Four years after infection, most people treated for long COVID in a specialist clinic still hadn’t returned to their previous level of health🧵
This prospective cohort study followed 3,590 people with long COVID for up to four years in a specialist post-COVID clinic in London.
Most patients were not hospitalised during their acute infection, the majority were working-age adults, and nearly two-thirds were women.
The most common symptoms were
fatigue (80%)
breathlessness (68%)
brain fog (54%)
muscle pain, sleep disturbance, and autonomic symptoms
Patients typically reported multiple symptoms at once (median = five).
Functional impact
About one-third of working patients were unable to work!
Quality of life scores were markedly reduced
The level of impairment was comparable to ME/CFS, and in some respects worse than chronic heart or lung disease
Only one-third of patients reached a level of health they considered at least 75% of their pre-illness baseline during follow-up.
Median time to recovery = 200 days
Non-hospitalised patients recovered more slowly than those who had been hospitalised
In other words, most patients did not fully recover, even after prolonged follow-up.
The strongest predictors of persistent illness were
severity of fatigue , autonomic / postural symptoms, muscle pain.
Patients with very high fatigue scores had the lowest likelihood of recovery over several years.
COVID-19 vaccination was associated with faster recovery, especially when given before infection.
This is an association, not proof of causation, but the signal was consistent.
Long COVID led to substantially increased healthcare utilisation.
After referral to the specialist clinic
emergency department visits decreased
outpatient visits increased
This suggests a shift from crisis-driven care to structured, ongoing management, rather than resolution of the condition.
Individuals aged ≥18 years with long covid (hospitalised and non-hospitalised) from April 2020 to March 2024.
Sum:
Long COVID is often prolonged, disabling, and resource-intensive, particularly in patients with severe fatigue.
Specialist services do not fix the condition quickly, but they reduce chaos, improve coordination of care, and reveal the scale of ongoing need.
Prashar at al., Trajectory, healthcare utilisation and recovery in 3590 individuals with long covid: a 4-year prospective cohort analysis. BMJ. bmjopen.bmj.com/content/16/1/e…
Nearly three-quarters of patients were never hospitalised, yet they had substantial functional impairment, recovered more slowly, made up the majority of long COVID workload.
This directly challenges the idea that long COVID is mainly a complication of severe acute disease.
A mild acute infection does not protect against long-term disability.
Fatigue severity was by far the strongest predictor of non-recovery.
This matters because it suggests -
fatigue reflects core pathophysiology, not secondary deconditioning
simple clinical tools (like fatigue scales) can meaningfully stratify risk
In practice, fatigue behaves almost like a functional biomarker for long COVID severity.
Nearly three-quarters of patients were never hospitalised, yet they had substantial functional impairment, recovered more slowly, made up the majority of long COVID workload.
This directly challenges the idea that long COVID is mainly a complication of severe acute disease.
A mild acute infection does not protect against long-term disability.
Fatigue severity was by far the strongest predictor of non-recovery.
This matters because it suggests -
fatigue reflects core pathophysiology, not secondary deconditioning
simple clinical tools (like fatigue scales) can meaningfully stratify risk
In practice, fatigue behaves almost like a functional biomarker for long COVID severity.
Patients with autonomic symptoms or prominent myalgia had significantly worse trajectories.
This supports the idea that long COVID is not one condition, but several overlapping phenotypes - some of which are much harder to recover from.
Referral to a long COVID service reduced emergency visits but increased planned outpatient care.
That tells us -
long COVID creates ongoing healthcare demand
specialist services convert crisis-driven care into managed, visible chronic care.
Not a failure - it’s a sign that long COVID is a chronic condition, not a transient complaint.
This study paints a consistent picture -
long COVID can be long-lasting and disabling
healthcare systems must plan for long-term management, not short-term reassurance
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Infection of the adaptive immune system as a hidden disease mechanism?
We often explain severe or chronic viral illness as excessive inflammation.
But a new FIP (feline infectious peritonitis) study suggests something deeper -
Coronaviruses may directly disrupt T and B cells - the core of adaptive immunity.🧵
What we thought for years?
FIPV = a macrophage-restricted virus.
What this study shows?
Viral RNA and protein in T and B lymphocytes
subgenomic RNA (sgRNA) inside T cells - a marker of active replication
That’s not just background inflammation.
Why this matters biologically?
If a virus affects
T cells - impaired immune control, exhaustion, failure to regulate inflammation
B cells - dysfunctional immune memory, abnormal antibody responses
Then disease may reflect failure of adaptive immunity, not just an overactive inflammatory response!
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.