Hi everyone,
I can’t believe we are on edition 88! 12 more until 100. Thanks again for the continued support.
Giorgia Lupi, who published the amazing NYT Guest Essay on LC, is up for a Webby! Please vote if you have some time!
In this edition of the LC Weekly, we look into the pivotal role of patient-led research and the evolving landscape of treatment trials. The seminal paper in 2021 by the Patient-Led Research Collaborative has not only advanced our understanding of Long COVID but also underscored the necessity of patient contributions to high-quality research. Meanwhile, recent studies reveal the limitations of antiviral drugs like Paxlovid in shortening COVID-19 symptoms in fully vaccinated individuals, alongside the heightened risks for patients with unmet social needs developing severe Long COVID symptoms and neuropsychiatric sequelae. Moreover, we explore research into the immune responses of discharged COVID-19 patients, the incidence of allergic diseases post-COVID, and the impact of post-COVID pain on quality of life.
The article I would like to highlight this week is from Nature, Incident allergic diseases in post-COVID-19 condition: multinational cohort studies from South Korea, Japan and the UK. It feels like a lot of the articles are scientifically validated hypotheses from the LC community. LC is implicated in people developing allergic diseases like asthma and allergic rhinitis. The multinational cohorts from South Korea, Japan, and the UK confirm the increased risk of allergic diseases following COVID-19 across different populations.
Here are the interesting excerpts:
The study underscores a notable time attenuation effect on the risk of developing allergic diseases post-COVID-19, indicating that while the risk decreases over time, it remains elevated compared to those who were not infected. This temporal dimension suggests that the immune system's response to COVID-19 and its impact on allergic disease susceptibility may evolve over time, necessitating long-term follow-up and management strategies for affected individuals.
Despite potential limitations such as misclassification of pre-existing conditions and the exclusion of pediatric cases, the study's robust multinational dataset and detailed analyses strengthen the evidence linking COVID-19 to a higher incidence of allergic diseases.
Media
Article: Long COVID still has no cure — so these patients are turning to research | Nature
SUMMARY:
The initial survey study from 2021 conducted by the Patient-Led Research Collaborative (PLRC) is widely considered a seminal paper in Long Covid research, and one that put Long Covid on the map.
For Lisa McCorkell of the PLRC, the impact of the study is even more basic. “What we demonstrated with the survey is that patients can lead high-quality research, and that it’s really necessary in order to have the most comprehensive look at a condition.”
“There are a lot of clinical trials that are focused on more behavioral and on non-pharmaceutical interventions, and that is really not a priority to the patient community,” McCorkell says. “It is a misunderstanding of how severe the condition is, and how much of an impact on people’s quality of life it has taken.”
To more fully understand the disease, researcher Wes Ely of Vanderbilt University turned to the patient community. He, Hannah Davis of PLRC, and Jaime Seltzer, director of scientific and medical outreach at the non-profit ME Action, eventually drafted a clinical trial together to test the medication baricitinib, an immunomodulatory drug. “I wanted to learn from people who are living with this disease,” says Ely. The trial has now been funded by the NIH and will start enrolment later this year.
According to Seltzer, the lived experiences of patients can shape research priorities in several key ways:
finding the most efficient way to allocate limited funds on the basis of symptom burden
offering context on the prevalence and severity of symptoms
identifying how the trial design can capture improvement most effectively
All of this can help lead to faster breakthroughs in treatments, which is of benefit to both patients and researchers, Seltzer says.
Article: Among fully vaccinated, study shows Paxlovid does not shorten symptoms | CIDRAP
SUMMARY:
A recent study published in the New England Journal of Medicine found that Paxlovid, an antiviral drug, did not significantly reduce the duration of COVID-19 symptoms in fully vaccinated individuals with at least one risk factor for severe COVID-19.
The phase 2/3 trial involved 1,296 participants, half of whom received Paxlovid and the other half a placebo, within 5 days of symptom onset. The study ran from July 2021 to July 2022, including only those fully vaccinated with risk factors for severe disease or those unvaccinated.
Participants logged daily symptom severity on a 4-point scale. The primary endpoint was sustained alleviation of symptoms, with the median time to relief being 12 days for Paxlovid recipients and 13 days for the placebo group, showing no significant difference.
A secondary outcome measured COVID-19-related hospitalizations or deaths within 28 days of the trial, showing slightly lower, yet statistically insignificant, numbers in the Paxlovid group compared to the placebo.
Experts, including Michael Osterholm, caution against applying these findings to older, high-risk populations, for whom Paxlovid may still be beneficial. The median participant age was 42, and only 5% were over 65.
The editorial accompanying the study highlighted the need for longer-term studies to assess Paxlovid's effectiveness in preventing Long Covid and emphasized that the drug's benefits may be more pronounced in high-risk individuals.
My Take (Amy):
There is already evidence showing Paxlovid reduces the risk of long COVID by 26% (JAMA Internal Medicine) and I’m worried that doctors will take this new study as evidence to not prescribe it for low-risk or hi-risk patients, even though (IMO) it should be prescribed more, not less.
Research
SUMMARY:
This study highlights how patients with unmet social needs face a higher risk of developing severe long COVID symptoms and neuropsychiatric sequelae post-infection.
Addressing social determinants of health is crucial in improving outcomes for vulnerable populations affected by COVID-19.
The findings underscore the importance of creating equitable healthcare systems that account for socioeconomic disparities to mitigate the impact of long COVID.
Understanding the interplay between social determinants and health outcomes can guide targeted interventions to support individuals experiencing prolonged health consequences post-COVID-19 infection.
The study emphasizes the need for a comprehensive approach to patient care that extends beyond the acute phase of illness to address the long-term effects and challenges faced by COVID-19 survivors with unmet social needs.
Efforts to identify and support these vulnerable populations can help reduce health inequities and enhance recovery among individuals grappling with the lingering effects of COVID-19 infection.
DEFINITIONS:
Receptor Binding Domain (RBD): A component of the spike protein on the SARS-CoV-2 virus that mediates its binding to host cells.
Memory T cells: Specialized immune cells that remember previous infections and mount a quicker immune response upon subsequent encounters with the same pathogen.
SUMMARY:
This study evaluated the humoral and cellular immune responses specific to SARS-CoV-2 in a cohort of 1041 hospitalized COVID-19 patients at 12 months after infection. It compared the humoral and cellular immune profiles of patients with long Covid and those who had fully recovered.
The study found that the RBD-IgG in LC (long Covid) patients was significantly higher than that in CC (convalescent control) patients (0.40 ± 0.22 vs 0.37 ± 0.20; P = .022). However, no statistical difference was observed in other antibodies between the LC and CC groups.
Previous research has indicated that the failure to detect viral fragments does not rule out the possibility of persistent viral fragments in vivo. Additional factors such as autoimmunity and chronic inflammation could contribute to the sustained high levels of RBD-IgG antibodies as they indicate a persistently active immune system. These mechanisms may play a role in the continuation of long Covid symptoms.
DEFINITIONS:
Propensity Score Matching: A statistical technique used in observational studies to create a control group that is statistically similar to the treatment group, aiming to mimic the conditions of a randomized controlled trial.
Hazard Ratio (HR): A measure used in survival analysis to compare the risk of a certain event happening at any time point in one group to the risk of it happening in another group.
ICD-10: The International Classification of Diseases, Tenth Revision, a medical classification list by the World Health Organization (WHO) that codes for diseases, signs and symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or diseases.
SUMMARY:
The study explores the long-term risk of developing allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergy in individuals who have recovered from COVID-19, utilizing large-scale, population-based cohorts from South Korea, Japan, and the UK.
It found a significantly increased risk of developing allergic diseases following a COVID-19 infection, with the most notable risks being for asthma and allergic rhinitis. This risk persists over time but gradually decreases, remaining evident for at least 6 months post-infection.
The severity of the initial COVID-19 infection correlates with an increased risk of developing allergic diseases, highlighting a dose-response relationship where more severe COVID-19 cases lead to a higher risk of subsequent allergic conditions.
Vaccination against COVID-19, especially receiving at least two doses, is associated with a protective effect against the development of allergic diseases post-COVID-19, reducing the risk to levels similar to those who were never infected.
The study's findings are consistent across different countries and ethnicities, indicating a global relevance of the post-COVID-19 condition's impact on allergic diseases.
Despite its strengths, including large cohort sizes and diverse populations, the study acknowledges limitations such as potential misclassification of pre-existing allergic conditions, reliance on ICD-10 codes for disease identification, and the absence of vaccination data in some cohorts.
SUMMARY:
This was a household cross-sectional study of 12,925 SARS-CoV-2 cases in Bangladesh. The study aimed to elicit the clinical presentation of pain and determine the relationships between QoL (Quality of Life) and pain in Long Covid Syndrome.
In the study, 22.45% (563 out of 2507) of participants reported experiencing Long Covid symptoms, while the remaining 77.54% (1944) were asymptomatic.
Five types of pain were identified among those with Long Covid symptoms, and the prevalence of pain ranged from 0.3 to 3.1% where most individuals had myalgia and arthralgia.
The study’s findings also confirmed a compromised Quality of Life across all the domains of the WHOQOL-BREF (World Health Organization Quality of Life questionnaire) when compared to asymptomatic participants.
There was a strong and inverse relationship between painful symptoms, duration of Long Covid, and number of Long Covid symptoms in all the domains of QoL majors.
DEFINITIONS:
Vascular Component: Refers to the part of the lung's gas exchange system involving blood vessels (capillaries) that transport blood to and from the alveoli for oxygen and carbon dioxide exchange.
Alveolar Capillary Volume (Vc): The volume of blood in the lung capillaries available for gas exchange.
Membrane Diffusing Capacity (Dm): A measure of the lung's ability to transfer gas from the air in the alveoli across the alveolar membrane to the blood in the capillaries.
DLNO and DLCO: Techniques for measuring the diffusing capacity of the lungs for nitric oxide (DLNO) and carbon monoxide (DLCO), respectively, which help assess different aspects of gas exchange efficiency.
SUMMARY:
This study, aimed at understanding gas exchange abnormalities a year after severe COVID-19 infections, finds these abnormalities are primarily driven by changes in the vascular component rather than the diffusive conductance of the alveolar membrane or alveolar capillary volume.
Methods and Measurements: Utilizing combined nitric oxide (NO) and carbon monoxide (CO) gas transfer techniques (DLNO and DLCO), researchers were able to distinguish between the effects on membrane diffusing capacity (Dm) and alveolar capillary volume (Vc), revealing significant vascular compromise in gas exchange.
Findings: Among 33 severe COVID-19 survivors without prior lung disease, gas exchange impairments were chiefly due to vascular compromise, with a significant reduction in Vc observed in 73% of patients, while Dm was reduced only in 9%. This vascular pattern of gas exchange impairment was identified in 76% of the sample.
Correlation with Imaging: No significant correlation was found between gas exchange impairment and the extent of chest CT alterations, which were generally mild. This indicates that the vascular compromise may not always manifest prominently in imaging.
Conclusion: The study concludes that gas exchange abnormalities in long Covid are primarily due to impairment in the vascular component. This has implications for understanding the long-term sequelae of COVID-19 and suggests that vascular compromise plays a significant role in persistent symptoms.
Implications: This insight adds to the body of evidence on long Covid, emphasizing the importance of focusing on vascular health in survivors and the potential for systemic capillary compromise even in cases where traditional imaging shows minimal abnormalities.
DEFINITIONS:
Oropharyngeal microbiomes: The collection of microorganisms present in the throat and mouth that can influence health and disease outcomes.
Operational Taxonomy Units (OTUs): Groups of closely related sequences or microorganisms used for simplifying the identification of microbial organisms.
Conditional pathogens: Microbes that typically exist in the human body but may cause infections under specific conditions.
Proportion of Disease (POD): An index used for diagnostic purposes to assess the likelihood of disease based on microbial markers.
Principal Coordinate Analysis (PCoA): A statistical method to visualize and analyze multivariate data in various dimensions.
SUMMARY:
The paper explores the changes in the oropharyngeal bacterial microbiomes during the infection and recovery of the COVID-19 Omicron variant.
The study found differences in microbial diversity, composition, and abundance between patients with the Omicron variant and healthy controls.
A diagnostic model using microbial markers accurately distinguished patients infected with the Omicron variant from healthy individuals.
Subgroup analysis revealed differences in the oropharyngeal microbiome based on vaccination times and disease severity among patients with the Omicron variant.
Comparison of oropharyngeal microbiota in confirmed cases of the Omicron strain and its recovery showed different microbial composition characteristics compared to the original strain.
DEFINITIONS:
Type I interferon signaling: A pathway that represents the body's defense against pathogens, primarily affected by COVID-19.
It mediates cognitive dysfunction upon dysregulation following synaptopathy, microgliosis, and neuronal damage.
Alzheimer's disease: A neurodegenerative disorder characterized by cognitive impairment and neuronal damage.
Type I interferon dysregulation in the brain is linked to potential contributions to Alzheimer's disease pathology.
DAMPs (Danger-Associated Molecular Patterns): Molecules that initiate and perpetuate immune responses in the absence of an invading pathogen, such as proteopathic seeds.
DAMPs can stimulate a feed-forward IFN-I dysregulation leading to neuroinflammation and neurodegeneration.
SUMMARY:
The article explores the impact of COVID-19 on the human brain, particularly on cognition and neuronal damage.
It discusses how Type I interferon signaling is affected by COVID-19 and contributes to cognitive dysfunction and neurodegeneration.
The model presented suggests that dysregulation of IFN-I in the brain following COVID-19 leads to neuroinflammation, potentially establishing feed-forward dysregulation and neurodegeneration.
The implications for Alzheimer's disease are highlighted, showcasing a potential link between IFN-I dysregulation, cognitive impairment, and Alzheimer's pathology.
The study proposes a mechanistic model where peripheral IFN-I dysregulation can lead to cognitive impairment, with downstream effects on neuroinflammation and neuronal damage.
This model highlights the importance of IFN-I signaling in both COVID-19-related cognitive impairment and Alzheimer's disease pathogenesis.
DEFINITIONS:
Joint Hypermobility (JH): A condition in which joints can move beyond the normal range expected for a particular joint. It is often seen in hypermobile Ehlers-Danlos Syndrome (hEDS) but can occur in the general population.
Ehlers-Danlos Syndrome (EDS): A group of disorders that affect the connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. hEDS is the most common subtype, characterized by joint hypermobility.
Beighton scoring system: A standardized scoring system to evaluate the presence of joint hypermobility. It includes a series of physical maneuvers where points are given for each maneuver that can be performed, indicating greater laxity and range of motion in the joints.
SUMMARY:
Research utilizing the You + ME Registry data investigated Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients, comparing those with joint hypermobility (JH+) to those without (JH-).
It aimed to identify if JH+ ME/CFS patients exhibit distinct disease characteristics, comorbidities, and health-related quality of life (HRQOL).
The study found that 15.5% of ME/CFS patients were JH+.
These patients were more likely to report Ehlers-Danlos Syndrome (EDS), Postural Orthostatic Tachycardia Syndrome (POTS), and a family history of EDS. They experienced worse HRQOL, particularly in physical functioning and pain, and had a higher number of symptoms across several categories.
A focused comparison revealed that ME/CFS patients with both JH+ and EDS had more severe symptoms and greater functional impairment than those without JH or EDS. This suggests that ME/CFS with concurrent JH+ and EDS may represent a distinct, more severely affected subgroup.
[PAYWALLED]
SUMMARY:
This study highlights the correlation between reduced cortical thickness and cognitive dysfunction in individuals with the post-COVID-19 condition, shedding light on potential long-term neurological effects of the virus.
This research emphasizes the importance of neuroimaging in understanding the underlying brain changes associated with cognitive symptoms post-COVID-19, providing valuable insights for clinical management and care of affected individuals.
The findings underscore the need for continued monitoring and support for individuals experiencing cognitive impairment after recovering from COVID-19 to ensure appropriate interventions and management strategies are implemented.
I especially liked two articles on the possible neurocognitive effects of the virus. I had a CT/PET scan done two days ago and will keep you posted of anything relevant they discover!
Michael (class of 2020)
So many interesting studies here - thank you! Was there any mention of activated mast cells in the study about allergies?
Thanks for the Webby award link too. Her graphic depiction of love with LC was truly a work of art (and so accurate). I will link in my newsletter too.