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Vipin M. Vashishtha

@vipintukur

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/

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/

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/

Read 4 tweets

Vipin M. Vashishtha

@vipintukur

Mar 13

New research finds that SARS-CoV-2 spike protein can persist in the gut of people with #LongCOVID, even months after infection.

➡️ This persistent viral antigen may drive ongoing immune changes in intestinal tissue.

➡️ Scientists detected viral spike RNA and protein in colon and ileum biopsies from Long COVID patients.

➡️ In these regions, genes linked to inflammation, immune dysfunction, and tissue stress were altered. 1/

Persistent spike-positive areas in the colon showed increased immune cell activity, including:

• Macrophages
• Plasma cells
• Regulatory T cells

Suggesting an active local immune response in the gut.

➡️ Researchers also found disrupted expression of key immune-signaling genes, indicating impaired immune coordination and chronic inflammation in gut tissues. 2/

SARS-CoV-2 persistence is a proposed driver of Long COVID (LC), but the in-situ relationship between residual viral antigen and immune dysregulation remains poorly defined.

➡️ This NEW study provides robust evidence that persistent SARS-CoV-2 Spike protein detection in the gut is not immunologically inert.

➡️ Instead, it is actively associated with distinct, immune cell composition shifts and a dysfunctional pro-inflammatory transcriptional profile, supporting the hypothesis that retained viral antigen drives chronic immune dysregulation in tissue of LongCOVID subjects. 3/

Read 4 tweets

Vipin M. Vashishtha

@vipintukur

Mar 10

New research suggests that gut bacteria may contribute to neurological symptoms in #LongCOVID.

➡️ Small particles released by gut microbes—called extracellular vesicles—may trigger inflammation affecting both the body and the brain.

➡️ Scientists found that people with Long COVID and neurological symptoms show a persistent imbalance in gut microbiota.

➡️ This altered microbiome may disrupt the intestinal barrier and promote systemic inflammation. 1/

In experiments, transferring gut microbes from LongCOVID patients into mice caused intestinal barrier damage and signs of brain inflammation.

➡️ This suggests a biological link between the gut and neurological symptoms. 2/

Gut microbe–derived vesicles were shown to activate inflammatory pathways and immune cells, including microglia in the brain.

➡️ These processes may contribute to symptoms such as brain fog. 3/

Read 4 tweets

Vipin M. Vashishtha

@vipintukur

Feb 22

Scientists have identified a possible new cause of chronic constipation — called “bacterial constipation.”

➡️ Certain gut bacteria can damage the mucus layer in the colon, making stool dry and hard to pass.

➡️ The researchers found that two bacteria work together to cause this problem:

• Akkermansia muciniphila
• Bacteroides thetaiotaomicron

➡️ They break down intestinal mucus that normally keeps stool moist and easy to pass. 1/

This discovery may explain why some people with chronic constipation do not respond to usual treatments.

➡️ The problem may not always be slow bowel movement — it could be changes in gut bacteria. 2/

Researchers also found higher levels of these mucus-destroying bacteria in Parkinson’s disease patients, who often have long-standing constipation.

➡️ Gut bacteria may play a role in symptoms previously blamed only on nerve damage. 3/

Read 4 tweets

Vipin M. Vashishtha

@vipintukur

Feb 18

New study links #LongCOVID symptoms with mitochondrial dysfunction.

➡️ Patients with PASC had lower levels of circulating mitochondrial DNA and poorer cognitive performance than recovered controls. 1/

Key findings in 228 adults:

• LongCOVID group showed worse cognition
• Higher psychological distress
• More inflammation
• Lower circulating mitochondrial DNA levels

➡️ Suggests energy-production problems may underlie symptoms. 2/

Researchers found:

-Better cognitive function was linked to higher mitochondrial DNA levels in the blood.

-Higher inflammation markers were linked to lower mitochondrial DNA. 3/

Read 5 tweets

Vipin M. Vashishtha

@vipintukur

Feb 17

A small brain-imaging study found that people with #LongCOVID showed slower thinking and reaction times during a cognitive task.

➡️ Advanced MRI scans revealed changes in how important brain networks communicate with each other, especially those involved in attention, language, and decision-making. 1/

Researchers found altered connectivity in key brain networks:

• Salience network
• Language network
• Central executive network
• Sensorimotor and visual networks

➡️ These systems are essential for attention, decision-making, and task control. 2/

The most prominent deficits were seen in the salience network, which helps the brain detect and respond to important stimuli.

➡️ Connectivity problems in this network were more severe with longer illness duration. 3/

Read 5 tweets

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