A major new review from Yale (Moen, Baker, Iwasaki, 2025) offers the most comprehensive picture yet of what SARS-CoV-2 does to the nervous system.
The conclusion is stark:
Long COVID is a chronic neuroimmune disorder affecting brain, spinal cord, and peripheral nerves.🧵
Warning Sign #1: The pandemic didn’t end - it just changed shape.
The virus keeps evolving. The acute symptoms may fade.
But for many, the infection never truly ends.
Even young, previously healthy people experience:
mental fog,
dizziness when standing,
sensory disturbances,
exhaustion after minimal effort,
racing heart.
That’s Long COVID.
Warning Sign #2: The virus leaves behind molecular debris - and the immune system won’t let it go.
Sometimes it’s spike protein fragments in the blood.
Sometimes viral RNA in the olfactory bulb or even the skull.
This triggers persistent immune alarms:
T cells get activated
Inflammation spreads to the brain
Neuronal connections start breaking down
The war continues - long after the virus is gone.
Warning Sign #3: The brain gets sick - even when standard scans look “normal.”
MRI often misses it. But PET imaging shows:
reduced glucose metabolism in the brainstem,
limbic inflammation,
microglia digesting synapses.
Patients say:
“I know what I want to say, but I can’t get it out.”
It’s inflammatory disruption of higher brain function.
Warning Sign #4: It’s not just the brain - the body’s autopilot system begins to fail.
The autonomic nervous system - which controls heart rate, blood pressure, digestion - goes haywire.
Blood pools in the legs; the brain is starved of oxygen.
POTS, dizziness, blackouts, heat intolerance
Even the vagus nerve - the main communication line between brain and body - shows structural damage in some studies.
Warning Sign #5: The immune system may start attacking the nervous system itself.
After infection, some people develop autoantibodies:
against adrenergic receptors,
against cholinergic synapses,
against neurons.
In experiments, these antibodies from Long COVID patients were transferred to mice - and caused neurological symptoms.
This isn’t just immune activation. It’s autoimmunity.
Warning Sign #6: Smell loss isn’t just a quirky symptom - it’s a red flag.
Olfactory tissue often shows:
inflammation,
neuronal destruction,
lingering T cells months after infection.
Even after viral clearance, the damage and local immune activity can persist - blocking recovery.
Smell loss may signal long-term damage to the central nervous system.
Warning Sign #7: Spike protein isn't just debris - it can fuel clotting and inflammation.
Persistent spike fragments have been found in blood and even skull tissue months post-infection.
They bind fibrin - form resistant microclots
These can obstruct capillaries, disrupt brain perfusion, and trigger microglial activation, cause ischemia-reperfusion injury
Even without active virus, brain tissue can be damaged by the aftermath of infection.
Warning Sign #8: SARS-CoV-2 may accelerate brain aging.
Evidence from autopsies, mice, and imaging shows:
damage to dopamine neurons,
loss of neurogenesis in the hippocampus,
inflammatory profiles resembling Parkinson’s and Alzheimer’s.
For some, COVID acts as an accelerant for neurodegenerative processes.
Warning Sign #9: No one is exempt. Not the young. Not the recovered.
Reinfections raise the risk.
Immunological imprinting may alter long-term responses.
Long COVID is not rare - it’s the aftermath of a system-wide disruption.
With no diagnostic test.
No cure.
And millions affected globally.
Bottom line: Long COVID isn’t “just fatigue.”
It’s:
chronic neuroinflammation,
immune dysregulation,
vascular dysfunction,
autonomic breakdown.
It’s a warning that infectious disease can leave lasting biological scars - not just in “high-risk” groups, but in anyone. @szupraha @ZdravkoOnline
Severe COVID doesn’t end with a negative test.
In the worst cases, we see epigenetic rewiring of genes that control mitochondria - the cell’s energy system. And once that switch flips, it doesn’t always flip back🧵
This isn’t a random epigenetic signal.
The changes concentrate in promoters of genes controlling respiratory chain complexes I and IV - the core machinery that turns oxygen and nutrients into usable energy (ATP).
Complex I is especially critical.
It’s the main entry point for electrons into mitochondrial respiration.
When its regulation is disturbed, cells make less ATP and more oxidative stress - a combination that accelerates cellular failure.
A new study in Journal of Clinical Medicine shows that after COVID-19, many patients have persistent impairment of oxygen transfer in the lungs (DLCO/KCO) - lasting 12 to 22 months, even when basic spirometry looks almost normal🧵
Key point?
FEV1 remains largely stable, while FVC improves only slowly over time.
This doesn’t look like classic airway obstruction. It points instead to restrictive and diffusion-level damage.
In simple terms.
Patients may breathe fine on spirometry, yet oxygen doesn’t pass efficiently from the lungs into the blood.
One of the strongest - and most concerning - studies so far. A true before/after design, a clear tau signal in persistent neurological symptoms, and nearly half exceeding Alzheimer’s research pTau-181 thresholds🧵
Related evidence. A large UK Biobank longitudinal analysis in Nature Medicine - Duff et al., 2025 -compared plasma Alzheimer’s-related biomarkers before vs after SARS-CoV-2 infection (with matched controls).
They found that SARS-CoV-2 infection was associated with a shift toward an AD-like biomarker profile - notably a reduced plasma Aβ42:Aβ40 ratio, and in more vulnerable participants lower Aβ42 and higher pTau-181.
In people with neurological long COVID, infection is followed by a significant increase in pTau-181, and in a subset this is accompanied by changes in amyloid markers!
This biomarker pattern is compatible with tau-related pathology and may point to a worse long-term prognosis🧵
A new prospective study in eBioMedicine followed 227 individuals with blood samples collected before and after COVID-19.
That matters - this isn’t a cross-sectional snapshot, but a true within-person biological change after infection.
The focus was neurological PASC (N-PASC). Persistent symptoms like brain fog, loss of smell/taste, dizziness, balance problems, behavioral changes.
Only this group showed a marked post-COVID rise in pTau-181!
For years, Epstein–Barr virus (EBV) has been linked to multiple sclerosis.
The association was strong.
But the mechanism remained frustratingly abstract - until now.🧵
This new paper in Cell (2026) finally does what’s been missing.
It doesn’t just connect EBV and MS statistically -
it shows how the immune system gets it wrong.
Instead of focusing on antibodies, the authors look at CD4+ T cells.
Long-lived memory cells.
The ones that shape immune behavior over decades.
People with Long COVID often describe brain fog, mental fatigue, slowed thinking.
For a long time, we lacked direct biological evidence that something measurable was wrong in the brain.
Now we have one🧵
This new study used 31P magnetic resonance spectroscopy.
Unlike standard MRI, it doesn’t look at brain structure - it looks at cellular energy metabolism.
Specifically, it measures the balance between
ATP, the cell’s immediate energy currency
phosphocreatine (PCr), a fast energy reserve - basically a buffer/backup battery