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
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.

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 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:
 

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 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

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


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.

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

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.

https://twitter.com/weselymd/status/1560222715159756800

1/🧵 COVID & Autoimmune Diseases - more data 💥

My patient w #LongCOVID has new Raynaud’s and SLE (Lupus). She’s in tons of pain and is losing her fingers.

Study: N=4M people. COVID ⬆️ risk of new autoimmune Dz & vaccine was protective

https://t.co/Y4Wr0tItEmbit.ly/45dZMuH




2/ New Autoimmune Diseases in #LongCOVID

There are multiple studies showing this now…

Here are two helpful figures from this Lancet article.

Note the hazard ratios >2 for Anti-phospholipid Ab syndrome, pemphigoid, and multiple sclerosis.

https://t.co/wQzYso2urIbit.ly/45dZMuH

1/🧵Long COVID Brain Problems are a global disaster

📌Hiding in plain sight
📌Too often ignored by doctors
📌Read our new Lancet-RM article
📌On the intersection of #LongCOVID & #PICS
📌I’ll unpack below

Link gives 6 weeks of open access:
authors.elsevier.com/c/1hR8b7tFB1Tt… 2/ This figure we created presents scientific mechanisms of “Neuro” #LongCOVID

We show hypothesized points for interventions that we & others around the 🌍 are testing via robustly designed randomized controlled trials to get answers for those suffering this very real disease.

1/🧵Fusion of Neurons in COVID
 
🔹At 2 yrs many #LongCOVID pts still suffer 🧠
🔹We’re beginning to understand why
🔹“Fusogens” activated by viruses like COVID can create irreversible cell-to-cell damage & miscommunication

Pic = Spike infected neuron

Link in Tw 3 2/ Infections like SARS-Cov-2 drive expression of viral fusogens

These cause irreversible fusion of brain cells, causing bad neuronal communication

One of several possible explanations of brain pathology in #LongCOVID

Pic= Fused neurons w Spike & ACE2

Living w Disability

🔹I don’t know what you’re going through
🔹Is every day a struggle?
🔹Greg suffers #DownSyndrome, Alz Dz, Depression, Catatonia
🔹 Yet today he said, “Sunday’s donut day, but let’s have ‘chockle’ anyway & I’ll be ok.”

Be inspired‼️

(pic w perm)
#Recovery #DownSyndrome #NothingDownAboutIt #UpSyndrome #MoreAlikeThanDifferent #DifferentNotLess #TheLuckyFew #ExtraChromosomeExtraCute #DownSyndromeLove #AdvocateLikeAMother #AdvocateLikeAFather #FindYourTribe #Tribe321 #DownSyndromeAwareness #Trisomy21 #T21 #SeeTheAbili

2/ The heartbreak we see has scientists working to discover answers💔

Drs. @VirusesImmunity & @PutrinoLab explore hypotheses

📍viral persistence
📍vital reactivation
📍autoimmunity
📍inflammation

Testing antivirals, immune modulators, blood thinners. bit.ly/45E1F4v 3/ Data from 223 unvaxxed Mild/Mod COVID survivors

✔️ Show abnormal MRI 🧠 white matter inflammation at 9 mo vs matched controls
✔️Prolonged cellular changes occur & we don’t yet know the significance
✔️Clinical outcomes vary strikingly across studies

bit.ly/43f0vL2

1/🧵 Long COVID’s “Disability Roulette”

🔺No longer a mass Death event…
🔺COVID-19 is an ongoing mass #Disability event
🔺You & I might get #LongCOVID
🔺But society is yawning

This thread unpacks science, policy & hope.

No Paywall Boston Globe link:
bit.ly/3OGfSb1

https://twitter.com/weselymd/status/1662061662935957505

Friends, I have an entire 20 tweet thread 🧵 uploading here (links, PDF images, etc etc -

but it’s stuck in twitter world.

I apologize for the glitch here. Oy!

1/🧵The Haunting Brain Science of Long COVID
 
📍Here I use science to raise awareness of a growing public health nightmare hiding in plain sight
📍Matt & Barbara tell their stories
📍20 relevant medical articles
📍See 🧵unpacking science in Tweet #2
 
bit.ly/3ItiANv 2/🧵👇Here’s the science I included in the above @statnews piece

…one medical article after another, with take home messages about neuro #LongCOVID you can digest to keep yourself safe, find hope & teach other people what we’ve learned…

https://twitter.com/WesElyMD/status/1622575466010882048

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

Simulation in ICU - #Empathy👇

A doctor volunteer trying to understand what it’s like to be tied down & sedated.

More & more we must dive down into what we do to others to understand their experiences

To improve our care…#A2Fbundle

https://twitter.com/daytonicu/status/1620764427825061890

Asking:

“What is causing their agitation? How can you respond to it? Do they have contraindications to mobility? How do you start?”

1/🧵COVID Re-Infection⚠️

Let’s learn
🔹Re-infection is a worry
🔹⬆️ plasma Nucleocapsid (N) Antigen levels predict outcomes
🔹If you get COVID, the best predictor of ⬇️ N-Ag levels (ie, viral replication) is having Spike Ab
🔹You get S-Ab by Vaxx

Read on
bit.ly/3Ha8q2g 2/ These data (N=2540) come from ACTIV-3 study of adults hospitalized for COVID in 114 centers in 10 countries Aug 2020-Nov 2021
 
I’m going back over this because there are so many people walking around without adequate protection due to waning immunity over time.

1/🧵 Real-World Long COVID
 
🔹She got COVID Oct 2020
🔹59 y/o walked 5mi 4x /wk
w no prior cognitive problems
 
🔹“I got better but 4 mo later my memory faded. I struggled.
🔹HR came after me, ‘You can’t do your job.’”
 
Husband: “I want my wife back!”

(Pics & story w perm) 2/ Could her new #dementia be unrelated to COVID?

Maybe, but…
 
Her excellent neurologist feels her negative work-up, young age, speed of demise, temporal onset in relation to COVID all fit LongCOVID-related brain dysfunction & not a pattern of Alzheimers.
 
They want to share

1/🧵COVID & Death: #JAMA
 
📍N=1,846 pneumonia patients w versus w/out COVID
📍COVID didn’t “invent” a new lung disease
📍We freaked out saying vents needed to be so different
📍Docs erred as we deviated from our evidence-based

Why should YOU care?
 
bit.ly/3QIp2Tl 2/ COVID is a very long pneumonia process, but we exacerbated it…

This graph shows that Death occurs similarly, but COVID #death takes longer (10 vs. 7 days).

Time to discharge alive is twice as long (10 vs. 5 days) in COVID vs non-COVID pneumonia.

We caused a lot of this 😞

1/🧵Gratitude is Pain’s big brother
 
▪️Prof Greg teaches me to accept life on life’s terms
▪️ICU pts teach me how to traverse pain
▪️Gratitude is their close companion
▪️Gratitude is not just a tenet of etiquette – it’s an essential quality of well-being

#UpSyndrome
Pics w perm 2/ I can’t pay gratitude w a checkbook, only from the ❤️

📍My Gratitude Ledger is in deficit because I don’t nurture #Wisdom
 📍I underutilize this superpower of recovery
 📍Gratitude is Greg’s antidote to victimhood
📍It helps him rise above any situation

#TheLuckyFew

1/🧵Risk Factors for Long COVID❓
 
📌7k COVID+ healthcare workers followed in clinic
📌Data show being more vaxxed (3 or 4 shots) & <2 COVID infections were both predictive of better recovery at 1 mo
📌But there are limitations

Here are my critiques…
 
bit.ly/3VPt0ul 2/ Definitions
Cases: +COVID test & symptoms c/w CDC definition at 1mo N=1.9k (27%)

Controls: +COVID test & resolution at 1mo N=5.1k (73%)
 
Of those w symptoms at 30 dys, 51% had 3 or more👇

IMO the @WHO 90 dy cut-off is more specific & meaningful for #LongCOVID

1/🧵 Fake Science is BIG Business💰💰

What’s a “paper mill?

📍>500 “fake science” papers are being retracted
📍“Paper Mills” create made-up papers, trick peer review
📍People pay for authorship to boost academic credentials

Let me explain

bit.ly/3WXnhDx 2/ In this example👇…

manipulated peer-review was proven & >500 papers are being pulled! 🤯

H/T Neuroscientist @Schrag_Matthew explained:

“It's a bad look for Wiley!”

Investigators found irregular reviewer activity & ‘bad actors’ across publications

bit.ly/3WXnhDx

1/🧵 Our cell’s genes are rewired in MILD COVID 🧬
 
Stunning data in @Nature
 
White Cells (monocytes) switch gene expression from an established innate immune profile to a pro-clotting signature in COVID.
 
We’re immunocompromised.

Let’s unpack this…
 
go.nature.com/3GeDygW 2/ These data explain how the COVID virus places our bodies at risk for macro (large) blood clots in acute dz (which we see often), brain disease due to down-stream micro-clotting, and possibly later cardiovascular dz.
 
What did these London investigators find?