[FRIAM] Papers on asymptomatic transmission and serology

[Steven A Smith]

Barry -

Really great writeup from your daughter in Wellington.   It reinforces
and adds well to what I've been hearing from my own daughter (Molecular
Biologist in FlaviVirus lab at OHSU in Oregon) who have actually run PCR
based tests using the WHO information on themselves (a dozen or so
scientists/techs) as preparation for possibly participating in the
testing with their own gear.  

Joanna's clarification on the likely problem with the "failed" test kits
was useful in particular.

The talk about asymptomatic transmission is central to my own personal
thinking and the models we are assuming in the SimTable work in-progress
that Stephen described yesterday.   It doesn't do as much good to only
build contact graphs with people who are already diagnosed (or
self-diagnosed via symptoms) as it does to have location/contact
information for the pre-symptomatic as well as (fully?) a-symptomatic.  

I am also wondering what others are hearing about (or better have
references to) the possibility of COVID19 survivors antibodies being a
resource for transmitted (via transfusion?) immunity.   Something to
recruit all those "irresponsible youth" for... as I said on the call
yesterday "pay them to stay on the beach in drunken revelry another
month until they all pass it around and recover"   and THEN impress
(persuasively not conscriptively) them into providing serum to their
grandparents instead of having them return from Spring break to closed
schools and moving in with their grandparents, accidentally killing them
in the process <satire>.

How, by the way, is NZ doing with this themselves?  I always think of
them as a sort of safe-haven being as relatively isolated as they are
yet with an anglophone first-world embedding.

- Steve

> In the distributed FRIAM meeting yesterday I mentioned these results,
> but I thought you might also want to see the commentary with them.
> This is an email from last week from one of my daughters (Joanna) who
> is a microbiologist at Victoria University in Wellington, NZ.
>
> —Barry
>
> ————————————
>
> First, the tests. I don't know what happened in the US with testing,
> maybe some of that has come out or maybe will come out. What I do know
> is that testing for RNA viruses is pretty straightforward - you
> extract RNA from the sample and try to quantify it using a PCR-based
> method. This is done around the world for routine surveillance of
> various RNA viruses (norovirus, influenza). There may be a few viruses
> that use antibody-based testing, but that wouldn't be used for the
> coronavirus. The RNA genome sequence of this virus was published early
> on by Chinese scientists, which countries were meant to use to design
> tests. The WHO normally only provides tests to low income countries,
> relying on high income countries (like the US or NZ) to develop their
> own tests. The primers and other reagents that work, all that
> information is out there. There was no need to reinvent the wheel with
> the tests, but from what I understand, the problem with some of the
> kits sent out by the CDC early on had a problem with one of the
> reagents (not the science behind the test). Validation is of course
> important, but again, tests have been clearly validated overseas. The
> usual regulatory safeguards will have to be relaxed around the world
> to keep up with the need for mass testing. The WHO says, test, test,
> test! That is going to be the key to beating this thing. I should add
> that I have full confidence that, despite initial missteps, the US is
> going to eventually get the testing right. It's absolutely essential
> if you (1) don't want to be under nationwide lockdown for 18 months,
> or (2) don't want 2 million Americans to die.
>
> The craziest thing about this virus is the degree to which
> transmission is being driven by asymptomatic people. A Science paper
> just came out claiming about 85% of cases were transmitted by an
> asymptomatic person. Asymptomatic people may be less contagious, but
> they likely make up for it by going to family dinners, work, getting
> on airplanes, shaking hands, giving hugs, etc. Here's the Science paper:
>
> https://science.sciencemag.org/content/early/2020/03/13/science.abb3221
>
> When I first heard about asymptomatic transmission of the virus being
> key, I was very skeptical. Asymptomatic people don't cough or sneeze -
> so how do they transmit the virus? It turns out that they shed large
> amounts of virus anyway - such that breathing or talking is enough to
> infect someone nearby. I became less skeptical when I saw how insanely
> rapid the spread of this thing has been around the world. When
> asymptomatic people are your vectors, tests are absolutely critical.
> It's the only way of knowing if someone could be transmitting the
> disease. And if you don't have testing, you have to assume everyone is
> infected, which is why lockdown is the only alternative response.
>
> The other reason I was skeptical about asymptomatic transmission, or
> the presence of a lot of asymptomatic people, is that this virus
> kills. How can it kill 15-20% of people over 80 but cause an
> asymptomatic infection in so many other people? I don't have an answer
> for that, but it's the essential reason that this virus has shut down
> the globe like it has. All our usual tricks don't work particularly
> well. I will say that microbes with these two extreme outcomes (no
> apparent illness, vs deadly infection) are relatively unusual, and
> that's why we are in this unprecedented situation. On the other hand,
> that particular combination is probably what largely drove the AIDS
> epidemic, so some of this is not new. But for a respiratory infection,
> it is unusual, and unlike AIDS, it is spreading much more rapidly.
>
> And there is still much we don't know about asymptomatic people. Are
> many people never showing symptoms? Or do most of those asymptomatic
> people eventually go on to develop illness? This information is coming
> - for that you need serology - a retrospective look into a population
> to see who was actually exposed to the virus. The great news is that a
> paper that was posted in the past couple of days describes the first
> ELISA test for the virus. That is, they synthesised the (presumed)
> main viral antigen, the spike protein, in the lab, coated plates with
> it, and are now able to tell whether people have antibodies to that
> spike protein. Although this paper hasn't been peer-reviewed yet, it
> is out of a credible lab.
>
> If you want to read the paper yourself:
> https://www.medrxiv.org/content/10.1101/2020.03.17.20037713v1
>
> The implications of this paper are important:
> They only tested a small sample, but people who'd recovered from the
> virus clearly had antibodies to the spike protein. Non-infected
> people, and one person who had recently recovered from a confirmed
> infection with a common, milder coronavirus (which has a similar spike
> protein, attaches to the same human cell receptor) had ZERO
> antibodies. To make a huge extrapolation, there is likely little or no
> existing immunity to this thing (possible exception of SARS
> survivors), which is another explanation for why it has spread so rapidly.
> Scaling up will enable screening of people to see whether they have
> protective immunity to the virus (due to natural infection). This
> would enable you to deploy healthcare workers with immunity to the
> frontlines - i.e., hospitals, caretakers in nursing homes.
>
> This will also enable people to go back and study the wider population
> of places like Wuhan or Seattle. The current data suggest that about
> 20% of Wuhan residents got the illness. But it's possible that many
> more people were infected entirely asymptomatically (i.e., never
> became ill but carry antibodies to the virus). If only 20% of your
> population infected crashes the healthcare system, there is no clear
> strategy for relying on herd immunity. If it turns out it was actually
> closer to 60 or 80% who were infected (enough for herd immunity) that
> changes things. Specifically, it would suggest that Wuhan is less
> likely to get a resurgence of disease if restrictions are eased. At
> this point we have no idea.
> Adoptive antibody transfer - giving antibodies from someone who has
> recovered to someone fighting off the illness - can be explored.
>
> To extrapolate even further, it may turn out that the differences in
> mortality or degree of sickness are not due to preexisting immunity;
> more likely the answer will be in variations in our underlying
> physiology (for example, maybe the virus mainly infects a cell type
> that hasn't matured in most children, rather than that children are
> largely immune).
> In the meantime, we all want to avoid crashing the healthcare system,
> as has now happened in Wuhan, Italy, and Iran. And avoid getting ill,
> especially if in a more vulnerable category. I don't think there's any
> reason to assume that you will necessarily eventually get it. Even in
> the worst case scenarios being played out, it is not 100% of the
> population that is infected. Being very careful, until there is a
> vaccine, can ensure you can be in that part of the population that can
> avoid it altogether. Life is long, and we'll get through this
> challenge together!
>
>
> ============================================================
> FRIAM Applied Complexity Group listserv
> Meets Fridays 9a-11:30 at cafe at St. John's College
> to unsubscribe http://redfish.com/mailman/listinfo/friam_redfish.com
> archives back to 2003: http://friam.471366.n2.nabble.com/
> FRIAM-COMIC http://friam-comic.blogspot.com/ by Dr. Strangelove
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://redfish.com/pipermail/friam_redfish.com/attachments/20200321/330d7751/attachment.html>