In this issue, we highlight significant legislative proposals by Senator Bernie Sanders aimed at boosting Long COVID research, as well as new clinical trials and scientific studies that reveal challenges and innovations in tackling LC. From groundbreaking studies published in reputable journals like The Lancet and Nature Immunology to crucial legislative movements, there is a lot to cover this week.
As highlighted in the prior paragraph, the article we wanted to focus on was Chairman Bernie Sanders' ambitious legislative proposal to combat Long COVID. Sanders, the Chairman of the Senate Health, Education, Labor, and Pensions (HELP) Committee, has released a draft aiming to confront Long COVID as a significant public health emergency. His proposal suggests allocating $1 billion annually for the next ten years towards Long COVID research at the National Institutes of Health (NIH). Of note, there is an important call to action to let the Senate know that we want “and associated conditions” to be added to the wording of the legislation. To support that, please sign the open letter here, or send an email to LongCOVIDcomments@help.senate.gov.
Here are some interesting quotes from the full proposal:
As Chairman of the Senate Health, Education, Labor, and Pensions (HELP) Committee, it is my strong belief that the crisis of Long COVID is a public health emergency that we can no longer ignore. This issue demands immediate attention and substantial resources to better understand and combat the widespread impacts of this condition.
This draft proposal would provide $1 billion in mandatory funding per year for 10 years to the National Institutes of Health (NIH) to respond to the Long COVID crisis with the sense of urgency that it demands. These funds are crucial for accelerating research and improving treatment options for millions of Americans suffering from this debilitating condition.
The legislation aims to create a centralized coordinating entity for the majority of Long COVID research activities at NIH, with a clear leadership structure that includes patients who have lived experience with Long COVID. This approach ensures that our research is not only comprehensive but also inclusive, reflecting the real-world impacts of Long COVID on patients' lives.
Media
SUMMARY:
The letter from Chairman Bernie Sanders of the Senate Health, Education, Labor, and Pensions (HELP) Committee addresses the significant public health emergency of Long COVID.
In response to the urgency of addressing Long COVID, the HELP Committee convened a hearing in January 2024, which led to the drafting of legislative proposals aimed at intensifying the research and management of Long COVID.
Key provisions of the proposed legislation include:
Allocating $1 billion annually for ten years to the National Institutes of Health (NIH) for Long COVID research.
Establishing a centralized coordination for Long COVID research within NIH.
Creating a new grant process for clinical trials focusing on Long COVID.
Forming an NIH research advisory board composed of scientists, healthcare providers, and patients.
Developing a Long COVID database for research purposes.
Implementing continuous education on Long COVID for healthcare providers and the public.
The letter invites stakeholders to provide feedback on the draft proposal by a specific deadline, emphasizing collaborative efforts to tackle the crisis. Send email to LongCOVIDcomments@help.senate.gov.
My Take:
This is a great initiative but I highly doubt it gets passed in its current form - however, this is still a step in the right direction!
SUMMARY:
The study found that 9.2% of specimens from individuals in the post-acute phase of COVID-19 had detectable SARS-CoV-2 antigens, with spike antigen being the most commonly detected.
Participants hospitalized for acute COVID-19 were nearly twice as likely to have detectable SARS-CoV-2 antigens compared to those not hospitalized.
Post-acute SARS-CoV-2 antigen persistence was influenced by events during the acute phase of infection, suggesting the establishment of a persistent viral reservoir.
Understanding the specificity of immune-based assays detecting SARS-CoV-2 antigens is crucial, as cross-reactivity with related pathogens or host antigens can occur.
Article: Long Covid trials aim to clear lingering virus—and help patients in need | Science | AAAS
SUMMARY:
Shelley Hayden, a sufferer of Long Covid, began a clinical trial for monoclonal antibody treatment at UCSF.
With no established treatments, these symptoms have significantly affected patients' lives.
Hayden's participation marks her as one of the early individuals in trials focusing on the underlying biology of Long Covid, specifically the theory that residual SARS-CoV-2 contributes to ongoing symptoms.
These trials are crucial, as they target potential viral reservoirs in the body.
Clinical trials for Long Covid are limited and small-scale, often involving a placebo group. Despite the challenges in measuring success due to the lack of clear biomarkers,
these trials are a critical step in understanding and potentially treating Long Covid.
The research involves diverse approaches, including antivirals and immune system modulators, aiming to address symptoms and eradicate the virus.
The scientific community continues to explore the persistence of RNA viruses, like SARS-CoV-2, which historically were not thought to linger in the body. This new understanding could reshape approaches to treatment and management of the virus and its long-term impacts.
MY TAKE:
(My highly subjective opinion) Even with ‘Despite the challenges in measuring success due to the lack of clear biomarkers’ I would argue measuring fluctuations in QOL is a good measurement.
SUMMARY:
Rates of long COVID have stabilized, affecting approximately 1 in 10 adults who have had COVID.
The ongoing gap between the total number of adults who had COVID and those experiencing long COVID indicates that many individuals are recovering from the condition.
However, those with long COVID report difficulties accessing and affording healthcare, which could pose additional challenges in the future.
As the focus on COVID shifts towards treating it as another respiratory virus, individuals with long COVID might face increased barriers to healthcare.
Research
DEFINITIONS:
Myeloid Inflammation: Inflammation mediated by myeloid cells: a type of white blood cell that includes monocytes, neutrophils, and macrophages, important for immune defense but also involved in inflammatory diseases when dysregulated.
Complement Activation: Part of the immune system's response where a series of proteins act in a cascade to fight infections but can also cause inflammation and tissue damage if improperly regulated.
Multivariate Penalized Logistic Regression Model: A statistical method used to analyze data that reduces the risk of overfitting by penalizing larger coefficients in the model, helping to highlight the most relevant variables in predicting outcomes.
SUMMARY:
This study analyzed 368 plasma proteins in 657 participants who were hospitalized due to COVID-19 and then experienced varying degrees of long Covid symptoms or recovery after three months.
It aimed to understand inflammatory processes underlying long Covid, using a multivariate penalized logistic regression model to explore associations between clinical covariates, immune mediators, and long Covid symptom subtypes.
The study identified specific inflammatory pathways associated with different long Covid subtypes.
Elevated markers of myeloid inflammation and complement activation were common across all long Covid subtypes.
Specific proteins like IL-1R2, MATN2, and COLEC12 were notably associated with cardiorespiratory symptoms, fatigue, and anxiety/depression, while C1QA was linked to cognitive impairments and gastrointestinal symptoms.
The analysis suggested that different mechanistic subtypes of long Covid could be identified based on the symptomatology and underlying inflammatory markers.
For example, MATN2 and CSF3 were elevated in patients with gastrointestinal symptoms, indicating potential tissue-specific inflammatory responses.
The study's findings were consistent with other research, validating the use of the specific inflammatory markers and the analytical approach used.
Future research could explore these biomarkers in larger, more diverse cohorts and potentially in non-hospitalized long Covid patients to expand the applicability of the findings.
My Take:
Understanding the underlying inflammatory processes in patients with long Covid is crucial for targeted management and potential therapeutic interventions.
The identification of distinct inflammatory patterns in patients with cognitive impairment or gastrointestinal symptoms highlights the need to consider subphenotypes in the management of long Covid.
The findings support the use of antiviral or immunomodulatory agents in controlled therapeutic trials and emphasize the importance of personalized treatment strategies for long Covid patients.
DEFINITIONS:
Serum NGAL (sNGAL): Neutrophil Gelatinase-Associated Lipocalin, an acute-phase protein secreted in response to tubular damage, used as a biomarker for kidney injury and other inflammatory conditions.
SUMMARY:
The study assessed the role of sNGAL as a biomarker in patients with post-acute COVID-19 syndrome (PACS).
COVID-19 convalescents were categorized into different severity groups based on their acute phase symptoms and treatment received.
sNGAL levels were evaluated in relation to the presence of PACS symptoms including dyspnea, sleep, and cognitive disorders.
The study also analyzed cytokine concentrations and other biochemical markers in the participants.
DEFINITIONS:
Microglia: Specialized immune cells in the central nervous system responsible for removing waste and toxins. They are crucial for maintaining brain health and supporting neuroplasticity.
Neuroplasticity: The brain's ability to reorganize itself by forming new neural connections throughout life, which allows the brain to recover from injuries, adapt to changes, and learn new information.
BDNF (Brain-Derived Neurotrophic Factor): A protein that supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses.
Synaptic Remodeling: The process by which neural connections within the brain are reorganized, which is influenced by learning, memory, and response to the environment.
SUMMARY:
The study discusses how microglia, the central nervous system's immune cells, are crucial for brain development and health.
Microglia respond to environmental changes and stressors, contributing to the formation and remodeling of neural circuits, which is essential for neuroplasticity in both children and adults.
In long Covid, microglial dysfunction is highlighted as a significant factor contributing to long-term cognitive and neurological sequelae.
This dysfunction is associated with reduced levels of brain-derived neurotrophic factor (BDNF), altered immune cell interactions, increased inflammatory markers, and disruptions in critical signaling pathways that regulate synaptic remodeling.
The dysregulation of microglial function affects both the structural and functional aspects of neuroplasticity, potentially leading to cognitive impairments, learning disabilities, and neurodevelopmental disorders in affected individuals, including children.
The pathogenesis of COVID-19 involves neuroinflammation mediated by microglia and astrocytes.
This inflammation can disrupt cerebral homeostasis and contribute to neurological symptoms that persist long after the acute phase of the infection.
DEFINITIONS:
Nirmatrelvir/ritonavir: Antiviral combination used in the treatment of high-risk COVID-19 outpatients.
Remdesivir: Antiviral medication targeting SARS-CoV-2.
High-risk COVID-19 outpatients: Patients with certain risk factors for disease progression.
SUMMARY:
Conducted in a tertiary care center in Mexico City, this study evaluated the effectiveness of two antiviral treatments, nirmatrelvir/ritonavir and remdesivir, against all-cause hospitalization or death in high-risk COVID-19 outpatients.
Utilizing a propensity score-matched cohort study design, the research included 1566 high-risk COVID-19 outpatients treated from January 2022 to July 2023. Participants were either untreated, treated with remdesivir, or treated with nirmatrelvir/ritonavir based on their risk factors and time from symptom onset.
Nirmatrelvir/ritonavir was associated with a 90% relative risk reduction and an 8.8% absolute risk reduction for all-cause hospitalization or death.
Remdesivir was associated with a 66% relative risk reduction and a 6.4% absolute risk reduction for the same outcome.
Early antiviral treatment with either nirmatrelvir/ritonavir or remdesivir significantly lowers the risk of hospitalization or death in high-risk COVID-19 outpatients, underscoring the importance of timely therapeutic intervention in managing disease progression.
DEFINITIONS:
Propensity-matched: A statistical matching technique that attempts to estimate the effect of a treatment by accounting for the covariates that predict receiving the treatment.
Kaplan–Meier survival analysis: A statistical method used to estimate the survival function from lifetime data, particularly useful in measuring the fraction of patients living for a certain amount of time after treatment.
Major Adverse Cardiovascular Events (MACE): Serious heart-related events that include heart attacks, strokes, and death due to cardiovascular disease.
Neuroimaging: The use of various techniques to directly or indirectly image the structure, function/pharmacology of the nervous system. This is a key tool in both basic neuroscience research and clinical diagnosis.
SUMMARY:
The study included 414 patients with significant neurological manifestations and 1,199 propensity-matched patients without neurological manifestations, all of whom were initially hospitalized with COVID-19 at the Montefiore Health System in the Bronx. Neurological manifestations ranged from acute strokes and seizures to headaches and muscle injuries.
Post-hospital discharge, a higher percentage of patients with neurological involvement were sent to acute rehabilitation or skilled nursing facilities compared to their counterparts without neurological symptoms, who were more often discharged home.
Over three years, patients with neurological involvement experienced higher rates of hospital readmission, stroke, and major adverse cardiovascular events (MACE).
They also exhibited a higher mortality rate, as demonstrated by Kaplan–Meier survival analysis, indicating a significantly shorter time-to-death compared to the control group.
DEFINITIONS:
Case Definition: A set of standard criteria for determining whether a person has a particular disease or condition, used in research and clinical diagnostics to ensure consistency across studies and treatments.
Functional Impairment: A decrease in a patient's ability to perform daily activities due to the effects of a medical condition.
Heterogeneity: In medical research, this refers to the variation in disease presentation and progression among different individuals with the same diagnosis.
SUMMARY:
This study aimed to assess whether different clinical practices across seven U.S. specialty clinics lead to variations in the identification of ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) characteristics.
Researchers utilized standardized questionnaires and data collection methods to compare patient characteristics and clinical features across these clinics.
The results showed that despite slight statistical differences in demographic and clinical characteristics across sites, there were no clinically significant differences in the presentation of ME/CFS symptoms and functions among the clinics.
This suggests that different clinical practices do not lead to significant variations in how ME/CFS is identified and managed among specialists.
The study confirmed a wide range of symptom severity and functional impairment among ME/CFS patients, highlighting the inherent heterogeneity of the disease. All clinics reported a broad distribution in symptom scores and health measures.
The study also examined the use of different case definitions for ME/CFS and found varying proportions of patients meeting each criterion across clinics, indicating that the choice of case definition can influence disease recognition and research outcomes.
DEFINITIONS:
Extracellular Vesicles (EVs): Small particles released from cells that contain proteins and other molecules, involved in cell communication.
Neuronal-Enriched EVs (nEVs): EVs that are rich in neuronal (nerve cell) proteins, important for studying brain-related conditions.
Hybrid EV Microfluidic Affinity Purification (EV-MAP): A technique combining microfluidics with affinity purification to isolate specific types of EVs with high precision.
OLINK platform: A technology used for protein analysis that can simultaneously measure multiple proteins in a small sample volume.
BST1: A protein involved in brain development and immune response, showing varied levels in different diseases in this study.
SUMMARY:
The study aimed to identify neuronal proteins in extracellular vesicles (EVs) linked to Long Covid, HIV infection, and Alzheimer's Disease (AD) using a new hybrid EV Microfluidic Affinity Purification (EV-MAP) technique.
The use of the EV-MAP technique and OLINK platform allowed for the analysis of 384 neurological proteins, providing a broad spectrum of biomarkers to examine the diseases' impact on neuronal health.
Significant proteins were identified in EVs from patients with Long Covid (11 increased, 2 decreased), AD (14 increased), and HIV (40 increased, 1 decreased). The study found six proteins common between Long Covid and AD, indicating potential similarities in neurological impact. No common proteins were found between HIV and AD.
A single protein, BST1, showed opposing trends between Long Covid (decreased) and HIV (increased), suggesting different neurological effects of these conditions.
DEFINITIONS:
Hyposmia: Partial loss of the sense of smell.
Hypogeusia: Partial loss of the sense of taste.
Anosmia: Total loss of the sense of smell.
Ageusia: Total loss of the sense of taste.
Dysgeusia: A persistent bad or altered taste in the mouth.
Parosmia: A distortion of the sense of smell.
Phantosmia: Perception of non-existent smells.
Chemesthesis: Ability to detect chemical irritants.
SUMMARY:
This qualitative study explores the perspective of individuals with long Covidwho experienced loss of taste and/or smell as predominant symptoms.
Participants described their daily life challenges, changes in habits, self-care, and strategies for coping with these symptoms.
Three main themes emerged: Living with taste and smell disorders, highlighting the changes in daily life and emotions; Changes and challenges due to these disorders, focusing on habit alterations, self-care, and risks in daily activities; Coping with taste and smell disorders, discussing daily coping strategies and healthcare received.
I have a question. Do the studies only include persons who were hospitalized? I had the really bad Covid for almost 3 months. Didn’t go to hospital (probably should have) mostly because I didn’t have any insurance at the time. Once I was able to get a job and insurance went and checked my antibodies they were thru the roof. That’s how I know what it was. My cardiologist has confirmed the my tachycardia is caused from Covid. I have lung issues, neurological issues, gut issues that got worse, and brain fog. This has literally sat me down and has changed my whole lifestyle. Please include patients that were not hospitalized like me. There are so many of us.
The phenotyping article got my attention. I don't seem to have the cardiopulmonary LC challenges so much, but the gastrointestinal and neurological/cognitive challenges, most definitely! And interesting how yet again there might be a brain-gut connection.
For the gut challenges, my body is responding very well to ginger tea. I have noticed a significant reduction in constipation!