Discussion:
Treating Disease with Survivors' Antibodies in Reality and SF
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p***@hotmail.com
2020-04-08 01:49:54 UTC
Permalink
A few days ago the Minneapolis StarTribune had a story about a joint
project between the Mayo Clinic and the University of Minnesota
to treat COVID-19 by infusing patients with plasma obtained from
donors who had recovered from coronavirus and who had antibodies
for the disease in their blood:

https://www.startribune.com/mayo-clinic-to-lead-national-covid-19-plasma-trial-coronavirus-treatment-minnesota/569355782/

This is an old technique, going back at least to the 1918 flu epidemic. It
will have to be used with discretion because the lung damage in COVID-19
is suspected to be caused at least partly by immune system over-reaction.

As it happened, when I saw this in the paper I had just finished reading
_The Med Series_, a collection of Murray Leinster's _Med Ship_ stories about
Doctor Calhoun of the Interstellar Medical Service. Antibody infusion is
used in almost every one of these stories, written from 1957 to 1966.

It makes sense in context. In a future with FTL travel and extensive human
colonization of the galaxy but no FTL communication except for ships, the
Med Service is an austerely funded star-spanning NGO that spreads new medical
techniques and responds to health emergencies. People like Dr. Calhoun in
their minimally sized ships try to see to it that every settled world gets
a planetary health inspection every few years. Needless to say, the published
stories involve situations that are other than routine: pestilence, war,
famine, death, or some combination thereof. As Heinlein pointed out, the
four horsemen are always saddled up and ready to ride. Under these conditions
antibody infusion becomes a very useful technique out in the field with no
immediate back up.

Each ship has one human and one tormal, a non-terrestrial animal perhaps half
a meter tall, similar to a monkey in many respects. Tormals have a very
capable immune system and have never been known to die of disease. If exposed
to a pathogen they will be producing useful antibodies within hours. In itself
this can treat a small number of people and, in conjunction with a modern
medical system, the antibodies can be analyzed and replicated on any scale.
The only time we see this method fail is in _Quarantine World_, where a
bacteria lethal to humans simply doesn't affect tormals, so they don't
need to produce antibodies against it.

This premise of course invites the question of whether a non-terrestrial
animal would produce antibodies that could interface with a terrestrial
immune system. Antibodies are big and complex enough that it not at all
clear that there is only one way to make them. If I were to write something
like this today I would probably make the tormals an organism genetically
engineered from terrestrial stock, similar in concept to Leinster's
Kodiak bears in _Exploration Team_.

Peter Wezeman
anti-social Darwinist
Johnny1A
2020-04-08 03:16:44 UTC
Permalink
Post by p***@hotmail.com
A few days ago the Minneapolis StarTribune had a story about a joint
project between the Mayo Clinic and the University of Minnesota
to treat COVID-19 by infusing patients with plasma obtained from
donors who had recovered from coronavirus and who had antibodies
https://www.startribune.com/mayo-clinic-to-lead-national-covid-19-plasma-trial-coronavirus-treatment-minnesota/569355782/
This is an old technique, going back at least to the 1918 flu epidemic. It
will have to be used with discretion because the lung damage in COVID-19
is suspected to be caused at least partly by immune system over-reaction.
As it happened, when I saw this in the paper I had just finished reading
_The Med Series_, a collection of Murray Leinster's _Med Ship_ stories about
Doctor Calhoun of the Interstellar Medical Service. Antibody infusion is
used in almost every one of these stories, written from 1957 to 1966.
It makes sense in context. In a future with FTL travel and extensive human
colonization of the galaxy but no FTL communication except for ships, the
Med Service is an austerely funded star-spanning NGO that spreads new medical
techniques and responds to health emergencies. People like Dr. Calhoun in
their minimally sized ships try to see to it that every settled world gets
a planetary health inspection every few years. Needless to say, the published
stories involve situations that are other than routine: pestilence, war,
famine, death, or some combination thereof. As Heinlein pointed out, the
four horsemen are always saddled up and ready to ride. Under these conditions
antibody infusion becomes a very useful technique out in the field with no
immediate back up.
Each ship has one human and one tormal, a non-terrestrial animal perhaps half
a meter tall, similar to a monkey in many respects. Tormals have a very
capable immune system and have never been known to die of disease. If exposed
to a pathogen they will be producing useful antibodies within hours. In itself
this can treat a small number of people and, in conjunction with a modern
medical system, the antibodies can be analyzed and replicated on any scale.
The only time we see this method fail is in _Quarantine World_, where a
bacteria lethal to humans simply doesn't affect tormals, so they don't
need to produce antibodies against it.
This premise of course invites the question of whether a non-terrestrial
animal would produce antibodies that could interface with a terrestrial
immune system. Antibodies are big and complex enough that it not at all
clear that there is only one way to make them. If I were to write something
like this today I would probably make the tormals an organism genetically
engineered from terrestrial stock, similar in concept to Leinster's
Kodiak bears in _Exploration Team_.
Peter Wezeman
anti-social Darwinist
In Jack Williamson's _Seetee_ stories, there's an old, semi-literal spacer named McGee. He's got some funny talents, and it develops that he's a mutant of sorts, space adapted. His blood, or rather substances derived from it, turn out to be a cure for extreme radiation exposure, even for patients near the end of the 'walking dead' phase.
Carl Fink
2020-04-08 11:15:54 UTC
Permalink
Post by p***@hotmail.com
This is an old technique, going back at least to the 1918 flu epidemic. It
will have to be used with discretion because the lung damage in COVID-19
is suspected to be caused at least partly by immune system over-reaction.
No.

Survivor plasma contains antibodies, not the actual disease organism. It
doesn't provoke an immune reaction in the patient, it acts directly against
the pathogen.

(If it did provoke an immune reaction, they would not approve it for use.
Obviously there could be bad reactions in a minority of patients.)
--
Carl Fink ***@finknetwork.com
https://reasonablyliterate.com https://nitpicking.com
If you want to make a point, somebody will take the point and stab you with it.
-Kenne Estes
Chrysi Cat
2020-04-08 12:06:49 UTC
Permalink
Post by Carl Fink
Post by p***@hotmail.com
This is an old technique, going back at least to the 1918 flu epidemic. It
will have to be used with discretion because the lung damage in COVID-19
is suspected to be caused at least partly by immune system over-reaction.
No.
Survivor plasma contains antibodies, not the actual disease organism. It
doesn't provoke an immune reaction in the patient, it acts directly against
the pathogen.
(If it did provoke an immune reaction, they would not approve it for use.
Obviously there could be bad reactions in a minority of patients.)
Oy. What's next, distributing the breast-milk of survivors, since it's
known to be able to supplement a baby's immune system with Mom's
antibodies even after said system is starting to tune for itself?

Not that _I_, of all people, would turn down the continuing
infantailisation of the world...
--
Chrysi Cat
1/2 anthrocat, nearly 1/2 anthrofox, all magical
Transgoddess, quick to anger.
Call me Chrysi or call me Kat, I'll respond to either!
p***@hotmail.com
2020-04-08 23:24:53 UTC
Permalink
Post by Carl Fink
Post by p***@hotmail.com
This is an old technique, going back at least to the 1918 flu epidemic. It
will have to be used with discretion because the lung damage in COVID-19
is suspected to be caused at least partly by immune system over-reaction.
No.
Survivor plasma contains antibodies, not the actual disease organism. It
doesn't provoke an immune reaction in the patient, it acts directly against
the pathogen.
(If it did provoke an immune reaction, they would not approve it for use.
Obviously there could be bad reactions in a minority of patients.)
From the Minneapolis StarTribune:

Mayo Clinic announced Friday it is leading a national trial to use donated
plasma from patients who have recovered from COVID-19 as a treatment for
others infected by the novel coronavirus that causes the illness.

The cooperative effort with 40 institutions in 20 states could verify a vital treatment, given that nobody has immunity against the coronavirus that has quickly spread across the globe.

Administered in a handful of U.S. cases already, plasma from recovered
COVID-19 patients could provide immune system boosts to others with the illness.

“Theoretically, it gives them an antibody boost, which should help them clear
the virus,” said Dr. Michael Joyner, the Mayo doctor leading the program.

Joyner said hospitalized patients will be targeted for the therapy, but not
just those with the worst symptoms in intensive care. Immune system
overreactions could actually be hurting some of these patients, meaning that
plasma therapy could be ineffective or even harmful in such cases.

“Certainly in patients that are extremely ill in the ICU, this is a
possibility,” Joyner said. “The thought is that historically this type of
therapy [in other conditions] has been most effective when used relatively
early in the course of disease as people are getting sicker and sicker.

“We’re going to have people trying it for different indications, but I think
that rescue therapy [for severe cases] is going to be an area where it’s
probably going to be relatively less effective.”

................................

It does seem to me that Dr. Joyner is saying that immune system overreaction
rather than the virus itself is part of the problem in some cases. There has
been a lot of back-and-forth from physicians in the media about COVID-19
associated lung problems.

This is from NPR yesterday. I couldn't get a link to work:

It's a strange and tragic pattern in some cases of COVID-19: The patient
struggles through the first week of illness, and perhaps even begins to
feel a little better.

Then suddenly they crash.

"We've seen some patients rapidly worsen," says Dr. Pavan Bhatraju, an
assistant professor at the University of Washington who works in the
intensive care unit at Harborview Medical Center in Seattle. "They initially
were just requiring a little bit of oxygen. In 24 hours they're on a
ventilator."

A recent study by Bhatraju and others found that the patients' lungs appeared
to deteriorate quickly. The crash typically happens seven days into the
disease and can occur in young, otherwise healthy victims of COVID-19.

Now doctors and researchers are increasingly convinced that, in some cases at
least, the cause is the body's own immune system overreacting to the virus.
The problem, known broadly as a "cytokine storm," can happen when the immune
system triggers a runaway response that causes more damage to its own cells
than to the invader it's trying to fight.

Cytokines are a wide cast of small molecules in the body that are released by
certain cells to help coordinate the battle against infection.

Although there's limited data on how the release of too many of these
molecules (the cytokine storm) affects COVID-19 patients, some doctors are
already treating people who have the disease with powerful anti-inflammatory
drugs to try and slow or stop the process. Anecdotally, they say that the
approach appears to be helping.

"The impact was dramatic," says Dr. Daniel Griffin, chief of infectious
disease for ProHEALTH Care Associates, a group of physicians that serves the
New York City area. The first six patients he treated all appear to be
improving, at least for now, he says. "Yesterday was a good day."

But other researchers caution that the untested treatments carry significant
risks. Suppressing the body's immune system at the exact moment it's trying
to fight off the deadly coronavirus could have all sorts of unintended
consequences, warns Dr. Tobias Hohl, the chief of infectious disease at
Memorial Sloan Kettering Cancer Center in New York City. "The infection
could get worse," Hohl says.

Nevertheless, Hohl and others believe that controlling cytokine storms will
turn out to be a critical way to help at least some of the sickest COVID-19
patients. And clinical trials already underway in New York and elsewhere could
soon provide data about how existing drugs should be used.

"I think in a month or two we're going to be able to help patients with
COVID-19, who are dying from cytokine storms, and potentially bring the
mortality rate down," says Dr. Randy Cron, an immunologist at the University
of Alabama at Birmingham.

The body's immune system is, at the moment, the most effective weapon people
have against COVID-19. The majority of patients can cure themselves of the
disease simply by resting at home — enabling a small army of their own cells
to attack the infection. Those cells make it harder for the virus to replicate,
and help to develop antibodies that prevent it from infecting new cells. Those
antibodies also likely help provide some protection against reinfection by
the COVID-19 virus further down the road.

But the army of the immune system can also do collateral damage, Jessica
Hamerman, an immunologist at Benaroya Research Institute in Seattle, explains.
When immune cells try to fight an infection, "they make a lot of toxic
molecules, and those toxic molecules can cause a lot of tissue damage." The
results are familiar to many people who've had the flu: Aches, fever and
inflammation are actually symptoms of the immune system's attack, not of
the influenza virus itself.

The body's immune system is, at the moment, the most effective weapon people
have against COVID-19. The majority of patients can cure themselves of the
disease simply by resting at home — enabling a small army of their own cells
to attack the infection. Those cells make it harder for the virus to replicate,
and help to develop antibodies that prevent it from infecting new cells. Those
antibodies also likely help provide some protection against reinfection by
the COVID-19 virus further down the road.

But the army of the immune system can also do collateral damage, Jessica
Hamerman, an immunologist at Benaroya Research Institute in Seattle, explains.
When immune cells try to fight an infection, "they make a lot of toxic
molecules, and those toxic molecules can cause a lot of tissue damage." The
results are familiar to many people who've had the flu: Aches, fever and
inflammation are actually symptoms of the immune system's attack, not of the
influenza virus itself.

Peter Wezeman
anti-social Darwinist
Carl Fink
2020-04-09 03:19:07 UTC
Permalink
Post by p***@hotmail.com
It does seem to me that Dr. Joyner is saying that immune system overreaction
rather than the virus itself is part of the problem in some cases. There has
been a lot of back-and-forth from physicians in the media about COVID-19
associated lung problems.
Overreaction TO THE VIRUS, not to the antibodies transfused from a different
person.
--
Carl Fink ***@finknetwork.com
https://reasonablyliterate.com https://nitpicking.com
If you want to make a point, somebody will take the point and stab you with it.
-Kenne Estes
Quadibloc
2020-04-09 05:32:18 UTC
Permalink
Post by Carl Fink
Survivor plasma contains antibodies, not the actual disease organism. It
doesn't provoke an immune reaction in the patient, it acts directly against
the pathogen.
True. But since antibodies are produced by the donor's immune reaction, could they
damage the recipient's lungs too?

John Savard
Chrysi Cat
2020-04-09 08:58:58 UTC
Permalink
Post by Quadibloc
Post by Carl Fink
Survivor plasma contains antibodies, not the actual disease organism. It
doesn't provoke an immune reaction in the patient, it acts directly against
the pathogen.
True. But since antibodies are produced by the donor's immune reaction, could they
damage the recipient's lungs too?
John Savard
Apparently not, because almost identically to Spanish Flu, the real
killing is done by the cytokine storm, and cytokines aren't antibodies.
They're a product of white-blood-cell activation. Of course, if
antibodies were doing a sufficient job, white blood count wouldn't GO
through the roof, so the question is whether antibodies are enough to
stop the virus from finding a suitable host cell in the first place.

(Incidentally, it also suggests that if antibody-based immunity isn't
sufficient to prevent re-infection, this thing could go like 1918 in
that the /stronger/ immune systems' owners are the ones killed off in
the reinfection waves. That would be a very "hard therapy" cure for
overpopulation until about 2050, and a brain-breaking moment as any
grandparents to get through Wave One would be burying their
over-12-years-of-age grandchildren in disproportionate numbers).
--
Chrysi Cat
1/2 anthrocat, nearly 1/2 anthrofox, all magical
Transgoddess, quick to anger.
Call me Chrysi or call me Kat, I'll respond to either!
Carl Fink
2020-04-09 14:01:01 UTC
Permalink
Post by Quadibloc
Post by Carl Fink
Survivor plasma contains antibodies, not the actual disease organism. It
doesn't provoke an immune reaction in the patient, it acts directly against
the pathogen.
True. But since antibodies are produced by the donor's immune reaction, could they
damage the recipient's lungs too?
"Could" is vague. Damage to the lungs is not caused by antibodies, but could
in principle be potentiated by it. Remember how I said, if testing shows
dangerous immune activation by the donor plasma it won't be used?

Note that the immune system has several interacting, overlapping, and
sometimes totally disconnected components. In ARDS, the components that
damage the lungs are neutrophils (a type of leukocyte) which migrate to the
lung and release substances that actually cause damage to the lung tissues.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279495/

(That's an oversimplification, but neutrophils seem to be the dominant
immune system component that damages the lungs in ARDS.)

None of this is directly mediated by antibodies, note. Note also that this
is only one component of ARDS, there are also non-immune factors--the virus
itself (in the case of SARS-COV-2 infection) damages the epithelium of the
lung, which can cause fluid leakage and thus ARDS.

A somewhat more technical (!) explanation of immune reaction to infections
is here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828790/

Note that I left out entire major components of the immune system, like the
complement system and T-killer cells. I am not an immunologist, but I
learned enough to know that it is way, way more complicated than non-experts
are even familiar with.
--
Carl Fink ***@finknetwork.com
https://reasonablyliterate.com https://nitpicking.com
If you want to make a point, somebody will take the point and stab you with it.
-Kenne Estes
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