Vipin M. Vashishtha Profile picture
Jan 31, 2025 12 tweets 4 min read Read on X
Researchers found a link between COVID-19 & blood markers linked to faulty proteins in the brain. They found people who had previously had COVID-19 were more likely to have increased levels of biomarkers linked to faulty amyloid proteins—a hallmark for Alzheimer's disease. 1/ Image
On average, the effects were comparable to 4 years of aging with the greatest effects seen in those hospitalized with severe COVID-19 or with underlying risk factors for dementia such as smoking or high blood pressure. 2/ Image
The findings suggest that mild or moderate COVID may accelerate biological processes that contribute to buildup of disease-promoting amyloid in brain. This raises possibility that COVID-19 might contribute to an increase in later risks of developing Alzheimer's disease. 3/ Image
These findings suggest COVID-19 may drive changes which contribute to neurodegenerative disease. This may be due to the inflammation triggered by the disease, although how this inflammation might impact the brain and changes to amyloid is not yet fully clear. 4/ Image
However, the researchers can’t say that catching the SARS-CoV-2 virus directly causes these changes, or if it does, by how much a single episode of infection increases someone's risk. 5/
But these findings do suggest that COVID-19 may increase the risk of Alzheimer's in the future—as has been suggested in the past for other kinds of infections—especially among people with pre-existing risk factors. 6/ Image
Amyloid is a common protein with a range of functions in the body. But the buildup of an abnormal form of the protein, called beta amyloid (Aβ), is a key component of many diseases. 7/ Image
Aβ forms the characteristic clumps seen in the brains of patients with Alzheimer's disease, which are thought to cause damage to the neurons in the brain, leading to changes in cognition and behavior. 8/ Image
In this study, the researchers found SARS-CoV-2 infection was associated w/ changes in several blood proteins previously linked to brain Aβ pathology. The magnitude of changes was similar to that associated w/ a well-known genetic risk factor for AD, a genetic variant: APOE4 9/ Image
Greater changes found in older participants & those hospitalized with COVID-19-19 or had a history of hypertension. These correlated with poorer cognitive test scores & measures of overall health as well as changes in brain imaging patterns associated w/neurodegeneration 10/ Image
More studies now are needed to prove any causal links. Ultimately, the more we know about factors that contribute to dementia risk—whether they are directly under our control, like lifestyle or diet, or modifiable by vaccines or early treatment for infectious diseases. 11/11 Image
Here is the link to the study👇

nature.com/articles/s4159…

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More from @vipintukur

May 17
SARS-CoV-2 spike protein may directly amplify brain inflammation.

➡️ Researchers found that spike proteins can colocalize with amyloid-β (Aβ) and trigger distinct inflammatory responses in microglia — the brain’s immune cells.

➡️ This raises important questions about potential long-term neurodegenerative consequences of COVID-19. 1/Image
Researchers developed advanced “expansion microscopy” techniques that physically enlarge human brain tissue, allowing scientists to see disease-related structures at near-nanoscale resolution using ordinary microscopes. 2/ Image
Applying this method to brains from some COVID-19 patients revealed tiny amyloid-like protein clusters closely associated with SARS-CoV-2 particles in a small subset of cases, suggesting a possible link between COVID-19, neuroinflammation, and abnormal protein aggregation in the brain.

The study highlights how ultra-high-resolution imaging could uncover previously hidden mechanisms of neurological disease. 3/Image
Read 4 tweets
May 12
#LongCOVID is increasingly emerging as an immune-mediated disorder driven by:

➡️ Viral persistence
➡️ Chronic inflammation
➡️ Immune dysregulation
➡️ Tissue remodeling

👉 The lungs may remain biologically altered long after acute infection resolves. 1/ Image
A new review highlights how persistent immune activation in LongCOVID may lead to:
• Fibrosis-like lung changes
• Endothelial dysfunction
• Microvascular injury
• Ongoing respiratory symptoms

COVID may end clinically—but not biologically.
#LongCOVID #Pulmonology 2/ Image
LongCOVID respiratory sequelae may result from a “perfect storm” of:

➡️ Aberrant immune signaling
➡️ Residual viral antigens
➡️ Microvascular dysfunction
➡️ Dysregulated tissue repair

👉 A unifying pathophysiology is slowly taking shape. 3/ Image
Read 9 tweets
Apr 22
COVID-19 may be, in part, a mitochondrial disease.

➡️ A Cambridge review shows SARS-CoV-2 disrupts mitochondrial function in lung cells—driving inflammation and worsening pneumonia.

➡️ Emerging studies suggest even after the active infection is resolved, residual viral proteins, particularly SARS-CoV-2 spike protein, may linger and continue to cause damage to the mitochondria by increasing oxidative stress and disrupting energy metabolism, offering a plausible mechanism for #LongCOVID. 1/

H/T: @CatchTheBabyImage
COVID-19 is not just viral—it’s metabolic.

SARS-CoV-2 hijacks mitochondria →
↓ Energy production
↑ Inflammatory signaling

A key pathway worsening lung injury. 2/ Image
Mitochondria may link acute COVID → #LongCOVID.

Viral disruption of mitochondrial function can persist, sustaining oxidative stress and immune dysregulation even after infection. 3/ Image
Read 5 tweets
Apr 16
How does COVID affect the brain?

➡️ New research highlights a key player: astrocytes—the brain’s support cells.

👉 SARS-CoV-2 can disrupt their function, with downstream effects on neurons. 1/ Image
Key mechanism:

➡️ The virus can infect or impair astrocytes, which normally:

• Support neurons
• Regulate metabolism
• Maintain brain homeostasis

➡️ Disruption → neuronal dysfunction 2/ Image
What happens next?

➡️ Altered astrocytes can:

• Trigger inflammation
• Impair energy supply to neurons
• Contribute to neuronal injury or death 3/ Image
Read 6 tweets
Apr 10
New study shows SARS-CoV-2 directly damages heart cell mitochondria—key energy engines—offering a mechanistic link to #LongCOVID cardiovascular symptoms. 1/ Image
#LongCOVID may be a mitochondrial disease: electron microscopy reveals structural damage & myofilament breakdown in cardiomyocytes. 2/ Image
Biopsies from LongCOVID patients confirm myocarditis with mitochondrial disruption—mirrored in infected animal models. Strong biological plausibility for persistent cardiac symptoms. 3/ Image
Read 5 tweets
Mar 24
Autoantibodies as drivers of #LongCOVID

➡️ Compelling new evidence strengthens the autoimmune hypothesis of long COVID.

Transfer of patient-derived IgG induces pain-associated behaviours in mice—suggesting a causal, not associative, role.

Key experiment:

➡️ Total IgG from long COVID patients → injected into mice

➡️ Result: mechanical hypersensitivity (allodynia)

This recapitulates a core clinical feature—chronic pain.

➡️ Strikingly, pathogenicity is durable:
IgG collected 2 years later from persistently symptomatic patients
→ still induces pain in vivo

Implies long-term stability of autoreactive clones. 1/Image
Not all LongCOVID is the same.

➡️ Patients stratified using:
• GFAP
• Neurofilament light chain (NFL)
• IFN-β

➡️ Distinct biomarker-defined subgroups with different pathogenic pathways.

Proteome-wide profiling reveals:

➡️ Subgroup-specific autoantibody signatures
➡️ Persistent over time
➡️ Independently validated

Supports biological heterogeneity rather than a single syndrome. 2/Image
Conceptually aligns with conditions like fibromyalgia:

👉 Chronic symptoms driven by functional autoantibodies
👉 Neuro-immune interface involvement

➡️ Clinical implications:

• Identifying pathogenic IgG could enable risk stratification
• Opens avenues for targeted immunomodulation (e.g., IVIG, plasmapheresis, B-cell therapies?)

➡️ Methodological strength:

-Functional transfer model (human → mouse)
-Longitudinal sampling
-Multi-omics support

➡️ Moves the field from correlation → causation. 3/Image
Image
Read 4 tweets

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