A significant discovery in the fight against #LongCovid!
➡️ Researchers have identified the epipharynx, a part of the pharynx, as a key site for chronic inflammation driven by residual SARS-CoV-2 RNA. 1/
Using a next-generation molecular mapping technology called Visium HD spatial transcriptomics, researchers from Japan provided the world's first high-resolution spatial gene expression analysis of the epipharynx in patients with longCOVID. 2/
According to the study, the viral RNA from SARS-CoV-2 can persist in the epipharynx for more than six months post-infection, and here they activate local immune signals in specialized cells like B cells, plasmacytoid dendritic cells, and ciliated epithelial cells. 3/
This signaling potentially contributes to the chronic symptoms experienced by patients with long COVID, which include fatigue, persistent cough, dizziness, and cognitive issues continuing for months after the acute phase of infection. 4/
Using advanced technique, the researchers found that the residual viral RNA isn't merely leftover debris; instead, it actively triggers immune responses and inflammation. 5/
The epipharynx is one of the most important sites for SARS-CoV-2 infection, yet its anatomical location makes it difficult to observe w/out endoscopic evaluation. This region will gain more research attention as a potential target in understanding and treating longCOVID 6/
To address the issue, the team explored epipharyngeal abrasive therapy (EAT) as a treatment. EAT is a treatment for chronic epipharyngitis that has been practiced in since the 1960s, involving the swabbing of the epipharynx with a 1% zinc chloride solution. 7/
After three months of weekly EAT treatment, the patients showed a remarkable improvement in symptoms. 8/
On a closer analysis, the researchers observed a significant reduction in the viral RNA and a suppression of inflammatory responses marked by a decrease in expression of signaling molecules like pro-inflammatory cytokines and antibody-related genes. 9/
The spatial gene analysis post-treatment revealed that EAT promotes the removal of damaged ciliated epithelium. Additionally, it also downregulates the overactive immune pathways, underscoring its promising role in immune modulation and tissue repair. 10/
Spatial transcriptomic analysis has enabled a deeper understanding of the biology of longCOVID from a completely different perspective than conventional approaches, including the potential application of a treatment already in clinical use in Japan. 11/
While most existing treatments focus on managing these symptoms, this study goes deeper, identifying the epipharynx as a hidden reservoir of viral RNA and immune disruption, thereby opening new avenues for more targeted therapies. 12/
The study marks a significant leap in medical science, especially in light of estimates showing that 31–69% of recovered COVID-19 patients continue to suffer lingering symptoms. 13/13
➡️ Compared with healthy controls,
✔ Long COVID patients had blunted morning cortisol peaks
✔ Higher evening cortisol
✔ Loss of normal circadian pattern
Blood cortisol alone failed to detect these changes. 2/
Key insight:
➡️ Salivary cortisol profiling may be a more sensitive marker of stress-system dysfunction in LongCOVID than standard blood tests.
➡️ HPA axis disruption could underlie:
• Fatigue
• Brain fog
• Sleep disturbance
• Dysautonomia. 3/
➡️ New review highlights that persistent cognitive symptoms in COVID survivors are strongly linked to pro-inflammatory cytokines and blood–brain barrier (BBB) dysfunction.
➡️ Key culprits include IL-6, TNF-α, IL-1β, IL-8, IL-13 and MCP-1 — many remain elevated months after infection.
🔥 COVID-19 is not just a respiratory disease.
➡️ Evidence suggests cognitive impairment can occur due to:
Post-COVID fatigue isn’t just subjective.
Using advanced MRI, researchers found real changes in brain blood flow and oxygen metabolism in people with Post-COVID-19 Syndrome (PCS) after mild infection.
➡️ Key finding:
PCS patients showed increased oxygen metabolism in the hippocampus (memory hub) but reduced metabolism in the anterior cingulate cortex (ACC) — despite no visible brain atrophy. 1/
Why this matters:
➡️ Higher hippocampal metabolism was linked to better cognitive performance, suggesting a compensatory response to maintain thinking and memory in PCS. 2/
In contrast, lower anterior cingulate cortex (ACC) metabolism correlated with:
Why do some people feel exhausted long after COVID-19?
➡️ New brain-imaging research shows that even after mild COVID, people with persistent fatigue can have subtle but real changes in brain structure.
➡️ These changes are not large or widespread, but tend to appear in connected brain networks, especially areas involved in attention, decision-making, and sensory processing. 1/
Importantly, the brain regions affected overlap with areas that naturally express TMPRSS2, a protein that helps SARS-CoV-2 enter cells — suggesting certain brain circuits may be more vulnerable to the virus. 2/
The study also links these changes to brain chemical systems involved in mood, energy, and cognition (serotonin, acetylcholine, glutamate, and cannabinoids). 3/
COVID-19 doesn’t just affect the lungs — it can disrupt how cells produce energy. New research shows that COVID-19 alters the genetic “switches” that control mitochondria, the structures that power our cells. 1/
By comparing people who died from severe COVID-19, those who recovered, and healthy individuals, researchers found lasting changes in how mitochondrial genes are regulated. These changes were most prominent in genes involved in energy production and metabolism. 2/
Importantly, people with COVID-19 showed abnormally high levels of proteins that control mitochondrial structure and stress responses, suggesting long-term damage to the cell’s energy system. 3/
#LongCOVID (LC) shares striking symptom overlap with hypermobility spectrum disorders (HSD/hEDS): fatigue, brain fog, dysautonomia, pain—especially in women.
➡️ A new case series explores whether some “intractable” LC may reflect undiagnosed hypermobility disorders.
➡️ Five women with persistent LC symptoms were evaluated at an hEDS/HSD clinic.
All met Beighton score criteria for hypermobility.
➡️ 4 diagnosed with hEDS, 1 with HSD
➡️ 3 had dysautonomia
None had prior hypermobility diagnoses. 1/
All patients carried MTHFR polymorphisms (C677T or A1298C)—recently linked to hEDS/HSD.
➡️ Several also showed features of mast cell activation, suggesting immune dysregulation may unmask latent connective tissue disorders after SARS-CoV-2 infection.
➡️ Targeted management (physical therapy, methylfolate/B12, mast cell stabilization, pain interventions) led to clinical improvement in all cases.
🔑 Takeaway: Consider hEDS/HSD in women with refractory Long COVID, especially with multisystem pain and dysautonomia. 2/
This case series suggests that some patients with severe, persistent #LongCOVID—especially women—may have previously undiagnosed hypermobility disorders (hEDS/HSD).
➡️ Five women with refractory LongCOVID symptoms were found to meet criteria for hypermobility, often with dysautonomia, mast cell–related features, and MTHFR polymorphisms.
➡️ Targeted management led to clinical improvement, highlighting the need to consider hEDS/HSD in patients with intractable Long COVID symptoms. 3/