
The neuroinvasive potential of SARS-CoV2 - processing
https://www.ncbi.nlm.nih.gov/pubmed/32104915
======
aazaa
From the paper:

> If the neuroinvasion of SARS-CoV-2 does take a part in the development of
> respiratory failure in COVID-19 patients, the precaution with masks will
> absolutely be the most effective measure to protect against the possible
> entry of the virus into the CNS. It may also be expected that the symptoms
> of the patients infected via facal-oral or conjunctival route will be
> lighter than those infected intranasally. The possible neuroinvasion of
> SARS-CoV-2 may also partially explain why some patients developed
> respiratory failure, while others not. It is very possible that most of the
> persons in Wuhan, who were the first exposed to this previously unknown
> virus, did not have any protective measure, so that the critical patients is
> much more in Wuhan than in other cities in China.

This is a good example of why writing off COVID-19 as no more dangerous than
the flu is itself so dangerous.

I should also point out that most people in the US face similar conditions to
those in Wuhan. The extent of infection is not known, and therefore protective
measures are not in place. We have been actively discouraged from "buying
masks" and told that they are ineffective.

~~~
morpheuskafka
Yes, only a N95 or better mask would protect you from incoming, as opposed to
outgoing, viruses, and these masks are both impractical for everyday wear and
need to be conserved for public health users.

~~~
bluGill
I have a small box of N95 masks in my shop - bought last summer for dust
protection. When is the right time for me to put them on my family. Part of
this is how long will they last before I must replace them. Or should I put
them on eBay for a million dollars and hope I life to enjoy my new found
wealth?

~~~
tdstein
Or you could donate them to your local hospital since there is a shortage. I’m
not sure they would take them, but it’s worth considering.

~~~
ceejayoz
Local hospitals are not going to be able to take masks from some random person
off the street.

------
thijsvandien
As a side observation: most reporting seems rather binary, i.e. you either die
or survive, period. What interests me the most, however, is how often survival
means full recovery, especially now that the nervous system comes up. Are
there any long term effects? Should one generally expect to come out of it
worse, the same, or stronger? I'm much less afraid to die from this than to
end up with chronic respiratory and/or neurological issues.

~~~
Proziam
EDIT - Just to be clear, I'm not saying that people shouldn't take precautions
or that it's not worth protecting vulnerable groups. I'm simply suggesting
that perhaps there is news coverage about other things (remember the whole
Hong Kong situation that we aren't hearing about suddenly?) that might still
deserve some air time.

The media is profiting off this story big time. It's like when the plane went
missing and a news station actually put some moron on the air who said there's
_technically_ a chance a black hole swallowed the plane. It's disgraceful, to
be honest.

That said, it looks like the rate of fatalities is overblown significantly
[0](0.2% in a healthy population (COMPARED WITH THE 3.4% NUMBER BEING SPOUTED
ALL OVER THE PLACE). I've yet to see coverage that is remotely reputable about
long-term health effects after recovery.

EDIT 2 - Case in point about premature statements being made.

> [1]“I think it is likely we’ll see a global pandemic,” said Marc Lipsitch, a
> professor of epidemiology at Harvard T.H. Chan School of Public Health. “If
> a pandemic happens, 40% to 70% of people world-wide are likely to be
> infected in the coming year. What proportion of those will be symptomatic, I
> can’t give a good number.”

followed by:

> [2]"Because I am now less certain of where the R0 will end up (and how it
> may vary geographically) I am going to revise downward the range of outcomes
> I consider plausible to 20%-60% of adults infected. This involves
> subjectivity about what range of R0 may turn out to be true."

[0] [https://institutefordiseasemodeling.github.io/nCoV-
public/an...](https://institutefordiseasemodeling.github.io/nCoV-
public/analyses/first_adjusted_mortality_estimates_and_risk_assessment/2019-nCoV-
preliminary_age_and_time_adjusted_mortality_rates_and_pandemic_risk_assessment.html)

[1][https://www.wsj.com/articles/how-many-people-might-one-
perso...](https://www.wsj.com/articles/how-many-people-might-one-person-with-
coronavirus-infect-11581676200?mod=rsswn)

[2][https://twitter.com/mlipsitch/status/1234879949946814464](https://twitter.com/mlipsitch/status/1234879949946814464)

~~~
NhanH
It is getting annoying that people keeps comparing different numbers to make
their points. If you are using 0.2% mortality rate in a healthy population,
you have to compare it with the flu mortality's rate in a healthy population,
which is still a magnitude lower. It's disgraceful, to be honest, to compare
mortality rates on different population at all. And I'm just gonna quote your
link directly to make my point, I'm fairly upset at people calling it a bad
flu at this point.

"While this correction does not change the assessment that COVID-19 exhibits
severe pandemic potential in the absence of effective interventions, the shift
in framing brought about by this three-fold revision from ‘possibly comparable
to the 1957 flu but not 1918’ to ‘possibly comparable to 1918’ may
meaningfully impact risk perception."

~~~
pbhjpbhj
I'm pretty sure the figures I read were 1% mortality with Covid19, 1:400,000
for flu (in UK). It was that order of magnitude.

So perhaps like saying chlorine is harmless because people drink it. It's a
"well yes, but no ..." situation.

~~~
eveningcoffee
[https://www.who.int/dg/speeches/detail/who-director-
general-...](https://www.who.int/dg/speeches/detail/who-director-general-s-
opening-remarks-at-the-media-briefing-on-covid-19---3-march-2020)

Its CFR is 3.4% according to WHO (actual number may be be higher than this
because it is an early statistic and does not take into account patients that
are still struggling and may eventually die).

------
hirenj
Whether you believe this or not comes down to whether you believe references
32-34 from the paper. I haven't read the stuff about transgenic expression of
human ace2 in mice, but it would sound a lot more like it was aberrantly
expressed, so I'm not counting that. "More evidence needed" is the correct
interpretation here, I believe.

There's other literature out there saying ACE2 is ubiquitously expressed
(including brain) - so that means one of two things: People saying it's
expressed everywhere are wrong, or SARS-COV-2 requires more than ACE2 for
infection. There are papers saying that transfecting cell lines with ACE2
doesn't always render the cells susceptible, so it's probably a good idea to
consider the requirement for a co-receptor.

Like anything, the true answer probably lies in between all these
possibilities.

------
hannob
This is almost a week old, I haven't read about it anywhere else. I have read
and heard plenty of interviews with scientists involved in this in the past
few days and noone has mentioned anything in that direction.

Anyone has any link to secondary sources where other scientists try to put
this in perspective?

------
vilhelm_s
> According to the complaints of a survivor, the medical graduate student (24
> years old) from Wuhan University, she must stay awake and breathe
> consciously and actively during the intensive care. She said that if she
> fell asleep, she might die because she had lost her natural breath

Sounds like something from a horror movie!

~~~
minxomat
Reminiscent of the Polio outbreak/iron lung era. A survivor described the
sound of clicking tounges in iron lung rooms after the electricity had failed
and a few nurses needed to rotate between devices, manually pumping air.
Tounge clicking because no one had the ability to exhale air and produce vocal
sounds.

------
sombremesa
I've only read the abstract, and it seems to clearly say that the virus can
get to the brain via the lungs. So I have no idea what people ITT are on about
regarding purposeful infection or masks for prevention. Regardless, this
abstract also does not explain the mildness of the disease except for the
immunocompromised and elderly, which to me renders the link between how you
get the infection and fatality a bit suspicious.

~~~
TheAdamAndChe
If you read more than the abstract, it explains that animals that are infected
nasally have much higher rates of brain infection than the fecal-oral route of
infection.

Edit: changed "oral/fecal" to "fecal-oral," thanks calmworm. Also removed a
period.

~~~
champagneben
I don't think that was calmworm's qualm with it. Heh.

------
majos
Not a biologist, but reading the paper, the chain of reasoning appears to be
summarized in this section:

> _Taken together, the neuroinvasive propensity has been demonstrated as a
> common feature of CoVs. In light of the high similarity between SARS-CoV and
> SARS-CoV2, it is quite likely that SARS-CoV-2 also possesses a similar
> potential. Based on an epidemiological survey on COVID-19, the median time
> from the first symptom to dyspnea was 5.0 days, to hospital admission was
> 7.0 days, and to the intensive care was 8.0 days 15. Therefore, the latency
> period is enough for the virus to enter and destroy the medullary neurons.
> As a matter of fact, it has been reported that some patients infected with
> SARS-CoV-2 did show neurologic signs such as headache (about 8%), nausea and
> vomiting (1%)._

There's also this rather disquieting anecdote used as evidence of a link to
the nervous system:

> _According to the complaints of a survivor, the medical graduate student (24
> years old) from Wuhan University, she must stay awake and breathe
> consciously and actively during the intensive care. She said that if she
> fell asleep, she might die because she had lost her natural breath._

Supposing that this neurological link is real,

> _the precaution with masks will absolutely be the most effective measure to
> protect against the possible entry of the virus into the CNS. It may also be
> expected that the symptoms of the patients infected via facal-oral [sic?] or
> conjunctival route will be lighter than those infected intranasally. The
> possible neuroinvasion of SARS-CoV-2 may also partially explain why some
> patients developed respiratory failure, while others not. It is very
> possible that most of the persons in Wuhan, who were the first exposed to
> this previously unknown virus, did not have any protective measure, so that
> the critical patients is much more in Wuhan than in other cities in China._

So let me ask a dumb question for someone with actual biomedical knowledge.
Are they saying that infection of the CNS is somehow easier through the nose,
in which case high-quality face masks actually do matter?

I'm also confused by this sentence in the introduction, which appears to
contradict the hypothesis that the upper respiratory tract is a high-impact
area?

> _However, different from SARS-CoV, SARS-CoV-2-infected patients rarely
> showed prominent upper respiratory tract signs and symptoms, indicating that
> the target cells of SARS-CoV-2 may be located in the lower airway._

I will note that, unlike some other papers on this topic, this one has been
peer-reviewed in what seems to be a legitimate medical journal (Journal of
Medical Virology), so there should be some genuine substance here.

~~~
chinathrow
> There's also this rather disquieting anecdote used as evidence of a link to
> the nervous system:

> According to the complaints of a survivor, the medical graduate student (24
> years old) from Wuhan University, she must stay awake and breathe
> consciously and actively during the intensive care. She said that if she
> fell asleep, she might die because she had lost her natural breath.

Would that explain people collapsing suddenly on the streets as seen in Wuhan
and Iran?

~~~
Enginerrrd
No, I think that'd be very unlikely because it'd be a late symptom after
substantial damage has been done. Compared to the frequency of syncopal
episodes I'd expect in people sick with any other cold or flu, I think it's
overwhelmingly more likely to be from other causes.

And if it actually were causing neurological damage, I'd expect still more
causes like seizures and the like.

------
jxy
I see a lot of "may", "possible", "if", ...

Is this how people typically write a paper to Medical Virology?

~~~
shanxS
> Is this how people typically write a paper to Medical Virology?

I wont assume that (I am software engg.)

I see where you are coming from. Here is my perspective, think of this like a
outage of your service. No one has exact answers so team starts to dive in and
starts sharing what they find.

These findings mostly prune the "solution space" of the problem.

~~~
DantesKite
I love that phrase: "...prune the 'solution space' of the problem."

Feels like a new weapon was added to my cognitive toolkit.

------
xenonite
The link should be changed to the publisher‘s page where the pdf is linked.

[https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25728](https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25728)

~~~
mobilefriendly
It's important to see the NIH summary though. Gives the study credibility.

~~~
CamperBob2
Which is actually a problem. Not uncommon to see obvious sham science
propagated with an official-looking PubMed link at nih.gov.

"I'm allergic to WiFi."

"No, you're not. Nobody is allergic to WiFi."

"Yes, I am. Here's an official PubMed citation:
[https://www.ncbi.nlm.nih.gov/pubmed/26372109](https://www.ncbi.nlm.nih.gov/pubmed/26372109)
. Why do you hate science?"

~~~
whatshisface
> _Provocation studies on EMF have yielded different results, ranging from
> where people with EHS cannot discriminate between an active RF signal and
> placebo, to objectively observed changes following exposure in reactions of
> the pupil, changes in heart rhythm, damage to erythrocytes, and disturbed
> glucose metabolism in the brain._

The paper you linked admits that there are studies that show it's the same as
a placebo. Just because most people aren't qualified to realize that the
studies in the first half of the sentence might be more reliable than the
studies in the second half doesn't mean the paper shouldn't be published.

~~~
CamperBob2
So? You can say exactly the same things about ESP or dowsing. Run enough
studies, even properly-conducted ones, and some of them _will_ yield the
results you're hoping for. At that point, all you have to do is either ignore
the others altogether, or leverage them to argue in favor of "teaching the
controversy," as is done in this particular paper.

This strategy is meaningless in terms of scientific value, but it certainly
sounds authentic enough to non-specialists.

------
john_moscow
PDF (link buried within the page):
[https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.25728](https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.25728)

------
liquidforce
If I understand this correctly, could wearing nose clips and only mouth
breathing be an effective strategy to reduce impact?

~~~
sspencer
> It may also be expected that the symptoms of the patients infected via
> facal-oral or conjunctival route will be lighter than those infected
> intranasally.

That seems like the hypothesis they suggest. Interesting implications.

~~~
adatavizguy
All the people who were made fun of in middle school for being a 'mouth
breather' will have the last laugh.

~~~
W4ldi
'mouth breathing' is actually really bad for you.

~~~
Kiro
How so?

~~~
throwanem
Your nasal passages include structures called "conchae" which, among other
purposes, secrete mucus to capture small and potentially disease-carrying
particles from incoming air. [1] It's not a perfect defense, of course, but
better to have it than not - and when you breathe through your mouth, you
don't get the benefit.

[1]
[https://en.wikipedia.org/wiki/Nasal_concha#Immunological_rol...](https://en.wikipedia.org/wiki/Nasal_concha#Immunological_role)

------
newsbinator
If it did turn out this virus is neuroinvasive and that is what causes acute
respiratory problems, how would this be prevented/mitigated/treated,
theoretically?

~~~
testplzignore
This may sound very stupid, but...

As a sort of "vaccine", would it make sense to have people intentionally
infected orally so they build up antibodies before it has a chance to spread
to their brain?

~~~
newsbinator
I was thinking the same thing. I'd love an expert to tell us to what degree
that's silly.

------
citboin
Great. I work in an E.R. and my neurological system is already being ravaged
by M.S. I'm not sure that I would not just walk off of the job if we are
inundated with COVID-19 patients.

------
vorticalbox
Question what effect is vaping having on the spread? Walking in a city in the
UK I see people leave large plumes of vaper which seems to me be an excellent
transport system.

Warm and wet.

~~~
geggam
Score one for the cigar / tobacco smoker

~~~
SketchySeaBeast
As it would seem to affect smokers harder, I'd call that a draw.

~~~
geggam
Cigar smokers FTW...they dont inhale ;)

~~~
SketchySeaBeast
In that case, it seems like an even weirder affect to take on - none of the
nicotine, all of the bad breath and mouth cancer.

~~~
geggam
You absorb nicotine in the mouth. You dont get tar in your lungs.

No smoking is good for you but then again the leading cause of death is birth
so enjoy the time you have. If cigars are your thing smoke it up

~~~
SketchySeaBeast
In that case I guess you probably shouldn't be trying to keep score in regards
to your vice.

------
endorphone
It is interesting how absolutely _passionate_ some people are about masks.
There is a pretty heady contingent here that seems to be of the "I DID MY
PART" sort (by mindlessly pushing an absurd anti-science anti-mask angle -- I
was one of the silly minority countering it a few days ago, to very little
effect).

"If you wear a mask your testicles will shrink and everyone will hate you!"

But the more important question: Is it time to stop trimming nose hairs?

------
biolurker1
Was this forced to second page?

------
pombrand
Airborne viral particle protection: N95 masks may only be effective used with
eye protection. Surgical masks may not help at all.

Looked for interventional studies testing whether face masks and eye
protection work in humans to protect against airborne viral particles. A
critical issue with many such studies is that medical staff only use masks
and/or eye protection at work, opening them to being infected outside of work.

Found a small study [1] getting around this problem by exposing subjects (n =
28, avg age 30.5 years) to monodispersed live attenuated influenza vaccine
particles by placing them in front of a vibrating-orifice aerosol generator
for 20 minutes, subsequently testing for infection using RT-PCR and culture in
nasal washes.

Surgical mask: 3M 1818 | N95 mask: 3M 1860/1860S | Eye Protection: Z87 Uvex
non-vented

\-----------------------------------------------

RESULTS

\-----------------------------------------------

No precautions: 4 out of 4 infected.

Ocular exposure only: 4 out of 4 infected.

Surgical mask only: 5 out of 5 infected.

Surgical mask + eye protection: 5 out of 5 infected.

N95 mask only: 3 out of 5 infected.

N95 mask + eye protection: 1 out of 5 infected.

1\. Bischoff WE, Reid T, Russell GB, Peters TR. Transocular entry of seasonal
influenza-attenuated virus aerosols and the efficacy of n95 respirators,
surgical masks, and eye protection in humans. J Infect Dis.
2011;204(2):193–199.

------
daun
I was actually wondering about this because both the Spanish Flu and the 2009
H1N1 pandemics left life-long brain damage for some survivors in the form of
narcolepsy with cataplexy. The vaccine for H1N1 caused it in a very small
amount of patients as well. After the Spanish Flu they called it "encephalitis
lethargica". It appears that it damages the hypothalamus.

------
daenz
Who wants to help make a design file for 3d printed nose plugs? If blocking
the intranasal path is effective in preventing the CNS infection, as this
paper suggests, nose plugs should be effective here.

------
nswest23
don't forget that the title includes the following:

"...may be at least partially..."

------
Santosh83
I thought papers dealing with this virus were to be made available publicly?

~~~
rolph
go here:

[https://sci-hub.se/10.1002/jmv.25728](https://sci-hub.se/10.1002/jmv.25728)

keep in mind this is a preliminary, the grammar used in this paper needs to be
revised so as to avoid as much as possible, people coming to errant
conclusions after misinterpreting poorly written phrases.

so that means that while reading this paper one should not skim but should
take the effort to interpret this paper.

there is an absence of references in the abstract, this makes it hard to
examine the basis for statements in abstract

~~~
rolph
if you head down to page 4 of the paper there is where you will find
references to background literature cited regarding "neuroinvasive potential"

[1] Glass WG, Subbarao K, Murphy B, Murphy PM. Mechanisms of host defense
following severe acute respiratory syndrome-coronavirus (SARS-CoV) pulmonary
infection of mice. J Immunol 2004;173:4030-4039.

[https://doi.org/10.4049/jimmunol.173.6.4030](https://doi.org/10.4049/jimmunol.173.6.4030)

[11] Li, Y.-C., Bai, W.-Z., Hirano, N., Hayashida, T., Taniguchi, T., Sugita,
Y., … Hashikawa, T. (2012). Neurotropic virus tracing suggests a membranous-
coating-mediated mechanism for transsynaptic communication.

[https://doi.org/10.1002/cne.23171](https://doi.org/10.1002/cne.23171)

------
vernie
How many fucking names does this thing have?

~~~
nkohari
Yes, it's a little confusing. [0]

2019-nCoV (2019 Novel Coronavirus) was a temporary name.

SARS-CoV-2 (Severe Acute Respiratory Syndrome-related Coronavirus 2) is the
official name for the virus.

COVID-19 (Coronavirus Disease 2019) is the official name for the disease that
the virus causes.

[0] [https://www.sciencemag.org/news/2020/02/bit-chaotic-
christen...](https://www.sciencemag.org/news/2020/02/bit-chaotic-christening-
new-coronavirus-and-its-disease-name-create-confusion)

------
clon
Would this explain the apparent sudden collapse of people on the streets in
China and Iran? [1]

[1] [https://www.snopes.com/fact-check/people-collapsing-
coronavi...](https://www.snopes.com/fact-check/people-collapsing-coronavirus/)

~~~
viggity
Folks, if you see someone collapse on the street and they're wearing a mask.
TAKE THE MASK OFF OF THEM. They're not getting enough oxygen. It is taxing to
breath through an N95 mask. Source: I passed out when I put on a surgical mask
while my wife was getting an epidural. Not from seeing the needle because I
didn't even see the needle, and I don't get squeamish anyway. I have low blood
oxygen and it was too hard to breath through the mask.

~~~
sdinsn
Perhaps I'm selfish, but if I see someone wearing a mask and they collapse,
the last thing I'm going to do is get near them...

