WesElyMD Profile picture
Dec 7, 2022 22 tweets 15 min read Read on X
1/🧵 Micro Clots & Endothelial Dysfunction in Long COVID

Plus new Epidemiology in @JAMA_current some say proves #LongCOVID is a hoax⁉️
 
Truth is…endothelial dysfunction plus inflammation can lead to life-altering brain & body dz.
 
Let’s explore data

Pic H/T @VirusesImmunity Image
2/ Remember that Vascular flow problems don’t occur in isolation from inflammation.

This new piece by @Jamie_Ducharme balances the discussion well.
 
It’s time for great studies & NOT immediate widespread treatment with blood thinners that might harm.
 
bit.ly/3He2FCj
3/ The urgency is that people are living w what amounts to newly acquired #dementia.
 
This WaPo piece starts w “Haze. Slow. Drunk. Lost.”
 
Our patients are adamant that descriptors like #fatigue & #brainfog don’t do justice to what makes them suicidal.
 
wapo.st/3YbRJLQ
4/ Recent epidemiology studies “inspire” us to see the scope of our challenges ahead, and they do NOT undermine the realities of #LongCOVID.
 
Take the INSPIRE study in @JAMA_current of 1,000 patients.

What can we learn here?
 
bit.ly/3H6Rdso
5/ 1,000 patients w infectious symptoms in the height of early COVID enrolled into an online cohort.

📌 75% w COVID & 25% without
📌 They self-reported systemic body problems at baseline & again at 3 mos
📌 Systemic problems in 87% Covid+ vs. 55% Covid-
 
bit.ly/3h3SDZR
6/ Overall, as the primary author @LaurenWisk told me yesterday, “40% of the COVID-positive and 54% of the COVID-negative group reported moderate to severe residual symptoms 3 months after enrolling.”
 
bit.ly/3iAevwp
7/ Some who tend to dis & deny #LongCOVID jumped on these INSPIRE data w the excitement of a puppy, saying, “I told you so, Long COVID isn’t real.”
 
Look into the eyes & lives of the disabled with LC, believe, and don’t be taken in by such rhetoric.

bit.ly/2Zb9S2J
8/ The authors themselves pointed out beautifully that their take is the pandemic’s negative impact on peoples’ SUBJECTIVE self-report was widespread across COVID plus non-COVID illnesses like pneumonia, RSV, and pharyngitis.

I agree.
9/ How about Cognitive Impairment?

📍PROMIS tools in INSPIRE are not an objective neuropsych battery
📍People w disabling brain dysfunction often opt out or are unable to self-report
📍They need in-person testing as we do @CIBScenter for people w #PICS

bit.ly/3h6zlTN
10/ The burden of brain dysfunction can be under-estimated by subjective data.

In addition, initially fearful COVID survivors may be pleasantly surprised at their recovery and under-report actual problems.

bit.ly/3iIXm3A
11/ An earlier landmark study by Ballering in Lancet with normal controls reported 12.7% develop #LongCOVID

It was early & they didn’t ask about brain-fog or mental health problems, which together we now understand occur in as many as 1 in 3 patients.
 
bit.ly/3h6EtHq
12/ Let’s get back to blood vessels & clotting🩸
 
👎 Early in COVID, we saw examples of patients who developed insane degrees of blood clotting.
👎 Here’s a picture of my patient’s blood that was solidly clotted even in the face of full-dose heparin.
13/ You may also remember when Autumn encouraged us to share her story…

She lost her hands & feet because of arterial clotting in COVID.

These are macro (large) clots of acute Covid. What we are seeing now months & years later are micro-clots.

(pic w her signed permission)
14/ The immune system is linked to blood clotting.

✔️We’ve known this for decades w bacterial sepsis
✔️COVID is viral sepsis
✔️It was the foundation of our 2001 NEJM study
✔️A blood thinner + immune modulator that was FDA approved for sepsis in 2002

bit.ly/3FvfdEf
15/ There are many ways to study the hypothesis of endothelial dysfunction as one cause of #LongCOVID.

Endo-PAT is one of the best
noninvasive methods to examine vascular reactivity.

See this cohort study of ~2,000 pts by Hamburg in Circulation 2008

bit.ly/3h0j6aX
16/ Endothelium is the lining cells of our🩸vessels. It’s the engine of bleeding & clotting.
 
In some people after COVID, things don’t go back to normal. This causes “reactive hyperemia” seen by Endo-PAT using finger arterial pulse wave measurements.
 
bit.ly/3UBuAz6
17/ These blood flow abnormalities in our small vessels essentially indicate a signal of disease that was initially thought helpful as a predictor of atherosclerosis.

This testing is being repurposed to discovery widespread damage in COVID survivors.
 
bit.ly/3BdmE0i
18/ While Endo-PAT is automated & objective w less user bias than other tools, vascular reactivity is only one function of the endothelium.
 
Others require biomarkers like e-selectin & PAI-1.
 
Celermajer Circ 2008 bit.ly/3P5WfXO
19/ Right now we don’t know the risk vs. benefit of blood thinning or anti-platelet medications.
 
The micro-clot hypothesis of Long COVID must be subjected to appropriate study before we begin prescribing medications based on endothelial dysfunction.
 
bit.ly/3uhlHQC
20/ Another area of vascular pathology we just learned is that #SickleCell trait is a risk factor for 77X higher odds of COVID-related death.
 
Yet another burden on people of color who are disproportionately affected by the pandemic.
21/ Diabetes & Long COVID

Now we have solid data from 8 studies of 4.2M COVID pts w 42.2M controls that Diabetes is a major public health burden with a 66% higher rate of incident DM regardless of age or sex.

go.nature.com/3iCFx6n
22/fin
Are we having fun yet?
 
Are you annoyed when you hear others #poopoo this public health nightmare?

I am‼️
 
Science, caring, validation & community are needed for #LongCOVID #MECFS #LongLyme #Fibromyalgia
 
Long COVID pts, please don’t lose hope. We’re finding answers…

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More from @WesElyMD

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

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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
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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
Aug 17, 2023
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


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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

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Here is an earlier tweet on same topic…
Read 4 tweets

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