WesElyMD Profile picture
Feb 6, 2023 29 tweets 23 min read Read on X
1/🧵Your brain “on COVID”🧠
 
Let’s integrate >20 studies on #LongCOVID neuropathology
 
My 24 y/o patient explained: “I don’t have a future because I can’t think anymore.”
 
Let’s talk:
Autopsy Studies
Viral persistence
Brain Size & Disability
Recovery & Hope

H/T pic 👁️ tw 13 Image
2/ Autopsy Data 🧠

Despite initial improvement from COVID, these (N=27) pts got progressively sicker & died

From their autopsies, the authors found “SARS-Cov-2 infection persisted significantly longer than suggested by standard PCR-negative tests.”

bit.ly/3JrcX3l ImageImage
3/ Brain donation from 1st wave COVID patients (N=9) shows widespread endothelial activation, microclots & platelet aggregation supporting COVID as a vascular disease that yields real brain pathology.

IMAGE👇shows microglial nodules & neuronal injury

bit.ly/3kVCW8M ImageImageImage
4/ This autopsy study (N=44) showed COVID virus throughout the body persisted for months in some people w viral evidence in the hypothalamus, infected neurons of cervical spine, spinal ganglia, cerebellum
 
go.nature.com/3PVptZX ImageImage
5/ Stein’s @Nature autopsy study (tw#4👆) sparked upcoming Paxlovid clinical trials

Authors: “We provide the most comprehensive analysis of cellular tropism, quantification & persistence of SARS-CoV-2 across the human body including the brain.”

Tropism?

bit.ly/3visKcz Image
6/ What’s Tropism?
 
Tropism is when a organism (eg plant, cell, organ tissue) is involuntarily directed by a stimulus (eg, COVID) to turn & march in a new direction
 
Instead of healing, in #LongCOVID patients this tropism is a response toward aging & entropy:

ie, Senescence Image
7/ The exact cause of brain disease in #LongCOVID is unknown.

Damaged executive function occurs in many. Why?

This small study found much less Cortical Gray Matter 🧠 than expected on MRI, which complements large, controlled UK Biobank data (next tweet)

bit.ly/3wvNs9k ImageImage
8/ It turns out that “Size Does Matter” when it comes to brain function.

Loss of actual brain tissue is found in #LongCOVID pts & helps explain newly-acquired cognitive dysfunction.👇
9/ Some people actually lose cortical gray matter, which is made up on trillions of neurons.

This is supported by multiple PET studies showing impaired frontal lobe hypo-metabolism at 6 months.

Here’s one:
bit.ly/3WjfEaN ImageImageImage
10/ Other Long COVID PET studies correlate this hypometabolism w numerous functional complaints & symptoms of ongoing problems with smell, memory & cognitive disabilities, chronic pain & sleep disruption that halts recovery👇
11/ What’s “hurt” in our brains in LC?
 
Clues: think Glial Cell injury
 
Biomarkers of disease (eg, CCL11) are popping up in animals & humans. TY @michelle_monje & @VirusesImmunity
 
White Matter injury (axons) can indirectly hurt Gray Matter (neurons)
 
bit.ly/3g2XkCV ImageImageImage
12/ GENES: Why do some get Long COVID & others don’t?

We’re learning that different patterns of gene expression in acute COVID predict symptom patterns 1-yr later

This study establishes a connection between acute & long COVID based on gene responses

go.nature.com/3FMcois ImageImage
13/ Does Severe COVID accelerate aging⁉️

Authors: “genes associated w inflammation & stress were ⬆️ active in brains of people after COVID than controls

Conversely, genes linked to cognition & formation of connections between brain cells were ⬇️ active”

go.nature.com/3Wa3noH
14/ Persistent Immunity can be a Double-Edged Sword
 
In some it means #Recovery
 
In others?

These authors conclude that in some kids, activated cells in tonsillectomy tissue after COVID may lead to long-COVID & multisystem inflammatory syndrome
 
go.nature.com/3FIQV8F ImageImage
15/ Auto-Immune Diseases like Lupus wreak havoc 🧠

This well-done study of 640k pts w PCR-proven COVID vs. 1.9M controls prior to vaccines (Dec 2020) found lots of Autoimmune Dz 15 mos later.

42% new diagnoses of Graves, Sjogrens, Rheum Arthritis

bit.ly/3JjaZlq Image
16/ The family of autoimmune diseases found in COVID survivors most often involved blood vessels

Fitting since COVID is a disease of blood vessels

Others are finding that persistent anti-nuclear antibodies (think Lupus) predict #LongCOVID

bit.ly/3CJkvuo ImageImageImage
17/ Reinfection with COVID matters

This study of 440k w 1 infection vs 40k with >=2 infections vs 5M controls found 2X death, 3X hospitalization, and more #LongCOVID after reinfections.

This was true regardless of Vaxx status

go.nature.com/3VSzysX ImageImageImageImage
18/ These two figures explain our emerging insights into the bleeding & vascular🩸consequences of COVID.

The authors discuss potential therapeutic options for #LongCOVID
 
Mitra bit.ly/3BoAvRF ImageImageImage
19/ The Story Unfolds:

ACE-2 rich areas of the brain from our cortex, thalamus & hypothalamus, brain stem and cerebellum are involved - causing neurotransmitter imbalances & neuropsychiatric dz.
 
bit.ly/3xSonHg ImageImage
20/ What do we about acquired brain problems after COVID?
 
🔹Validate & be present
🔹Believe patients as the experts of their own illness
🔹Take steps to prevent re-infection (mask & vaxx)
🔹Rest & seek personalized care in LC clinics
🔹Enroll in Trials

@EricTopol Dignity 🥇👇
21/ Avoid stigmatizing Long COVID patients

Researchers @nisreenalwan found 95% of sufferers experience stigma & 76% experience it “often” or “always” – even more often w formal diagnosis.

Instead of denial & frustration, let’s explore ideas & solutions?

bit.ly/3G02YOT
22/ Crossword Puzzles sharpen our brains in MCI - will they work in LC-related cognitive deficits?
 
Investigators thought “games” would be better than Crossword

Instead, they found the opposite - scores were better at 3 mo & 2 yrs in crossword group 👍
 
bit.ly/3v8mlR3 ImageImageImageImage
23/ These results in (non-COVID) MCI have practical everyday applications
 
It’s gratifying to see cognitive improvement from straightforward cognitive training interventions that can be performed at home.
 
Needs studying in Long COVID.
 
bit.ly/3G6XdQP ImageImage
24/ Extrapolating to Long COVID:

📍It’s early & we need more data of course
📍Pacing would be required to avoid PEM
📍Cognitive training can give pts & families a feeling of efficacy & empowerment
📍We need non-invasive non-pharma treatments…

Patience & understanding Image
25/ fin
Read the most well-researched review on Long COVID to date
 
@ahandvanish & @EricTopol legitimize brain 🧠 signaling dysfunction & offer pacing & post-concussion syndrome protocols
 
Science + Empathy = Step 1 in our Long COVID path
 
go.nature.com/3GL7L7w ImageImageImageImage
“I can't cope with multiple inputs': a qualitative study of the lived experience of 'brain fog' after COVID-19

@trishgreenhalgh et al help us learn to invoke the personal, social & occupational context plus specialist services

bit.ly/3RAC2La
26/👇Here’s a refresher from a past 🧵 on BRAIN HEALTH in COVID…

I’m so encouraged by the progress science is making YET acknowledge how slow it must feel for the millions suffering without a medical cure 😔
27/ 🔑 It can be difficult to distinguish PICS from Long COVID

▪️Some pts have #PICS, some #LongCOVID, some BOTH
▪️It may not matter as the pathology may be similar
▪️We don’t know yet
▪️15-20% of BOTH hosp & non-hosp pts had memory loss at 2-years

bit.ly/3PSKNiZ ImageImage
Here's the @statnews article covering the science in this 🧵plus 2 powerful patient stories to bring it to life...I hope this helps us grasp the magnitude of the problem of brain disease & disability in #LongCOVID & the need for hardcore clinical trials.

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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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