Long Covid Weekly #100(!): 100 Edition! Research Database Completed!
Hi everyone,
It’s with immense joy that we announce the release of our 100th edition! Reflecting on the journey that began just over two years ago, it’s hard to believe how far we've come together.
I am profoundly thankful for every reader, contributor, and supporter who has joined us along the way—your engagement and feedback have been the driving force behind every newsletter we publish. A special thank you goes to Aimee, whose dedication and hard work behind the scenes have been nothing short of transformative. Her contributions have been essential to our success, and I am grateful for her tireless efforts.
Notion Database - Link
This is also a special newsletter because we are thrilled to announce the launch of our first-ever Notion database, a comprehensive resource dedicated to compiling all of the research ever covered in this newsletter. This curated collection is designed to hopefully empower patients, researchers, clinicians, and all stakeholders in LC and other post-infectious illnesses to learn more about various parts of the condition.
So far, our database includes over 500 research articles from leading scientific publications such as Nature, BioRxiv, Science, and the New England Journal of Medicine. We've focused on making this resource as accessible as possible by ensuring that all included articles are available in full text and free of charge.
Database Features Include:
Comprehensive Article Details: Each entry provides the article title, a concise summary, direct URLs to full texts, journal name, list of authors, publication date, and more.
New Metadata Tracking: Enhanced data fields such as Volume & Issue, DOI, Funding Source, and Study Type offer deeper insights and easier referencing.
Community Contributions: We invite you to help us keep our database current and accurate. Your contributions via our new Google Forms, whether adding new articles or updating existing ones, are invaluable to maintaining the quality and relevance of this resource.
Why This Matters: As participants and advocates in the Long Covid community, we understand the importance of reliable, accessible information. By compiling and updating these articles, we aim not only to keep our readers informed but also to track trends and conduct analyses that could inform future research and policy.
This project is a work in progress, and we welcome your feedback, suggestions, and assistance. To contribute to our database or report any discrepancies, please use the provided Google Forms or contact us at longcoviddatabase@gmail.com. We plan to update our database monthly with newly published articles to ensure our community has access to the most current research available.
We apologize for the funny-looking URL - to not lose track of it, please bookmark the link.
Notion Database - Link
Media
Article: Dr. Ziyad Al-Aly earns recognition for Long COVID research - VA News
SUMMARY:
Dr. Ziyad Al-Aly, a researcher at VA, has been recognized for his work on understanding the long-term effects of COVID-19, known as Long COVID.
Dr. Al-Aly's work was inspired by stories of Veterans and other Americans experiencing lingering health issues post-COVID-19, prompting him to delve deeper into understanding these patients' needs.
Article: The long arm of COVID - Isthmus | Madison, Wisconsin
SUMMARY:
Over 5% of Wisconsin's population, approximately 247,000 adults, suffer from Long COVID, with common symptoms including fatigue, brain fog, and post-exertional malaise.
This condition significantly limits daily activities for about 73% of those affected.
Individuals like Tim Gittings, an actor, and Autumn Bonner, a physical therapist, share their personal battles with Long COVID, highlighting severe impacts on their professional lives and physical capabilities.
Long COVID is described as a "diagnosis of exclusion," where other underlying conditions must be ruled out first, complicating the path to proper diagnosis and treatment.
The financial strain is severe, as seen in Bonner's experience of closing her practice and struggling with insurance claims. The approval of her disability claim came after a rigorous evaluation and significant personal hardship.
Dr. Aurora Pop-Vicas emphasizes that Long COVID is a societal issue requiring community-based services and support, including financial assistance and advocacy.
SUMMARY:
Dr. Phillip Alvelda highlights the dangers of Long COVID, discussing the devastating impact on individuals' lives and the challenges they face in recovering.
The National Academy's report underscores the rising cases of Long COVID and the multitude of symptoms it can cause.
Dr. Alvelda criticizes the inadequacy of government and health agencies in managing Long COVID and advocates for accountability and immediate action to address this ongoing health crisis.
The discussion touches on the impact of Long COVID on mental health and the challenges individuals face in affording treatment.
Dr. Alvelda also discusses the implications of COVID on brain function, motor control, and the increased risks of accidents and fatalities.
The conversation emphasizes the need for improved testing to differentiate COVID-related illnesses and the importance of recognizing and addressing Long COVID as a chronic illness.
My Take:
This is a month or so old but I thought it was a really good read!
SUMMARY:
Some patients with Long COVID exhibit uncharacteristic immune cell activity across multiple organs, with traces of SARS-CoV-2 RNA in their guts up to two years post-infection.
The study conducted PET scans on 24 individuals who had recovered from COVID-19, revealing prolonged T cell activity and viral RNA presence in the gut.
Abnormal immune cell activity was observed in the brain stem of patients experiencing brain fog, emphasizing the impact on neurological symptoms.
The findings suggest that Long COVID is a legitimate biological illness and that the virus can persist in the body longer than previously thought.
Identifying metabolic and immune irregularities in Long COVID patients provides insights into potential treatment targets and management strategies.
SUMMARY:
A study funded by the NIH suggests that reinfections from COVID-19 tend to have similar severity as the original infection, with severe cases often preceding severe reinfections.
The research analyzed health data from over 200,000 individuals who experienced reinfections, highlighting patterns related to severity, age groups, and underlying health conditions.
Reinfections were also found to be more common during the circulation of certain variants, indicating potential factors contributing to increased exposure.
The study additionally discovered a higher likelihood of Llong COVID after the initial infection compared to reinfections, emphasizing the persistence of symptoms post-recovery.
Lower levels of albumin, a liver-produced protein, were associated with a higher risk of reinfection, suggesting a potential risk marker that may warrant further investigation.
COVID-19 vaccines were also noted to have a protective effect against reinfections during the study period.
Research
DEFINITIONS:
Return-to-Work (RTW):
The process of starting to work again after an extended period due to illness or injury.
Systematic Review and Meta-Analysis:
Research methods that collect and critically analyze multiple research studies or papers to derive conclusions about a specific area of interest.
SUMMARY:
This systematic review and meta-analysis aimed to evaluate the impact of post-COVID-19 on the work ability and return-to-work (RTW) rates of patients who were infected with SARS-CoV-2. It included studies with patients experiencing post-COVID symptoms longer than 12 weeks post-infection, using the PRISMA guidelines for systematic reviews.
The review found a considerable variation in RTW rates, with about 60.9% of post-COVID-19 patients managing to return to work. Required modifications to their work roles due to ongoing symptoms like fatigue were common, and significantly impacted their work ability.
Key factors facilitating RTW included workplace accommodations, supportive policies, and occupational rehabilitation programs. Early intervention and tailored rehabilitation significantly improved RTW outcomes.
Rehabilitation was highlighted as crucial in supporting recovery and enhancing work ability, emphasizing the importance of personalized recovery plans and workplace adjustments to accommodate residual symptoms.
The review recommended that healthcare providers, employers, and policymakers collaborate to create supportive work environments and develop strategies to support individuals affected by post-COVID conditions in their return to work.
DEFINITIONS:
EHR (Electronic Health Record):
Digital version of a patient's paper chart. EHRs are real-time, patient-centered records that make information available instantly and securely to authorized users.
Kaplan–Meier curves:
A statistical tool used to measure the fraction of patients living for a certain amount of time after treatment.
SUMMARY:
Reinfection Overview: The study, using a cohort from the National COVID Cohort Collaborative (N3C), finds that the incidence of COVID-19 reinfections is at 6.9%, predominantly during the Omicron variant epoch. Reinfections were more frequent in individuals who had severe initial infections.
Biomarkers and Severity: Lower levels of albumin were noted leading up to reinfection, suggesting a potential biomarker for predicting reinfection risk. There is a statistically significant association between the severity of the initial infection and reinfection.
Long COVID Analysis: Long COVID was more commonly diagnosed following the initial infection compared to reinfections, with fewer cases of Long COVID following reinfections in the same epoch.
Methodology: Utilized data from over 3 million patients, employing statistical tools such as Kaplan–Meier curves and chi-squared tests for the analysis.
Implications for Future Research: The findings encourage further investigation into the mechanisms of reinfection and long-term outcomes of COVID-19, especially concerning the management and prevention of Long COVID.
DEFINITIONS:
Acute Macular Neuroretinopathy (AMN):
A relatively rare retinal disorder characterized by dark, reddish-brown macular lesions leading to scotomas and visual impairment.
Vogt‒Koyanagi‒Harada Syndrome (VKH):
An immune-mediated disorder involving bilateral uveitis often associated with pan-uveitis and multifocal serous retinal detachment.
Rhino-orbital-cerebral mucormycosis (ROCM):
A serious fungal infection that can invade the orbit and lead to orbital apex syndrome causing retinal artery obstruction.
SUMMARY:
Multicenter and multimodal imaging study found rare fundus lesions in 90 patients after SARS-CoV-2 infection, with patients developing various conditions like Acute Macular Neuroretinopathy (AMN), VKH-like uveitis, and ROCM.
AMN was the most prevalent manifestation post-infection, with patients typically experiencing central or paracentral scotomas and visual complaints with characteristic fundus lesions on multimodal imaging.
AMN lesions showed specific abnormalities on OCT imaging, such as outer retinal hyperreflectivity, ellipsoid zone loss, and thinning of the outer nuclear layer, correlating with visual impairment and scotomas.
Other patients developed conditions like VKH-like uveitis and MEWDS, exhibiting symptoms of pan-uveitis and serous retinal detachment following fever post SARS-CoV-2 infection.
ROCM, a severe fungal disease, was also observed in patients with symptoms of orbital involvement, retinal damage, and necrosis, highlighting the need for early diagnosis and management to prevent vision loss.
DEFINITIONS:
TRPM3:
Transient Receptor Potential Melastatin 3, an ion channel involved in various physiological processes including pain sensation, temperature regulation, and immune cell function.
Natural Killer (NK) Cells:
A type of white blood cell that plays a crucial role in the body's immune response by targeting tumor cells and microbial infections.
Low-Dose Naltrexone (LDN):
A pharmacological treatment involving very low doses of naltrexone, an opioid antagonist, used off-label to treat various chronic autoimmune and inflammatory diseases.
SUMMARY:
The article discusses the potential role of TRPM3 ion channel dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and its implications for understanding the pathology of the disease.
It highlights the therapeutic potential of low-dose naltrexone (LDN) in treating TRPM3 dysfunction.
TRPM3 dysfunction in natural killer (NK) cells and other tissues like small nerve fibers and the brain may contribute to the symptoms of ME/CFS.
The study suggests that LDN can improve TRPM3 function, potentially ameliorating symptoms.
TRPM3 channels, crucial for pain transduction and immune defense, show altered function in ME/CFS, affecting NK cell activity, pathogen clearance, and possibly contributing to chronic symptoms.
The findings support using LDN to target TRPM3 dysfunction, which could be a promising treatment for ME/CFS, particularly in alleviating symptoms related to immune dysregulation and neurological dysfunction.
DEFINITIONS:
Cross-Sectional Survey:
A type of observational study that analyzes data from a population, or a representative subset, at a specific point in time.
Adjusted Odds Ratios (aORs):
A statistical measure used to describe the strength of association or non-independence between variables in a model adjusted for potential confounders.
SUMMARY:
This research investigates whether preexisting sleep issues like insomnia, poor sleep quality, and varying sleep durations are associated with the risk of developing Post-Acute Sequelae of SARS-CoV-2 infection (PASC) or Long COVID, using three different models to define PASC.
A cross-sectional survey involving 24,803 U.S. adults was conducted to explore the relationship between sleep disturbances and PASC. The study utilized three definitions of PASC (COPE, NICE, and RECOVER PASC Score) to assess prevalence and associations.
Insomnia, poor sleep quality, and sleeping less than six hours were consistently linked with a higher prevalence of PASC across all definitions. Notably, sleeping more than nine hours did not correlate with increased PASC risk. Vaccination status did not alter the association between sleep disturbances and PASC risk.
The study suggests that addressing sleep issues might play a role in reducing the risk of developing Long COVID, highlighting the potential benefits of sleep quality interventions.
DEFINITIONS:
Histopathological:
The microscopic examination of tissue in order to study the manifestations of disease.
Mitochondrial Swelling:
An increase in the size of mitochondria, usually due to damage or dysfunction.
Endoplasmic Reticulum Dilatation:
Expansion of the endoplasmic reticulum, a network within cells that synthesizes proteins and lipids, often in response to stress or damage.
Hepatocyte Apoptosis:
Programmed cell death affecting hepatocytes, the main type of cell in the liver.
Cholestasis:
A condition where bile cannot flow from the liver to the duodenum.
Secondary Sclerosing Cholangitis:
A serious liver disease in which the bile ducts inside and outside the liver become narrower due to inflammation and fibrosis.
SUMMARY:
This review explores the direct histopathological impacts of SARS-CoV-2 on liver tissue, highlighting cellular changes such as mitochondrial swelling, endoplasmic reticulum dilatation, and hepatocyte apoptosis.
The study draws from a variety of sources including liver biopsies, complete autopsies, and in vitro analyses to examine the pathways through which SARS-CoV-2 enters liver cells and causes cellular damage.
Direct viral damage to liver cells was evident, with additional findings of necrosis, steatosis, cholestasis, and lobular inflammation commonly observed in COVID-19 patients. The study also notes the potential for long-term complications such as secondary sclerosing cholangitis.
The review underlines the severity of SARS-CoV-2 infection beyond the respiratory system, emphasizing significant implications for liver health and patient management.
DEFINITIONS:
Nucleated Red Blood Cells (NRBCs):
These are immature forms of red blood cells that normally do not enter the bloodstream until they are mature. Their presence in blood usually indicates severe stress or damage to the bone marrow.
Logistic Regression:
A statistical method used to model a binary outcome with one or more explanatory variables.
Survival Analysis:
A branch of statistics that deals with the analysis of time-to-event data, often used to measure the time to death in medical research.
SUMMARY:
The research evaluates the prognostic significance of nucleated red blood cells (NRBCs) in predicting mortality among patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS).
This observational study assessed the daily NRBC values in adult patients with ARDS due to SARS-CoV-2, correlating these levels with mortality rates during their ICU stay.
Higher NRBC levels were significantly associated with increased mortality, with a cut-off value of ≥500/µl identified as an independent risk factor for death. Patients above this threshold had notably worse survival rates.
Logistic regression and survival analyses were used to substantiate the NRBC cut-off value, showcasing its robustness in risk stratification.
DEFINITION:
In-Hospital Delirium:
A state of altered consciousness characterized by confusion, cognitive impairment, disturbances in attention, and perceptual disturbances.
SUMMARY:
The study analyzed the association of in-hospital delirium with functional disability and cognitive impairment over a 6-month period after discharge in older adults hospitalized for COVID-19.
The cohort included 311 older adults aged 60 years or older who had survived a COVID-19 hospitalization.
In-hospital delirium was assessed using chart-based screening tools.
The primary outcomes measured were disability in functional activities and cognitive impairment at 1, 3, and 6 months post-discharge.
The results demonstrated that in-hospital delirium was significantly associated with increased functional disability and cognitive impairment in older survivors of COVID-19 hospitalization.
The association remained significant over the 6-month follow-up period.
Functional disability and cognitive impairment are important concerns affecting the post-hospitalization recovery and quality of life in older adults who experienced delirium during their COVID-19 hospital stay.
SUMMARY:
Evidence suggests a potential association between COVID-19 infection and higher rates of new-onset asthma in adults, raising concerns about its impact on children.
This retrospective cohort study of children 5-18 included data from the TriNetX US Collaborative Network, a multicenter national health network across all 50 states of the United States.
Cohort 1 included 257,506 unvaccinated children with and without COVID-19 infection (128,753 in each group); Cohort 2 included 46,994 vaccinated children with and without infection (23,497 in each group). The study period was from January 1, 2021, to December 31, 2022.
The study found a significantly higher incidence of new-onset asthma in COVID-19 infected children compared to uninfected children, regardless of vaccination status.
In Cohort 1, 4.7% of COVID-19 infected children without vaccination developed new-onset asthma, versus 2.0% in their non-COVID-19 counterparts within a year (HR = 2.26).
In Cohort 2, COVID-19 infected children with vaccination showed an 8.3% incidence of new-onset asthma, higher than the 3.1% in those not infected (HR = 2.745).
Subgroup analyses further identified higher risks in males, children aged 5–12 years, and Black children.
The study highlights a strong link between COVID-19 infection and an increased risk of new-onset asthma in children, which is even more marked in those vaccinated.
This study emphasizes the critical need for ongoing monitoring and customized healthcare strategies to mitigate the long-term respiratory impacts of COVID-19 in children, advocating for thorough strategies to manage and prevent asthma amidst the pandemic.
*Must click on PDF to access this free article
SUMMARY:
This study used machine learning techniques to capture granular patterns of moderate-to severe symptoms reported at 6-months post-infection to better characterize and define PCC phenotypes and their risk factors.
1,988 SARS-CoV-2 positive U.S. Military Health System beneficiaries with quantitative post-COVID symptom scores were included in this analysis.
Three symptom-based clusters were identified: a sensory cluster (loss of smell and/or taste), a fatigue/difficulty thinking cluster, and a difficulty breathing/exercise intolerance cluster.
The sensory cluster were all outpatients during their initial COVID-19 presentation. The difficulty breathing cluster had a higher likelihood of obesity and COVID-19 hospitalization compared to those with no/mild symptoms at 6-months post-infection.
Multinomial regression linked early post-infection D-dimer and IL-1RA elevation to fatigue/difficulty thinking, and elevated ICAM-1 concentrations to sensory symptoms.
Study authors measured a broad panel of inflammatory mediators to determine if specific early (<20 days post-first positive) post-infection inflammation biomarkers played a role in the risk of specific, or any, PCC phenotypes delineated in this analysis.
Study results emphasize that PCC is not a single symptom-based disease: it comprises at least three distinct symptom-based phenotypes which are remarkably stable over a 3- to 12-month period.
This work provides external validation of the NIH RECOVER study, which identified similar symptom phenotypes despite differences in study populations, measurement instruments, and methods. That foundational work was extended here and shows that these three distinct phenotypes have different clinical predictors and early post-infection inflammation patterns.
DEFINITIONS:
Resting state electroencephalography (EEG):
EEG is a test to detect abnormalities in the electrical activity of the brain, used to evaluate several types of brain disorders. Resting state EEG captures brain activity in awake individuals without specific cognitive tasks.
Source connectivity analysis:
A technique using neuroimaging data to examine complex interactions between brain regions. It identifies functional or effective linkages among cerebral sources that reflect cognitive shifts in conditions like depression and schizophrenia.
EEG microstate analysis:
A methodology that provides deep insights into spontaneous brain activity. It assumes EEG stability over short time periods, segments EEG signals into brief, stable scalp electrical topographies, and uses cluster analysis to reveal potential functional changes.
Hjorth parameter:
Commonly used in EEG analysis and epilepsy detection studies, it consists of three elements: activity (HA), mobility (HM), and complexity (HC).
Hurst index:
An exponent that identifies the long-term memory of a time series, providing insight into brain activity and function. It also highlights differences in EEG signals across brain regions, age groups, and mental states.
Sequential linear analysis:
Statistical analysis where the sample size is not fixed in advance.
Summary:
The primary aim of this study was to bridge the gap in understanding the cognitive effects of SARS-CoV-2 in individuals presenting mild symptoms, with a focus on EEG patterns across different age groups, especially in children and adolescents.
This longitudinal cohort study in China collected pre- and post-infection resting-state electroencephalogram (EEG) data from 185 participants and 181 structured questionnaires of long-term symptoms across four distinct age groups. The study analyzed EEG changes of SARS-CoV-2 by potential biomarkers across age groups using both spatial and temporal approaches.
Data was segregated into six distinct frequency bands using a specialized filter bank, covering the full frequency spectrum: full band (0.5–45 Hz), delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta (12–30 Hz), and gamma (30–45 Hz).
Sequential linear analyses showed that SARS-CoV-2 infection is associated with a marked rise in low-complexity, synchronized neural activity within low-frequency EEG bands. This is evidenced by a significant increase in Hjorth activity within the theta band and Hjorth mobility in the delta band.
Sequential nonlinear analysis indicated a significant reduction in the Hurst exponent across all age groups, pointing to increased chaos and complexity within the cognitive system following infection.
The observed concentration of alterations within the delta frequency band presents a pioneering insight, proposing that this band may be particularly susceptible to the neurological impacts of SARS-CoV-2.
The findings underscore the enduring neurological impacts of SARS-CoV-2 infection, marked by cognitive decline and increased EEG disarray.
The outcomes of this study distinctly highlight the amplified susceptibility of young adults to cognitive deficits following a SARS-CoV-2 infection, a demographic that has traditionally not been considered as high risk. These modifications in the temporal lobe, a key area for the functions of memory, language, and emotional processing, could potentially result in cognitive deterioration, displaying patterns akin to those observed in cases of ADHD and MCI.
The findings propose a more profound impact of SARS-CoV-2 on young adults in comparison to adolescents and children.
Brandon, I can’t express enough gratitude for your time and commitment in this collection and wealth of information . I work in research and know how tedious this can be. I have come to depend on your assemblage of articles with accurate interpretations not only for myself, but to share with treating physicians, staff education and information for my family to better understand what is going on. Keep fighting the good fight on informing us with knowledge- knowledge is power in the fight for treatments and hopeful cures for the debilitating, misunderstood, complex disease.
Thank you. Incredible information and effort. I am cognitively challenged, and I believe I must fit all three phenotypes (mentioned in one machine learning article). My brain is swollen. I tried to learn notion. But I can barely spend an hour answering emails much less a new computer program. Any quick easy way to learn? Or someday the "plain language" version of these resources? I was a home visitor/early educator for 30 years, before disabled with LC. Most of my work was with families with low resources and literacy. We learned to communicate important information with simple language. I love what you do. Wish my weary brain could keep up. Thanks again!