Thread by @ZdenekVrozina

Researchers looked at markers of cellular and mitochondrial damage in the blood of people with Long COVID and linked them to cognition, psychological distress, and inflammation. They identified several surprising associations🧵

Finding 1. Long COVID = lower relative ccf-mtDNA
At first glance, this is surprising.
People usually expect - mitochondrial damage - more mtDNA released into blood.
But here, researchers found lower relative levels.

But this does not necessarily mean less damage.
It likely reflects dysregulation of mitochondrial quality control (mitophagy).

When mitochondrial cleanup does not work properly, it can lead to -
accumulation of partially damaged mitochondria inside cells,
chronic cellular stress and inflammatory signaling,
energy deficits (the brain is especially sensitive to this)

Finding 2. Cognition tracks with the mitochondrial marker.
The strongest relationship in the study.
Better overall cognition - higher relative ccf-mtDNA.

This supports a simple biological model - when mitochondrial function or quality control is impaired,
cognitive performance declines.
In other words, brain fog aligns with measurable biological signals.

Finding 3. Inflammation moves in the opposite direction
Higher CRP - lower relative ccf-mtDNA
This suggests a link between mitochondrial stress and systemic inflammation.
A possible cycle -
mitochondrial dysfunction - inflammatory signaling - further mitochondrial stress.

Finding 4. A subgroup shows low-grade inflammation
About 25% of Long COVID patients had measurable chronic low-grade inflammation.
Long COVID is heterogeneous.
Not everyone shows strong inflammatory markers, but mitochondrial dysregulation may still be present.

This study brings something new in two key ways.

It’s detectable in a simple blood marker
This is crucial.
Until now, mitochondrial dysfunction in Long COVID was mainly shown through muscle biopsies, metabolomics studies, PET

Here, it appears in peripheral blood and is directly linked to cognition
That’s quite a strong signal.

The direction of the relationship is not intuitive.
not more damage = more mtDNA
but lower relative mtDNA = worse condition

What is truly surprising?
That a simple circulating marker of mitochondrial quality control so closely tracks cognitive function.
This supports a model in which, for at least a subset of Long COVID, the primary problem is not structural brain injury,
but chronic energy imbalance and cellular stress dysregulation.

Sum:
Long COVID may involve disrupted mitochondrial quality control, linked to cognitive function and interacting with chronic inflammation.

Matits at al., Circulating mitochondrial and cellular damage markers in long COVID: Links to cognitive function, psychological distress, and inflammation. nature.com/articles/s4138…