Hi Everyone!
In the spirit of the holidays, I want to donate the pledges of this newsletter to a Long Covid/ ME/CFS charity. Thanks to the generosity of some of the readers, the pledge total is currently around $2500! In the spirit of this newsletter’s mission I would like to give this money to a non-profit leading private research in Long Covid or ME/CFS.
In particular, I am interested in groups looking into any of the following topics:
Off-label treatments for Long Covid and ME/CFS
Viral Persistence (Covid, EBV, CMV etc.)
Mast Cell role in Long Covid and ME/CFS
Given that this is a community newsletter, I would like to have this judgment call shaped by the readers,I put together a Google Form with three different foundations (although I am open to others as well).
If anyone has a point of contact, I can reach out to before donating, that would be appreciated, as I want to chat with someone from the team prior to donating.
Up until this point, I have not turned payments on. If you have pledged money in the past, and would like to unpledge, I will give 2 weeks to do so (until around December 11th).
In this edition, we delve into the impact of long Covid on the brain, with articles highlighting MRI studies that reveal changes in brain structure and function. Furthermore, we examine the effects of Covid-19 on the retina, explore the link between asthma and general fatigue in long Covid patients, and discuss the potential role of growth hormone replacement therapy in managing acute and post-acute Covid-19. Additionally, we uncover the presence of antiphospholipid antibodies and their relation to thrombotic risk.
Media
Article: Novel MRI reveals brain changes in long-COVID | EurekAlert!
DEFINITIONS:
Diffusion microstructure imaging (DMI): a novel MRI technique that studies the movement of water molecules in tissues to provide detailed information on the microstructure of the brain.
SUMMARY:
People with long COVID exhibit patterns of changes in the brain that are different from fully recovered COVID-19 patients.
Diffusion microstructure imaging (DMI), a novel MRI technique, is a promising approach to understanding the basis of long COVID.
The study compared MRI brain scans of three groups: patients with long COVID, patients who had contracted COVID-19 but did not report long-term symptoms, and healthy controls.
The results showed that COVID-19 infection induced a specific pattern of microstructural changes in various brain regions, and this pattern differed between those with long COVID and those without long-term symptoms.
There were correlations between these microstructural changes and symptom-specific brain networks associated with impaired cognition, sense of smell, and fatigue.
Article: Berlin Cures announces expansion of long Covid drug study
SUMMARY:
Swiss biopharmaceutical company Berlin Cures has announced the expansion of the Phase II clinical trial of its long Covid drug candidate, BC 007, in Europe.
A total of 12 sites in Germany, Switzerland, Austria, Finland, and Spain are collaborating to advance clinical research into long Covid.
The company expects to add more trial locations in Spain, Switzerland, and Germany shortly.
Berlin Cures is planning to publish the first results from the trial next year.
If the results are favorable, the company aims to conduct a larger Phase III study, which will be a necessary step for the approval of BC 007.
My Take:
The expansion of the Phase II clinical trial of BC 007 by Berlin Cures is a significant development in the search for effective treatments for long Covid.
The collaboration of multiple clinical institutions across Europe highlights the urgency and dedication to finding a therapeutic solution for this condition.
The planned publication of trial results next year will provide valuable insights into the efficacy of BC 007 and may pave the way for further research in Phase III studies.
Article: Neck injection could improve smell issues in some long Covid patients
DEFINITIONS:
Parosmia: a distorted sense of smell that is a fixture of some long Covid illnesses.
Stellate ganglion block: a procedure involving the injection of an anesthetic into the stellate ganglion, a tangle of nerves in the neck that deliver signals to the head, neck, arms, and upper chest, used to treat chronic pain.
SUMMARY:
New research from Jefferson Health in Philadelphia suggests stellate ganglion block is somewhat effective at reducing parosmia in patients who suffered from the condition for at least six months after their Covid illness and didn’t respond to pharmaceutical or topical therapies.
Out of 37 patients at Jefferson Health who received the procedure and followed up with doctors afterward, 22 reported that their smell distortion had improved one week after the injection.
After the first injection, 26 people returned for a second injection on the other side of their neck at least six weeks later.
Most people who responded to the first treatment reported additional improvement after the second one.
My Take:
This is a treatment that has been explored in prior editions of this newsletter but for different purposes.
Research
DEFINITIONS:
Blood–CSF barrier (BCB): a selective barrier that regulates the exchange of substances between the blood and the cerebrospinal fluid in the central nervous system.
Albumin CSF/serum ratio (QAlb): a measure of blood–CSF barrier function, with elevated QAlb indicating barrier dysfunction.
Pleocytosis: an abnormal increase in the number of cells in the CSF.
SUMMARY:
In patients with post-COVID-19 syndrome (PCS) and neurological symptoms, the majority of cerebrospinal fluid (CSF) samples did not show any pathologies.
The most frequent pathological finding was elevation of total protein in the CSF.
A blood–CSF barrier dysfunction, indicated by elevated albumin CSF/serum ratio (QAlb), was the second most prevalent abnormality.
Pleocytosis, indicative of intrathecal inflammation, was only found in a small percentage of samples.
DEFINITIONS:
Mast cell: a type of immune cell that is involved in allergic reactions and the immune response to pathogens.
SUMMARY:
Mast cells have a potential role in disorders with dysautonomia and neuroinflammation.
Mast cells are located close to nerve endings and sites in the body that allow them to regulate and be affected by the autonomic nervous system.
Mast cells can be stimulated by triggers from the autonomic nervous system, leading to the release of various mediators.
Dysfunctional mast cell activation may be associated with conditions such as postural orthostatic tachycardia syndrome (POTS), autism spectrum disorder (ASD), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and Long-COVID syndrome.
My Take:
In my opinion, I believe mast cells play a prominent role in the progression of Long Covid for many.
Would love to see more research in this area.
DEFINITIONS:
Optical coherence tomography angiography (OCT-A): a non-invasive imaging technique that visualizes the retinal microvasculature.
Spectral domain-OCT (SD-OCT): a type of OCT that measures retinal thickness and provides detailed structural information of the retina.
Retinal nerve fiber layer (RNFL): a layer of nerve fibers in the retina that carries visual information to the brain.
Ganglion cell layer (GCL): a layer of cells in the retina that receives visual information from the photoreceptor cells and sends signals to the brain.
SUMMARY:
The study investigates the long-term effects of SARS-CoV-2 infection on the retinal microvasculature in patients with post-COVID-19 syndrome (PCS).
The study uses optical coherence tomography angiography (OCT-A) to analyze the retinal circulation and spectral domain-OCT (SD-OCT) to measure retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness.
There were no significant differences in the OCT-A parameters or RNFL and GCL thicknesses between PCS patients and healthy controls, suggesting no long-term damage in the retinal microvasculature and layers.
SUMMARY:
This study aimed to identify the specific risk factors for general fatigue in long COVID.
This study highlights the impact of general fatigue in patients with long COVID and identifies asthma as an independent risk factor for persistent fatigue during the 12-month follow-up period.
There was no relationship between asthma and respiratory symptoms, cough and sputum, suggesting that acute exacerbation and/or poor control of asthma might not cause prolonged general fatigue in patients with asthma.
Based on this finding, lung–brain axis in patients with asthma may be the causative role in persistent fatigue in long COVID.
DEFINITIONS:
ACE-2 receptor: The angiotensin converting enzyme 2 receptor, the main receptor for viral entry of SARS-CoV-2.
Gut-brain axis: The bidirectional communication between the gut and the brain, involving hormonal, neural, and immune pathways.
HPA axis: The hypothalamic-pituitary-adrenal axis, a central stress response system involving interactions between the hypothalamus, the pituitary gland, and the adrenal glands.
GH replacement therapy: Growth hormone replacement therapy, a treatment option for individuals with growth hormone deficiency.
SUMMARY:
Both acute SARS-CoV-2 infection and PASC are associated with gut microbiome dysbiosis and alterations in the gut-brain and HPA-axis in a subset of the infected.
Disrupted GH secretion could cause or exacerbate long-lasting neuropsychological symptoms as seen in other similar manifesting conditions.
Ongoing clinical research has shown promising improvement in PASC patients with fatigue and cognition complaints can be achieved via GH replacement therapy.
GH stimulation testing should be considered in PASC workups and future research should delve deeper into the mechanistic effects of GH on acute COVID and PASC.
My Take:
This is the first time I have seen GH Therapy connected to Long Covid as a possible treatment
This is a bit out of my comfort zone here so I am not really sure what to make of it
DEFINITIONS:
Antiphospholipid antibodies (aPL): antibodies that are associated with the antiphospholipid syndrome (APS), an autoimmune disease characterized by the presence of these antibodies and a predisposition to thrombosis and pregnancy complications.
COVID-19-associated coagulopathy: a condition characterized by abnormal blood clotting and increased risk of thrombosis in patients with COVID-19.
Thrombotic events: the formation of blood clots in blood vessels, which can lead to serious complications such as heart attacks and strokes.
SUMMARY:
Antiphospholipid antibodies are enriched post-acute COVID-19 but do not modulate the thrombotic risk.
COVID-19-associated coagulopathy displays phenotypic features of the antiphospholipid syndrome (APS), a prototype antibody-mediated autoimmune disease.
IgM autoantibodies against annexin V (AnV), β2-glycoprotein I (β2GPI), and prothrombin (PT) are enriched upon infection with SARS-CoV-2.
PT, β2GPI, and AnV IgM as well as cardiolipin (CL) IgG antiphospholipid levels were significantly elevated in the COVID-19 patients but not in the influenza or control groups.
The major correlate for thromboses was SARS-CoV-2 disease severity.
My Take:
The presence of antiphospholipid antibodies, specifically PT, β2GPI, AnV IgM, and CL IgG, is elevated in COVID-19 patients.
However, these antibodies are not associated with a higher incidence of thrombotic events.
Article: SciELO - Brasil - Post-COVID-19 irritable bowel syndrome: an integrative review - SciELO
DEFINITIONS:
Irritable Bowel Syndrome (IBS): a disorder of the gut-brain interaction characterized by recurrent abdominal pain, associated with changes in bowel habits such as diarrhea, constipation, or both.
SUMMARY:
Patients previously diagnosed with COVID-19 are at greater risk of developing Irritable Bowel Syndrome (IBS) compared to uninfected individuals.
Studies have shown that 0.6% to 11.6% of COVID-19 patients develop IBS after a minimum of 6 months of infection.
Risk factors for developing post-COVID-19 IBS include female gender, severity of COVID-19, presence of gastrointestinal symptoms during the acute phase, and depression/anxiety.
The pathophysiological mechanisms linking COVID-19 to the development of IBS are still not fully understood.
DEFINITIONS:
Neutralizing antibody: An antibody that can bind to and neutralize a pathogen, preventing it from infecting host cells.
SUMMARY:
The study analyzed plasma samples collected from 184 participants with and without Long COVID symptoms for up to 4 months following acute COVID-19 infection.
Antibody neutralization responses were highest to the original infecting SARS-CoV-2 strain and the Alpha and Delta variants, with levels declining over time.
Cross-neutralization of the Omicron BA.5 variant was associated with greater odds of experiencing Long COVID symptoms and with persistent gastrointestinal and neurological symptoms.
Longitudinal modeling demonstrated significant associations between the levels and rates of decay of neutralizing antibodies and Long COVID phenotypes.
My Take:
These findings suggest that the breadth and durability of the antibody response may play a role in the development of Long COVID.
DEFINITIONS:
Vagus nerve dysfunction: dysfunction of the vagus nerve, which can lead to symptoms such as dysphonia, dysphagia, dyspnea, dizziness, and gastrointestinal disturbances.
SUMMARY:
Vagus nerve dysfunction could explain some Long Covid symptoms, including dysphonia, dysphagia, dyspnea, dizziness, and gastrointestinal disturbances.
A pilot cross-sectional study evaluated subjects with Long Covid and found that they were more likely to show thickening and hyperechogenicity of the vagus nerve, reduced esophageal-gastric-intestinal peristalsis, gastroesophageal reflux, and hiatal hernia.
Subjects with Long Covid also showed flattening of diaphragms and reductions in maximum inspiratory pressure, suggesting respiratory muscle weakness.
SUMMARY:
This study investigated the effectiveness of primary covid-19 vaccination against PCC (post-Covid condition) among individuals vaccinated before infection using real world data. In the study population (including 589, 722 residents from Sweden), unvaccinated individuals had an almost fourfold higher proportion of PCC diagnoses compared with those who were vaccinated before infection.
Study authors found a vaccine effectiveness against PCC of 58% for any dose within the primary vaccination series. Vaccine effectiveness increased with each dose in the series: 21% for one dose, 59% for two doses, and 73% for three or more doses.
The results from this study highlight the importance of complete primary vaccination coverage against Covid-19, not only to reduce the risk of severe acute Covid-19 infection but also the burden of PCC in the population.
SUMMARY:
This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT or HBO2 therapy) on post-COVID-19 patients with ongoing symptoms for at least 3 months after confirmed infection.
Following HBOT, there was a significant group-by-time interaction in global cognitive function, attention and executive function. Significant improvement was also demonstrated in the energy domain. sleep, psychiatric symptoms, and pain interference.
Clinical outcomes were associated with significant improvement in brain MRI perfusion and microstructural changes in the supramarginal gyrus, left supplementary motor area, right insula, left frontal precentral gyrus, right middle frontal gyrus, and superior corona radiate.
These results indicate that HBOT can induce neuroplasticity and improve cognitive, psychiatric, fatigue, sleep and pain symptoms of patients suffering from post-COVID-19 condition.
HBOT’s beneficial effect may be attributed to increased brain perfusion and neuroplasticity in regions associated with cognitive and emotional roles.
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