Long Covid Weekly #99: LC's impacting in Washington, Next Steps for LC research and More
Welcome to this week's edition of our Long COVID Research newsletter. This week, we review a CDC report on the burden of Post-COVID-19 Condition in Washington State, explore criticisms and recommendations for the NIH's RECOVER Initiative, and examine novel approaches in biomarker identification and therapeutic development.
Please note that we will be taking a break next week in observance of the July 4th holiday in the US and to finalize our database. For those who celebrate, enjoy your holiday, and we'll see you back soon!
This week's highlighted article, "Acute and Long COVID Intestinal Changes in an Experimental Model of Coronavirus in Mice," offers critical insights into the gastrointestinal impacts of COVID-19 and potential therapeutic interventions. This study is significant because it elucidates the complex pathological changes in the intestine due to MHV-1 infection (A coronavirus used in experimental models to study the effects of viral infections in mice. It shares similarities with SARS-CoV-2, the virus responsible for COVID-19.)
Here are the most interesting tidbits:
Whereas the precise mechanisms by which SARS-CoV-2 affects the small intestine remain under investigation, several hypotheses have been proposed. These include direct viral invasion of enterocytes expressing the angiotensin-converting enzyme 2 (ACE2) receptor, dysregulation of the gut microbiota, immune-mediated damage, and systemic effects of cytokine release.
e found significant changes in this model. These alterations could parallel COVID-induced colonic issues, as shown in Figure 2. Panel B emphasizes early pathological features following MHV-1 infection, characterized by visible mucosal layer sloughing (red arrow) accompanied by inflammatory alterations within the muscularis mucosa layer (black arrow) and generalized inflammation (blue arrow). These findings resonate with reports of COVID-induced colonic manifestations, such as mucosal injury and inflammatory responses.
Media
SUMMARY:
An estimated 6.4% of adults in Washington State had Post-COVID-19 Condition (PCC) as of October 2023. The prevalence varied significantly by county, age group, sex, and race/ethnicity.
The study used reported COVID-19 cases, hospitalizations, and estimates of SARS-CoV-2 infections from March 2020 to October 2023. Data were integrated into a compartmental model to estimate PCC incidence and prevalence across various demographics and geographic areas.
The study estimated that significant activity limitations due to PCC affect approximately 117,000 adults in Washington State, resulting in annual healthcare costs of about $1.76 billion.
The study acknowledged limitations due to missing data and the evolving understanding of PCC. It emphasized the need for continued surveillance, research, and tailored public health interventions to address the varied impacts of PCC.
Article: How to Fix $1.6 Billion Long COVID Program: Experts Weigh In | Medscape Medical News
DEFINITIONS:
The NIH's $1.6 billion RECOVER Initiative, launched in 2021 to study long COVID, faces criticism for poor scientific coordination, limited treatment options, and a lack of clinical trials focused on pharmaceutical interventions.
Experts suggest improving coordination among researchers and establishing an advisory board of top long COVID experts. Physicians experienced with similar conditions like chronic fatigue syndrome should also be included in the effort.
Researchers emphasize the importance of moving beyond symptom management to understanding the biological mechanisms of long COVID. Large-scale molecular research is necessary to find treatments that offer long-term remission.
There is a call for more clinical trials rather than observational studies. Patients and advocates stress the need for trials on off-label pharmaceutical drugs that have shown promise in case studies but lack large-scale testing.
Critics argue against the focus on "soft therapies" like melatonin and exercise therapy, advocating for pharmaceutical interventions with plausible mechanisms for addressing the disease's pathology.
Long COVID patients, like Charlie McCone, express frustration with the slow progress and limited treatment options. The urgency for effective treatments is highlighted by the significant impact on patients' lives and livelihoods.
My Take:
Huge fan of some of these suggestions!
Article: Refining the search for long-COVID biomarkers | Nature Portfolio
SUMMARY:
The project, led by Thomas Vogl at the Medical University of Vienna, aims to identify biomarkers in the gut microbiome that are associated with long COVID. By screening for antibodies against 357,000 microbiota and viral antigens, the team hopes to find indicators of a person’s risk of developing long COVID and potential therapeutic targets.
The research focuses on the interaction between human antibodies and the gut microbiome. The human immune system produces vast amounts of antibodies that interact with the microbiome, which can influence immune responses. The study aims to understand these interactions better, especially in the context of long Covid.
The project collaborates with the University Medical Center Groningen, utilizing blood samples from the COVID-HOME cohort (patients with SARS-CoV-2) and the Lifelines cohort (general population over 15 years). This allows for a unique comparison of antibody responses before and after COVID-19 infection and between patients with and without long COVID.
The study employs phage display immunoprecipitation sequencing (PhIP-Seq), a technique that uses bacteriophages to display specific antigens and detect which antigens bind to human antibodies. This method enables the identification of relevant interactions from millions of possibilities and helps train machine-learning algorithms to pinpoint potential biomarkers.
The technique has been used to identify biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and to study immune–microbiota interactions in inflammatory bowel diseases. There are symptomatic similarities between ME/CFS and long COVID, making this research particularly relevant.
The project aims to find microbial signatures associated with long COVID, which could serve as diagnostic markers and reduce stigma. Identifying these markers could transform the treatment and prevention of long COVID and offer insights into basic infection biology.
Article: GeNeuro's long COVID trial fails, triggering layoffs | Fierce Biotech
SUMMARY:
GeNeuro's phase 2 trial investigating the anti-HERV-W-Env antibody temelimab in long COVID patients failed to show significant improvements in health outcomes.
Despite evidence suggesting the potential role of the targeted protein in driving neurological symptoms in long COVID, the trial did not meet its primary endpoint or most secondary objectives.
The company responded to the trial's failure by laying off staff and seeking strategic alternatives to conserve cash and move forward.
GeNeuro joins other companies that have trialed therapies for long COVID and failed, including Pfizer's Paxlovid, Tonix Pharmaceuticals, and Axcella which recently ran out of money while going after long COVID.
My Take:
I highlight this to show how difficult the pharmaceutical industry can be.
I feel terrible for laid off employees.
This high failure rate shows how much $ LC research needs. Many trials will fail but some will not.
Research
DEFINITIONS:
Nirmatrelvir and Ritonavir (Nmr/r):
Antiviral medications used together to inhibit SARS-CoV-2 protease, reducing viral replication.
SOFA Score:
A scoring system to track a patient's status during an ICU stay, assessing the function of six organ systems to predict outcomes.
Propensity Score-Matched Cohort:
A statistical technique used to create a cohort with similar baseline characteristics to reduce bias in observational studies.
Glomerular Filtration Rate (GFR):
A measure of how well the kidneys are filtering blood, indicating kidney function.
SUMMARY:
This study evaluated the efficacy and safety of nirmatrelvir and ritonavir (Nmr/r) in treating inpatients with severe or critical COVID-19 beyond five days of symptom onset. The study was a propensity score-matched, multicenter, retrospective cohort analysis using data from 6695 adult inpatients in China.
A total of 1870 patients with severe or critical COVID-19 were included, with 302 receiving Nmr/r plus standard treatment and 1568 receiving only standard treatment. The primary outcome measured was the improvement in SOFA (Sequential Organ Failure Assessment) score by at least 2 points on the seventh day following Nmr/r initiation.
Patients in the Nmr/r group showed a significantly higher improvement in SOFA score compared to the standard treatment group. Additionally, the Nmr/r group had lower rates of new intubation and more no intubation days within the first seven days of treatment. However, there was no significant difference in the levels of inflammatory markers between the two groups.
Subgroup analysis indicated that older patients (≥60 years) benefited similarly to the overall cohort, with significant reductions in new intubation rates. The study also found no significant decrease in glomerular filtration rate (GFR), indicating the safety of Nmr/r in this patient population.
Article: A causal link between autoantibodies and neurological symptoms in long COVID | medRxiv
SUMMARY:
This preprint study highlights a correlation between autoantibodies targeting CNS and PNS tissues and neurological symptoms in patients with long COVID.
A subset of patients with high neurological symptom burden in the Mount Sinai-Yale long COVID (MY-LC) cohort exhibited diverse neuronal and glial autoantibodies, suggesting an autoantibody-mediated mechanism underlying neurological symptoms.
Passive transfer of IgG samples from these patients to mice resulted in the development of neurological symptoms resembling those in donors, providing evidence for a causal link between autoantibodies and long COVID neurological symptoms.
Targeting autoantibodies could be a potential treatment approach to alleviate neurological symptoms in a subset of long COVID patients.
SUMMARY:
An ex vivo human precision-cut lung slice (hPCLS) platform has been established to study SARS-CoV-2 pathogenesis and drug efficacy.
The platform reflects the actual lung niche, cellular heterogeneity, and 3D architecture of the lungs, making it a valuable tool for studying COVID-19.
Results from the platform suggest that SARS-CoV-2 infectivity in hPCLS varies among different cell types, highlighting the importance of cell diversity in studying viral pathogenesis.
The platform allows for evaluating virus replication kinetics, induction of proinflammatory cytokines, cytopathic effects, gene expression profiles, and proteomic changes in response to SARS-CoV-2 infection.
Antiviral drug testing in hPCLS shows potential for evaluating drug efficacy, immune response modulation, and histopathological changes, providing valuable insights into potential therapeutics.
The hPCLS platform offers a standardized approach for evaluating COVID-19 pathogenesis and antiviral drug efficacy, contributing to a better understanding of the disease.
My Take:
It seems like hPCLS platform will allow us to study SARS-CoV-2 pathogenesis and evaluate potential antiviral therapies.
DEFINITIONS:
CD8+ T Cells:
A type of immune cell that plays a crucial role in killing virus-infected cells and cancer cells. They are part of the body's adaptive immune system.
ORF1ab Proteins:
Non-structural proteins encoded by the SARS-CoV-2 genome, involved in viral replication and transcription.
Memory-like Phenotype (CD127+ PD-1+):
A subset of T cells that have encountered an antigen previously and can respond more rapidly and effectively upon re-exposure to the same antigen.
SUMMARY:
This study evaluated the CD8+ T cell responses to SARS-CoV-2 in patients with severe COVID-19 and compared them to vaccinated healthcare workers.
The aim was to understand how these responses correlate with disease severity and the development of long COVID (PASC).
The study included 26 patients with severe COVID-19 from an ICU and 32 vaccinated healthcare workers without prior infection. Blood samples were analyzed at one month and ten months post-infection for patients and after the second vaccine dose for healthcare workers.
SARS-CoV-2-specific CD8+ T cell responses were higher in the acute phase and persisted, albeit at lower levels, during convalescence. Responses were mainly against non-structural ORF1ab proteins. Infected patients had a less effective immune response to spike protein-derived peptides compared to vaccinated individuals.
CD8+ T cells maintained a memory-like phenotype and were functionally active during the convalescence phase. Vaccinated individuals showed a higher percentage of memory-like CD8+ T cells compared to those with severe infection.
Patients who developed long COVID had a lower percentage of SARS-CoV-2-specific CD8+ T cells during the acute phase. The presence of specific CD8+ T cells early in the infection could help predict the likelihood of developing long COVID.
Article: SPIKENET: An Evidence-Based Therapy for Long COVID | Viruses
DEFINITIONS:
ACE2 Receptor:
Angiotensin-converting enzyme 2, a protein on the surface of many cell types, acts as the entry point for SARS-CoV-2 to infect human cells.
Computational Docking:
A method used in molecular modeling to predict how a small molecule, like a peptide, interacts with a receptor or enzyme.
Molecular Dynamics Simulations:
A computer simulation method to study the physical movements of atoms and molecules, helping to predict the behavior of a peptide in binding to a receptor.
Oxidative Stress:
An imbalance between free radicals and antioxidants in the body, leading to cell and tissue damage.
Fibrosis:
The thickening and scarring of connective tissue, usually as a result of injury.
SUMMARY:
The study introduces SPIKENET (SPK), a 15-amino-acid synthetic peptide designed to target the ACE2 receptor binding domain of SARS-CoV-2. SPK aims to prevent the virus from attaching to the host, offering potential therapeutic benefits for both acute and long COVID-19.
SPK binds specifically to the ACE2 binding domain of the SARS-CoV-2 spike protein, inhibiting viral entry into host cells. This binding affinity has been demonstrated through computational docking, molecular dynamics simulations, and spectroscopic analysis.
In MHV-1 mouse models, SPK showed significant protective effects against acute and long-term COVID-19 symptoms. It mitigated severe inflammation, oxidative stress, tissue edema, and organ damage, improving survival rates and reducing pathological changes in multiple organs, including the brain, lungs, heart, liver, kidneys, and skin.
The study highlights the long-term sequelae of COVID-19, including severe and irreversible pathological changes in the brain, lungs, and heart. SPK treatment demonstrated significant attenuation of these long-term complications, suggesting its potential to restore tissue homeostasis and mitigate chronic COVID-19 symptoms.
SPK can be administered via various routes, including intravenously and orally, with specific dosing regimens. It showed no compromise in cell survival or mitochondrial function, indicating a favorable safety profile. SPK also effectively reduced abnormal protein expression associated with COVID-19 pathology.
DEFINITIONS:
Murine Hepatitis Virus-1 (MHV-1):
A coronavirus used in experimental models to study the effects of viral infections in mice. It shares similarities with SARS-CoV-2, the virus responsible for COVID-19.
SPIKENET (SPK):
A 15-amino-acid synthetic peptide that inhibits the binding of the spike glycoprotein-1 of coronaviruses with host receptors. It has potent anti-inflammatory properties.
Goblet Cell Hyperplasia:
An increase in the number of goblet cells, which produce mucus to protect the lining of the intestine.
Villous Atrophy:
The flattening and loss of the villi, which are finger-like projections in the intestine that increase surface area for nutrient absorption.
SUMMARY:
The study aimed to investigate the acute and long-term intestinal changes caused by murine hepatitis virus-1 (MHV-1), a coronavirus, in mice.
This model provides insights into similar changes seen in humans with COVID-19. The research also evaluated the efficacy of SPIKENET (SPK), a synthetic peptide, in mitigating these changes.
The study involved 8-week-old female A/J mice infected with MHV-1.
The mice were divided into groups to assess the effects of MHV-1 infection alone, healthy controls, SPK treatment alone, and SPK treatment following MHV-1 infection. Histopathological changes in the intestines were analyzed using various staining and microscopy techniques.
MHV-1 infection in mice caused significant intestinal alterations similar to those seen in inflammatory bowel disease (IBD) and celiac disease.
These included mucosal inflammation, lymphoid hyperplasia, goblet cell hyperplasia, immune cell infiltration, villous atrophy, and altered epithelial integrity.
SPK treatment effectively mitigated the intestinal damage caused by MHV-1 infection. It restored tissue architecture, reduced inflammation, and normalized goblet cell numbers and villous structures. These findings suggest that SPK has therapeutic potential for treating intestinal damage in long COVID.
Long COVID in mice showed intricate inflammatory profiles, including nests of erythrocytosis, increased goblet cells, and Paneth cell abnormalities. SPK treatment in long COVID models demonstrated significant improvements in intestinal structure and function, highlighting its potential to restore tissue homeostasis.
My Take:
Really, really interesting piece. The first I can remember specifically studying the intricate effects of C19 on intestines. Would love to see these attempt to be replicated in humans.
DEFINITIONS:
Epigallocatechin-3-gallate-monopalmitate (EC16m):
A lipid-soluble derivative of EGCG, a major polyphenol in green tea, known for its antiviral, anti-inflammatory, antioxidant, and neuroprotective properties.
Mucoadhesive Nanoformulations:
Nasal formulations designed to adhere to the mucosal lining, enhancing drug retention and efficacy.
MucilAir Human Nasal Model:
A 3D in vitro model that mimics human nasal epithelium, used for testing mucociliary safety of nasal formulations.
Zeta Potential:
A measure of the stability of nanoparticle suspensions; higher absolute values indicate greater stability.
Cilia Beat Frequency (CBF):
The rate at which cilia in the nasal epithelium beat, which is crucial for clearing mucus and pathogens.
SUMMARY:
The study aimed to evaluate the safety and efficacy of novel nasal mucoadhesive nanoformulations containing epigallocatechin-3-gallate-monopalmitate (EC16m) for treating Long COVID. The persistence of SARS-CoV-2 in nasal neuroepithelial cells contributes to long-lasting neurological symptoms and anosmia in Long COVID patients.
EC16m nanoformulations were tested for mucociliary safety using the MucilAir human nasal model and their antiviral activity against the OC43 viral strain. Particle size, Zeta potential, tissue integrity, cytotoxicity, cilia beat frequency, and viral inactivation were assessed.
The EC16m nanoformulations showed no significant difference in mucociliary safety compared to saline, indicating they are non-toxic and safe for nasal application. Formulations C and D (FC and FD) were chosen for their favorable safety profiles.
Both FC and FD formulations demonstrated potent antiviral activity, with over 99.9% inactivation of the OC43 virus within 5 minutes of contact. FD also showed significant inhibition of viral replication post-infection, reducing viral replication by more than 99%.
DEFINITIONS:
Multiple Correspondence Analysis:
A statistical technique used to identify clusters or patterns in categorical data.
Odds Ratio (OR):
A measure of association between an exposure and an outcome. An OR greater than 1 indicates an increased odds of the outcome with the exposure.
SUMMARY:
The study aimed to identify symptom clusters in acute SARS-CoV-2 infections and their associations with Long COVID fatigue, with a focus on sex-specific differences. It analyzed data from 450 COVID-19 outpatients using the Fatigue Assessment Scale (FAS) and grouped forty-two symptoms into seven clusters through multiple correspondence analysis.
Fatigue was more prevalent and severe in women than in men (45% vs. 25%). The strongest association between symptom clusters and Long COVID fatigue was observed for the cluster “cognitive and mental symptoms.” Each additional symptom in this cluster increased the FAS score by 5.13% and the odds of fatigue by 42%.
Seven symptom clusters were identified: cognitive and mental symptoms, eyes/hair/skin/stings, ear/nose/throat, loss of taste/smell, and others. The “cognitive and mental symptoms” cluster had the most significant impact on the development and severity of Long COVID fatigue.
Women exhibited higher FAS scores and a higher prevalence of fatigue compared to men. The association between cognitive and mental symptoms and fatigue was significant in both sexes but stronger in women.
DEFINITIONS:
Endothelial Dysfunction:
A condition where the inner lining of blood vessels (endothelium) does not function normally, which can contribute to various cardiovascular diseases
SUMMARY:
The review explores various mechanisms behind Long Covid (LC), such as viral persistence, autoimmunity, reactivation of latent viruses, chronic low-grade systemic inflammation, and endothelial dysfunction. It highlights how these mechanisms interact to produce long-term health consequences.
LC symptoms do not always correlate with the severity of the initial COVID-19 infection. LC can affect individuals of all ages, including children, leading to persistent symptoms like fatigue, cognitive impairments, and respiratory issues. Reinfections may increase the likelihood of LC.
Low-grade inflammation, characterized by moderate cytokine levels and immune system activation, is a key feature of LC. This form of inflammation can impact various body systems, leading to conditions such as neuroinflammation, cardiovascular disease, and metabolic dysfunction.
The review suggests that managing LC may require a combination of personalized medicine and standardized protocols. It emphasizes the potential of anti-inflammatory treatments, such as NSAIDs and natural anti-inflammatory compounds, to alleviate symptoms.
DEFINITIONS:
Viroporin:
Small, hydrophobic viral proteins that form ion channels in host cell membranes, altering cell permeability and contributing to viral replication and pathogenesis.
Hippocampal Neurons:
Neurons located in the hippocampus, a brain region involved in memory and learning.
Endoplasmic Reticulum (ER):
An organelle in cells responsible for protein and lipid synthesis, as well as calcium storage and release.
Apoptosis:
Programmed cell death, a process by which cells undergo an orderly and controlled death to eliminate damaged or unnecessary cells.
Cytosolic Ca2+:
Calcium ions within the cytoplasm of a cell, essential for various cellular processes including signaling, muscle contraction, and neurotransmitter release.
SUMMARY:
The study investigates the effects of the SARS-CoV-2 envelope protein (E protein) on calcium (Ca2+) release and neuron cell death in rat hippocampal neurons aged in vitro. Using fluorescence microscopy and calcium imaging, the researchers analyzed E protein localization, neuron damage, and intracellular Ca2+ homeostasis.
E Protein Localization:
The E protein quickly enters hippocampal neurons and localizes with the endoplasmic reticulum (ER) in both young and aged neuron cultures, suggesting it influences ER activities.
Neuron Damage:
The E protein induces apoptosis (cell death) in aged neurons but not in young neurons, indicating an age-dependent vulnerability.
Ca2+ Release:
The E protein causes variable increases in cytosolic Ca2+ concentration by releasing Ca2+ from ER stores. This Ca2+ release is significantly larger in aged neurons compared to young neurons.
Mechanism of Ca2+ Release:
The study confirms that the E protein acts as a viroporin, forming Ca2+-permeable channels in the ER, leading to Ca2+ store depletion and neuron apoptosis.
DEFINITIONS:
Hemoglobin:
A protein in red blood cells responsible for carrying oxygen from the lungs to the rest of the body and returning carbon dioxide from the tissues back to the lungs.
Anemia:
A condition characterized by a decrease in the number of red blood cells or hemoglobin, leading to fatigue, weakness, and other symptoms due to insufficient oxygen delivery to tissues.
Logistic Regression:
A statistical method used to examine the relationship between a dependent variable (e.g., fatigue) and one or more independent variables (e.g., hemoglobin levels).
Spearman Correlation:
A non-parametric measure of the strength and direction of the association between two ranked variables.
SUMMARY:
The study investigates the relationship between hemoglobin levels and fatigue in Long-COVID patients 3-6 months after SARS-CoV-2 infection. It examines correlations between hemoglobin and inflammatory biomarkers.
This prospective cohort study involved 95 patients in the Netherlands, mostly hospitalized, aged 40-65 years. Hemoglobin levels, anemia prevalence, inflammatory biomarkers, and fatigue severity were assessed. Logistic regression was used to analyze the association between hemoglobin and fatigue.
16.4% of participants had anemia 3-6 months post-infection.
Hemoglobin levels increased by 0.3 mmol/L on average compared to the acute phase (p = 0.003).
No correlation was found between hemoglobin levels and inflammatory biomarkers.
Logistic regression indicated that a 1 mmol/L increase in hemoglobin was associated with decreased fatigue (adjusted OR 0.38 [95% CI 0.13–1.09]).
Hemoglobin impairment may contribute to Long-COVID fatigue. Further research is needed to understand the mechanisms behind hemoglobin changes in Long-COVID patients.
Article: Epidemiologic Features of Recovery From SARS-CoV-2 Infection | JAMA Network Open
SUMMARY:
This cohort study evaluated 4708 participants across 14 ongoing National Institutes of Health–funded cohorts that have enrolled and followed participants since 1971. The study includes data collected on adults aged 18 years or older with self-reported SARS-CoV-2 infection starting in April 1, 2020 through February 28, 2023
The median self-reported time to recovery from SARS-CoV-2 infection was 20 days, and an estimated 22.5% had not recovered by 90 days.
Women and adults with suboptimal prepandemic health, particularly clinical cardiovascular disease, had longer times to recovery.
Vaccination prior to infection and infection during the Omicron variant wave were associated with shorter times to recovery.
Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99).
No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms.
Results were similar for reinfections.
These findings suggest that interventions to reduce severity of acute infection, such as vaccination, may help to mitigate the increased risk of persistent symptoms observed in women and adults with suboptimal prepandemic health.
SUMMARY:
Using data from the German National Cohort (NAKO Gesundheitsstudie), study authors investigated risk factors for self-reported post-infection symptoms (any PCC was defined as having at least one symptom, and high symptom burden PCC as having nine or more symptoms).
Sixty percent of 109,707 participants reported at least one previous SARS-CoV-2 infection; 35% reported having had any symptoms 4-12 months after infection; among them 23% reported nine or more symptoms.
Individuals who did not develop Post-COVID Condition (PCC) after their first infection, had a strongly reduced risk for PCC after their second infection (50%) and a temporary risk reduction, which waned over nine months after the preceding infection.
Within variants, there was no effect of the number of preceding vaccinations, except for a strong protection by the fourth vaccination compared to three vaccinations for the Omicron variant (odds ratio=0.52; 95% confidence interval 0.45-0.61).
The risk of developing PCC strongly depended on the virus variant.
In conclusion, previous infections without PCC and a fourth vaccination were associated with a lower risk of PCC after a new infection, indicating diminished risk under hybrid immunity. The two components of risk reduction after a preceding infection suggest different immunological mechanisms.
DEFINITION:
Stellate Ganglion Block (SGB):
An injection of anesthetic medication into a collection of nerves called the stellate ganglion. These nerves are located in the neck, on both sides of the voice box. Stellate ganglion block (SGB) is used for the treatment of many medical conditions including complex regional pain syndrome, post-traumatic stress disorder (PTSD), and peripheral vascular disease.
SUMMARY:
This was a retrospective chart analysis study on individuals treated with sequential bilateral stellate ganglion blockade (SGB) over the course of six months (2021−2022).
27 patients were eventually included in the final analysis.
Nine severely affected patients experienced a positive but unsatisfactory initial response and immediately undertook additional treatments (e.g., “Partial Responders”), which required exclusion of their data from analysis due to deviation from treatment protocol.
For each symptom, post-treatment values were subtracted from post-COVID values for each individual and differences were averaged to yield mean improvement values. Significance was determined using paired t-test (alpha = 0.05).
At one month following treatment, all symptoms improved significantly, with striking improvement in symptoms that characterize Post-Exertional Malaise.
This study suggests that neuromodulation may provide relief of Long COVID symptoms for at least a subset of individuals, and provides support for prospective studies of this potential treatment.
DEFINITIONS:
Resting-state functional magnetic resonance imaging (rs-fMRI):
A method of functional magnetic resonance imaging (fMRI) that is used in brain mapping to evaluate regional interactions that occur in a resting or task-negative state, when an explicit task is not being performed. These brain networks are observed through changes in blood flow in the brain which creates what is referred to as a blood-oxygen-level dependent (BOLD) signal that can be measured using fMRI.
Functional magnetic resonance imaging (functional MRI or fMRI) is a specific magnetic resonance imaging (MRI) procedure that measures brain activity by detecting associated changes in blood flow.
False discovery rate adjusted-p-value (p-FDR):
The FDR is the ratio of the number of false positive results to the number of total positive test results: a p-value of 0.05 implies that 5% of all tests will result in false positives.
SUMMARY:
Based on recent evidence, this study evaluated whether cerebral hemodynamic changes contribute to post-COVID syndrome (PCS). Patients presented with high levels of fatigue (79%) and daytime sleepiness (45%).
Using resting-state functional magnetic resonance imaging, the study investigated brain perfusion and oxygen level estimates in 47 patients (44.4 ± 11.6 years; F:M = 38:9) and 47 individually matched healthy control participants.
The study found widespread decreased brain oxygen levels, most evident in the white matter (false discovery rate adjusted-p-value (p-FDR) = 0.038) and cortical grey matter (p-FDR = 0.015).
Delayed patient caudate nucleus perfusion was associated with better executive function (p-FDR = 0.008).
Delayed perfusion in the cortical grey matter and hippocampus were associated with a reduced risk of daytime sleepiness (hazard ratio (HR) = 0.07, p = 0.037 and HR = 0.06, p = 0.034).
Decreased putamen oxygen levels were associated with a reduced risk of poor cognitive outcome (HR = 0.22, p = 0.019).
Meanwhile, lower thalamic oxygen levels were associated with a higher risk of cognitive fatigue (HR = 6.29, p = 0.017).
Our findings of lower regional brain blood oxygen levels suggest increased cerebral metabolism in PCS, which potentially holds a compensatory function.
These hemodynamic changes were related to symptom severity, possibly representing metabolic adaptations.