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Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
@NickAnderegg
Jul 29, 2024 • 37 tweets • 15 min read • Read on X
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Let me start by saying AAAAAAAAAAAAAAAAAAAAAA.

Turns out SARS-CoV-2 RAPIDLY infects the NERVOUS SYSTEM long BEFORE it even enters the bloodstream.

These findings have huge implications! Here's an analysis of the study, written for a general audience. (Sorry in advance!)

1/many Published July 28, 2024 in IJMS: "SARS-CoV-2 Rapidly Infects Peripheral Sensory and Autonomic Neurons, Contributing to Central Nervous System Neuroinvasion before Viremia" Abstract: "...little attention has been paid to susceptibility of the PNS to infection [by SARS-CoV-2] or to its contribution to CNS invasion. Here we show that sensory and autonomic neurons in the PNS are susceptible to productive infection with SARS-CoV-2 and outline physiological and molecular mechanisms mediating neuroinvasion. Our infection of K18-hACE2 mice, wild-type mice, and golden Syrian hamsters...
Overall, it's pretty extensive: They examined the productivity of neuronal infection in multiple animal models and multiple neuronal cell cultures, and found productive neuronal infection across the board.

It's also a long one, but we'll pick up the pace as we go!

2/ Figure 3. SARS-CoV-2 infection of the olfactory bulb and various brain regions in hACE2 and WT mice. SARS-CoV-2 RNA was detected in increasing concentrations from 3 to 6 dpi in the olfactory bulb (a), hippocampus (b), cortex (c), brainstem (d), and cerebellum (e) of hACE2 and WT mice in both inoculum groups.
So, as you may already know, neurological symptoms are actually VERY common when it comes to COVID, with several different types of neurological issues being notable features of Long COVID. There's seriously so much evidence beyond these 13 citations!

3/ "Up to 80% of people infected with SARS-CoV-2, the virus responsible for COVID-19, report neurological symptoms. ... including [with] sensory and autonomic systems [1–3]. Both central and peripheral symptoms, such as fatigue, memory issues, “brain fog”, hyper/hypoesthesia, and autonomic dysfunction, can persist as part of postCOVID-19 syndrome (“long COVID”) long after acute infection [4]. Detection of the virus, viral RNA, and antigens in the cerebrospinal fluid and brains of COVID-19 patients indicates SARS-CoV-2 is neuroinvasive, which has also been documented for common cold and ep...
The ability of SARS-CoV-2 to invade the nervous system is not news on its own! (For example, see )

This study, instead, looks at all the other possible routes of neuroinvasion that have been somewhat neglected UNTIL now!

4/
 pandemicpatients.org/home/covid-19-…

"As anosmia is a primary symptom of COVID-19, early studies assessed CNS invasion via olfactory sensory neurons (OSNs) using transgenic mice expressing human angiotensin converting enzyme 2 (hACE2), the receptor for SARS-CoV-2. ... However, the oronasal mucosa and target organs of SARS-CoV-2 (lungs, gut) are heavily innervated by sensory and autonomic neurons of the PNS, providing an alternative route of entry directly into peripheral neurons from the mucosa rapidly upon infection, which could facilitate invasion into functionally connected CNS tissues. However, little attention has be...
Their goal was to "determine if infection of the PNS [peripheral nervous system] preceded and contributed to CNS [central nervois system] infection," by examining the mucosal tissues with lots of PNS connections.

[Spoiler: Turns out, it super-duper does.]

5/ "To determine if infection of the PNS preceded and contributed to CNS infection, we assessed early neuroinvasion of CNS tissues functionally connected to peripheral neurons innervating oronasal and gut mucosa (lumbosacral spinal cord and specific brain regions [olfactory bulb, cortex, hippocampus, brainstem, cerebellum]). ... We focused on early neuroinvasion of ancestral SARS-CoV-2, as differences in neurological symptoms between variants are only beginning to be reported. A recent epidemiological study has shown the odds ratio for developing post-COVID-19 syndrome following infectio...
In the first reported study, they did a comparison between:
- "wild type" mice (WT)
- human ACE2-expressing mice (hACE2)

which were exposed to the SARS-CoV-2 variant from 2020—specifically, the isolate from one of the first cases detected in the US! (So, first wave.)

6/ "4.3. Viruses SARS-CoV-2 isolate USA-WA1/2020 (NR-52281; BEI Resources) was passaged twice using Vero E6 cells (ATCC, CRL-1586) by the Bertke Lab to produce viral stock for mouse and primary neuronal culture infections. USA-WA1/2020 was recovered from an oropharyngeal swab taken from a 35-year-old male in Washington state in January 2020 who was diagnosed with COVID-19 after returning from visiting family in Wuhan, China. ... 4.4. Mouse Infections Eight to ten-week-old immunocompetent adult male and female B6.Cg-Tg(K18-ACE2) 2Prlmn/J mice and their wild-type C57BL/6J counterparts we...
The mice were innoculated with SARS-CoV-2 (by spraying it up their noses), then letting it run its course, with various diagnostic tests along the way.

They confirmed low levels of blood and lung infection at 3 and 6 days post-infection in both groups, as expected!

7/ "2. Results 2.1. Clinical Data To assess the susceptibility of PNS and CNS neurons to SARS-CoV-2 infection, we intranasally (IN) inoculated hACE2 and WT mice with 10 3 or 10 5 PFU SARS-CoV-2 USAWA1/2020 (n = 12/group; Figure S1a). Animals were monitored daily and tissues collected three and six days post-infection (dpi). Weight loss began 3 dpi and death occurred 6 dpi (14%) in hACE2 mice inoculated with 10 5 PFU (Figure S1b). While only one hACE2 mouse in the 10 5 PFU inoculated group succumbed to infection during our study, infection likely would have been universally fatal at la...
The Trigeminal Ganglia (TG) connects *sensory nerves* from the mouth and nose to the brainstem.

The Superior Cervical Ganglia (SCG) is part of the *sympathetic nervous system*, connecting glands (saliva, tears) and head/brain vasculature to the CNS.

8/ "2.2. PNS Sensory Trigeminal Ganglia (TG) and Sympathetic Superior Cervical Ganglia (SCG) Neurons Innervating the Oronasopharynx Are Susceptible to Infection Both sensory and sympathetic pathways through TGs and SCGs, respectively, could serve as neural routes for neuroinvasion of the CNS. Trigeminal nerves provide sensory innervation to oronasal mucosa, projecting their central processes into the brainstem. SCGs provide sympathetic innervation to salivary and lacrimal glands and vasculature of the head and brain, with preganglionic neurons residing in the spinal cord. Thus, sensory a...
Before we get to the results, I want to pause to note that if you are reading this, what happened to these mice has DEFINITELY NOT happened to you to anywhere near the same extent! If the mice weren't euthanized for dissection, they would have ALL died from the infection.

9/
SARS-CoV-2 was found in both TGs and SCGs, in BOTH groups—hACE2 mice AND WT mice.

In both group, the viral concentration increased over time, suggesting there was active viral genome replication occurring.

But, hACE2 neurons in the SCG, in particular, basically fell apart.

10/ "To assess susceptibility of these peripheral neurons to infection with SARS-CoV-2, TGs and SCGs were assessed for viral RNA, proteins, and infectious virus. We detected viral RNA at 3 and 6 dpi in TGs and SCGs in both inoculum groups in hACE2 and WT mice. Viral RNA concentrations were lower in WT than hACE2 mice (Figure 1a,b) but increased over time in TGs and SCGs of both, suggesting genome replication. Immunostaining detected nucleocapsid (SARS-N) in ≈ 41% of TG neurons of hACE2 mice and ≈ 37% of TG neurons of WT mice (Figures 1c,d and S2a). Nearly all SCG neurons from hACE2 mice ( ...
In the hACE2 mice infected with SARS-CoV-2, about 97% of the neurons in the SCG were positive for the nucleocapsid (N) protein, "showing substantial pathology with vacuolated neurons and loss of ganglionic architecture."

So... not great.

11/ Note: - Trigeminal Ganglia (TG) connects mouth/nose sensory nerves to brainstem. - Superior Cervical Ganglia (SCG) connects tear/saliva glands and head/brain vasculature to CNS --- Figure 1d. Immunofluorescence for SARS-CoV-2 nucleocapsid (SARS-N, grey)- and NeuN (red)-labeled neurons in TG and SCG sections at 6 dpi in 10 5 PFU-inoculated mice. SARS-N was more prevalent in hACE2 than in WT but observable in both. No SARS-N was detected in ganglia from uninfected animals. Neurons in SCG were particularly sensitive to infection; in the magnified single z-plane of the area shown in the yello...
If you're now wondering about the spike protein: They found it in both ganglia, in hACE2 and WT groups!

However, infectious virus "was not detected in SCGs." Why?

"SARS-CoV-2 may have produced such significant cytotoxicity that production of viral progeny was impossible."

12/ Figure 1e. Immunofluorescence for SARS-CoV-2 spike (SARS-S, grey)- and NeuN (red)-labeled neurons in TG and SCG sections at 6 dpi in 10 5 PFU-inoculated mice. Immunostaining was similar to that for SARS-N, with greater SARS-S in hACE2 neurons, but present in both. Vacuolization was again observed in SCG neurons. SARS-S was absent in uninfected neurons.
That's a very scientific way of saying "it so thoroughly damaged the cells of the hACE2 Superior Cervical Ganglia that they kinda stopped being cells."

Thus, they conclude "TGs may serve as a route of CNS invasion" AND "neuroinvasion can occur independently of hACE2."

13/ "Immunostaining detected spike (SARS-S) in both ganglia similar to detection of SARS-N (Figures 1e and S2b). Viral genome replication was confirmed by double-stranded RNA (dsRNA) immunostaining in both ganglia (Figures 1f and S2c). Infectious virus was recovered in TGs from one 10 5 PFU-inoculated hACE2 mouse at 3 dpi (5 PFU/mg homogenate) and another at 6 dpi (2 log PFU/mg homogenate). Infectious virus was not detected in SCGs. The pathology of the ganglia suggests SARS-CoV-2 may have produced such significant cytotoxicity that production of viral progeny was impossible. The use of mu...
Now that we've have the conceptual groundwork for what they're doing, we can go a bit quicker! I'm also going to stop writing out terms from the excerpts that are identified by acronyms, for brevity.

Next up, nerves for sensory information from limbs and internal organs!

14/
The LS-DRG is a PNS nerve cluster that "conveys sensory information (pain, pressure, position) from the periphery [limbs] and internal organs" to the LS-SC. The LS-SC is the part of the spinal cord where the peripheral nerve bundle connects to the CNS.

15/
"2.3. PNS Sensory Lumbosacral Dorsal Root Ganglia (LS-DRG) and CNS Lumbosacral Spinal Cord (LS-SC) Neurons Are Susceptible to Infection Extending our investigation beyond PNS innervations of the oronasopharynx, we assessed the LS-DRG and LS-SC as above. The LS-DRG conveys sensory information (pain, pressure, position) from the periphery and internal organs to the LS-SC."
Image
Viral RNA was found in both LS-DRG and spinal cord, for both the hACE2 and WT mice.

The nucleocapsid protein was found in about 42% of LS-DRG neurons of hACE2 mice (24% for WT mice), and results for the spike protein were similar.

Satellite glial cells were also infected.

16/ 2.3. PNS Sensory Lumbosacral Dorsal Root Ganglia (LS-DRG) and CNS Lumbosacral Spinal Cord (LS-SC) Neurons Are Susceptible to Infection Extending our investigation beyond PNS innervations of the oronasopharynx, we assessed the LS-DRG and LS-SC as above. The LS-DRG conveys sensory information (pain, pressure, position) from the periphery and internal organs to the LS-SC. Similar to our results from TGs, we detected viral RNA at 3 and 6 dpi in LS-DRGs in both inoculum groups in hACE2 and WT mice (Figure 2a). RNA concentrations increased over time, suggesting genome replication. Similar result...
Furthermore, they stained the spinal cord nerve cells and found a diffuse signal (not pictured).

"These data further demonstrate that PNS sensory neurons, as well as functionally connected neurons in the spinal cord, are susceptible to infection with SARS-CoV-2."

17/ Figure 2: (d) Immunofluorescence for SARS-N (grey) and NeuN (red) in LS-DRG sections from 10 5 PFU-inoculated and uninfected hACE2 and WT mice at 6 dpi. SARS-N was more prevalent in hACE2 than in WT but observable in both. No SARS-N was detected in uninfected mice. Detection of RNA and SARS-N in peripheral neurons with no direct connection to the oronasopharynx suggests spread via hematogenous dissemination or via axonal transport. (e) Immunofluorescence for SARS-S (grey) and NeuN (red) in LS-DRG sections from 10 5 PFU-inoculated hACE2 and WT mice at 6 dpi. SARS-S immunostaining was simila...
Next, they looked at multiple brain regions (olfactory bulb, hippocampus, cortex, brainstem, and cerebellum).

They found viral RNA in all of them at 3 days post-infection, which then increased at 6 dpi.

The quantities of RNA in WT mice suggests ACE2-independent spread!

18/ "2.4. Individual Brain Regions Support Varying Levels of Viral Invasion and Reproduction To determine if SARS-CoV-2 was present in specific brain regions with functional connections to PNS ganglia, we assessed the olfactory bulb, hippocampus, cortex, brainstem, and cerebellum. Previous studies have tested brain homogenates to assess viral RNA and infectious virus in the brain, which does not allow for spatial analysis and may obscure detection of low levels of virus in specific brain regions [14,16,26–28]. We detected viral RNA in all brain regions at 3 dpi, which increased by 6 dpi, ...
Viral RNA and infectious virus were recovered from allll over the brains of both the hACE2 mice and (unexpectedly) the WT mice. They note that "viral RNA and the infectious virus were readily recoverable throughout WT brains"

19/ "Infectious virus was recovered from the hippocampus and brainstem as early as 3 dpi in hACE2 mice, supporting viral spread into the CNS from the PNS. Unexpectedly, infectious virus was also recovered from the hippocampus and brainstem from WT mice at 6 dpi. These results indicate that viral invasion and replication in the brain is not uniform, that the highest concentrations of virus are found in areas connected to the trigeminal and limbic systems, and that neuroinvasion is not solely dependent on hACE2 .... To further assess localization of SARS-CoV-2 in brain regions, we immunostai...
They conclude: "These results indicate that viral invasion and replication in the brain is not uniform, that the highest concentrations of virus are found in areas connected to the trigeminal and limbic systems, and that neuroinvasion is not solely dependent on hACE2..."

20/ Figure 3. SARS-CoV-2 infection of the olfactory bulb and various brain regions in hACE2 and WT mice. SARS-CoV-2 RNA was detected in increasing concentrations from 3 to 6 dpi in the olfactory bulb (a), hippocampus (b), cortex (c), brainstem (d), and cerebellum (e) of hACE2 and WT mice in both inoculum groups.
Then, when they cultured the virus in neurons, they found infectious virus in the PNS sensory neurons, but not the autonomic neurons. This suggests that while autonomic neurons can be infected, they can't produce viral progeny.

Weird!

21/
"2.5. SARS-CoV-2 Productively Infects Primary Cultured PNS Sensory but Not Autonomic Neurons from Adult Mice To confirm that PNS sensory and autonomic neurons are both susceptible and permissive to infection with SARS-CoV-2, resulting in release of infectious virus, and to establish basic replication kinetics of SARS-CoV-2 in PNS neurons, primary neuronal cultures were established from LS-DRGs, TGs, and SCGs from 8-10-week-old hACE2 and WT mice. ... Viral RNA levels increased in SCG neurons of hACE2 and WT mice, although the increase was mostly in cells, not media (Figure 4a). Infecti...
Figure 4. SARS-CoV-2 infection of primary PNS neuronal cultures from SCG, TG, and LS-DRG of hACE2 and WT mice. (c) hACE2 neuronal cultures: immunofluorescence for SARS-N (grey)... SARS-N was observed in neurons from each of the ganglia. ... At 3 dpi, many infected neurons exhibited cytopathologies such as degraded neurites, enlarged multi-nucleated cell bodies (arrow) compared to uninfected neurons (arrowhead), and SARS-N+ puncta reminiscent of viral replication compartments. (d) WT neuronal cultures: immunofluorescence for SARS-N (grey)... Immunostaining revealed a similarly heterogenous...
Headline result: Does neuroinvasion of the PNS/CNS occur BEFORE the virus enters the bloodstream?

"By 18 [hours post-infection], although no viral RNA was detected in blood..., viral RNA was detected in all PNS ganglia and the majority of functionally connected CNS tissues"

22/ "2.6. Neuroinvasion of the PNS and CNS Occurs before Viremia To determine if neuroinvasion is driven by hematogenous entry or direct neuronal entry, PNS and CNS tissues were assessed 18 and 42 hpi after intranasal inoculation of hACE2 and WT mice (Figure 5a,b). By 18 hpi, although no viral RNA was detected in blood at this time point, viral RNA was detected in all PNS ganglia and the majority of functionally connected CNS tissues in both hACE2 and WT mice. Additionally, viral RNA was present in the salivary glands, innervated by SCG."
Then, at 42 hours post infection, the virus was still only found in the blood of a single hACE2 mouse, but there was increased viral RNA in the brain.

They replicated this study with a different animal model and got roughly the same results. This is thorough work!

23/ "By 42 hpi, viremia was only detected in a single hACE2 mouse, and viral RNA had increased in all hACE2 PNS and CNS tissues except SCGs. In WT mice, viremia was not detected, and viral RNA was no longer detected in salivary glands, SCGs, or LS-DRGs but had increased in some brain regions by 42 hpi. Immunostaining did not detect SARS-N in any tissues, indicating the virus was transiting through PNS tissues when collected but had not yet begun replication or was below the level of detection... To verify that these results were reproducible in an alternative non-transgenic animal model, ...
In the other animal model (hamsters), they conclude "neuroinvasion occurs rapidly..., is mediated by invasion of and transport along neurons, can occur independent of hACE2, and functionally impacts PNS sensory neurons, resulting in allodynia [pain from mild stimulation]."

24/ "In light of the LS-DRG/spinal cord infection observed in mice, the functional impact of infection on the sensory nervous system was assessed. Using the von Frey assay, a significant decrease (p = 0.0001) in the amount of pressure required to elicit a withdrawal reflex was noted, demonstrating allodynia (Figure 6d). Allodynia occurred rapidly as a consequence of infection; 55% (n = 5 of 9) of hamsters demonstrated allodynia by 18 hpi, and all remaining hamsters (n = 3 of 3) by 3 dpi. Thus, neuroinvasion occurs rapidly after infection, is mediated by invasion of and transport along neur...
So what's the deal with non-hACE2 mice and hamsters getting infected? How is infection occurring independent of ACE2 receptors?

It just uses a different receptor to enter the cells: NRP-1.

It was previously known SARS-CoV-2 could use this receptor, and this supports that!

25/ "2.7. Neuronal Entry in the PNS Involves Neuropilin-1 (NRP-1) NRP-1 has been shown to interact with SARS-S, thereby enhancing viral binding/ entry in non-neuronal cells [30-32]. ...we investigated the contribution of NRP-1 to entry in primary PNS sensory neurons. ... Primary cultured LS-DRG neurons from hACE2 and WT mice were pretreated with EG00229, a selective NRP-1 antagonist, infected with SARS-CoV-2, and viral RNA concentrations were assessed 2 dpi, the first peak for genome replication as determined in our growth curves. Neurons were observed daily for cytopathic effect from tre...
Three big takeways:

1. SARS-CoV-2 can infect PNS neurons very rapidly after exposure, long before it gets near the bloodstream
2. The virus can move from PNS to CNS via axonal transport before it enters the blood
3. NRP-1 is how it does it independently of hACE2

26/ "While OSNs are a key constituent of the nasal neuroepithelium, the oronasopharynx is innervated by other PNS sensory and autonomic pathways through which SARS-CoV-2 may enter the nervous system. Utilizing hACE2 mice, WT mice, golden Syrian hamsters, and primary PNS neuronal cultures, we show susceptibility of PNS neurons to SARS-CoV-2 infection very early following infection within 18 h of exposure, demonstrating differential replication kinetics and cytopathic outcomes following infection of sensory, autonomic, and central neurons. We also show evidence supporting axonal transport of...
But here's the thing: Not ALL of these results are new. Some of them are just now being tied together neatly in this one study.

IMO, widespread short-sighted research practices made these conclusions take so long to reach. The ball is being dropped with autopsy studies!

27/ "Invasion of the brainstem along projections of the TG could damage nuclei important in cardiorespiratory regulation, a feature of severe COVID-19, and at least one imaging study of a COVID-19 patient with AHNE suggested invasion of the brainstem via the TG [7]. While viral RNA and proteins have been detected in salivary glands of COVID-19 patients, and infectious virus has been recovered from saliva, no assessments of the SCG have been made in human autopsies [39-42]. The SCG provides sympathetic nervous system innervation to the oronasal mucosa, salivary and lacrimal glands, and oron...
At this point, we are only BEGINNING to understand the impact COVID can have on the brain and nervous system.

You know what we DO understand well? How to filter airborne particulate! Wear a filtering respirator in shared air to protect yourself.

28/
"The impact of SARS-CoV-2 on the nervous system is only beginning to be understood, with sensory and autonomic disorders lasting well beyond initial infection, indicating the need for a comprehensive understanding of its impact on the entire nervous system, not just the brain. Case reports/series have described post-COVID-19 syndrome symptoms involving the TG (trigeminal neuralgia), SCG (Horner syndrome), LS-DRG (radicular pain), and spinal cord (transverse myelitis). ... Our revelation of the susceptibility of the TG and SCG to infection may provide insight into clinical observation...
Neuroinvasion "is not a rare event following SARS-CoV-2 infection" and occurs "well before the onset of symptomatic disease."

Now that the pandemic has been DECLARED over, COVID-19 is transitioning to "an endemic disease associated with long-term neurological sequelae."

29/ "We show that neuroinvasion is not a rare event following SARS-CoV-2 infection and that it occurs well before the onset of symptomatic disease. The rapidity of neuroinvasion, as early as 18 hpi, severely limits the availability of human autopsy samples to investigate early neuroinvasion events, as most samples are collected from patients well into their disease process. The presence of infectious virus in these tissues preceding viremia shows that neuroinvasion occurs early in infection via peripheral neural pathways. Further research into these sites of neuroinvasion is necessary with...
Endemic doesn't mean "good." It just means "now we're stuck with it."

Just sit there and stew in that for a minute: "an endemic disease associated with long-term neurological sequelae."

You can ignore it, but it doesn't give a shit what you think! You're just an incubator.

30/ "We show that neuroinvasion is not a rare event following SARS-CoV-2 infection and that it occurs well before the onset of symptomatic disease. The rapidity of neuroinvasion, as early as 18 hpi, severely limits the availability of human autopsy samples to investigate early neuroinvasion events, as most samples are collected from patients well into their disease process. The presence of infectious virus in these tissues preceding viremia shows that neuroinvasion occurs early in infection via peripheral neural pathways. Further research into these sites of neuroinvasion is necessary with...
This paper, however, is pretty damn solid! It really ties a LOT of different lines of research together.

Published today (July 28, 2024) in IJMS, open access:

31/31mdpi.com/1422-0067/25/1…
Even if you're specifically familiar with it in the context of SIRS, it doesn't change the fact that "viremia" literally means, BY DEFINITION, "presence of viruses in the blood."

Your "correction" is 45 years out of date.



32/31
meshb.nlm.nih.gov/record/ui?ui=D…


Viremia MeSH Descriptor Data 2024 Scope Note The presence of viruses in the blood. Previous Indexing specific virus (1966) specific virus disease/blood (1967-1979)
1. Infections > Virus Diseases > Viremia 2. Pathological Conditions > Pathologic Processes > Inflammation > Systemic Inflammatory Response Syndrome > Sepsis > Viremia
Believe me, I went deep on looking for flaws in this one! My day yesterday was just picking apart this paper and cross-referencing every claim that seemed too convenient or tidy. Unfortunately, they did their due diligence and it's pretty solid!

33/31
Moreover, there's not really anything new about this study *methodologically*!

When the references are solid, the stats are solid, and the method is basically just "we followed manufacturer instructions for this protocol x10," there's not much else to poke at for flaws!

34/31
Yup, it's EXACTLY why!

Anosmia is frequently a result of damage to the olfactory nerve:

And several issues people have in LC (including with chewing!) also aligns with the trigeminal nerve:

35/31
ncbi.nlm.nih.gov/books/NBK55605…
ncbi.nlm.nih.gov/books/NBK48228…


"The Olfactory Nerve, Olfactory Tract and Bulb, Filaments, Nasociliary nerve, Nasopalatine nerve"
Trigeminal Nerve Divisions. This illustration shows the distribution of the 3 trigeminal nerve divisions. The ophthalmic division gives rise to the lacrimal nerve and supplies the superior third of the face and skull. The maxillary division supplies the midfacial region. The mandibular division innervates the muscles of mastication and gathers sensory information from the lower third of the face. The trigeminal nerve's semilunar ganglion and sensory and motor roots are also shown.
Oh, yeah... wasn't there some quack on here a few days ago who was saying there's no "disease mechanism" that could explain why chewing is difficult in LC?

It must be humiliating to be a doctor and not be familiar with the concept of trigeminal nerve dysfunction!

36/31 Neuroanatomy, Cranial Nerve 5 (Trigeminal) "The trigeminal nerve is the 5th cranial nerve (CN V) and the largest of the cranial nerves (see Image. Cranial Nerves in the Orbit). CN V provides most of the face's sensory innervation and the mastication muscles' motor stimulation. The nerve's 3 main branches are the ophthalmic (V1), maxillary (V2), and mandibular (V3) nerves. These branches join at the trigeminal ganglia within the Meckel cave in the middle cranial fossa. Trigeminal nerve dysfunction can result in painful conditions like trigeminal neuralgia and difficulties with chewing...
Here is the entire thread about "SARS-CoV-2 Rapidly Infects Peripheral Sensory and Autonomic Neurons, Contributing to Central Nervous System Neuroinvasion before Viremia" on a single page: readwise.io/reader/shared/…

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More from @NickAnderegg

Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Feb 1
Many people are asking for recommendations about what storage media to buy, so here's a buying guide from an experienced data hoarder (me)

The MOST IMPORTANT thing to know is that SOLID-STATE MEDIA IS NOT DURABLE. Flash drives, SSDs, SD cards, etc. are NOT long-term storage.

1/
That's not to say that it's impossible to use solid-state media for long-term storage. It's just that anything with durability guarantees gets prohibitively expensive quickly. Spinning hard drives—as well as DVDs and Blu-ray discs!—are your friend.

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- The way data is stored in solid-state media makes it much more susceptible to bit rot than other media.
- In a spinning hard drive, the moving parts are the most common point of failure.
- When you burn a DVD, that shit is fairly permanent.

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Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Jan 9
I wish people would understand that insurance underwriters have armies of actuaries calculating risks, and if an insurance company drops you, it's because things have changed in such a way that insuring you will take more out of the financial pool than you're putting in

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It sucks, but it's a direct result of the fact that humans are widely inhabiting locations that are rapidly becoming impossible to inhabit safely. If you can't find insurance for your home, it means there's a high likelihood you'll need to move soon anyway.

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You get insurance so that you can replace all of your stuff in the event of a disaster. When the insurance company effectively says "the risk of disaster is so high that insuring you would almost certainly cause us to lose a lot of money," it ALSO means your life is in danger

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Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Jan 5
So here’s the thing about some of the subtle neuro damage related to SARS-CoV-2 infection that I think a lot of people miss: some of the known deficits are correlated with things like impulsiveness and poor emotional control, so we might expect to see deficits there are well

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Consider how impatient people seem to be on the road in the last couple years relative to the 2010s, and I think we have a perfect example of where this is LIKELY already manifesting.

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Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Jan 3
Let's review some major points in the Nukit controversy, since some people are unclear:

- Someone criticized someone's use of Nukit lanterns.
- Nukit attacked the critic because, as noted, this is how they market
- Nukit now demands "mediation" with the community (how??)

1/ @marigoldglitter: "these tools should be used for people who must be in public despite the dangers, not for white men who want to eat in restaurants and maintain the status quo. if this is what you're gonna use these for, give them to a disabled person who can't go to the doctor b/c of risk." Nukit: ""White man" in this case is buying those products from non-white small businesses who are focused on providing the community with effective, tested mitigations at far, far lower costs than anyone else." OP: "Like why are you coming at me with this aggressive...
Nukit: "If you are in the US, and would like to purchase Far-UVC products, we cannot help you at this time. We tried to resolve the issues there, but the US COVID-Aware community was uninterested in mediation or intercession. As a result of that disinterest, a great deal of harm was done. When stock is finished, we will not be selling our products to the Us anymore. If you are in the US and want Nukit products, would like 333 million Americans, many disabled or immune compromised, to be able to access the most affordable Far-UVC on the market, kindly address the people who made it unsa...
So let's look at this a bit more critically. Here is the "evidence" Nukit provided that the didn't say anything racist. First of all, these aren't the comments in question, but it's worth a look anyway.

2/ Ok, I get that "evidence," "citations," and "personal accountability" are going to be called racist, but since people insist on just spewing lie after lie without any pushback- here's what actually happened. @marigoldglitter- a white woman attacked a Nukit customer who was supporting us by showing our products. This is something we rely on to fund research and donations. If our customers do not do this, that money goes to paid advertising. So yes, attacking our customers is attacking our company and directly harming marginalized folks who receive our products. ...
Seems to be framed this way because Nukit knows it's not an adequate explanation, so they're acting like anyone who criticizes them is in the wrong. --- A bigoted comment is a bigoted comment, even if it's not directed at someone who might be personally offended. Of course, Nukit didn't include the comments people actually call racist! --- Nukit is explicitly saying here that they view any criticism as an "attack," because criticisms can potentially hurt their business goals. Fundamentally, Nukit is angry that this usage of their products are being criticized. --- After Nuki...
Let's be clear about what happened here: Someone lamented the unequal access to protective measures and criticized someone who seems to be using a certain device to *maintain the status quo*, and the manufacturer of the device found it unacceptable.

3/
Read 16 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Oct 9, 2024
NEW STUDY! This exploratory study identifies a SPECIFIC PHENOTYPE OF LONG COVID that appears related to NEUROMUSCULAR DISTURBANCE rather than lung damage—and they've termed it Complex Ventilatory Dysfunction!

Breakdown of the paper (thread written for a general audience!)...

1/ Published Oct 7, 2024: "A new phenotype of patients with post-COVID-19 condition is characterised by a pattern of complex ventilatory dysfunction, neuromuscular disturbance and fatigue symptoms" Abstract: Background Patients with post-COVID-19 condition frequently suffer from chronic dyspnoea. The causes and mechanism for dyspnoea in these patients without evidence of structural lung disease are unclear. ... Results ... A pattern of reduced forced vital capacity (FVC), but normal total lung capacity (TLC), termed complex ventilatory dysfunction ... was observed and occurred mo...
Broadly speaking, there are two groups of acute covid outcomes involving dyspnea (shortness of breath) as a long-term symptom:

- Severe cases that may have physical lung damage
- "Mild" cases that now have ME/CFS-like features, but who have no evidence of lung damage!

2/ "Current evidence suggests that cellular damage, a robust innate immune response with inflammatory cytokine production and a procoagulant state induced by SARS-CoV-2 infection are factors potentially contributing to post-COVID-19 sequelae such as dyspnoea, fatigue, and cognitive and mental disturbances... Dyspnoea has been well characterised as a major clinical symptom of post-COVID condition after severe and critical COVID-19 and is correlated with impaired lung function in terms of pulmonary restriction, and with reduced diffusion capacity as a possible consequence of pulmonary remod...
In this study, they explored this distinction further and identified a distinct subset of patients with a pattern of breathing abnormality that they have termed complex ventilatory dysfunction (CVD).

So how did they arrive at this conclusion? Let's dig in!

3/16 "We hypothesise that patients suffering from post-COVID-19 condition who have fatigue and exertional intolerance also have a reduction in respiratory muscle strength, causing a dysfunctional breathing pattern which is distinct from typical pulmonary sequelae after COVID-19 such as obstruction, restriction or impaired diffusion capacity. Based on clinical observations, we describe a new breathing abnormality termed complex ventilatory dysfunction (CVD), defined as total lung capacity (TLC) - forced vital capacity (FVC) >10% predicted value and absence of restriction (TLC ≥ lower limit o...
Read 16 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Sep 22, 2024
NEW STUDY! It VERY thoroughly supports the hypothesis that SARS-CoV-2 emerged as a zoonotic spillover event in the Huanan Seafood Wholesale Market—using multiple methods!

Breakdown of the paper (written for a general audience!)...

1/many (but it's worth it, I promise!) Published Sep 19, 2024 in Cell: "Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic" Highlights: - Common ancestor of SARS-CoV-2 linked to Huanan market matches the global common ancestor - Wildlife mitochondrial DNA identified in samples from stalls positive for SARS-CoV-2 Abstract: "... We demonstrate that market-linked severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic diversity is consistent with market emergence and find increased SARS-CoV-2 positivity near and within a wildlife stall. We identify wildlife DNA in...
This paper reanalyzes the same data from the April 2023 paper in Nature that cast doubt on the Huanan Market hypothesis (pictured).

In the new paper published in Cell this week, another group conducted far more detailed (and statistically sound) analyses!

2/
Original paper that analyzed this same data: "Surveillance ofSARS-CoV-2 at the Huanan Seafood Market" "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019, emerged in December 2019. Its origins remain uncertain. It has been reported that a number of the early human cases of coronavirus disease 2019 had a history of contact with the Huanan Seafood Market...."
"...It should be noted that the selection of shops for sampling was biased because shops selling wildlife as well as shops linked to early cases were prioritized for sampling. The origin of the virus cannot be determined from the analyses available so far. Although gene barcode analysis of animal species in the study suggested that Myotis, Nyctereutes and Melogale-species that have been recognized as potential host species of sarbecoviruses-were present at the market, these barcodes were mostly detected within the SARS-CoV-2 RT-qPCR-negative samples from the environment. It remains pos...
This new paper starts by reviewing the evidence supporting the Huanan Market hypothesis, and some of the details are FASCINATING!

To begin with, of the 174 COVID cases identified with an onset of December 2019, 32% had a link to the Huanan Market.

In a city of 12 million.

3/ "INTRODUCTION Many of the earliest known cases of COVID-19 worked at or visited the Huanan Seafood Wholesale Market ("Huanan market") in the city of Wuhan, a link first made by clinicians at different hospitals throughout the city. Retrospective review of early COVID-19 cases identified 174 patients with onset in December 2019, 32% of whom had an ascertained link to this location, within a city of over 12 million."
Read 24 tweets

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