COVID Brain Fog Explained; Could ISRIB REALLY Help?!!

Hesham Mashhour
7 min readJun 7, 2021

Here’s a bit of personal background for you..

I got COVID towards the end of last year, sometime in October 2020 and though I was lucky enough to make a full recovery; for the next several months I was left with this unnerving brain fog I just could not shake.

The best way I could describe it is that.. I just didn’t feel as sharp as I previously had been or was used to being. Let me put it this way..

If you’re someone who needs prescription glasses; it would be a bit like you taking these prescription glasses off and seeing the world around you without them. Everything would (understandably) be a little blurry — depending on the prescription of course!

But it wasn’t my vision that was the problem. It was my mind and thinking that felt blurry; the thing that I, like most people I know, treasure the most about my health.

“Brain Fog” appears to be one of the key features of “long COVID;” a constellation of varied symptoms experienced by people long after they’ve recovered; or at least test negative for the coronavirus.

According to most sources, “brain fog” symptoms include finding it hard to concentrate and multitask along with reduced cognition and impairments in both short and in long term memory.

And so today I’ll do my best to explain the science behind “brain fog” and how a new experimental nootropic wonder drug, “ISRIB,” may just be the key to rescuing our brains from the perpetual fog.

This article is part three of part three. Over the last couple of weeks I published two other articles; one on the toxic effects chronic stress has on the brain and the other on how exercise improves and protects brain health and function.

Should you wish to read those two pieces; you obviously can and absolutely should. There should be links above so make sure to have a read once you’re done with.

One of the key features of COVID that is responsible for many of its symptoms is a double aged sword we call — inflammation

Inflammation can be best described as being your immune system’s response to being attacked by the outside world. It’s what your body does to make sure it destroys an invading pathogen, like a virus.

And if the virus is the reason people get sick with COVID, then inflammation is the reason why they stay sick.

At least, that’s according to several studies that were able to illustrate the presence of inflammation in the absence of any viral particles in the brains of deceased COVID-19 patients.

And inflammation in this context, where there are no real viruses to fight against, is just bad. But it’s actually worse for the brain that you might initially think..

Because brain cells are constantly churning out new proteins.

These proteins, they do just about everything inside your cells and so, naturally, they’re incredibly complex.

But this complexity, to me at least, is an Achilles’ heel. Because it makes a vital process like protein synthesis; incredibly sensitive to a wide range of things — like inflammation.

So inflammation gets in the way and makes this process more error prone. Structural errors will translate to misfolded proteins that are unable to perform their function adequately.

And what you really don’t want to be doing is building “wonky” deformed proteins in the brain, as these deformed proteins are in the habit of accumulating in brain tissue thus contributing to the development and progression of neurodegenerative diseases..

Like Alzheimer’s and Parkinson’s.

Now your cells have a way of dealing with this conundrum and that is through the “integrated stress response

As you can tell from the name, the “integrated stress response” is a signalling network whose job is to sense stress inside the cell, in this case, inflammation.

The response will be to cut back on protein synthesis in an effort to reduce the likelihood of these deformed proteins forming. But this has the unintended consequence of resulting in memory impairment.

This is because protein synthesis is an absolute requirement for the formation of long lasting memories in almost all known species.

So much so, that activation of the “integrated stress response” in old age has been implicated in brain ageing and the age-associated decline in memory.

In other words, as one grows older, the “integrated stress response” becomes more active, fewer proteins are made inside the brain and thus fewer things can be remembered.

And a very similar thing could be happening right now inside the brains of those people experiencing brain fog.

Runway inflammation could be activating the integrated stress response signaling pathway; thus inhibiting the synthesis of new proteins and impairing memory and other cognitive functions. Which is why..

Which is why I think you might find a one page PDF summary of this video’s key points helpful to look over. This one page PDF summary also includes a comprehensive list of all my references so make sure to check it out if you’re interested! Now back to brain fog!

So I’m really really excited to tell you about this promising new nootropic agent that can effectively inhibit the cellular “integrated stress response.”

It’s name is fittingly “integrated stress response inhibitor,” or just “ISRIB” for short.

Older mice treated with ISRIB showed significant improvements in memory function, locating an escape tunnel (on average) 20 seconds faster than the mice who did not receive the treatment. They also made fewer errors on memory tests and performed almost identically to the much younger mice on a battery of cognitive tests.

And similar improvements in long term memory were observed following ISRIB administration on birds.

The effect is so profound that ISRIB treatment has been dubbed as being able to “reset” the brain, potentially reversing age-related memory decline.

And while “reset” is a particularly strong word; there is good reason to use it here as even brief ISRIB administration was found to have long lasting effects on the integrated stress response and on memory function.

One way ISRIB treatment could achieve this is through reversing the age associated increase in after-hyperpolarisation — making it easier for nerve cells to fire signals to other nerve cells around them and thus communicate.

There is a staggering amount of research which suggests that ISRIB holds so much promise in treating age-related memory loss and traumatic brain injury — and I for one, would like to think that it may prove invaluable in the treatment of brain fog too.

After all, “brain fog” shows many of the core features of “integrated stress response” overactivation and there is a similar invasion of T cells and microglia to that which is observed in the brains of older individuals.

Alas, we’re still a pretty long way away from ISRIB being approved for the treatment of any condition.

So if you’re looking for something to help you with your brain fog today rather than several years down the line; then let me suggest the thing I found worked best for me helping relieve much of the brain fog’s worst effects — physical exercise..

Your brain potentially stands to benefit the most out of physical exercise through increased circulation to the brain, elevated dopamine and BDNF levels and epigenetic modifications.

In short, exercise may really be the best way to improve and protect your brain. To learn more, check out my video on just that topic.



Hesham Mashhour

Cambridge Graduate. I write about #health #medicine and will occasionally share my thoughts about the latest #music and trash coming out of #Netflix