Thread
1/š§µYour brain āon COVIDāš§
Letās integrate >20 studies on #LongCOVID neuropathology
My 24 y/o patient explained: āI donāt have a future because I canāt think anymore.ā
Letās talk:
Autopsy Studies
Viral persistence
Brain Size & Disability
Recovery & Hope
H/T pic šļø tw 13
Letās integrate >20 studies on #LongCOVID neuropathology
My 24 y/o patient explained: āI donāt have a future because I canāt think anymore.ā
Letās talk:
Autopsy Studies
Viral persistence
Brain Size & Disability
Recovery & Hope
H/T pic šļø tw 13
2/ Autopsy Data š§
Despite initial improvement from COVID, these (N=27) pts got progressively sicker & died
From their autopsies, the authors found āSARS-Cov-2 infection persisted significantly longer than suggested by standard PCR-negative tests.ā
bit.ly/3JrcX3l
Despite initial improvement from COVID, these (N=27) pts got progressively sicker & died
From their autopsies, the authors found āSARS-Cov-2 infection persisted significantly longer than suggested by standard PCR-negative tests.ā
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.
IMAGEšshows microglial nodules & neuronal injury
bit.ly/3kVCW8M
IMAGEšshows 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
go.nature.com/3PVptZX
5/ Steinās @Nature autopsy study (tw#4š) sparked upcoming Paxlovid clinical trials
Authors: āWe provide the most comprehensive analysis of cellular tropism, quantification & persistence of SARS-CoV-2 across the human body including the brain.ā
Tropism?
bit.ly/3visKcz
Authors: āWe provide the most comprehensive analysis of cellular tropism, quantification & persistence of SARS-CoV-2 across the human body including the brain.ā
Tropism?
bit.ly/3visKcz
6/ Whatās 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
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 š§ than expected on MRI, which complements large, controlled UK Biobank data (next tweet)
bit.ly/3wvNs9k
Damaged executive function occurs in many. Why?
This small study found much less Cortical Gray Matter š§ than expected on MRI, which complements large, controlled UK Biobank data (next tweet)
bit.ly/3wvNs9k
8/ It turns out that āSize Does Matterā when it comes to brain function.
Loss of actual brain tissue is found in #LongCOVID pts & helps explain newly-acquired cognitive dysfunction.š
Loss of actual brain tissue is found in #LongCOVID pts & helps explain newly-acquired cognitive dysfunction.š
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.
Hereās one:
bit.ly/3WjfEaN
This is supported by multiple PET studies showing impaired frontal lobe hypo-metabolism at 6 months.
Hereās 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 recoveryš
11/ Whatās āhurtā 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
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 donāt?
Weāre 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
Weāre 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 agingāļø
Authors: āgenes associated w inflammation & stress were ā¬ļø active in brains of people after COVID than controls
Conversely, genes linked to cognition & formation of connections between brain cells were ā¬ļø activeā
go.nature.com/3Wa3noH
Authors: āgenes associated w inflammation & stress were ā¬ļø active in brains of people after COVID than controls
Conversely, genes linked to cognition & formation of connections between brain cells were ā¬ļø activeā
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
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 š§
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
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
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
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 & vascularš©øconsequences of COVID.
The authors discuss potential therapeutic options for #LongCOVID
Mitra bit.ly/3BoAvRF
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
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?
š¹Validate & be present
š¹Believe patients as the experts of their own illness
š¹Take steps to prevent re-infection (mask & vaxx)
š¹Rest & seek personalized care in LC clinics
š¹Enroll in Trials
@EricTopol Dignity š„š
š¹Validate & be present
š¹Believe patients as the experts of their own illness
š¹Take steps to prevent re-infection (mask & vaxx)
š¹Rest & seek personalized care in LC clinics
š¹Enroll in Trials
@EricTopol Dignity š„š
21/ Avoid stigmatizing Long COVID patients
Researchers @NisreenAlwan found 95% of sufferers experience stigma & 76% experience it āoftenā or āalwaysā ā even more often w formal diagnosis.
Instead of denial & frustration, letās explore ideas & solutions?
bit.ly/3G02YOT
Researchers @NisreenAlwan found 95% of sufferers experience stigma & 76% experience it āoftenā or āalwaysā ā even more often w formal diagnosis.
Instead of denial & frustration, letās explore ideas & solutions?
bit.ly/3G02YOT
22/ Crossword Puzzles sharpen our brains in MCI - will they work in LC-related cognitive deficits?
Investigators thought āgamesā would be better than Crossword
Instead, they found the opposite - scores were better at 3 mo & 2 yrs in crossword group š
bit.ly/3v8mlR3
Investigators thought āgamesā would be better than Crossword
Instead, they found the opposite - scores were better at 3 mo & 2 yrs in crossword group š
bit.ly/3v8mlR3
23/ These results in (non-COVID) MCI have practical everyday applications
Itās gratifying to see cognitive improvement from straightforward cognitive training interventions that can be performed at home.
Needs studying in Long COVID.
bit.ly/3G6XdQP
Itās 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:
šItās early & we need more data of course
šPacing would be required to avoid PEM
šCognitive training can give pts & families a feeling of efficacy & empowerment
šWe need non-invasive non-pharma treatmentsā¦
Patience & understanding
šItās early & we need more data of course
šPacing would be required to avoid PEM
šCognitive training can give pts & families a feeling of efficacy & empowerment
šWe need non-invasive non-pharma treatmentsā¦
Patience & understanding
25/ fin
Read the most well-researched review on Long COVID to date
@ahandvanish & @erictopol legitimize brain š§ signaling dysfunction & offer pacing & post-concussion syndrome protocols
Science + Empathy = Step 1 in our Long COVID path
go.nature.com/3GL7L7w
Read the most well-researched review on Long COVID to date
@ahandvanish & @erictopol legitimize brain š§ signaling dysfunction & offer pacing & post-concussion syndrome protocols
Science + Empathy = Step 1 in our Long COVID path
go.nature.com/3GL7L7w
āI 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
@trishgreenhalgh et al help us learn to invoke the personal, social & occupational context plus specialist services
bit.ly/3RAC2La
26/šHereās a refresher from a past š§µ on BRAIN HEALTH in COVIDā¦
Iām so encouraged by the progress science is making YET acknowledge how slow it must feel for the millions suffering without a medical cure š
Iām so encouraged by the progress science is making YET acknowledge how slow it must feel for the millions suffering without a medical cure š
27/ š It can be difficult to distinguish PICS from Long COVID
āŖļøSome pts have #PICS, some #LongCOVID, some BOTH
āŖļøIt may not matter as the pathology may be similar
āŖļøWe donāt know yet
āŖļø15-20% of BOTH hosp & non-hosp pts had memory loss at 2-years
bit.ly/3PSKNiZ
āŖļøSome pts have #PICS, some #LongCOVID, some BOTH
āŖļøIt may not matter as the pathology may be similar
āŖļøWe donāt know yet
āŖļø15-20% of BOTH hosp & non-hosp pts had memory loss at 2-years
bit.ly/3PSKNiZ