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May 1, 2022 25 tweets 10 min read Read on X
Ok. As promised, here is a super-🧵 on cognition and #LongCovid. This will be a combination of published material and things that we have observed in-clinic. This is not intended to be definitive nor epidemiological and so it is highly likely that your personal experience (1/n)
may deviate significantly. This is about my reading and experience of cognition and #LongCovid but from what I have seen shared in the comments of my tweet yesterday, it seems that much of this may apply to other infection-associated chronic illnesses (h/t @microbeminded2) (2/n)
such as #MECFS, #Lyme and #dysautonomia/#POTS to name a few. Let’s start out with naming. I try not to use the term “brain fog” because I don’t think it conveys the seriousness. People with LC are experiencing cognitive dysfunction that often results in cognitive impairment (3/n)
So what sorts of cognitive dysfunction are people experiencing? Most often, we observe issues with high-level cognitive functions: executive function (the ability to process and synthesize information, form plans, emotionally regulate), speech production (esp. word finding) (4/n)
less often, we are seeing issues with short and long-term memory. Now, let me qualify this because I know so many people feel like their short-term memory is shot: if I test your short-term memory exclusively, I.e. I say “remember these five words”, *most* folks with LC can (5/n)
recall the five words I give them. However, in their day-to-day they have short-term memory fails them because they have issues with executive function: issues with selecting which things are *important* to attend to and remember, and therefore they don’t remember. In cases (6/n)
of hospitalized COVID and #PICS we are seeing more pure memory issues presenting, which is another example of how PICS is a different kettle of fish to #LongCovid and shouldn’t be conflated. So. Executive function and language issues are the big areas of cog dysfunction (7/n)
we are seeing with LC. What sort of cognitive impairment does this result in? The majority of ppl we see have “mild” cognitive impairment (a misnomer because anything that messes with your sense of identity should never be called “mild”), but in this context it means that (8/n)
they can still function, but everything takes more cognitive effort. I.e. can still drive, but you need a minute to recover. Can still be on an intense, challenging work zoom, but need to dim the lights and chill for 20 mins afterwards. The general ability to “function” but (9/n)
not thrive in the way that they used to which is not only incredibly distressing but also incredibly maddening when it is met with “you know, everyone forgets things” or, “this is just normal aging” from a health care provider. #LongCovid cog impairment is real and NOT (10/n)
just some by-product of social isolation, depression or natural aging. That is a lazy clinical association that is indicative of how little we understand how to diagnose and treat these things. In addition to folks with mild cog impairment, many ppl with LC experience (11/n)
mod-severe impairment. These are the people who can no longer safely drive, no longer work the hours or the job that they used to and in many cases require assistance with activities of daily living. Sadly, just so you know where the line is, with our current evaluations (12/n)
of cognitive disability sometimes even this level of cognitive impairment does not trigger the need for intervention b/c you can still “function” I.e. you don’t need a home health aide at your house every day to assist you. This is extremely frustrating and needs to change (13/n)
because so many with #LongCovid, #MECFS, #POTS, #Lyme and many others (don’t even get me started on acquired brain injury) get no care because they’re “high functioning enough” to “get by” according to payors, worker’s comp and long-term disability. This is criminal. (14/n)
Also of note is that much of this cognitive impairment can be intermittent (it comes and goes), meaning that you can see your doctor and feel fine (due to time of day of the appointment or the fact that your nervous system is primed for your appointment) but be highly (15/n)
symptomatic as soon as you leave or the day or week after. That’s why #medtwitter I implore you, don’t stop at “well you look fine to me”, or “all your tests are within normal limits” to your #LongCovid patients. LISTEN to them, UNDERSTAND that cog impairment is often (16/n)
intermittent (not just in LC but many conditions) AND that most cognitive screenings (like the MOCA) have significant ceiling effects, meaning that someone can pass the MOCA with flying colors and still have serious cognitive dysfunction. And impairments. So, we have a (17/n)
situations where somewhere in the neighborhood of 60-90% (depending on the study) of ppl with #LongCovid are reporting some form of cognitive dysfunction. The next question is “why”? We are still searching for answers, but let me give you my best theories based on the lit. (18/n)
Our brains account for about 20% of our overall energy requirements, which is staggering given that it accounts for 2% of our total body mass. The brain is an energy hog, and the more publications that emerge (in both #LongCovid and #mecfs) we see that these are so often (19/n)
conditions where our physiology is in energy crisis: chronically low waking cortisol, mitochondrial dysfunction, issues with getting blood where it needs to go due to platelet pathology and microclots (h/t @resiapretorius, @dbkell, @doctorasadkhan and #teamclots) and (20/n)
neuroinflammation and autoantibody production (h/t @VirusesImmunity and @michelle_monje) all leads to a perfect storm of cognitive dysfunction that is serious, but often intermittent, affects highest functioning parts of our brain first - executive function requires a LOT (21/n)
of energy - and can be MASSIVELY affected by our environment and daily demands (body position, environmental temperature, level of exertion (emotional, cognitive, physical), diet, hydration, sleep, etc). Ok. So what do we do? Test, test, test everyone’s cognition, and test (22/n)
regularly. I know, I know all my cog neuroscience friends - we don’t have baselines. Guess what - DOESN’T MATTER. Test everyone regularly to get a sense of their personalized cognitive performance “fingerprint” and work WITH them to optimize. My team does this EVERY DAY (23/n)
with high cognitive performers like eSports athletes and F1 drivers and it works to improve performance. So this is where we start. Use cognitive tests without ceiling effects that will show you where your patient lands in a normative population. We personally use (24/n)
@BrainCheck, but there are many that do a good job. Cognitive remediation therapies and cog rehab will help so long as they aren’t too exerting, but they must not replace the need for clin research that addresses physiology. I’m out of tweets on this thread, hope this helped! 🙏🏻

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More from @PutrinoLab

Mar 26
Excited to finally get this one out in @Nature_NPJ! In the largest study of its kind to date, we used data from the @visible_health platform to answer a simple question: can we predict symptom fluctuations and crashes from both the physiological and

1/nature.com/articles/s4174…
patient-reported data? The answer to this question is yes. Not perfectly, but actually quite well. A few important takeaways:
1) Just as we have seen previously in people living with chronic pain, the ability to predict symptom flares and crashes in ppl with #LongCOVID,
2/
#MECFS and other complex chronic illnesses can represent a massive life upgrade. The ability to prepare for or expect a crash or a bad symptom day is preferable to many than these things just seemingly randomly appearing with no warning.
2) The fact that physiological signal
3/
Read 12 tweets
Mar 25
I want to thank everyone for the interest in this work that we completed in a #LongCOVID cohort with this novel device. I always appreciate feedback and want to thank folks for holding me accountable to a high standard of communication. To that end, I want to re-clarify this
1/
thread: this was a safety/feasibility trial which means that our primary endpoints were related to safety and feasibility. In the paper, we state clearly that we hit those endpoints: no device-related adverse events and 100% adherence to the protocol in all participants. That
2/
is great for a safety/feasibility trial. I then went on to express excitement that some cognitive scores moved. I understand that folks have (rightly) pointed out that without a larger sample size and correcting for multiple comparisons we can’t make definitive statements
3/
Read 8 tweets
Mar 24
Excited to get this out in preprint: triple-blind, placebo-controlled microtesla magnetic therapy (MMT) is safe, feasible and effective in reducing cognitive impairment in people with #LongCOVID. I get excited about interventions for cognitive symptoms

1/medrxiv.org/content/10.648…
as they can be so disabling and frightening because you don't know if the symptoms are going to be permanent. This paper makes us feel hopeful that Long COVID cognitive impairment related to neuroinflammation is something that is treatable. This was a first-in-human safety-
2/
feasibility trial. Typically in trials like this, because they haven't been done in humans and only in animals, we're happy if we see safety and good adherence to the protocol, but we're not usually expecting to see efficacy because the dosage is a bit of a "best guess".
3/
Read 10 tweets
Mar 13
Proud to have worked with the brilliant @drmfreire on this new study looking into spike protein in #LongCOVID. The most important part of this study that doesn't just look for spike protein in folks with LC and healthy controls, but it also uses a technique called
1/
spatial transcriptomics to better understand how spike protein might be interacting with the tissue around it. Here's what is interesting about this trial: lots of gut tissue samples, in both healthy controls and #LongCOVID showed evidence of persistent spike protein. However,
2/
in the folks with #LongCOVID that persistent spike protein was causing problems in the tissue: pro-inflammatory, tissue-damaging trouble. So not only do folks with LC have more spike, but the spike is actively irritating and damaging the surrounding tissue compared to healthy
3/
Read 7 tweets
Feb 17
Crucial paper published Friday that deserves much more attention in the #LongCOVID world: .

TLDR: 13/15 immunocompromised patients who had chronic COVID infections (>200 days) cleared the virus in under 2 weeks when given combo antivirals/monoclonals

1/nature.com/articles/s4159…
The caveat: yes these were cancer patients who were severely immunocompromised, and the "haters" are going to say that it isn't appropriate to draw parallels between this patient group and folks with #LongCOVID.

That's incorrect.

It is perfectly acceptable to draw such

2/
parallels and here is why: we (and others) have shown over and over again that immune dysregulation is associated with #LongCOVID, and T Cell Exhaustion, specifically, is a key feature of this dysregulation (first paper here: ). Why is T Cell exhaustion
3/nature.com/articles/s4158…
Read 9 tweets
Jan 5
Great win early in the year to receive notification that our case series looking into Dr Pridgen’s Valacyclovir, Celecoxib and Paxlovid protocol seems to really help some folks with #LongCOVID. This paper is a start, not the be-all and end-all:


1/frontiersin.org/journals/immun…
It is a small, open-label case series, but there are some interesting things that are worth noting that give me hope that what we are seeing is real and will hold up in a larger trial
1) People got to choose between Val/Cel only (called ‘IMC-2’ in the paper) and Val/Cel + Pax
2/
The people who chose the latter reported greater benefit. 2) The subset of people who started with Val/Cel only but then chose to retry the protocol with Paxlovid added experienced more benefit with the three drugs together than they did with the two drugs
3) The follow-up
3/
Read 6 tweets

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