Thread by @WesElyMD

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

“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

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.