6/ Hamsters infected with COVID developed inflammation and glial priming that was not present in the Flu infected 🐁 .
Even when virus was not present any longer, ongoing problems in the kidneys, lungs, and olfactory lining were seen.
7/ Olfactory lining tissue was thinned out “permanently” in the COVID (not Flu) infected animals, which increases vulnerability to bacterial infections.
Similar findings were seen in autopsy findings of humans thought to be healed from COVID who went on to die of other causes.
8/ I think of all the ICU patients we watched die weeks & months after initial COVID infections.
It’s all adding up…ongoing lung, kidney & “body tissue” lining abnormalities in mice & humans…
This is a helpful yet scary next step in understanding the plight of #LongHaulers
9/ Interferon (IFN) biology seems key 🔑
It’s been known since early 2020 that autoantibodies to Type-1 IFN elevate risk in acute COVID
11/ Frere found an #interferon response in hamsters that correlated w brain/behavioral changes extending a month after viral clearance (which is years in human time)
This supports LC as a biological disease.
That’s important because too many people are disbelieved at MD’s appt.
12/ #LongCOVID therapies will be difficult because it’s a family of problems, not just 1 disease.
Eg, targeting IFN as Cytokine Tx will be difficult because of its short half-life, difficulty targeting specific cells & knowing what stage of immune response for optimal delivery.
13/ Summary of things we are learning:
Chronic inflammation in the olfactory system affects our emotional, sensory, and brain function (cognition).
Hamsters, for example, after the virus is gone, have problems with normal behavior.
Guess what? So do people.
Let’s build more…
14/ The olfactory bulb is directly connected to the limbic system.
Smell is connected to emotion & memory‼️
This would explain (even when the virus is long gone) problems in #LongCOVID pts’ ability to heal fully from newly minted #brainfog & #mentalhealth disorders.
17/ These clusters of PET-proven hypometabolism in different brain regions matter on a human level.
They are associated with more numerous functional complaints & symptoms of ongoing problems with smell, memory/cognitive disabilities, chronic pain, and sleep disorders.
18/ Brain PET studies in other #LongCOVID pts showed hypometabolism
(think hibernating/abnormal neurons)
in areas explaining problems with smell, fatigue, etc.
The authors ✍🏻 this supports a hypothesis of post-viral, persistent systemic inflammation.
🔸Let’s Unpack @NEJM
🔸Hear from patients
🔸We call LC a disease state
🔸It’s a clinical definition
🔸Adding Inclusion/Exclusion Criteria to our @theNASEM definition fosters great research definitions
🔸 I admit my early mistake…
“Long Covid is an IACC occurring after SARS-CoV-2 infection & present >=3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems.”
Read caveats in text box…
3/ Patients describing Long COVID – read text box
“My long Covid life remains terrifying. Last weekend I washed my car, dried it, put it back in the garage. Then I got violently sick and could hardly get up to get food. I was unable to read or even call my mom. I’m a shell of myself. But my physical issues aren’t half as bad as my brain problems. It’s hard to describe. You can say brain fog, but that doesn’t come close to doing it justice.”
“At work my brain is just begging for rest. I struggle with finding words and completing tasks in a timely manner. … I’ll be in a meeting and know exactly what I want to say before I say it. …I’ll get to a word, and I just cannot think of the word. I’ll just be like, ‘Give me a moment,’ and I’ll go through my brain cycling through words. This week the word was “consistent.” I couldn’t think of the word consistent. I kept thinking it was coincident or concentric or constant. I used to build prototypes multiple days a week, and now if I do anything in the lab, I’m pretty much wiped out for a week. …I mean, I’ve had to dig real deep. How much longer will I feel like this? I’m scared.”
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.
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
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:
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.”
📌 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.
📌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
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.
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.
📌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.
✏️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.