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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

Jan 26
Reflecting on the past week a few basic themes and lessons that strike me as worth repeating over and over:
1) First contact providers for #LongCOVID, #MECFS, chronic tick-/vector-borne illness and other infection-associated chronic conditions should be PCPs/family medicine. 1/
These are the folks that most people will come to with the non-specific symptoms that often emerge at the start of IACCs, so it is imperative that these professionals know how to identify and diagnose them. IACCs should be a categorical part of a coherent differential Dx for 2/
first-contact providers hearing patients describing fatigue, post-exertional symptoms, exercise intolerance and cognitive symptoms. This is a critical educational goal that we need to meet on the ground floor this second.

2) Physiatrists and neurologists should be trained as 3/
Read 11 tweets
Jan 23
Those who have been following me for a while will know that I have been a voice for @NIH reform for quite some time. Regardless of the changes the current administration will bring to NIH, the events of the past 24hrs have been extreme and have caused, IMO, unnecessary stress 1/
and instability to hundreds of thousands of researchers and research support staff. I would strongly argue that whatever steps toward reform that the NIH want to take can be done without media blackouts, mass confusion and complete shutdown with no indication of next steps. 2/
As a researcher who is NOT reliant on NIH funding, I would ask the incoming @NIHDirector to please consider that the longer everyone is kept in the dark, the more mental health emergencies we are going to have to manage in researchers around the country. Many researchers 3/
Read 6 tweets
Jan 16
Since my episode with the wonderful @longcovidanswer has been released highlighting viral persistence as a major driver of some #LongCOVID pathology, I’ve been asked repeatedly, “what should we do about it?” - totally fair question. Here is my proposed roadmap: 1/
First, let me point out that there are antiviral programs and drugs out there that people have been trying to mixed effects: e.g. Truvada, Maraviroc, Maraviroc + Statins, Valtrex, Valtrex + Celebrex, Paxlovid and various combos of these. This is NOT medical advice or urging 2/
anyone to try these things without knowing your history, but more to say that people are trying them for persistence and the results are mixed. Similarly, there are many monoclonal products that may hold promise on their own and in combo with antivirals: evusheld, aerium, 3/
Read 17 tweets
Dec 21, 2024
@Gmwetz Hi Marco, what a great question. I'll start by saying that unfortunately it is hard to get drugs approved for improving mitochondrial function because it is so hard often to measure modulations in mitochondrial function in a person. There are supplemental approaches, of course 1/
@Gmwetz but many of these supplements haven't necessarily been proven to boost mitochondrial function, but they are able to boost materials that mitochondria need to make energy or reduce oxidative stress. These are supplements like NMN, NAD+, nicotinamide riboside, glutathione, 2/
@Gmwetz alpha lipoic acid, vitamin C, CoQ 10, Astaxanthin, Curcumin and many others. However, as I said: we can't guarantee these will boost mitochondrial function or remove reactive oxygen species - that is yet to be proven definitively and that is also hard: genetic and epigenetic 3/
Read 10 tweets
Dec 18, 2024
Banger of a #LongCovid paper in pre-print today showing that replicating viral DNA can persist in hamsters up to 80 days after intranasal infection.

The study team were able to isolate and amplify infectious virus in 84% of experimental animals. 1/

biorxiv.org/content/10.110…Image
This is really interesting data that, once again, provides rationale and paves the way for the need for more antiviral and monoclonal trials (and combination antiviral + monoclonal trials!). For those following the actual persistence data this is just one more study confirming 2/
what we already knew, but it sure is nice to keep a running tally of studies that show persistence of *replicating* viral RNA. For the deniers: I’m delighted to inform you that your job just got a little harder. Every day we learn more about the reality of pathogen persistence 3/
Read 5 tweets
Dec 7, 2024
After a fairly fraught week I just want to take a moment to take a moment to say that IMO violence and the taking of a human life is almost always morally wrong. However, I think there is also a message that everyone should hear: 1/
Denying healthcare to people who have paid into it for their entire lives based on arbitrary or algorithmic factors is violence. Threatening to stop covering the cost of anesthesia for a surgery if that surgery surpasses an arbitrary amount of time is violence. Making the 2/
sickest and most disabled among us exert themselves and jump through endless hoops to prove they are sick is violence. Working everyday with people who have #LongCOVID, #MECFS, chronic #lyme, #Stroke, #spinalcordinjury, #ALS and many other conditions, I am constantly aware 3/
Read 7 tweets

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