Hi everyone,
This week covers quite a bit! For example, recent advancements include the use of monoclonal antibodies to potentially eradicate lingering viral reservoirs. Moreover, insights into neurological impacts, such as the elevated plasma levels of neurofilament light chain in patients, underline the connections between LC and CNS damage.
We Need Your Input!
Amy here from Long Covid Weekly! As we continue to summarize and analyze over 600+ impactful medical articles, we're exploring the idea of creating a publically accessible and downloadable database for our readers, patients, and researchers alike. But before we proceed, we need to hear from you! Would such a resource be useful to you? What categories should we include? Are you interested in contributing? Please share your thoughts and suggestions by filling out this survey . Your input is invaluable as we strive to make this important research more accessible to everyone.
I also want to highlight Metrodora Institute, a new initiative co-founded by Fidji Simo, the CEO of Instacart. Launched a year ago, the Institute is making strides in the battle against chronic, complex conditions, including LC. As someone who has demonstrated immense success in the tech industry, Fidji Simo's involvement is particularly significant. Fidji is helping to ensure that the Metrodora Institute can offer new hope and advanced care to patients suffering from these debilitating conditions. Website
This week, we highlight a significant article titled "The persistence of SARS-CoV-2 in tissues and its association with long COVID symptoms: a cross-sectional cohort study in China." I think the title is pretty self-explanatory, but it shows some very related results on viral persistence. Here are three noteworthy sentences from the study's results, discussion, and conclusion:
Results: "Detection of viral RNA in recovered patients was significantly associated with the development of long COVID symptoms (odds ratio 5·17, 95% CI 2·64–10·13, p<0·0001)."
Discussion: "Our research clearly showed an association between long COVID symptoms at 4 months after infection and the persistence of residual SARS-CoV-2 RNA."
Conclusion: "We have identified an association between viral persistence in various tissues of the body and long COVID symptoms, suggesting that SARS-CoV-2 persistence in tissues might be associated with long-term immune dysregulation."
Media
Article: NIH RECOVER makes long COVID data easier to access | National Institutes of Health (NIH)
SUMMARY:
The NIH RECOVER initiative has made deidentified data from more than 14,000 adults with long COVID available to authorized researchers through BioData Catalyst (BDC).
By providing secure data, analysis tools, and resources, the BDC ecosystem aims to accelerate research on heart, lung, blood, and sleep disorders related to long COVID.
The addition of RECOVER data to BDC can help investigators identify and explore connections related to long COVID that may benefit future studies.
Article: Telehealth startups turn to complex chronic diseases - STAT
SUMMARY:
Telehealth startups are focusing on complex chronic diseases that have been traditionally overlooked, aiming to provide specialized care remotely.
Patients with conditions like dysautonomia are benefiting from access to informed specialists through telehealth services, reducing the need for long-distance travel for medical consultations.
This shift towards telehealth reflects a growing demand for convenient and accessible healthcare solutions for chronic disease management.
SUMMARY:
Sanders's focus on researching long COVID is crucial, but it neglects other chronic conditions like Myalgic Encephalomyelitis (ME/CFS) that have been waiting for research funding for decades.
The severity of this illness was dismissed and victims were ridiculed in the popular press after the CDC renamed the disease “chronic fatigue syndrome” in 1988.
One reason for this neglect has been the public’s failure to understand how high their chances of acquiring Myalgic Encephalomyelitis are and just how serious it actually is.
The overlap in symptoms between long COVID and ME/CFS suggests potential shared physiological disruptions that could benefit from similar interventions.
Advocates for earmarked funds for Myalgic Encephalomyelitis have been stymied in the past by NIH’s claims going back to the 1980s that scientists aren’t interested in working on this condition.
Article: Are Monoclonal Antibodies the Future of Long COVID Treatments? | Technology Networks
DEFINITION:
Monoclonal antibodies: Lab-produced molecules that can restore, enhance, or mimic the immune system's attack on cells.
SUMMARY:
The article discusses the potential for monoclonal antibodies to treat long COVID by targeting residual SARS-CoV-2 viral reservoirs in the body.
Research suggests that long COVID symptoms can persist due to ongoing immune responses triggered by hidden viral reservoirs in tissues.
Some studies have shown that infusions of monoclonal antibodies, such as Regeneron™, can lead to the disappearance of long COVID symptoms in certain patients by flushing out the virus from reservoirs.
Research
DEFINITIONS:
Neurofilament Light Chain (pNfL): A protein found in neurons, used as a biomarker for neuronal damage.
Single Molecule Array (SIMOA): A technology used for detecting and quantifying biomarkers at extremely low concentrations, enhancing sensitivity and specificity.
ANOVA (Analysis of Variance): A statistical method used to compare means of three or more samples to find differences among them.
Mann–Whitney U Test: A non-parametric test for assessing whether two independent samples come from the same distribution.
SUMMARY:
The study investigates the potential of pNfL as a biomarker for central nervous system (CNS) involvement in patients with long COVID exhibiting post-acute neurocognitive symptoms.
A cohort of 63 long COVID patients, who had mild initial COVID-19 symptoms and were not hospitalized, underwent neurocognitive assessments.
Plasma samples were analyzed for pNfL levels using the Single Molecule Array (SIMOA) technology.
Patients with long COVID and neurocognitive symptoms (specifically cognitive impairment and fatigue) showed significantly higher levels of pNfL compared to healthy controls and those without these symptoms.
This suggests ongoing CNS damage.
Elevated pNfL levels in Long COVID patients with mild disease histories suggest that pNfL can serve as a useful biomarker for detecting and monitoring CNS involvement and damage.
DEFINITIONS:
Basal Ganglia: A group of structures in the brain involved in coordinating movement and behavior.
Dopamine: A neurotransmitter important for transmitting signals in the brain and crucial for reward, motivation, and motor functions.
PET (Positron Emission Tomography): An imaging test that helps reveal how tissues and organs are functioning, often used to detect disease.
MRI (Magnetic Resonance Imaging): A technique that uses magnetic fields and radio waves to create detailed images of the organs and tissues in the body.
SUMMARY:
This review aims to synthesize existing research on the basal ganglia's involvement in long COVID fatigue, exploring the underlying mechanisms and potential treatments.
The review utilizes sources from major databases like PubMed, Scopus, and Web of Science, focusing on neuroimaging evidence and therapeutic interventions.
The basal ganglia, a group of subcortical nuclei involved in various functions including motivation and motor control, are highlighted as key players in the manifestation of fatigue in long COVID patients.
Neuroimaging studies indicate disruptions such as inflammation, metabolic dysfunction, and altered connectivity within these structures, particularly affecting areas linked to dopamine regulation.
The review discusses several theories on how basal ganglia dysfunction could lead to fatigue, including inflammation-induced disturbances in dopamine signaling, disruption of motivational pathways, and loss of excitatory input to arousal centers.
These mechanisms suggest that the basal ganglia’s impaired functionality might underlie the severe fatigue experienced by long-COVID sufferers.
DEFINITIONS:
Digital Droplet PCR (ddPCR): A highly sensitive technique for detecting DNA or RNA molecules, providing precise, absolute quantification without needing external standards.
RNA In-Situ Hybridisation: A method used to detect specific RNA sequences within tissue samples, helping to locate the presence of viral RNA within specific cells.
Immunofluorescence: A technique using antibodies labeled with fluorescent dyes to detect specific antigens in tissue sections under a microscope, allowing for the visualization of proteins in different cell types.
Peripheral Blood Mononuclear Cells (PBMCs): Blood cells that have a single round nucleus, such as lymphocytes and monocytes, important in the immune system's response to infections.
Subgenomic RNA: Shorter segments of RNA found in viruses, produced during infection, which can indicate ongoing viral replication.
Odds Ratio (OR): A measure used in statistical analysis that describes the strength of association or non-independence between two data values, often used in case-control studies to determine whether exposure to a particular factor increases the risk of a specific outcome.
SUMMARY:
This study aimed to investigate the persistence of SARS-CoV-2 in various tissues of patients who recovered from mild COVID-19 and its relation to those with long COVID symptoms. Conducted at the China–Japan Friendship Hospital, it involved collecting tissue samples from patients at 1, 2, and 4 months post-infection to detect viral presence using digital droplet PCR, RNA in-situ hybridisation, and other methods.
Samples included 201 surgical specimens, 59 gastroscopy samples, and 57 blood component samples from 225 patients.
Viral RNA was detected across multiple tissue types and time points, with a declining detection rate from 30% at one month to 11% at four months post-infection.
Viral RNA was found in solid tissues such as the liver, kidney, and brain, among others. Interestingly, immunocompromised patients showed a higher prevalence of viral RNA in blood components compared to immunocompetent patients.
Subgenomic RNA, indicating active viral replication, was also detected in several samples.
A significant association was found between the detection of viral RNA and the development of long COVID symptoms (odds ratio 5.17, p<0.0001)
Patients who tested positive for viral RNA were more likely to report symptoms such as fatigue, the most common symptom reported.
Patients with higher virus copy numbers had a higher likelihood of developing long COVID symptoms.
The study suggests that SARS-CoV-2 can persist in multiple organs after recovery from mild COVID-19 and that this persistence is associated with long COVID symptoms.
My Take:
This seems like a big deal…
My Take (Amy):
This ABSOLUTELY seems like a big deal…
DEFINITIONS:
Double-blind: A type of clinical trial where neither the participants nor the researchers know who is receiving the active treatment or the placebo, to prevent bias in the results.
hs-CRP: High-sensitivity C-reactive protein, a marker of inflammation in the body.
TNF-α: Tumor Necrosis Factor alpha, a cytokine involved in systemic inflammation, often measured to assess inflammation levels.
SUMMARY:
Conducted at Razi Hospital in Iran, this double-blind, randomized clinical trial involved 64 participants aged 18-70 with moderate COVID-19.
Patients received either 300 mg of magnesium daily or a placebo from admission until discharge.
Magnesium supplementation significantly reduced the number of patients requiring oxygen therapy and improved arterial oxygen saturation compared to the placebo group. However, it did not significantly affect respiratory rate, fever, hs-CRP, or TNF-α levels.
There was a notable improvement in quality of life and mental health measures, particularly depression scores, in the magnesium group.
No significant differences were observed in other clinical or biochemical variables.
The study suggests magnesium’s role in improving respiratory function and possibly modulating immune responses in COVID-19 patients, highlighting its potential as a supportive treatment strategy.
DEFINITIONS:
Hyperglycemia: A condition in which an excessive amount of glucose circulates in the blood plasma.
Insulin Resistance: A condition in which cells in the muscles, fat, and liver don't respond well to insulin and can't easily take up glucose from your blood. As a result, your pancreas makes more insulin to help glucose enter your cells.
Glycemic Control: The typical levels of blood sugar (glucose) in a person with diabetes. The degree of glycemic control is fundamental to the management of diabetes.
SUMMARY:
This review discusses the risks of developing diabetes mellitus (DM) as a consequence of SARS-CoV-2 infection.
The article explores evidence linking SARS-CoV-2 infection to significant organ damage and systemic inflammation, which may contribute to the onset of diabetes.
Historical data from the SARS outbreak in 2003, which showed similar diabetes onset in patients, suggests that the more infectious SARS-CoV-2 could have a significant impact on glucose metabolism and insulin sensitivity.
The review looks into potential cellular and molecular mechanisms, highlighting how SARS-CoV-2 may affect glucose handling pathways.
The virus's interaction with ACE2 receptors, found in various organs including the pancreas, disrupts normal cellular functions and may lead to beta-cell damage, thus impairing insulin secretion and glucose regulation.
The text discusses various studies that have observed hyperglycemia in COVID-19 patients and examines controversies surrounding the management of these conditions with insulin. Some studies suggest insulin treatment in the hospital may increase mortality, whereas others indicate it could be beneficial if managed correctly.
DEFINITIONS:
Electroencephalogram (EEG): A method of recording electrical activity in the brain using electrodes placed on the scalp, often used in neurological research.
Wasserstein Generative Adversarial Networks (WGANs): A type of Generative Adversarial Network (GAN) that trains a model to generate synthetic data resembling real data samples by minimizing the Wasserstein distance between real and generated data distributions.
Convolutional Neural Networks (CNN): Deep learning models designed for processing grid-like data, such as images or time series data, by applying filters to extract spatial patterns.
Long Short-Term Memory (LSTM): A model in machine learning that is a type of recurrent neural network capable of learning and retaining long sequences of data, ideal for modeling temporal dependencies in sequential data.
Bidirectional Long Short-Term Memory (BiLSTM): An extension of LSTM networks that allows information to flow not only in the forward direction but also in the backward direction through the sequence, enhancing the model's understanding of temporal patterns.
Continuous Wavelet Transform (CWT): A mathematical technique used to extract time-frequency information from signals or data for further analysis.
SUMMARY:
The study introduces a novel method to detect the likelihood of post-acute sequelae of SARS-CoV-2 (PASC) or Myalgic Encephalomyelitis (ME) using a wearable four-channel headband that collects Electroencephalogram (EEG) data.
Machine learning models such as CONVLSTM, CNN-LSTM, and Bi-LSTM are employed to process raw EEG signals and differentiate between healthy participants and those affected by PASC or ME, with promising accuracy results.
Synthetic spectrograms generated using Wasserstein Generative Adversarial Networks (WGANs) significantly enhanced model performance in detecting PASC and ME effects, demonstrating the potential of synthetic data in augmenting datasets and preserving patient privacy.
Convolutional Neural Networks (CNN) and Long Short-Term Memory (LSTM) networks were utilized to analyze the nuanced patterns in EEG data, contributing to the early identification and management of neurological conditions.
Deep learning models like LSTM networks enable the capture of complex temporal dependencies in EEG data, providing insights into the cognitive impairments associated with PASC and ME.
DEFINITIONS:
Heart Rate Recovery (HRR1): The speed at which the heart rate declines after exercise, used as an indicator of autonomic nervous system function.
Inspiratory Muscle Training (IMT): A rehabilitation technique involving exercises that strengthen the respiratory muscles, improving breathing efficiency.
Peak Oxygen Uptake (peakVO2): The maximum amount of oxygen the body can utilize during intense exercise, a measure of cardiovascular fitness.
SUMMARY:
The study investigated the association between heart rate recovery at one minute post-exercise (HRR1), as a marker of autonomic dysfunction, and exercise intolerance in patients with long COVID.
The study also assessed the impact of a 12-week home-based inspiratory muscle training (IMT) program on these patients.
This was a post hoc subanalysis of a randomized trial involving 26 long COVID patients divided into two groups: one received the IMT program and the other received usual care.
Lower baseline HRR1 was significantly correlated with reduced exercise capacity (measured as peakVO2). Patients with a lower initial HRR1 demonstrated greater benefits from the IMT program, showing notable improvements in peakVO2 and HRR1.
Lower HRR1 is linked to exercise intolerance among long COVID patients, making it a useful marker for identifying those who might benefit most from targeted interventions like IMT.
[PAYWALLED]
SUMMARY:
This was a population-based matched cohort study, including all people with HIV (PWH) that were ≥16 years in an HIV cohort in Catalan. The study assessed the effect of COVID-19 on the risk of cardiovascular events (CVEs) among people with HIV (PWH).
The study found that the cumulative CVE incidence was higher among PWH after COVID-19 compared with PWH without COVID-19 during the first year (log-rank p=0.011).
The increased subsequent risk of CVE after COVID-19 was 30% (adjusted hazard ratio 1.30 [95% CI, 1.09–1.55])
An increased risk was also seen when only including individuals without previous CVD (1.60 [95% CI, 1.11–2.29]) or nonhospitalized patients (1.34 [95% CI, 1.11–1.62]).
The authors suggest that COVID-19 should be considered an additional CVD risk in people with HIV in the short term.
DEFINITIONS:
Synucleinopathies: Neurodegenerative diseases characterized by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, nerve fibers or glial cells.
Multiple System Atrophy (MSA): A rare and eventually lethal condition of the nervous system. It affects the body's ability to control automatic processes (body functions that you don't have to think about) such as breathing, digestion, heart rate, movement, and blood pressure.
SUMMARY:
Although not a research study, this manuscript interestingly summarizes the research that reports potential correlation between neurological disorders and viral pandemic outbreaks with a historical perspective.
The article discusses the studies providing evidence of neurodegeneration due to COVID-19 infection by focusing on viral Parkinsonism.
Olfactory dysfunction occurs in both PD (Parkinson’s Disease) and COVID-19 - such dysfunction could reflect a common link between the two. Olfactory impairment appears to be one of the most reliable markers of a number of neurodegenerative disorders, including AD (Alzheimer’s Disease), PD (Parkinson’s Disease), Multiple System Atrophy (MSA), and some other synucleinopathies.
According to the article, since a number of cases have been reported linking COVID-19 and sporadic PD, COVID-19 infection might be considered as a potential “environmental factor” in triggering the development of PD in people who are genetically susceptible.
To precisely identify the affected neural circuits and to understand the causes of COVID-19 pathologies, the authors stress that multipronged experiments employing animal models are sorely needed. Such experiments will help to connect the dots between long COVID, olfactory dysfunction, the development of PD and a number of other neurodegenerative diseases.
RNA Viral persistence in the vaccinated needs to be explored.
Hi Brandon,
thanks for your excellent Long Covid Newsletter!
I would like to draw your attention to our world's largest LongCovid and ME/CFS conference, organised by people affected by the disease themselves, of which I am one, which will take place online on 15 and 16 May and will provide a stage for top specialists such as Akiko Iwasaki, David Putrino, Daniel Altmann, Resia Pretorius and many more high-calibre speakers.
The conference is organized by five long haulers and is community-driven. It’s totally free of charge and has an inclusive approach.
We would be very grateful if you could draw attention to the conference in your newsletter. You can find more information on our website (unitetofight2024.world) and on Twitter (https://twitter.com/U2Fight_World).
Many thanks and best regards,
Chris, co-organiser UniteToFight