PolyBio Fall Symposium 2024 thread 🧵
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Amy Proal introduces the Fall Symposium. PolyBio is a non-profit org building a collective to solve diseases like Long COVID, ME/CFS, and more
They recently published a new project page to see how these projects map to the human body
2/polybio.org/consortium-pro…
They recently published a new project page to see how these projects map to the human body
2/polybio.org/consortium-pro…
She mentions a new grant about being able to ship samples from severe patients and how they were successful doing home visits in projects.
Goes over how each group is working on what with beautiful visualizations.
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Goes over how each group is working on what with beautiful visualizations.
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Seeing all the projects for the immune system organized by "project type".
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They mention they share samples across sites for Long COVID and ME/CFS.
For example Yale shares a mouse model w/ LC and treatments. UCSF can send human tissue to them to validate them.
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For example Yale shares a mouse model w/ LC and treatments. UCSF can send human tissue to them to validate them.
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Truvada was used to control EBV & MS. Working to build a protocol for patients with Long COVID.
Patients mentioned they were benefitting from Maraviroc.
Blood collected throughout and Yale analyzes this to crunch the data for responders.
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Patients mentioned they were benefitting from Maraviroc.
Blood collected throughout and Yale analyzes this to crunch the data for responders.
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Nicolas Huot
THEMIS may regulate NK cells like it does T cells, aiding in infection response and balancing inflammation.
It could help NK cells fight SARS-CoV-2 and might impact long COVID symptoms by controlling immune dysfunction.
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THEMIS may regulate NK cells like it does T cells, aiding in infection response and balancing inflammation.
It could help NK cells fight SARS-CoV-2 and might impact long COVID symptoms by controlling immune dysfunction.
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David Price
No major differences in immune cell types between LC patients / healthy.
However, non-spike-specific T cells in long COVID show higher levels of exhaustion markers, suggesting prolonged immune activation
Upregulated proteins, complement activation, etc.
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No major differences in immune cell types between LC patients / healthy.
However, non-spike-specific T cells in long COVID show higher levels of exhaustion markers, suggesting prolonged immune activation
Upregulated proteins, complement activation, etc.
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David Price pt 2.
Evidence suggests long COVID involves ongoing immune activation from lingering viral antigens and weak antibody response, potentially causing tissue damage.
Hidden viral reservoirs may drive symptoms. Testing is underway to confirm this at infection site
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Evidence suggests long COVID involves ongoing immune activation from lingering viral antigens and weak antibody response, potentially causing tissue damage.
Hidden viral reservoirs may drive symptoms. Testing is underway to confirm this at infection site
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Resia Pretorius
NETs and myeloperoxidase are trapped in microclots
Fibrinogen found as a main component in microclots
Biofilm links to microclots
Syndecan, an endothelial marker, appears
Stroke clots extracted for study
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NETs and myeloperoxidase are trapped in microclots
Fibrinogen found as a main component in microclots
Biofilm links to microclots
Syndecan, an endothelial marker, appears
Stroke clots extracted for study
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Morgane Bomsel
Finds megakaryocytes and platelets in Long COVID patients hold SARS-CoV-2 RNA and Spike proteins.
Suggests these cells may act as viral reservoirs, possibly driving persistent symptoms.
Platelets can release infectious virus to other cells.
Spike in plasma.
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Finds megakaryocytes and platelets in Long COVID patients hold SARS-CoV-2 RNA and Spike proteins.
Suggests these cells may act as viral reservoirs, possibly driving persistent symptoms.
Platelets can release infectious virus to other cells.
Spike in plasma.
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Johan Van Weyenbergh
Elevated SARS-CoV-2 markers and viral RNA in long COVID, suggesting persistent viral activity.
Biomarkers (viral antisense RNA + FYN RNA) identify long COVID with 94% sensitivity and 92% specificity, correlating with anxiety/depression symptoms.
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Elevated SARS-CoV-2 markers and viral RNA in long COVID, suggesting persistent viral activity.
Biomarkers (viral antisense RNA + FYN RNA) identify long COVID with 94% sensitivity and 92% specificity, correlating with anxiety/depression symptoms.
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Johan Van Weyenbergh
Patients tracked personalized symptom scores, resulting in an average 32% drop in symptoms after 15 days (p=0.0032).
A promising look at grassroots, off-label treatment options for long COVID.
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Patients tracked personalized symptom scores, resulting in an average 32% drop in symptoms after 15 days (p=0.0032).
A promising look at grassroots, off-label treatment options for long COVID.
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Marcus Buggert
GI tract and tonsils (n=220) if SCV2 persists in tissues, triggering immune responses
Examine GI cells, immune cell responses, microbiome shifts, and tissue integrity
Organoids to mimic conditions and track T cell activation, focusing on chronic symptoms.
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GI tract and tonsils (n=220) if SCV2 persists in tissues, triggering immune responses
Examine GI cells, immune cell responses, microbiome shifts, and tissue integrity
Organoids to mimic conditions and track T cell activation, focusing on chronic symptoms.
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Marcus Buggert
Links protein pathways to lung disease and severe breathlessness.
Chronic inflammation, cancer growth, and artery disease pathways elevated.
Biomarkers predict severe symptoms like lung collapse and liver issues.
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Links protein pathways to lung disease and severe breathlessness.
Chronic inflammation, cancer growth, and artery disease pathways elevated.
Biomarkers predict severe symptoms like lung collapse and liver issues.
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Michela Locci
Fewer germinal center B cells and weaker antibodies in Long COVID up to 400 days post-infection.
Suggests Long COVID linked to hindered immune memory.
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Fewer germinal center B cells and weaker antibodies in Long COVID up to 400 days post-infection.
Suggests Long COVID linked to hindered immune memory.
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Akiko Iwasaki
Our bodies carry many chronic viruses and ancient viral DNA.
About 40% of our genome has viral origins, with some retroviruses permanently embedded.
In autoimmune disease SLE, ERVK-10 is overexpressed, hinting at a virus-disease link.
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Our bodies carry many chronic viruses and ancient viral DNA.
About 40% of our genome has viral origins, with some retroviruses permanently embedded.
In autoimmune disease SLE, ERVK-10 is overexpressed, hinting at a virus-disease link.
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Akiko Iwasaki
Antibodies have a Y shape. The top binds invaders. The Fc region controls function.
They neutralize threats, signal immune cells, and activate pathways.
In Long COVID, antibodies target EBV and ERVs, showing new immune roles through advanced tests.
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Antibodies have a Y shape. The top binds invaders. The Fc region controls function.
They neutralize threats, signal immune cells, and activate pathways.
In Long COVID, antibodies target EBV and ERVs, showing new immune roles through advanced tests.
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Akiko Iwasaki
Truvada and Maraviroc to be tested based on the findings above.
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Truvada and Maraviroc to be tested based on the findings above.
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John Wherry
CD8 T cells respond quickly, especially to the Spike protein, peaking around days 5-7. Long COVID patients have lasting spike-specific T cells, hinting at a role in lingering symptoms.
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CD8 T cells respond quickly, especially to the Spike protein, peaking around days 5-7. Long COVID patients have lasting spike-specific T cells, hinting at a role in lingering symptoms.
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John Wherry
EBV and VZV antigens activate CD8 T cells during acute COVID-19 and in long COVID cases, but CMV and flu antigens don’t.
Using BEAM technology, researchers identified specific CD8 T cell responses to various antigens
Protein persistence detected by T cells
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EBV and VZV antigens activate CD8 T cells during acute COVID-19 and in long COVID cases, but CMV and flu antigens don’t.
Using BEAM technology, researchers identified specific CD8 T cell responses to various antigens
Protein persistence detected by T cells
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Michael Peluso
Replicated work showing significance in RECOVER cohorts.
Tissue program faster than expected.
Expansion to IACC (ME/CFS, Lyme, etc)
Trials going strong AER002 results in 1-2 months.
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Replicated work showing significance in RECOVER cohorts.
Tissue program faster than expected.
Expansion to IACC (ME/CFS, Lyme, etc)
Trials going strong AER002 results in 1-2 months.
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Michael Peluso
SARS-CoV-2 RNA may persist in cells, fueling long COVID.
Immunotherapy, monoclonals, or antivirals could help.
Studies need to focus on viral persistence, drug reach, and reinfection.
Targeted trials and tracking variants are crucial.
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SARS-CoV-2 RNA may persist in cells, fueling long COVID.
Immunotherapy, monoclonals, or antivirals could help.
Studies need to focus on viral persistence, drug reach, and reinfection.
Targeted trials and tracking variants are crucial.
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Timothy Henrich
Found weakened T cell and NK cell responses and lingering inflammation in several body systems.
25% had EBV in saliva, suggesting viral reactivation plays a role in persistent symptoms.
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Found weakened T cell and NK cell responses and lingering inflammation in several body systems.
25% had EBV in saliva, suggesting viral reactivation plays a role in persistent symptoms.
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Timothy Henrich
New trial (INTERRUPT-LC) aims to boost NK and T cell activity to clear lingering virus in Long COVID using Anktiva (IL-15 based therapy).
PET scans to w/ mAbs spot viral proteins in tissue, showing how long SARS-CoV-2 persists, possibly fueling symptoms.
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New trial (INTERRUPT-LC) aims to boost NK and T cell activity to clear lingering virus in Long COVID using Anktiva (IL-15 based therapy).
PET scans to w/ mAbs spot viral proteins in tissue, showing how long SARS-CoV-2 persists, possibly fueling symptoms.
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Esen Sefik
Humanized mice reveal SARS-CoV-2 triggers human neutrophils to form NETs, worsening lung damage.
Mice with these neutrophils show more severe symptoms. Infected human macrophages also contribute to lung inflammation.
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Humanized mice reveal SARS-CoV-2 triggers human neutrophils to form NETs, worsening lung damage.
Mice with these neutrophils show more severe symptoms. Infected human macrophages also contribute to lung inflammation.
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Esen Sefik
Blocking NETosis may reduce harmful immune responses in COVID-19.
Human neutrophils infected by SARS-CoV-2 activate more, risking inflammation.
Paxlovid reduces infection in these cells.
PAD inhibitors and Pefabloc promising.
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Blocking NETosis may reduce harmful immune responses in COVID-19.
Human neutrophils infected by SARS-CoV-2 activate more, risking inflammation.
Paxlovid reduces infection in these cells.
PAD inhibitors and Pefabloc promising.
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Michael VanElzakker
Explores how inflammation affects the brain by scanning neural activity linked to inflammatory markers.
New microfluidic tools analyze microclots, and blood/saliva samples test for COVID RNA, immune and vascular markers, and antibodies.
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Explores how inflammation affects the brain by scanning neural activity linked to inflammatory markers.
New microfluidic tools analyze microclots, and blood/saliva samples test for COVID RNA, immune and vascular markers, and antibodies.
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Petter Brodin
Men face more severe outcomes than women globally.
Early interferon response helps clear virus; delays increase severity with inflammatory “cytokine storms.”
Women have stronger vaccine responses but higher autoimmune risk.
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Men face more severe outcomes than women globally.
Early interferon response helps clear virus; delays increase severity with inflammatory “cytokine storms.”
Women have stronger vaccine responses but higher autoimmune risk.
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Petter Brodin
Testosterone changes monocyte activity and shifts immune balance between interferon and TNF.
This affects inflammation and may influence pregnancy risks.
"IFN-I and TNFa balances each other and is calibrated by sex hormones."
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Testosterone changes monocyte activity and shifts immune balance between interferon and TNF.
This affects inflammation and may influence pregnancy risks.
"IFN-I and TNFa balances each other and is calibrated by sex hormones."
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Lael Yonker
Pediatric Long COVID is understudied/underrecognized.
Worrisome symptoms. Refusal of school. Daytime sleepiness. etc
Surveys ran to suspect it in children. Less likely to diagnose if younger and vaccinated.
MIS-C <> Long COVID is a spectrum.
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Pediatric Long COVID is understudied/underrecognized.
Worrisome symptoms. Refusal of school. Daytime sleepiness. etc
Surveys ran to suspect it in children. Less likely to diagnose if younger and vaccinated.
MIS-C <> Long COVID is a spectrum.
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Lael Yonker
High NETosis levels found in kids with long COVID and MIS-C.
Spike protein triggers NETosis in a dose-dependent way, causing inflammation. E
levated cytokines suggest prolonged immune response in long COVID cases.
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High NETosis levels found in kids with long COVID and MIS-C.
Spike protein triggers NETosis in a dose-dependent way, causing inflammation. E
levated cytokines suggest prolonged immune response in long COVID cases.
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Marcelo Freire
Persistent immune and clotting issues in blood and saliva.
Samples showed increased clot breakdown, high neutrophil activity, and disrupted immunity.
Changes were worse in those with severe symptoms.
Didn't see persistence in blood.
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Persistent immune and clotting issues in blood and saliva.
Samples showed increased clot breakdown, high neutrophil activity, and disrupted immunity.
Changes were worse in those with severe symptoms.
Didn't see persistence in blood.
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Marcelo Freire
Lower IgA in blood and saliva, impacting immunity.
Patients have higher organ system scores, notably in nervous and respiratory areas, and altered protein expression linked to inflammation and cell health.
Experimental staining shows spike protein induces.
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Lower IgA in blood and saliva, impacting immunity.
Patients have higher organ system scores, notably in nervous and respiratory areas, and altered protein expression linked to inflammation and cell health.
Experimental staining shows spike protein induces.
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Rigel Chan
Lab-grown brain organoids to study HSV-1 infection.
They found it activated Alzheimer’s-related genes, suggesting a possible link.
SARS-CoV-2 replicated RNA but didn’t trigger Alzheimer’s genes.
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Lab-grown brain organoids to study HSV-1 infection.
They found it activated Alzheimer’s-related genes, suggesting a possible link.
SARS-CoV-2 replicated RNA but didn’t trigger Alzheimer’s genes.
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Rigel Chan
SARS-CoV-2 damages astrocytes without activating Alzheimer’s genes.
Spike protein exposure might increase HSV-1 vulnerability, possibly raising Alzheimer’s risk.
SARS-CoV-2 could also reactivate dormant herpes, adding risk.
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SARS-CoV-2 damages astrocytes without activating Alzheimer’s genes.
Spike protein exposure might increase HSV-1 vulnerability, possibly raising Alzheimer’s risk.
SARS-CoV-2 could also reactivate dormant herpes, adding risk.
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Zian Tseng
20,440 deaths in SF (2011-2014) found 525 sudden cardiac deaths. Autopsies (97% rate) showed main causes: arrhythmia (56%), coronary disease, hidden overdoses (14%).
Reveals need for thorough autopsies to uncover overlooked causes in sudden deaths.
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20,440 deaths in SF (2011-2014) found 525 sudden cardiac deaths. Autopsies (97% rate) showed main causes: arrhythmia (56%), coronary disease, hidden overdoses (14%).
Reveals need for thorough autopsies to uncover overlooked causes in sudden deaths.
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Zian Tseng
The COVID POST SCD study examines tissues from people who died suddenly to find clues about Long COVID.
Focus on hidden virus, immune issues, diabetes, and cell dysfunction.
Found spike RNA in neural tissue.
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The COVID POST SCD study examines tissues from people who died suddenly to find clues about Long COVID.
Focus on hidden virus, immune issues, diabetes, and cell dysfunction.
Found spike RNA in neural tissue.
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Gene Tan
Long COVID patients, especially women, show lower neutralizing antibody responses compared to recovered controls.
This reduced response, particularly targeting certain viral components, may affect immunity against reinfection.
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Long COVID patients, especially women, show lower neutralizing antibody responses compared to recovered controls.
This reduced response, particularly targeting certain viral components, may affect immunity against reinfection.
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Gene Tan
Patients show a stronger antibody response to the common cold virus OC43.
Additionally, female patients have elevated IgG responses to Epstein-Barr virus, suggesting increased immune activity against these viruses.
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Patients show a stronger antibody response to the common cold virus OC43.
Additionally, female patients have elevated IgG responses to Epstein-Barr virus, suggesting increased immune activity against these viruses.
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Chiara Giannarelli
SARS-CoV-2 in coronary arteries of COVID-19 patients, especially in vessel walls and foam cells.
Foam cells showed more virus and slower clearance, shedding light on COVID-19’s impact on blood vessels.
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SARS-CoV-2 in coronary arteries of COVID-19 patients, especially in vessel walls and foam cells.
Foam cells showed more virus and slower clearance, shedding light on COVID-19’s impact on blood vessels.
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Chiara Giannarelli
SARS-CoV-2 infection in atherosclerotic plaques triggers a pro-inflammatory response.
Foam cells showed higher levels of neuropilin-1 (NRP1), a receptor that increases susceptibility.
Blocking NRP1 reduced virus levels in foam cells
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SARS-CoV-2 infection in atherosclerotic plaques triggers a pro-inflammatory response.
Foam cells showed higher levels of neuropilin-1 (NRP1), a receptor that increases susceptibility.
Blocking NRP1 reduced virus levels in foam cells
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Christopher Dupont
Creating a “cell catalog” for tissues like lung and skin.
Bacterial and viral genomes mapped from oral plaque; spine ligament tests underway.
CRISPR and industry partnerships boost microbe detection, with a Lyme Disease test in progress.
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Creating a “cell catalog” for tissues like lung and skin.
Bacterial and viral genomes mapped from oral plaque; spine ligament tests underway.
CRISPR and industry partnerships boost microbe detection, with a Lyme Disease test in progress.
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Benjamin Readhead
In Alzheimer’s, CD83(+) microglia cells are linked to antibody production in the colon and increased brain plaques and tangles.
Study of 51 patients suggests these cells play a role in Alzheimer’s through genes like APOE.
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In Alzheimer’s, CD83(+) microglia cells are linked to antibody production in the colon and increased brain plaques and tangles.
Study of 51 patients suggests these cells play a role in Alzheimer’s through genes like APOE.
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Benjamin Readhead
Alzheimer’s study links CD83(+) microglia to increased IgG4 antibodies in the colon.
Analysis suggests unique antibody patterns tied to pathology.
Increased levels of IgG4 antibodies and HCMV, hinting at a potential viral and immune component.
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Alzheimer’s study links CD83(+) microglia to increased IgG4 antibodies in the colon.
Analysis suggests unique antibody patterns tied to pathology.
Increased levels of IgG4 antibodies and HCMV, hinting at a potential viral and immune component.
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Benjamin Readhead
Clinical trials on antivirals(Valacyclovir) for CD83(+) / HCMV Alzheimer's patients.
No biomarker. Validation of potential biomarker in new cohort of 200 samples.
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Clinical trials on antivirals(Valacyclovir) for CD83(+) / HCMV Alzheimer's patients.
No biomarker. Validation of potential biomarker in new cohort of 200 samples.
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Matthew Frank
Rat study, SARS-CoV-2’s spike protein stays in the brain, priming immune cells for months.
A second infection later leads to heightened brain inflammation, fatigue, and memory issues, mirroring long COVID symptoms.
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Rat study, SARS-CoV-2’s spike protein stays in the brain, priming immune cells for months.
A second infection later leads to heightened brain inflammation, fatigue, and memory issues, mirroring long COVID symptoms.
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Matthew Frank
Reduced cortisol was found in blood and brain areas, likely weakening inflammation control.
Spike protein seems to suppress this critical anti-inflammatory hormone, possibly contributing to persistent symptoms.
Can then be hit by future infections.
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Reduced cortisol was found in blood and brain areas, likely weakening inflammation control.
Spike protein seems to suppress this critical anti-inflammatory hormone, possibly contributing to persistent symptoms.
Can then be hit by future infections.
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Max Qian
Discusses challenges of finding groups/clustering Long COVID patients.
They found 15 clusters with top 6 symptoms. This led to different endotypes.
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Discusses challenges of finding groups/clustering Long COVID patients.
They found 15 clusters with top 6 symptoms. This led to different endotypes.
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Nadia Roa
Gut & reproductive tissues may harbor SARS-CoV-2.
Women are more prone to severe Long COVID; stronger immunity could drive this.
10 participants; advanced methods reveal insights into viral persistence and immunity.
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Gut & reproductive tissues may harbor SARS-CoV-2.
Women are more prone to severe Long COVID; stronger immunity could drive this.
10 participants; advanced methods reveal insights into viral persistence and immunity.
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Alessio Fasano
SARS-CoV-2 can linger in children’s gut for months post-illness.
This retention is linked to lasting symptoms and inflammation, notably in MIS-C.
Each rise in gut leakiness boosts long COVID risk by 44%, with viral particles persisting over a year.
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SARS-CoV-2 can linger in children’s gut for months post-illness.
This retention is linked to lasting symptoms and inflammation, notably in MIS-C.
Each rise in gut leakiness boosts long COVID risk by 44%, with viral particles persisting over a year.
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Alessio Fasano
Larazotide helps kids recover from COVID-19 by speeding up spike protein clearance, reducing GI symptoms, and lowering inflammation.
By Day 7, more children showed improvement, with benefits continuing through Day 21.
Kids returned to regular activity.
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Larazotide helps kids recover from COVID-19 by speeding up spike protein clearance, reducing GI symptoms, and lowering inflammation.
By Day 7, more children showed improvement, with benefits continuing through Day 21.
Kids returned to regular activity.
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Sara Cherry
Viral load peaks early, with varied persistence in lungs & gut. GI tract may harbor virus long-term in some.
Drug response differs across tissues.
Data reveal immune genes affected by infection.
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Viral load peaks early, with varied persistence in lungs & gut. GI tract may harbor virus long-term in some.
Drug response differs across tissues.
Data reveal immune genes affected by infection.
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Sara Cherry
SARS-CoV-2 activates shared immune genes in lung & gut, but gut has unique inflammatory pathways.
Immune modulators and antivirals affect each tissue differently, suggesting tailored treatment may be needed.
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SARS-CoV-2 activates shared immune genes in lung & gut, but gut has unique inflammatory pathways.
Immune modulators and antivirals affect each tissue differently, suggesting tailored treatment may be needed.
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Amy Proal
Rapamycin, first found in Easter Island soil, impacts the mTOR pathway, key for cell growth and balance.
Normally high-dosed for transplants, it’s now used in low weekly doses.
Alzheimer’s beta-amyloid might form quickly in response to infections
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Rapamycin, first found in Easter Island soil, impacts the mTOR pathway, key for cell growth and balance.
Normally high-dosed for transplants, it’s now used in low weekly doses.
Alzheimer’s beta-amyloid might form quickly in response to infections
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Amy Proal
In older adults, mTORC1 inhibition improved immunity and cut infections over a year.
It boosted immune genes and helped flu vaccine response by 20%.
Long COVID shows exhausted T cells, pointing to immune fatigue in lasting symptoms.
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In older adults, mTORC1 inhibition improved immunity and cut infections over a year.
It boosted immune genes and helped flu vaccine response by 20%.
Long COVID shows exhausted T cells, pointing to immune fatigue in lasting symptoms.
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Amy Proal
New pilot study on 80 Long COVID participants
6mg once a week.
Ramp up to the dose. 2mg->6mg once a week.
Measuring immune activity, T cell health, metabolic markers, hormones, and vascular health over 24 weeks.
Further adaptive arms for other conditions.
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New pilot study on 80 Long COVID participants
6mg once a week.
Ramp up to the dose. 2mg->6mg once a week.
Measuring immune activity, T cell health, metabolic markers, hormones, and vascular health over 24 weeks.
Further adaptive arms for other conditions.
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David Putrino
Talks about new trials never been done before.
LDN is spotty at best with mixed outcomes.
ROS increases with low energy magnetic fields applied to neurons.
Humanity Neurotech has made hardware for this.
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Talks about new trials never been done before.
LDN is spotty at best with mixed outcomes.
ROS increases with low energy magnetic fields applied to neurons.
Humanity Neurotech has made hardware for this.
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