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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

Feb 20
A tumultuous 24-ish hours since our preprint was released yesterday. I mentioned that this was a fraught issue and I genuinely do understand that people have mixed feelings about the work. I wanted to take some time to respond to some of the concerns and comments that have 1/
arisen. First, and most importantly: #LongCOVID (LC) and post-vaccine syndrome (PVS) both exist. Anyone claiming that all LC or even *most* LC is actually PVS is unserious and is making up nonsense that is not supported by the consensus science. I cannot stress this strongly 2/
enough. While we're talking about Long COVID and its clear distinction from PVS, I'd like to remind people that my team was talking about persistent effects of acute COVID in April and May of 2020. By November of 2020, we pre-printed our first LC paper:
3/medrxiv.org/content/10.110…
Read 22 tweets
Feb 19
Grateful to continue to be able to do great work with the amazing team at @YaleMed, led by @VirusesImmunity and @hmkyale. Today one of our preprints dropped on what is a fraught and divisive topic: vaccine injury or post-vaccine syndrome (PVS). Before
1/medrxiv.org/content/10.110…
we dig into the results, I want to state a few things very clearly about the team that conducted this work:
- We firmly believe in the value of vaccinations. However, we also believe that drugs will always have side-effects in a percentage of the population. Holding these two 2/
beliefs are not mutually exclusive and so important for honest and transparent discourse with the community.
- We have been studying PVS for many years and listening to the community since PVS cases started to emerge. This is a hard topic to study. People don't want to fund 3/
Read 16 tweets
Feb 13
This is an amazing example of how certain things simply cannot be broken down to a magic pill or formula and I think this is a wonderful #scicomm learning opportunity.

Note the communication from @hubermanlab. 1) Makes a statement about how a key opinion leader says you can 1/
*dramatically* increase endurance and strength. 2) Makes the caveat (“start slow”). Simple, direct, informative. Right?

Ok, so what’s the secret?
- Once a week, jog a mile with a kettle bell that is equal to 30% of your own weight in a briefcase carry. Switch arms from time 2/
to time. Start slow.

As a performance guy, and in consensus with many of the other performance folks who have already commented: This is an insanely hard physical task to do. The average Joe off the street SHOULD NOT try this.

When challenged, the caveat was raised: “I said 3/
Read 10 tweets
Feb 11
Honored to be a part of the work led by @polybioRF and @microbeminded2 published in @TheLancetInfDis discussing actionable strategies to adequately address SARS-CoV-2 persistence in #LongCovid. This paper covers discourse on how to look for and measure severity of persistence 1/
so that it can be used as an outcome measure in clinical trials, discussion about promising antiviral and monoclonal agents: what has the best chance of working and when combination therapies should be considered, the critical need for more sophisticated clinical trial designs 2/
such as adaptive platform trials and guidance on the recruitment of diverse populations into clinical trials: these drugs affect people with different hormonal profiles and different genetic profiles differently. To offer true precision medicine for pw LC, representation in 3/
Read 8 tweets
Feb 9
Feels like a good time for a little reminder: Countries aren't supposed to be run like businesses. Countries are supposed to spend money to support and serve their people. This means spending to support those living below the poverty line, the disabled and historically 1/
excluded groups. This means investing in research that doesn't immediately have a profitable output so that future innovations can be incubated and accelerated through companies that form within the country that supported the work. This means engaging in international aid so 2/
that when terrorism and anti-freedom sentiments try to take hold in other countries, it is shut down because the country being organized against is viewed as an ally. Government spending is supposed to serve the people. There's nothing wrong with questioning it, but so far, it 3/
Read 11 tweets
Feb 8
Wanted to check-in with these new @NIH changes that are going to affect so many. First let me remind everyone: I run 6 hybrid clinical/research centers, each with a specific clinical focus. Unlike the vast majority of my colleagues, federal funding sources account for less 1/
than 20% of my operational budget across all of these centers, so understand that my thoughts on this topic have nothing to do with self-preservation or any sort of self-serving agenda. First, sweeping change of this magnitude is going to cause great pain for thousands and 2/
thousands of Americans. Researchers, research staff, and administrators. This will cause layoffs, unemployment and for some, abandoning of scientific careers. To be clear, the people being affected by this aren’t going to be “lazy govt workers” or people “gaming the system”, 3/
Read 15 tweets

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