
Coronavirus: 'Baffling' observations from the front line - sjcsjc
https://www.bbc.co.uk/news/52760992
======
akkawwakka
The pathology of COVID-19 is really interesting. As the article describes, the
viral pneumonia is well-described, but there are a lot of knock-on effects
from infection of epithelial cells. Namely, virus binding to ACE2 receptors
causes oxidative stress which can give rise to disease and cardiovascular
events. MedCram did a really great video talking through some papers on this
subject. [1]

If you want to learn more, also check out This Week in Virology, a podcast
that has been covering COVID-19 in great detail the last few months. It
features a panel of virologists and other folks in the scientific field
(immunologists, etc) plus a doctor reporting about the situation at a clinical
level.

[1]: [https://youtu.be/Aj2vB_VITXQ](https://youtu.be/Aj2vB_VITXQ)

~~~
sradman
Oxidative stress, why? I’m really confused at why we don’t think of the
mechanics of this disease in terms of the cell and tissue types that express
ACE2 receptors. ACE and ACE2 receptors regulate fluid pressure. ACE increases
pressure by constricting tissue and ACE2 decreases pressure by dilating
tissue.

ACE2 receptors are found in the lungs, blood vessels, heart, kidneys, and
gastrointestinal system. This makes sense and matches the pathogenesis of
SARS-CoV. SARS-CoV-2 also infects the epithelial cells of the upper
respiratory tract, like the cold-like HCoV-NL63.

All the symptoms seem to match the spread of the virus to new tissue types.
The timing matches too, with each new tissue type having an independent
incubation period. Am I missing something? Children only seem to be
susceptible to gastrointestinal infection which looks like Kawasaki’s disease
when it spreads to adjoining blood vessels.

~~~
droopyEyelids
Thats a lot of disputin' for not having clicked the attached explanation
links.

------
mrfusion
These articles can certainly be scary. It might be good to keep the risks in
mind too.

“for people 49 and under, the agency [CDC] estimated that 0.05% of symptomatic
people will die.”

[https://www.cnn.com/2020/05/22/health/cdc-coronavirus-
estima...](https://www.cnn.com/2020/05/22/health/cdc-coronavirus-estimates-
symptoms-deaths/index.html)

~~~
droopyEyelids
That would be comforting if the outcomes were limited to 'death' or 'full
recovery'!

~~~
nkkollaw
From what I got, lung damage was actually caused by unnecessary ventilators.
We now know that the vast majority of people are out of oxygen because of
their blood and not lungs.

This is an extremely mild disease, I would assume that in a few months we'll
know enough to make it a minor inconvenience for most people (more than it
already is, since most people don't even experience symptoms today).

What long-term damage you know of (not saying there isn't, just curious)?

~~~
robbiep
Prolonged ventilation is damaging to the lungs. But ventilation is not given
lightly - usually it is for an acute deterioration and is life saving (ie
without it, patient would have died in that instance).

Interestingly in COVID it appears that positioning and CPAP/BIPAP can be more
effective that venting in edge cases. This is a very new phenomenon in
medicine, and we probably over vented in the early course of the pandemic. We
were acting in what we knew of other severe respiratory diseases, and the case
data from COVID hadn’t had enough time to present best treatment modalities.

However, to suggest that the lungs are not being absolutely ravaged by the
virus infecting, replicating and rupturing lung cells is ludicrous

~~~
nicc
> However, to suggest that the lungs are not being absolutely ravaged by the
> virus infecting, replicating and rupturing lung cells is ludicrous

I was talking about permanent damage. I actually read my comment again, and
that isn't really clear.

Doctors in Italy are saying that ventilators were thought to be useful because
people complained that they couldn't breath, but now they're saying that it's
not the lungs that aren't working, but it's oxygen that is not carried out in
the blood, and that ventilators can actually cause permanent damage in many
cases.

I'm not a doctor, so I just base everything on what the (supposed?) experts
are saying. As far as I know they might very well say that on TV because there
aren't enough ventilators, no idea.

~~~
robbiep
One of the reasons we worked out we could get people through without
ventilators was because we ran out of ventilators. And people with COVid are
being vented for 2 weeks plus. A normal time (and a time that would minimise
Kung damage from a vent) would be several days.

But if someone has saturation’s in the shithouse, they’re going to die. Lack
of oxygen (Hypoxia) in the blood is many many fold more common than severe
thrombosis or whatever else was suggested; and the answer is right there - if
the oxygen isn’t getting to the blood it’s because the lungs are shot. If we
have enough gear, we put someone in ECMO to solve the gas exchange problem.

Lung damage severe enough to do this is caused by the effects of the disease,
not the ventilator

~~~
thu2111
When did we run out of ventilators?

As far as I know nowhere ever ran out of ventilators, not even in Lombardy.
But I sure saw that claim made a lot of times back when people thought that
would happen. Spent a lot of time pointing out the authorities were denying
it'd happened too. I concluded it's very easy for people to mix up "we think
this is about to happen" with "this has happened".

~~~
robbiep
Lombardy was utilising operating theatres and had ICUs and trauma bays full
(70-80% is full because you have lost lost of your surge capacity), using the
vents in all these areas. There was a shift to NIV because once you have no
vents you let people die

~~~
thu2111
80% isn't full. 80% is 80% full and is about normal for an ICU. The whole
point of having some headroom is you can lose it without being full!

------
phyzome
Doctors often want to keep pneumonia patients "dry", that is, somewhat
dehydrated. (That's maybe contributing to the kidney failure.) To what extent
could this also be resulting in increased clotting?

~~~
actualdc1
As someone who has been treating COVID patients since early April, my working
theory has been that many if not most of the secondary disease processes (non-
respiratory effects of the virus), and even to some extent the worsening of
respiratory function, have been largely driven by micro-thrombotic disease.
Delicate capillary beds, like the ones seen in the lungs and kidneys, are
highly susceptible to becoming blocked in this sort of setting. When these
small vessels get plugged up, end-organ dysfunction necessarily follows. The
kidney won't work properly if the blood needing filtration can't reach the
nephron (functional unit of the kidney).

I'm in large part guessing here based on clinical observation, but my feeling
is that you can extend this logic to other syndromes that accompany COVID-19.
For example, we often see worsening liver function in the setting of this
illness (albeit delayed by a few days). This could be explained in a number of
ways, one of which is by impaired perfusion within capillary beds in the
liver. Further, there is a myocarditis-like picture we sometimes see as well
that could be explained by direct viral infection or again by impaired
perfusion of the cardiac muscle by small vessel clotting.

When the thrombotic disease progresses, you start to see a more macro version:
think strokes and pulmonary emboli in patients who are otherwise low risk at
baseline. Thus, there's some interpolation going on here.

Hope that makes some sense.

~~~
mirimir
Hey, it's great to see something from a professional !!!

A dear friend is dying of pancreatic cancer. And one of the key reasons that
she's still alive was getting thrombosis under control. Initially with IV
heparin, and now with Lovenox.

Are those commonly used for COVID patients? Or do they use oral
anticoagulants?

~~~
actualdc1
I'm sorry to hear about your friend. Unfortunately, cancer is one of the big
predisposing factors for thromboembolic disease, so I'm glad to hear that
controlling this issue has helped her along.

Based on our institutional protocol, hospitalized COVID-19 patients receive
therapeutic dose Lovenox, Eliquis, or IV heparin.[1] Lovenox is the first line
treatment, but is contraindicated in patients with, among others things,
severely impaired renal function. If these patients are able to tolerate oral
medications, they can be given Eliquis. If not, they’re typically put on IV
heparin drips (and are subject to the uncomfortable and burdensome blood draws
that come with them).

Typically, all of these patients are discharged on two weeks of Eliquis if
there are no major contraindications. The thinking is that the risk of damage
to the body by microthrombi doesn’t necessarily end just because the patient
is stable enough to go home.

Of course, with all of these medications, preventing clotting has to be
balanced with preventing bleeding. We’ve had to stay vigilant for things like
GI bleeds and hemorrhagic strokes, as these things become more common when
everyone in the hospital is being heavily anticoagulated.

[1] Therapeutic dosing in this case is higher than typical prophylactic
dosing. In the case of Lovenox, it would be something like 40 mg twice a day
for the therapeutic dose versus 40 mg once a day for the prophylactic dose,
which is what would be used in non-COVID-19 patients to prevent
thromboembolism.

------
OJFord
Naïvely I would think factor v Leiden defect (prone to clotting, DVTs) would
be a risk factor, but I understand it's most prevalent in white Europeans and
Americans, which is somewhat the opposite of covid's (suspected vitamin D
related) bias.

Has anyone seen any studies mention it, or otherwise know that it's a silly
suggestion that wouldn't be worth studying?

On second thoughts I think it raises the clotting risk particularly in the
event of severe blood loss, so maybe that's it. Covid patients are clotting
but for unrelated reasons?

~~~
robbiep
You’re choosing a narrow band of the population. Undoubtedly there are
thousands of groups out there who, by way of genotype, phenotype or lifestyle,
are at higher risk.

Teasing these all out is going to be the work of the next decade. It’s all in
the last paragraph - (to paraphrase) ‘we’re having to learn in months what
we’ve had hundreds of years to learn about other diseases’

When I was at Med school I naively thought ‘there will be no new
pathophysiology’ - we knew all the continents and had mapped most of the
interiors, in varying levels of detail. This is an entirely new continent. (So
was vaping associated lung injury actually)

It’s fascinating

~~~
OJFord
It's not that narrow among aforementioned populations though - 15% iirc.

Enough that (again, as a naïve layman) I'd have thought it would be noticed or
considered when discussing clotting and DVT/PEs? And enough to have an
counteracting impact on the opposite African/Caucasian divide that's actually
being seen - not to say that they couldn't coexist, but that if so it'd make
the latter even more dramatic.

~~~
robbiep
From UpToDate:

 _In the general population without a personal history of VTE, a study
involving 1690 unrelated individuals from Europe found a prevalence of FVL of
approximately 4 percent, and a study involving 356 individuals from Canada
found an incidence of approximately 5 percent [47,48]. In a series of 4047 men
and women participating in the Physicians ' Health Study and the Women's
Health Study (both in the United States), the following frequencies for FVL
heterozygosity were found [49]:

●Caucasians – 5.3 percent ●Hispanic Americans – 2.2 percent ●Native Americans
– 1.2 percent ●African Americans – 1.2 percent ●Asian Americans – 0.45 percent

A higher prevalence of FVL (12 to 14 percent) has been reported in populations
in parts of Greece, Sweden, and Lebanon_

Compared to a more likely cause for thrombophilia in the patient population,
ie inflammatory response, endothelial damage, up regulation of clotting
factors; I think focusing on factor V Leiden (and I’m speaking just as a
clinician, not as someone who has had to work with covid patients, we’ve had
relatively SFA here in Australia thankfully) is a footnote. And any patient
who is admitted is going to be on anticoagulants anyway, nullifying most of
any procoagulant effect of FVL in hospitalised patients.

It might show up in the data, it might be a footnote, but treatment would be
covered under normal VTE prophylaxis (and seems like many protocols are now
stepping up fairly significantly the prophylaxis regime)

------
Xcelerate
Anyone know the SNPs for ACE2 expression? Curious which variant I have...

~~~
rogerkirkness
More complex than having "more" or "less" because while the presence of
certain SNPs would mean more expression by default, the presence of the virus
downregulates them, which means you could tolerate "more" virus.

SNPs: rs4646127, rs1996225, rs2158082, rs4830974.

Source:
[https://selfdecode.com/blog/article/ACE2-coronavirus-128](https://selfdecode.com/blog/article/ACE2-coronavirus-128)

------
seemslegit
When your per-capita covid19 mortality rates are almost 200% of the US and
almost 600% of Germany you need all the bafflement your citizens can buy.

------
rapjr9
Personalized medicine has been a big deal lately, which makes me wonder if
perhaps the "weirdness" of COVID-19 is only due to the fact that this disease
is being studied at large scale, across the country and the world. It's
already known that not everyone reacts to drugs the same way, why would we
expect everyone to react to a disease the same way? Western medicine focused
on it's successes with a one disease, one drug model, but just like it's
obvious one drug doesn't always work for everyone, one disease could affect
different people in different ways and could in fact manifest as several
different diseases. Possibly if we had studied flu and colds at scale in the
population we would have found a wide variety of reactions that would also
surprise us.

I also wonder why we seem to never have even tried to cure the flu and colds
(there seem to be only a few tiny research groups studying either). We thought
mapping the genome was impossible till we tried it. The variety of viruses
causing flus and colds caused medicine to make the same claim, impossible to
solve because it's so complex, but is it really that complex? We have 100
candidates for a vaccine for what is essentially a cold virus after a few
months work. What if we'd started working on colds and flu seriously a few
decades ago? Cold and flu cost society tens of billions each year, why have we
lived with this disease burden for so long? I'm not an expert but the
complexity seems less than that of decoding DNA. Is the fact that colds and
flu only kill a few tens of thousands of people a year really a good reason
not to eradicate them? The cost/benefit ratio here seems skewed because the
benefit seems really high and the cost not so high. For one thing, it could
have saved us from this, previous, and future pandemics which have enormous
costs.

~~~
Discombulator
I do not have answers or facts to offer, but I suspect they are similar in
nature to those for the question of “why haven’t we solved security critical
bugs? Why haven’t we just heavily invested in software verification? Etc.”

------
lorsting
Every anti-opinion in the comments was [flagged]. I guess this is done by
algorithms. Only the anti-anti-opinion comments survived.

That above is the main issue with this disease.

~~~
pjc50
No, the situation is that everyone is fed up with contrarians and downvotes
them on sight. Cautious well evidenced dissent should still get through.

------
nkkollaw
This might be a rant, but it would be awesome if these new findings lead to
laws that required doctors to give accurate cause of death for people that
also test positive for COVID.

At least in Italy, doctors were pressured to put "COVID" as cause of death of
people that were given 10 days to live because of cancer and other diseases,
but also tested positive.

Newspapers went as far as saying that a policeman that was shot by a colleague
by accident and had been on a coma for 3 months was the country's youngest
COVID victim, because allegedly he tested positive (of course, they failed to
mention he had been shot and in a coma, other journalists exposed that lie).

From what I read and understood, since in the US hospitals get reimbursed by
number of patients doctors came out saying that they were pressured to put
"COVID" as cause of death even without testing, just because it was presumed
to be COVID because the symptoms matched.

Unfortunately, politicians want power and businesses want to make money—and
other people have their own agenda. This pandemic and been spun out of
proportion by people that gain from it, at the expense of workers and most
importantly small businesses, and at the advantage of China (and perhaps
Amazon)—who are the only ones who are actually making money.

I wish the world was less corrupt—or at least people that are given positions
of power in good faith.

~~~
pjc50
Citation for the shot police officer's name?

People seem to have chosen bad faith attack media and elected bad faith
leaders. That's why the US, UK, and Brazil are doing particularly badly.

~~~
snovv_crash
> That's why the US, UK, and Brazil are doing particularly badly.

And Russia.

~~~
kmlx
And Italy, Spain, France, Germany, Sweden, Turkey, Iran, etc etc

Does anyone know of any large country that managed to:

\- not lockdown

\- keep the disease under control

?

~~~
rumanator
> And Italy, Spain, France, Germany, Sweden, Turkey, Iran, etc etc

This assertion grossly misrepresents the facts.

Italy and Spain were one of the first countries after China to be massively
affected by covid19.

They endured a fast and entirely unexpected rise in infection rates during a
period where WHO was still repeating the Chinese regime's claims that covid19
didn't spread among humans.

Still, once they started to track the disease and register hundreds of of
deaths in patients infected with the disease, they acted decisively. Not only
regarding quarantine and social distancing but also putting up massive field
hospitals like Madrid's IFEMA hospital.

Spain and Italy's government did not overreacted or downplayed the threat. The
UK, US, Brazil and Russia's government started by either pretending it did not
existed, assumed they could ride the wave while doing nothing at all, or that
everything would just kill off a bunch of people and vanish without any need
to worry. Arguably, the government of Brazil is still in the denial stage.

That approach to an epidemic is world's apart than the approach taken by
either Spain or Italy or France or Portugal or Greece or Germany or any other
country in the world whose government decided to act responsibly and looking
after their citizens best interests.

~~~
wolfhumble
I agree about Italy, but I don't agree about Spain.

By March 8th 2020 there were 366 deaths in Italy and over 7000 registered
infected, according to:
[https://www.worldometers.info/coronavirus/country/italy/](https://www.worldometers.info/coronavirus/country/italy/)

The same day the Spanish government let hundred of thousands take part in the
8th of March International Women's Day rallies all over Spain:
[https://www.reuters.com/article/us-womens-day-spain-
idUSKBN2...](https://www.reuters.com/article/us-womens-day-spain-
idUSKBN20V0ZJ)

According to the Reuters article there were already 589 confirmed cases in
Spain at that time, 202 of them in Madrid.

Since Spain did not react earlier I don't think it is right to say the
following about Spain (not referring to Italy here): "Spain and Italy's
government did not overreacted or downplayed the threat".

~~~
Fargren
Spain was following the indications of the OMS at that point. The pandemic was
not declared until March 11th, three days after Woman's Day.

By default, anyone can rally in Spain at any point. They don't seek
authorization for the government, they have it by default. It can only be
revoked and not granted. While there probably was some thought given to
preventing the rallies, given what the OMS was saying at the time it looked
like an over reaction. It was, of course, an error in hindsight, but I don't
think it's indicative of a big failure of leadership.

~~~
narag
I'm afraid politics have been a big part of bad decisions. There were enough
cues to stop the rally and they still _encouraged_ people to go there.

Not that the other side isn't being as idiotic now, asking for raising the
restrictions immediately.

But there's no excuse for March 8th. Different agencies had clearly warned
what was happening and were ignored.

Edit: for fargren, what I mean encouraging:

[https://www.youtube.com/watch?v=9Juy7YnqCTQ](https://www.youtube.com/watch?v=9Juy7YnqCTQ)

For extrangers: it's the vice-prime minister saying on tv that all women
should go to the rallies because "it's a matter of live or death" to them.
Indeed.

There are many facts that have been arising later, like ministry of health
forbidding doctors to attend conventions, police acquiring masks massively and
several medical agencies and organizations advicing against the rallies.

It was a typical case of management discarding what every technician under
them was telling them for politics.

Edit 2: please don't adopt the typical partisan position with "the opposition
was also organizing rallies". No they weren't. There was _one_ party that had
its national convention around the same days. Still, it isn't comparable. The
government had the direct access to the official sources of information and
ignored and hid them.

This isn't a right vs. left matter. More to the left is labour minister Ribera
and she was correct to inform the public of how lockdown scenarios would
affect workplaces. No good deed goes unpunished, everybody attacked her from
all sides... until a few days later it became obvious that what she said was
unavoidable.

In the right wing, Ayuso was correctly willing to wait a couple of weeks more
to open Madrid, when her coalition partner Aguado forced her to ask for
immediate unlock. Central government didn't consent, so change of position was
useless, but now there's a left for lockdown, right for unlock division,
that's it.

I won't go into the masks issue. It's too painful to just recall.

~~~
rumanator
> There were enough cues to stop the rally

This is blatantly and shamelessly false. On the day of the rally there were
zero reported deaths by covid19 in the entire country, let alone Madrid. By
then the total number of confirmed cases in the entire country barely reached
1k.

There isn't a single nation or government in the history of humanity that
decided to lock down an entire country just because there was 1k cases of what
was described by then as a mere atypical form of viral pneumonia.

~~~
mdemare
By March 8th, they had been 3k deaths in Wuhan. It was blatantly obvious by
that time that Covid-19 was dangerous, and also that the testing situation was
such that no one knew how widespread the virus was. Since the strict Spanish
lockdown started just 6 days later, it seems clear that not halting the march
was a big mistake, although it seems unclear how many were actually infected
there.

