Hi everyone,
In this edition, we cover a range of topics, from ongoing trials seeking participants with cognitive symptoms to studies focusing on the lingering effects of the virus on the body. We delve into the potential links between Long Covid and vaccines, as well as the impact on various bodily functions such as gut microbiota and autoimmune responses.
The research I wanted to highlight today was Article: Unravelling shared mechanisms: insights from recent ME/CFS research to illuminate long COVID pathologies: Trends in Molecular Medicine. This review paper examines the similarities and differences in proposed disease pathologies between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and LC, with a focus on recent research findings in areas such as immune dysfunction, metabolic abnormalities, gut microbiome changes, neurological impacts, and vascular pathologies. By leveraging the longer history of ME/CFS research, the authors provide insights into how LC may progress over time.
Here are some of the excerpts I found the most interesting!
Reductions in white and grey matter regional volumes [73.], cortical thickness [74.], and density and microstructural complexity of axons [75.] across both cortical and subcortical regions represent maladaptive structural impacts on the CNS in ME/CFS. Functional CNS impacts have also been observed, including reduced functional connectivity within brainstem and brainstem–hippocampal connections during cognitive tasks [76.], reduced cerebral blood flow after tilt testing [77.], cerebral hypoperfusion in limbic and midbrain regions consistent with orthostatic intolerance [78.,79.], elevated choline metabolite in the anterior cingulate cortex, often seen with glial cell proliferation and demyelination [80.], and increased signs of intracranial hypertension and craniocervical obstruction [81.].
Vascular pathologies, including endothelial dysfunction, vascular inflammation, blood morphology changes, and the formation of microclots, are significantly associated with LC [95.]. The formation of fibrous amyloid microclots has been reported as a major pathology in LC and is a proposed diagnostic and therapeutic target [102.]. Fibrin amyloid clots are resistant to breakdown [103.] and are predicted to limit oxygen availability to tissues, thereby contributing to key symptoms of fatigue, exercise intolerance, cognitive impairment, and autonomic dysfunction. The clots are accompanied by hyperactivated platelets, which may arise due to an increase in adhesion factors, inflammation, and binding of virus to platelets [97.].
Viruses can bind to platelets! Super interesting.
Media
Article: Opinion: Long COVID and Cognitive Deficits | Medscape
SUMMARY:
Two new studies published in the New England Journal of Medicine discuss the impact of cognitive deficits after COVID-19 infection in large cohorts.
The studies show that COVID-19 has a significant impact on memory, executive function, and reasoning, with worse outcomes observed with the original virus and the Alpha variant.
The long-term impact of COVID-19 on cognitive function, particularly in individuals who tested positive for the virus, suggests a decline in memory over an extended period.
Article: Trial seeks people with long COVID cognitive symptoms - UW Medicine | Newsroom
SUMMARY:
The RECOVER Initiative led by the National Institutes of Health aims to evaluate therapies for individuals experiencing long COVID cognitive symptoms following a COVID-19 infection.
The RECOVER-NEURO trial, part of the RECOVER Initiative, focuses on interventions for brain fog, memory lapses, attention difficulties, and other cognitive problems seen in long COVID patients.
The team is actively enrolling participants for the RECOVER-NEURO trial, which will assess whether long COVID-based declines in cognitive function and attention might be improved by interventions that selectively focus on enhancing those areas. UW Medicine researchers will evaluate the effectiveness of online cognitive-training programs and transcranial direct-current stimulation to reduce these neurological symptoms.
My Take:
Glad they are researching treatments but this seems like a waste of resources when there are actual medical interventions to be tested
Article: COVID's Long Haul: Virus Lingers in Blood Years After Infection - Neuroscience News
SUMMARY:
SARS-CoV-2 can persist in the blood and tissue of patients for up to two years post-infection, leading to insights into long COVID.
Research found COVID antigens in blood samples up to 14 months after infection and in tissue samples for more than two years, challenging previous notions of COVID-19 as a transient illness.
The persistence of COVID antigens was more likely in individuals who experienced severe illness, highlighting a correlation between virus persistence and initial infection severity.
Research
[TBD - Study design]
SUMMARY:
This upcoming study will investigate the efficacy of immunoadsorption (removing antibodies from plasma) in patients with ME/CFS, including those with post-acute COVID-19 CFS.
Autoantibodies targeting various receptors have been identified in patients with ME/CFS and PACS-CFS, suggesting an autoimmune component in these conditions.
This double-blinded, randomized trial aims to evaluate the therapeutic effects of repeated immunoadsorptions on patient-reported outcomes, biomarker profiles, and cognitive and physical parameters in ME/CFS patients.
DEFINITIONS:
Autoimmune inflammatory rheumatic diseases (AIRDs): A group of conditions characterized by autoimmunity (the immune system attacking the body's own tissues) and chronic inflammation, primarily affecting the joints, muscles, and connective tissues. Examples include rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, and spondyloarthritis.
Ascertainment bias: A systematic distortion in measuring the true risk, prevalence or incidence of a disease due to the way in which the study participants were selected or the method of detecting the disease.
Propensity score matching: A statistical technique used in observational studies to estimate the effect of a treatment by accounting for confounding factors that predict receiving the treatment.
Cohort study: An observational study in which a group of individuals with a shared characteristic (e.g., SARS-CoV-2 infection) is followed over time and compared with a control group without that characteristic.
SUMMARY:
This study investigated the risk for developing autoimmune inflammatory rheumatic diseases (AIRD) 1, 6, and 12 months after developing COVID-19 infection.
This binational, longitudinal, propensity-matched cohort study evaluated over 10 million Korean patients and over 12 million Japanese patients aged 20 years or older, including those with COVID-19, between January 1st 2020 and December 31st 2021.
In the Korean cohort, 394,274 (3.9%) and 98,596 (0.98%) had a history of COVID-19 or influenza, respectively.
Beyond the first 30 days after infection, patients with COVID-19 were at increased risk for incident AIRD compared with uninfected patients (adjusted hazard ratio, 1.25) and compared with influenza-infected control patients (adjusted hazard ratio, 1.30).
The risk for incident AIRD was higher with more severe acute COVID-19. Similar patterns were observed in the Japanese cohort.
The comparison with influenza infection allowed study authors to determine whether any increased risk for AIRD after COVID-19 was specific to COVID-19 or is a common finding in viral respiratory infections.
Secondary outcomes were incident inflammatory arthritis, connective tissue disease, untreated AIRD, and treated AIRD 30 days after SARS-CoV-2 or influenza infection
!MUST READ
DEFINITIONS:
Autoantibodies: Antibodies produced by the immune system that target the body's own cells or tissues, leading to autoimmune reactions.
Glycolysis: Metabolic pathway that breaks down glucose into pyruvate to generate energy.
Mitochondrial respiration: Cellular process where mitochondria generate energy from nutrients in the presence of oxygen.
SUMMARY:
This comprehensive summary focuses on the similarities and differences between Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC), along with recent advancements in understanding their pathologies, biomarkers, and potential therapeutic approaches.
Clinical and Molecular Similarities between ME/CFS and LC:
Both conditions often follow an acute viral infection, suggesting a potential shared mechanism of transition from acute to chronic disease.
Around half of LC patients meet the diagnostic criteria for ME/CFS, indicating significant clinical overlap.
Common pathologies include immune system dysfunction, metabolic abnormalities (including a shift away from carbohydrates as energy sources), neuroinflammation, and alterations in the gut microbiota, particularly a reduction in butyrate-producing bacteria.
Research Highlights and Challenges:
Immune dysregulation is a key feature, with both conditions showing signs of chronic inflammation, altered immune cell function, and autoantibody production.
Metabolic changes in both ME/CFS and LC point towards impaired energy production, with evidence of mitochondrial dysfunction and an increased reliance on lipids and amino acids as energy sources.
Gut microbiota alterations are common, though the exact patterns of dysbiosis and their implications remain to be fully understood.
CNS dysfunction, including evidence of neuroinflammation and altered brain structure and function, is present in both ME/CFS and LC, contributing to symptoms such as cognitive disturbances and autonomic dysfunction.
Emerging Therapies and Clinical Trials:
Clinical trials for ME/CFS and LC are exploring various therapeutic strategies, including targeting immune dysregulation, metabolic dysfunction, and gut microbiota.
Some trials have shown promising results, but there is a need for further studies to confirm these findings and to explore new therapeutic targets based on our evolving understanding of the disease mechanisms.
DEFINITIONS:
Retrospective cohort study: A study where two groups are retrospectively identified and “prospectively” compared: A cohort of healthy subjects is subdivided into two groups – one exposed to a given factor and the other nonexposed to the same factor.
All-cause mortality: A term that refers to death from any cause. In statistics, all-cause mortality is usually a measure of the total number of deaths from any cause in a specific group of people over a specific period of time.
Clinical sequelae: any clinical complication or condition that results from a pre-existing illness, injury, or other trauma to the body.
Hazard ratio: A measure of how often a particular event happens in one group compared to how often it happens in another group, over time.
SUMMARY:
The risk of long-term health consequences of SARS-CoV-2 infection and the protection against such risk conferred by COVID-19 vaccination remains unclear.
Compared to non-infected controls, patients with SARS-CoV-2 infection were observed to incur a greater risk of clinical sequelae including major cardiovascular diseases, and all-cause mortality across patients with different COVID-19 vaccination status during the acute phase of infection.
Patients who received three or more doses of vaccines did not incur any significant increased risk in clinical sequelae from 91 days onwards from their initial infection. On the other hand, unvaccinated patients were at a greater risk of several clinical sequelae including all-cause mortality up to one year following infection.
This study provides real-world evidence supporting the effectiveness of COVID-19 vaccines in reducing the risk of long-term health consequences of SARS-CoV-2 infection and its persistence following infection.
DEFINITIONS:
Hyperbaric Oxygen Therapy (HBO): Treatment involving increased pressure and elevated partial pressure of oxygen to promote beneficial effects on oxygen levels in the body.
Oxidative stress: Imbalance between free radicals (reactive oxygen species) and antioxidants in the body, leading to damage at a cellular level.
SUMMARY:
This article was a clinical review that examined recent studies, including case series and randomized trials, that have shown that HBO can significantly improve a range of symptoms in long COVID patients, suggesting its potential as a safe and beneficial treatment option.
HBO's therapeutic efficacy in long COVID is attributed to its ability to modulate immune responses, reduce inflammation, improve mitochondrial function, enhance microcirculation, and stimulate neuroplasticity, directly targeting the complex pathophysiology of long COVID.
Clinical evidence supports HBO's effectiveness in improving cognitive function, reducing fatigue, enhancing cardiopulmonary capacity, and alleviating pain, with improvements also observed in brain MRI perfusion and microstructural changes.
The accumulating evidence underscores the potential of HBO in treating long COVID by addressing its multifaceted pathophysiology.
DEFINITIONS:
Hyperpolarized 129Xe MRI: A technique that uses hyperpolarized xenon gas for magnetic resonance imaging of lung function, particularly gas uptake efficiency.
RBC-TP Ratio: The ratio of red blood cell signal intensity to tissue or plasma in dynamic 129Xe spectroscopy, reflecting lung microvascular perfusion.
Microvascular Pulmonary Perfusion: Blood flow through tiny blood vessels in the lungs that facilitate gas exchange, essential for adequate lung function.
SUMMARY:
The study aimed to evaluate lung function in COVID-19 convalescents using MRI and hyperpolarized 129Xe imaging to assess diffusion limitation and microvascular perfusion.
Results indicated that COVID-19 convalescents showed persistent alveolar membrane function and microvascular perfusion impairment 12 weeks after symptoms, which resolved within 38 weeks post-symptom onset.
Significant differences were observed in the RBC-TP and various spectroscopic ratios between COVID-19 patients and healthy controls, suggesting long-term lung alterations post-COVID-19 infection.
DEFINITIONS:
Omics: A field of study that investigates the collective characterization and quantification of pools of biological molecules (e.g., transcriptomics for RNA, proteomics for proteins, metabolomics for metabolites).
Immunophenotyping: The process of characterizing and quantifying different subsets of immune cells based on their surface markers and functional properties.
Reservoir: In the context of viral infections, a reservoir refers to a site or cell type where the virus persists and can potentially reactivate or replicate, even after the initial acute infection has resolved.
Homeostasis: The tendency of a biological system to maintain a relatively stable internal environment, even in the face of external changes or perturbations.
PAMPs (Pathogen-Associated Molecular Patterns): Molecular signatures found in pathogens, such as bacterial or viral components, that are recognized by the innate immune system and trigger an immune response.
SUMMARY:
This review summarizes the current understanding of immune perturbations in Long COVID, covering both innate and adaptive immune responses, and the cytokines and analytes involved.
Immune dysregulation appears to be a common feature across many cases of LC, with studies revealing systemic inflammation, altered myeloid cell and neutrophil activity, perturbations in NK cells, elevated SARS-CoV-2 antibody levels, and changes in T cell phenotypes and function.
The persistent presence of SARS-CoV-2 reservoirs, particularly in the gut, is hypothesized to drive the ongoing immune dysregulation observed in LC by providing a source of antigens that continuously stimulate the immune system.
Multi-omics tools, including transcriptomics, proteomics, metabolomics, and immunophenotyping, have provided valuable insights into the immune perturbations associated with LC, although more tissue-focused analyses are needed.
Animal models of LC are currently lacking, hampering the ability to study the underlying mechanisms and test potential therapies.
Future research should focus on understanding the crosstalk between different components of the immune system in LC, identifying subtypes of LC, and developing targeted interventions to restore immune homeostasis.
DEFINITIONS:
Orthostatic Intolerance (OI): A condition where an individual's body reacts negatively to standing up, characterized by symptoms like dizziness, lightheadedness, and palpitations, often due to abnormal blood pressure and heart rate responses.
Orthostatic Hypotension (OH): A form of OI, characterized by a significant drop in blood pressure upon standing, causing symptoms like dizziness and fainting.
National Aeronautics and Space Administration Lean Test (NLT): A standardized test used to evaluate for OI, where heart rate and blood pressure are measured in different postures (lying down and standing) to identify abnormal responses.
SUMMARY:
Long COVID patients with a previous history of OI symptoms were more likely to meet the criteria for POTS or OH during the NLT; about 45% of patients with an abnormal NLT had no prior symptoms of OI.
This suggests that relying solely on symptoms may not capture all cases of autonomic dysfunction.
Relaxing the diagnostic thresholds for POTS from two consecutive abnormal readings to one abnormal reading during the NLT resulted in an additional 4% of long COVID participants meeting criteria for POTS, highlighting the importance of standardized testing protocols in diagnosing autonomic disorders.
Overall, the study recommends that all patients attending long COVID clinics should be offered an NLT and appropriate management to address potential autonomic dysfunction associated with orthostatic intolerance.
Article: Impact of SARS-CoV2 infection on gut microbiota dysbiosis | Microbiome Research Reports
DEFINITIONS:
Gut microbiota dysbiosis: an imbalance in the composition and function of the gut microbiota that can lead to adverse health events.
Short-chain fatty acids (SCFA): a group of fatty acids produced by the gut microbiota during the fermentation of dietary fibers.
Gut-lung axis: the bidirectional communication between the gut microbiota and the lung, influencing the immune response triggered by infections like SARS-CoV-2.
SUMMMARY:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been shown to impact the gut microbiota, leading to dysbiosis and gastrointestinal manifestations in COVID-19 patients.
Studies have identified alterations in the gut microbiome composition of COVID-19 patients, including enrichment of opportunistic pathogens and depletion of beneficial commensals.
The gut microbiota dysbiosis in COVID-19 patients is associated with changes in fecal metabolites, such as impaired short-chain fatty acid (SCFA) biosynthesis.
The gut-lung axis has emerged as a crucial player in the pathological immune response triggered by SARS-CoV-2, highlighting the intricate interplay between the respiratory mucosa and the gut microbiota.
Very interesting issue! Thanks, Brandon.
Did the end of the article get cut off?