Thread by @WesElyMD

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

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.

https://twitter.com/LaurenWisk/status/1598456654219341825

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.

https://twitter.com/weselymd/status/1521105255680860161

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)

https://twitter.com/weselymd/status/1426111637380009986

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…