With some back of a fag packet level reasoning, we have a virus that effectively transmits person to person, and importantly can be asymptomatic in many (possibly the majority of?) cases. On top of that, long term we will surely be planning to screen good and hard for this one, because governments world wide are going to want to quickly stamp on any flare ups. Is this enough to create a selection pressure on the virus to become "more asymptomatic", which it is clearly capable of being? Some of the data shows it is able to replicate independently in the throat and lungs, and it's the latter that causes the problems. A strain that loses the lung effects but retains the ability to transmit as a throat infection could have a big selection advantage, and one day become the dominant variant.

Does that make sense or is it just overoptimism?

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Re: SARS-CoV-2 testing

Post by Pucksoppet » Sat Mar 21, 2020 8:08 pm

AMS wrote:
Sat Mar 21, 2020 7:20 pm
I think I've heard the UK's chief science advisor comment that viruses tend to evolve to become less virulent over time, and I've been wondering about this. SARS-cov-2 certainly has its opportunity to evolve in the coming millions of cases.

With some back of a fag packet level reasoning, we have a virus that effectively transmits person to person, and importantly can be asymptomatic in many (possibly the majority of?) cases. On top of that, long term we will surely be planning to screen good and hard for this one, because governments world wide are going to want to quickly stamp on any flare ups. Is this enough to create a selection pressure on the virus to become "more asymptomatic", which it is clearly capable of being? Some of the data shows it is able to replicate independently in the throat and lungs, and it's the latter that causes the problems. A strain that loses the lung effects but retains the ability to transmit as a throat infection could have a big selection advantage, and one day become the dominant variant.

Does that make sense or is it just overoptimism?
I think the trick is to be asymptomatic for as long as possible, transmit as much as possible, and ideally, not kill your host (because the longer your host lives, the more you can transmit).

However, the chief science advisor might, possibly, be working with outmoded thoughts:

PLoS Pathog. 2014 Oct; 10(10): e1004387.
Published online 2014 Oct 23. doi: 10.1371/journal.ppat.1004387
PMCID: PMC4207818
PMID: 25340792
Theory and Empiricism in Virulence Evolution
Early theories of virulence suggested that pathogens would evolve to avirulent commensals since harming the host would be a poor long-term survival strategy. This view was challenged in the mid-20th century as evolutionary biologists and population geneticists considered how competition among different strains of a given pathogen would influence the evolution of virulence (see [6] for an excellent historical review).
[6] J Evol Biol. 2009 Feb;22(2):245-59. doi: 10.1111/j.1420-9101.2008.01658.x.
Virulence evolution and the trade-off hypothesis: history, current state of affairs and the future.

It has been more than two decades since the formulation of the so-called 'trade-off' hypothesis as an alternative to the then commonly accepted idea that parasites should always evolve towards avirulence (the 'avirulence hypothesis'). The trade-off hypothesis states that virulence is an unavoidable consequence of parasite transmission; however, since the 1990s, this hypothesis has been increasingly challenged. We discuss the history of the study of virulence evolution and the development of theories towards the trade-off hypothesis in order to illustrate the context of the debate.
And while not immediately relevant to the above, in my recent reading around, I was impressed by pneumonic plague. Pneumonic plague (which is bacterial) is nasty because it suppresses the immune system[1] and [2] while replicating like mad, so when you do finally start coughing, you are highly contagious. You tend to collapse and die pretty soon afterwards, though. This tends to get noticed, so encouraging people to adopt effective isolation tactics usually works. However, plague has swept through human populations more than once.

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Re: SARS-CoV-2 testing

Post by jstringer1980 » Sat Mar 21, 2020 11:12 pm

Would loop mediated isothermal amplification (LAMP) PCR be an option? Only a pre-print, but looks promising:

https://www.medrxiv.org/content/10.1101 ... 20025155v1

No thermal cycling, so could potentially be done with a lot less resources.

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Re: SARS-CoV-2 testing

Post by shpalman » Sun Mar 22, 2020 10:04 am

If anyone is interested, Compount Interest on the twitter have made a picture

Image
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Re: SARS-CoV-2 testing

Post by shpalman » Thu Mar 26, 2020 8:41 pm

magical test which doesn't exist will allow people to do something they currently cannot once it is invented

"The test can detect the virus in individuals who show no symptoms because it recognises the DNA structure of the virus in the samples."
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Re: SARS-CoV-2 testing

Post by jimbob » Fri Mar 27, 2020 5:02 pm

Meanwhile, after seeing a post by Duck on Facebook, I joined the flusurvey

https://flusurvey.net/

They have now sent me the following email
Hello jimbob,

To better understand the spread of coronavirus and improve its response, we would like to invite you to take part in a self testing survey. We will randomly select a proportion of Flusurvey participants who agree to participate as well as members of their households. If selected, you will receive a home test kit for yourself, as well as for your family members if you agree for them being tested.

The test kit(s) will contain instructions of how to self swab and should be used as soon as possible whether or not you and/or your household members are feeling unwell. Please follow the instructions and return the swab in the reply-paid envelope supplied as quickly as possible. The tests can be posted back to Public Health England using the pre-stamped return envelope included in the kit.

Please note that not everyone who agrees to participate will receive a test and the purpose of this testing is to understand the spread of coronavirus in the community. The testing survey is not designed to be an individual testing service and we may not be able to give you the result of your test. If you would like to help Public Health England better fight the spread of coronavirus and you/your household members consent to being selected to receiving home test kits, please click the link below to take part

Participate in our self swabbing survey.

Thank you so much for being a Flusurvey participant.

Best wishes,

The Flusurvey team
Have you considered stupidity as an explanation


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Re: SARS-CoV-2 testing

Post by Allo V Psycho » Sun Mar 29, 2020 8:45 am

I thought this was generally interesting, if not exactly OT.
https://www.nature.com/articles/s41591- ... lfaRtvcWsA

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Re: SARS-CoV-2 testing

Post by jimbob » Sun Mar 29, 2020 10:12 am

jimbob wrote:
Fri Mar 27, 2020 5:02 pm
Meanwhile, after seeing a post by Duck on Facebook, I joined the flusurvey

https://flusurvey.net/

They have now sent me the following email
Hello jimbob,

To better understand the spread of coronavirus and improve its response, we would like to invite you to take part in a self testing survey. We will randomly select a proportion of Flusurvey participants who agree to participate as well as members of their households. If selected, you will receive a home test kit for yourself, as well as for your family members if you agree for them being tested.

The test kit(s) will contain instructions of how to self swab and should be used as soon as possible whether or not you and/or your household members are feeling unwell. Please follow the instructions and return the swab in the reply-paid envelope supplied as quickly as possible. The tests can be posted back to Public Health England using the pre-stamped return envelope included in the kit.

Please note that not everyone who agrees to participate will receive a test and the purpose of this testing is to understand the spread of coronavirus in the community. The testing survey is not designed to be an individual testing service and we may not be able to give you the result of your test. If you would like to help Public Health England better fight the spread of coronavirus and you/your household members consent to being selected to receiving home test kits, please click the link below to take part

Participate in our self swabbing survey.

Thank you so much for being a Flusurvey participant.

Best wishes,

The Flusurvey team
BTW, if anyone wants to sign up to flusurvey after seeing this, my username is

jimbob
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Re: SARS-CoV-2 testing

Post by Pucksoppet » Sun Mar 29, 2020 10:40 am

Is there a clear text anywhere describing the false positive and false negative rates for PCR-based testing for SARS-CoV-2; and also antibody-based testing?

Laypeople, including me, tend to assume that tests always give correct results, and, crucially, behave as if this were true. I understand the situation is a little more nuanced than that, but apart from knowing that IABMCTT, I don't have a handle on the details.

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Re: SARS-CoV-2 testing

Post by AMS » Thu Apr 02, 2020 8:45 pm

This looks interesting - a new, quicker viral test from a Cambridge Uni / Addenbrookes spin out. Claims a 90 min turnaround on testing. Addenbrookes have been testing it in parallel to the PHE standard, and seem to be happy to run with it for real.

https://www.cam.ac.uk/research/news/rap ... -hospitals

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Re: SARS-CoV-2 testing

Post by shpalman » Fri Apr 03, 2020 8:37 am

Ash Paul on twitter is sharing lots of useful stuff, but in particular
rapid-test.jpg
rapid-test.jpg (74.94 KiB) Viewed 68 times
molto tricky

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