WesElyMD Profile picture
Jun 15, 2022 27 tweets 21 min read Read on X
1/🧵 Long COVID Brain Science: 🧠

For ~100M suffering 🌎, let’s use data to combat myths & #Misinformation

COVID is biologically dangerous long after virus is gone

#LongCOVID affects our….

📍Olfactory & Limbic Systems
📍 Interferon Autoimmunity
📍PET scans
📍Astrocytes

How? Image
2/ First, Epidemiological comparisons…

FLU vs. COVID

Survivors of viral infxns like #Flu don’t complain of 200 long-term symptoms & ~90% ongoing mood disorders.

#LongCOVID pts do.

Flu kills 0.5M/year vs COVID has killed 10X that (5M) in just 2 years.

bit.ly/3mJTBK4
3/ Consider this:

A study of 150k COVID survivors, hospitalized & not.

COVID survivors had 10-15X ‼️higher risk of considering #suicide at 1 year than 11M control patients.

This is horrifying, yet people still deny #LongCOVID’s importance.

WHY?

bit.ly/3HnHZpB ImageImageImage
4/ 💥 Animal Model of LC 💥

A @ScienceTM study provides fascinating data about realities of what #LongCOVID does to mammals. 🐁

@Justin_Frere & Team infected hamsters with Influenza A vs. COVID.

They compared long-term affects to human autopsies.

bit.ly/3zB7gLk Image
5/ Rodents won’t “dream up” symptoms or tissue changes.

An animal model of #LongCOVID helps STOP claims that this is just in patients’ minds.

Pts are too often victims of Testimonial #Injustice (being silenced) & asked, “Have you seen a psychiatrist?”

bit.ly/3zTJpqr
6/ Hamsters infected with COVID developed inflammation and glial priming that was not present in the Flu infected 🐁 .

Even when virus was not present any longer, ongoing problems in the kidneys, lungs, and olfactory lining were seen. Image
7/ Olfactory lining tissue was thinned out “permanently” in the COVID (not Flu) infected animals, which increases vulnerability to bacterial infections.

Similar findings were seen in autopsy findings of humans thought to be healed from COVID who went on to die of other causes. Image
8/ I think of all the ICU patients we watched die weeks & months after initial COVID infections.

It’s all adding up…ongoing lung, kidney & “body tissue” lining abnormalities in mice & humans…

This is a helpful yet scary next step in understanding the plight of #LongHaulers Image
9/ Interferon (IFN) biology seems key 🔑

It’s been known since early 2020 that autoantibodies to Type-1 IFN elevate risk in acute COVID

This is seen consistently (2 links👇 of many)

The heightened risk extends into long COVID…

bit.ly/3HokbSA

bit.ly/3b1mcry
10/ #LongCOVID in some pts is a disease of Auto-Immunity.

A person’s immune system fighting her body (💭 Lupus or Rheumatoid Dz).

Now we know there’s a link between these same Interferon Antibodies that predict severe acute dz & long term Autoimmunity.

bit.ly/3NUBdtU ImageImageImageImage
11/ Frere found an #interferon response in hamsters that correlated w brain/behavioral changes extending a month after viral clearance (which is years in human time)

This supports LC as a biological disease.

That’s important because too many people are disbelieved at MD’s appt.
12/ #LongCOVID therapies will be difficult because it’s a family of problems, not just 1 disease.

Eg, targeting IFN as Cytokine Tx will be difficult because of its short half-life, difficulty targeting specific cells & knowing what stage of immune response for optimal delivery.
13/ Summary of things we are learning:

Chronic inflammation in the olfactory system affects our emotional, sensory, and brain function (cognition).

Hamsters, for example, after the virus is gone, have problems with normal behavior.

Guess what? So do people.

Let’s build more…
14/ The olfactory bulb is directly connected to the limbic system.

Smell is connected to emotion & memory‼️

This would explain (even when the virus is long gone) problems in #LongCOVID pts’ ability to heal fully from newly minted #brainfog & #mentalhealth disorders.

See 🧵👇
15/ This is precisely what was found in the UK Biobank study of N=401 people…

most with MILD #COVID & not hospitalized…

w MRIs before & after infection

had Olfactory cortex, limbic system, and brain “size” problems compared to N=384 control patients.

go.nature.com/3ILTN4Z
16/ Still with me?

If the brain is abnormal, we’d expect it’s cellular metabolism to be diseased as well.

Sadly, it is.

PET Scans of COVID survivors show hypometabolism in…

AGAIN…

the Olfactory & Limbic systems as well as brainstem & cerebellum.

bit.ly/3GWsl4c ImageImage
17/ These clusters of PET-proven hypometabolism in different brain regions matter on a human level.

They are associated with more numerous functional complaints & symptoms of ongoing problems with smell, memory/cognitive disabilities, chronic pain, and sleep disorders. Image
18/ Brain PET studies in other #LongCOVID pts showed hypometabolism

(think hibernating/abnormal neurons)

in areas explaining problems with smell, fatigue, etc.

The authors ✍🏻 this supports a hypothesis of post-viral, persistent systemic inflammation.

bit.ly/3xcAWeT ImageImage
19/ Neuropsychiatric manifestations more frequently seen in #longCOVID include…

depression, anxiety, PTSD, sleep disturbances, fatigue & debilitating cognitive deficits

These negatively affect patients’ well-being.

Here’s an alarming review: bit.ly/3xSonHg ImageImage
20/ Here is an excellent, thoughtful synthesis of PET hypometabolism in 🧠 of patients suffering #LongCOVID.

Bottom line:

Think about #astrocytes - a type of glial cell (non-neuron) that gets “turned on” in LongCOVID.

bit.ly/3O1mayt ImageImage
21/ In #EveryDeepDrawnBreath, I wrote: p.199

“Glial cells, namely microglia & astrocytes, are central figures in the story of our brain’s
well-being.

Microglia are recognized as regulating brain inflammation.

Astrocytes are thought of as glue that holds the brain together. Image
22/ “Astrocytes are critical to maintain the blood-brain barrier, regulate immune responses, and contribute to the health and growth of neurons.”

In #LongCOVID, the complex interplay between these cell types will be the key to unlocking patients’ 🧠 recovery after injury

#Hope Image
23/ These problems of brain cell metabolism from inflammation are seen in KIDS & adults.

We’re learning, sadly, how kids with mild COVID can also suffer #LongCOVID brain problems.

This supports a biological disease.

Protect your kids – vaxx & mask.

bit.ly/3Q0zvsz ImageImage
24/ Astrogliosis: disease or repair?

Our thoughts on what it means when astrocytes increase in number are evolving.

📌 Old = an indicator of brain pathology, which it can be

📌 New = a natural defense mechanism for repair - a way to limit brain damage

bit.ly/39c7mxV ImageImageImage
25/fin ✔️✔️

#LongCOVID is a REAL, multi-faceted syndrome

It has cognitive, mental health & physical impairments

It can persist years after the virus is gone

It has an emerging molecular basis

Never lose hope for recovery

Sit & Listen

Pts are the expert of their own disease Image
People are DMing me to ask where they can get other timely information on #LongCOVID to accompany this 🧵...4 leaders include @Dr2NisreenAlwan, @VirusesImmunity, @Bob_Wachter & @EricTopol

Follow them and reap the rewards - each has kept my brain working w LC data. TY.
Read 🧵👇 of must-read data that would’ve in my thread on Long-COVID 🧠 had I seen this yesterday.

Mild respiratory #COVID leads to brain disease in mouse model. Microglial priming & much more. The brain is vulnerable!

TY @michelle_monje @VirusesImmunity @PutrinoLab

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More from @WesElyMD

Aug 1
1/🧵Long-COVID Defined

🔸Let’s Unpack @NEJM
🔸Hear from patients
🔸We call LC a disease state
🔸It’s a clinical definition
🔸Adding Inclusion/Exclusion Criteria to our @theNASEM definition fosters great research definitions
🔸 I admit my early mistake…

bit.ly/3Ys30u0
Image
2/ NASEM 2024 Long Covid Definition:

“Long Covid is an IACC occurring after SARS-CoV-2 infection & present >=3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems.”

Read caveats in text box… Image
3/ Patients describing Long COVID – read text box

“My long Covid life remains terrifying. Last weekend I washed my car, dried it, put it back in the garage. Then I got violently sick and could hardly get up to get food. I was unable to read or even call my mom. I’m a shell of myself. But my physical issues aren’t half as bad as my brain problems. It’s hard to describe. You can say brain fog, but that doesn’t come close to doing it justice.”
“At work my brain is just begging for rest. I struggle with finding words and completing tasks in a timely manner. … I’ll be in a meeting and know exactly what I want to say before I say it. …I’ll get to a word, and I just cannot think of the word. I’ll just be like, ‘Give me a moment,’ and I’ll go through my brain cycling through words. This week the word was “consistent.” I couldn’t think of the word consistent. I kept thinking it was coincident or concentric or constant. I used to build prototypes multiple days a week, and now if I do anything in the lab, I’m pretty much wiped out for a week. …I mean, I’ve had to dig real deep. How much longer will I feel like this? I’m scared.”Image
Read 14 tweets
Oct 17, 2023
1/🧵 Long COVID Disease State
 
COVID infects us & Interferon causes 3 dastardly plots:
📌 We absorb ⬇️ tryptophan & convert ⬇️ Serotonin
📌 Platelet pathology ⬇️ stores of Serotonin
📌 Vagal nerve signals peripherally ⬆️ impairs brain function & memory

bit.ly/3M5F9ZV
Image
2/ Tryptophan is an essential amino acid - we don’t make it.

So if we’re “programmed” to absorb ⬇️ from our diet, we sleep poorly, think worse, and all sorts of other bodily functions go awry.

Will SSRI & SNRI meds help, or anti-virals, or immuno-modulators?

Trials will tell. Image
3/fin
This study by @maayanLevy_lab is a marvel of dozens of avenues of science that all point to a greater understanding of the realities of #LongCOVID as a chronic disease state.

Through work like this, we legitimize not only LC, but also #MECFS #LongLyme etc & take one step closer to finding medical solutions for past & future post-infectious states + syndromes like #PICS

TY @cooney_liz for this @statnews piece!

Read 4 tweets
Oct 10, 2023
1/🧵Catatonia - shocking & hopeful insights into a mysterious neurological disorder 💥

Did Oliver Sacks’s Catatonic “Awakening” Patients have a treatable Autoimmune Disease?
 
Here I unpack story & science from a stunningly well-done @WashingtonPost article Image
2/ Amazing Discoveries of Autoimmune Disease causing Decades of Catatonia, Schizophrenia
 
Autoantibodies and treatment with immunosuppressive medications are waking some patients up with crazy cool results. Here’s the article and my highlighted excerpts:
 
3/ “The first conclusive evidence was in her bloodwork: It showed that her immune system was producing copious amounts and types of antibodies that were attacking her body. Brain scans showed evidence that these antibodies were damaging her brain’s temporal lobes, brain areas that are implicated in schizophrenia and psychosis.”
Read 25 tweets
Sep 27, 2023
1/🧵 Post-Infectious Syndromes

…a Doctor’s admission
 
📌 I didn’t think #MECFS was real till #LongCOVID opened my eyes
📌 It’s “mysterious” & we weren’t taught it in med school
📌 Yet 1,000s are suffering a disease traditional medicine doesn’t understand
 📌 Let’s find answers Image
2/ Long COVID is estimated at 6% of US Population… @CDCgov
 
“Prevalence of #longCOVID among U.S. adults ≥18 ⬇️ from 7.5% during June 2022 to 6.0% during June 2023.”

More than 1 in 4 w LC have activity limitations, ie, it’s a LIFE altering disability.
 
bit.ly/3sZH8s2
3/ What is #LongCOVID?

Well, it’s not new…update👇
 
Acute Covid triggers #MECFS as do other infectious agents.
 
“Triggers” means temporal association not “cause” in a mechanistic sense.”

Think also #LongLyme #Fibromyalgia & more

bit.ly/3RyMJ34
Read 8 tweets
Sep 6, 2023
1/🧵 Long COVID - new @TheLancet data

📌A picture is emerging
📌It’s not pretty
📌Most pts w months-long symptoms aren’t recovered @ 2-yrs
📌The cluster including neurocognitive & cardiovasc symptoms is ominous
📌These data fuel trial design

Thoughts…

bit.ly/3sHrwt9

Image
Image
2/ This Lancet investigation of just over 500 patients is not particularly large but is well done. The methodology used LC patients from Catalonia Spain from 3/2020 to 2/2022.

They included people who were unable to obtain Covid test but who had an acute onset of symptoms extremely consistent with the syndrome and who developed the same long-term definition of long Covid.

Some may argue about this point but the longCovid community has taught me how important these patients are to include in such research.
Image
3/ Looking at this figure you can see the heat map emphasizing symptoms in clusters B & C that the authors are most confident indicate persistence.

💥 fatigue, headache, neurocognitive, dyspnea, arthralgia, chest pain and tachycardia 💥 Image
Read 8 tweets
Aug 24, 2023
1/🧵This weeks 2 important studies on Long COVID
 
📌Include ~340k COVID patients vs ~7M controls out to 2 yrs
 📌Organ dysfunction persists in 33%
 📌Levels of disability from #LongCOVID exceed those of cancer & heart disease‼️
 
Links at end of this thread
Image
Image
2/ Remember that these data complement the 8 or so other studies showing similar findings, and EXTEND the information using VERY large control groups w censoring if those controls got COVID.
3/ CAVEATS:
First, these are US Military Veterans

✏️Thus, older and more white than the average #LongCOVID person
✏️They also do NOT help us with Delta and Omicron variant COVID
✏️These findings are robust and statistically sound and published by very astute and qualified investigators
✏️But they must be extended scientifically in cohorts that include a high number of younger women, people of color and lower SEC as well as newer COVID variants.
Read 6 tweets

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