Long Covid Weekly #107: Understanding PEM, Interstitial Lung Disease
Long Covid Weekly #107
From groundbreaking studies highlighting immune system interactions and vulnerability to post-exertional malaise, to community discussions about persistent fatigue, our articles aim to illuminate the multifaceted impacts of Long Covid on both physical health and quality of life. We also explore findings related to cognitive changes and the varied responses to covid vaccinations.
Article of the Week:
This week's highlighted article, "Towards an understanding of physical activity-induced post-exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post-COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome," looks into the complex mechanisms underlying post-exertional malaise (PEM) that affects many patients with post-COVID condition (PCC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The review synthesizes recent findings related to microvascular dysfunction, metabolic alterations, and immune responses that contribute to PEM.
A couple of key findings highlighted in the study include:
"Accumulating evidence suggests that these [reduced systemic oxygen extraction and oxidative phosphorylation capacity] are mediated by dysfunctions in mitochondrial capacities and microcirculation that are maintained by latent immune activation, conjointly impairing peripheral bioenergetics."
"The accumulation of molecules such as lactate, reactive oxygen species or prostaglandins might trigger local and systemic immune activation, leading to an exacerbation of existing pathologies and symptoms."
Here is the link to the Long Covid Weekly Database.
Media
Article: Long COVID inflicts deep scars on the lungs, but targeting specific immune cells could reverse damage − new research in mice | The Conversation
DEFINITIONS:
Mouse model: A laboratory technique using mice to study human diseases and evaluate potential treatments, leveraging physiological similarities between the two species.
Gas exchange: The process by which oxygen is absorbed into the bloodstream and carbon dioxide is expelled, an essential function of the respiratory system.
SUMMARY:
Researchers at the University of Virginia developed a new mouse model to study long COVID, demonstrating that blocking overactive immune cells can restore lung function.
The study revealed that mice infected with the influenza virus best replicated lung damage associated with long COVID, suggesting that the type of virus may be less critical than the resulting damage in recovery efforts.
By identifying abnormal immune cell clusters in the lungs, researchers found these cells hinder recovery processes and gas exchange in lung tissues, indicating new avenues for treatment.
There is potential for FDA-approved drugs, originally aimed at treating severe COVID-19, to be repurposed for long COVID symptoms.
SUMMARY:
Medical professionals are investigating connections between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), as both conditions exhibit overlapping symptoms and pathologies.
An estimated 15 million adults in the U.S. are living with long COVID, with approximately half meeting the criteria for ME/CFS.
Patients with ME/CFS frequently experience post-exertional malaise, where even minor physical or mental exertion can significantly worsen their symptoms.
The Santa Clara Valley Healthcare system has seen a notable decline in long COVID cases, attributing this reduction mainly to high vaccination rates and improved symptom management practices.
Article: New Study Provides Insight to Why Covid Vaccines Hit Some Harder than Others - UConn Today
DEFINITIONS:
Body Mass Index (BMI): A measure to assess healthy body weight for a given height, calculated by dividing weight in kilograms by height in meters squared.
Hormonal birth control: Contraceptive methods that contain hormones to regulate or suppress ovulation and menstruation.
SUMMARY:
A recent study by Catherine Andersen investigates why some individuals experience more severe side effects from COVID-19 vaccines than others.
Factors such as stress, exercise, body mass index (BMI), and hormonal birth control use contribute to varying perceptions of vaccine side effects.
The study surveyed 82 participants who received one of the three COVID-19 vaccines and found that stress significantly correlated with the intensity of reported side effects.
While there were no sex-dependent differences in side effects, women reported higher stress levels and less regular exercise compared to men.
Andersen's future research aims to explore individualized responses to health interventions to improve vaccine efficacy and minimize side effects.
Article: Alzheimer's-like brain changes found in long COVID patients | Medical Xpress
DEFINITIONS:
Astrocytes: Star-shaped glial cells in the brain and spinal cord that support neurons and maintain a healthy environment for neuronal function.
Neuroinflammation: An inflammatory response within the brain or central nervous system that may arise from injury, infection, or autoimmune diseases, potentially contributing to neurodegenerative disorders.
Electroencephalography (EEG): A non-invasive method used to record electrical activity of the brain, often employed for diagnosing neurological conditions.
SUMMARY:
New research from the University of Kentucky suggests that cognitive impairments in long COVID patients resemble those found in Alzheimer's disease and related dementias.
The study indicates that underlying brain changes, such as neuroinflammation and astrocyte activation, may connect long COVID and Alzheimer’s disease.
Researchers found that the "brain fog" experienced by many COVID-19 survivors—memory issues and confusion—resembles cognitive decline associated with dementia.
The interdisciplinary nature of the study, involving experts from six countries, highlights the collaborative effort to understand these neurocognitive challenges.
Conclusions from the research suggest advocating for regular brain function assessments with tools like electroencephalography (EEG) to detect early cognitive decline in affected populations.
Research
SUMMARY:
This review investigates the mechanisms of post-exertional malaise (PEM) in patients with Post-COVID Condition (PCC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
Evidence suggests that PEM is characterized by reduced systemic oxygen extraction and impaired mitochondrial function during physical exertion.
Patients with PCC show distinctive alterations in microcirculation and ongoing immune activation, contributing to their reduced exercise capacity.
Accumulation of metabolites like lactate and reactive oxygen species during exertion can provoke immune responses that exacerbate fatigue.
A subset of PCC patients experiences intensified symptoms even after minor physical activities, indicating significant dysfunction in their physiological responses.
MY TAKE:
This paper highlights the relationship between microvascular dysfunction, mitochondrial issues, and persistent immune activation in PCC and ME/CFS. The finding that mild physical activities can severely impact patients underscores the need for personalized management strategies to support their unique physiological responses.
DEFINITION:
Small fiber neuropathy: A condition affecting small nerve fibers that carry pain and temperature sensations, potentially leading to symptoms like pain and sensory changes.
SUMMARY:
Previous research has indicated a potential link between small fiber neuropathy and pain in long COVID cases.
In this case-control study, the researchers assessed 26 patients suffering from painful long COVID syndrome for signs of small fiber neuropathy.
Clinical data revealed that roughly 50% of those with painful long COVID had abnormalities consistent with small fiber neuropathy.
Demographic and clinical factors did not significantly differ among patients with small fiber neuropathy, those with painless long COVID, and asymptomatic controls.
DEFINITIONS:
Neuroinflammation: Inflammation of nervous tissue that can lead to cognitive decline and other neurological symptoms following an infection.
Microvascular damage: Damage to small blood vessels, which can reduce blood flow and contribute to symptoms like fatigue and cognitive dysfunction.
SUMMARY:
The mechanisms behind PASC include a combination of immune dysregulation, neuroinflammation, and microvascular damage linked to the virus.
While most patients with long COVID may experience symptom improvement over time, a significant minority remain severely affected.
Current research aims to understand these underlying abnormalities, with the hope that insights gained may also inform treatments for other post-infectious syndromes.
My Take:
Informative, albeit not introducing anything new.
DEFINITIONS:
Paraprobiotics: Non-viable probiotic microorganisms that provide health benefits by modulating immune responses and gut microbiota without the metabolic activity of live probiotics.
Dysautonomia: A disorder of autonomic nervous system function that affects bodily functions such as heart rate, blood pressure, and digestion, leading to symptoms including fatigue and dizziness.
Toll-like receptor 2 (TLR2): A receptor involved in recognizing pathogens and activating immune responses, particularly in inflammation and infection.
SUMMARY:
The study investigates the clinical and immunologic effects of paraprobiotics on patients suffering from long COVID, characterized by debilitating multi-system symptoms that persist after the initial infection.
In this pilot study, six long COVID patients were treated with defined paraprobiotics for four weeks, followed by a systematic evaluation of symptoms using validated questionnaires and wearable sensors.
Improvements were noted in several neurological symptoms, including dysautonomia, fatigue, and depression, as measured by self-reported outcomes and quantitative data from monitoring devices.
The treatment appeared to modulate immune responses, evidenced by reduced activation markers on immune cells, specifically TLR2 expression on T cells.
Despite promising findings, the small sample size and preliminary nature of this study necessitate further investigation to validate these effects and better understand the mechanisms underlying long COVID.
My Take:
By linking gut health with immune response, the research sheds light on the relationship between the microbiome and systemic health. Optimizing gut health may prove essential in managing chronic conditions arising from respiratory infections, potentially extending beyond COVID-19.
SUMMARY:
The study evaluates the psychometric properties of the DePaul Symptom Questionnaire-Short Form (DSQ-SF) in adults with Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and healthy controls.
Long COVID shares clinical similarities with ME/CFS, particularly symptoms such as severe fatigue and post-exertional malaise.
Researchers utilized machine learning algorithms to accurately classify these populations using the DSQ-SF.
The study found that the DSQ-SF effectively distinguishes between individuals with Long COVID, those with ME/CFS, and healthy participants with high sensitivity and specificity.
Identifying specific DSQ-SF symptoms that differentiate Long COVID from ME/CFS aids in diagnosis and informs tailored treatment interventions.
My Take:
This study highlights diagnostic overlaps between Long COVID and ME/CFS, emphasizing the need for specialized assessment tools in the current healthcare landscape. Although it seems like they were able to differentiate between the two with the DSQ-SF.
DEFINITIONS:
Chronic Obstructive Pulmonary Disease (COPD): A progressive lung disease characterized by airflow limitation and breathing difficulties, often caused by long-term exposure to harmful substances like cigarette smoke.
Airway Remodeling: Structural changes in the airway walls that may occur in response to chronic inflammation or injury, affecting lung function and airflow.
SUMMARY:
This study investigates chest CT measurements to compare airway and vascular changes in females with chronic obstructive pulmonary disease (COPD) and those with long-COVID.
Results indicate that females with long-COVID exhibit significantly smaller airway lumen areas and thinner airway walls compared to those with COPD, emphasizing unique remodeling patterns associated with long-COVID.
Notably, small vessel volume is greater in females with long-COVID compared to both ex-smokers and COPD patients, hinting at potential vascular complications following COVID-19.
Despite similar quality-of-life scores across the long-COVID, ex-smoker, and COPD groups, the functional consequences of airway remodeling appear comparable in all groups.
DEFINITIONS:
Post-COVID interstitial lung disease (ILD): A condition characterized by persistent lung inflammation and scarring in patients who have recovered from COVID-19, leading to respiratory symptoms and functional abnormalities.
Hypoxemia: A condition marked by insufficient oxygen levels in the blood, often leading to symptoms such as shortness of breath and fatigue.
High-resolution computed tomography (HRCT): A specialized imaging technique used to visualize lung structures in detail, aiding in the diagnosis of pulmonary conditions like ILD.
SUMMARY:
In the postacute phase of COVID-19, survivors may experience persistent symptoms and lung function abnormalities, leading to a new classification known as post-COVID interstitial lung disease (ILD).
This multicenter cross-sectional study evaluated the characteristics, risk factors, and clinical significance of post-COVID ILD among patients.
Of the 375 patients analyzed with post-COVID-19 syndrome, 262 were diagnosed with post-COVID ILD during a three-month follow-up.
Common symptoms included dyspnea (90.8%), exercise intolerance (63.4%), fatigue (54.2%), and cough (52%).
The mean oxygen saturation among patients with post-COVID ILD was 92.2%, and the average 6-minute walking distance was about 360 meters, indicating significant respiratory impairment.
DEFINITION:
Semaglutide (brand name Wegovy): A glucagon-like peptide-1 (GLP-1) receptor agonist that is 94% homologous to human GLP-1 (7-37), with antihyperglycemic and appetite regulating activities.
SUMMARY:
This study examined the effect of semaglutide 2.4 mg on all-cause death, cardiovascular (CV) death, and non-CV death, including death from COVID-19.
The SELECT (Semaglutide Effects on Cardiovascular Outcomes in Patients With Overweight or Obesity) trial randomized over 17,000 participants with CV disease to once-weekly subcutaneous semaglutide 2.4 mg or placebo.
Participants assigned to semaglutide vs placebo had lower rates of all-cause death, and non-CV death.
Semaglutide did not reduce the incidence of COVID-19. But participants treated with semaglutide who developed COVID-19 had fewer COVID-19–related serious adverse events and fewer deaths from COVID-19.
The mechanism by which semaglutide is associated with lower CV or non-CV mortality is unknown.
My Take (Amy):
Does it seem like semaglutide can do just about anything?
DEFINITION:
Nested case-control study: A type of study design that involves selecting a number of healthy controls for each case of a disease that occurs within a defined cohort. The controls are typically selected from those who were still under observation when the case developed the disease.
SUMMARY:
This was a nested case-control study of 108 participants evaluating differences in oral microbiota in individuals with and without long COVID (Symptomatic and Asymptomatic groups).
Using rRNA sequencing from tongue coating samples, a predictive model was achieved using machine learning based on specific microbial communities.
There were distinct variations in oral microbiota between COVID-19 patients with and without long COVID.
Study authors conclude that changes in oral microbiota may indicate long COVID.