Hi everyone,
Happy Monday!
There are a couple of pieces within this newsletter that highlight the microbiome. For those who are unfamiliar, the microbiome is ‘the collection of all microbes, such as bacteria, fungi, viruses, and their genes, that naturally live on our bodies and inside us.[Source[.' ‘The gut microbiome plays a very important role in your health by helping control digestion and benefiting your immune system and many other aspects of health.’ ‘An imbalance of unhealthy and healthy microbes in the intestines may contribute to weight gain, high blood sugar, high cholesterol and other disorders.’[Source]
📰 Media
16% of all North Carolinians have long COVID. Here’s an updated guide to the condition.
From the News & Observer:
About 16% of North Carolinians — one of the highest rates in the country — have experienced long COVID
Patients struggling with fatigue might be taught how to strategically allot their energy and prioritize their most important daily tasks.
As a doctor with long covid, I feel abandoned by the NHS
From the BMJ:
The covid-19 pandemic has thrown a spotlight on the treatment of NHS staff and their perceived value to their employers. Being a doctor was how I defined my life, but eventually I was unable to carry on working. Now I’m in constant pain.
The contrast in the way that healthcare workers have been treated is stark: from being lauded as heroes when needed by the system and government to being abandoned if they can now no longer work in the way they once did.
Like many people with long covid, I struggle living in a world where covid-19 has been declared “over” even though I still have not recovered my former health and more people are falling ill all the time.
Staff with long covid still have a lot to contribute to the NHS, but they need compassion and understanding.
My Take: Riveting piece. Shows the heartlessness of the medical system, especially for the people who keep it running.
Family caregivers of people with long COVID bear an extra burden
From NPR:
For Louise Salant, long COVID has meant new stress, new responsibilities, and multiple medical crises to manage. It's transformed her life. Louise found that being a caregiver for someone with long COVID, as for other serious and chronic medical conditions, is not just being an aide. It's running the patient's life. "Every single day, there's something she'd need," Louise says.
Stories like the Salants' reveal another unfortunate reality about dealing with a complex chronic disease like long COVID, in contrast to an illness with a more straightforward diagnosis: Meeting the demands of the health care system itself can be a major burden.
🔍 Research
Multi-‘omics of gut microbiome-host interactions in short- and long-term myalgic encephalomyelitis/chronic fatigue syndrome patients
⏰ Must Read Paper of the week!
From Cell Host & Microbe:
Notably, the most significant microbial dysbiosis occurred in short-term ME/CFS
There are several potential explanations for this early-stage dysbiosis. First, short-term patients suffer more GI disturbances, and gut microbiome changes may reflect these environmental changes. Second, it is possible that patients may try a range of interventions that impact their gut microbiome, which is dynamic and influenced by numerous intrinsic and extrinsic factors, including age and diet
The return of the gut microbiome of long-term patients to a configuration more similar to healthy controls (with notable differences nonetheless, in low-abundance species and in heterogeneity) as well as the reduced occurrence of GI illness in this cohort, suggests a return to a relative homeostasis. However, we conjecture that microbial dysbiosis seen in short-term patients may have cumulative and long-term effects, where damage may be caused by an initial trigger, resulting in cascading events
Thus, we hypothesize that ME/CFS progression may begin with loss of beneficial microbes, particularly SCFA producers, resulting in more pervasive GI phenotypes that is later reflected in plasma metabolite level
Finally, we believe that recent potential associations between the chronic immune dysfunctions in ME/CFS patients and “long COVID” increase the relevance of the results reported here
My Take: I have long hypothesized for myself, that the microbiome is a contributing factor to my illness but once you go down the microbiome rabbit hole your realize how complicated it is! Curious to see where this research goes!
Cardiovascular and autonomic dysfunction in long-COVID syndrome and the potential role of non-invasive therapeutic strategies on cardiovascular outcomes
From Frontiers:
It has been proposed that long-COVID emerges as a consequence of remnant viral particles after acute COVID infection that drives a sustained systemic inflammatory response, which in turn drives cardiovascular, respiratory, neurological, and/or metabolic sequela
There are several direct and indirect clinical tools for diagnosing dysautonomia, including measurements of plasma catecholamines, heart rate variability analysis (HRV), spontaneous baroreflex sensitivity analysis, skin sympathetic nerve activity, skeletal muscle microneurography, and the COMPASS-31 survey, among others
In support of this notion, an expert panel recently convened by the American College of Cardiology recommended that all patients who have had COVID-19 should be tested for abnormal cardiac function especially those with known immunosuppression and older adults at risk for suffering adverse cardiovascular events associated with long-COVID
Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2
☣️Preprint only
CD4+ T Cells: CD4+ T cells, or helper T cells, are one type of lymphocyte that helps coordinate the immune response against infection and disease. They interact and activate other cells in the immune system.
CD8+ T Cells: Cytotoxic CD8+ T cells play a key role in the elimination of intracellular infections and malignant cells and can provide long-term protective immunity.
From Biorxiv:
Our findings demonstrate that individuals with LC exhibit systemic inflammation and immune dysregulation.
Individuals with LC harbored increased frequencies of CD4+ T cells poised to migrate to inflamed tissues, and exhausted SARS-CoV-2-specific CD8+ T cells. They also harbored significantly higher levels of SARS-CoV-2 antibodies, and in contrast to non-LC individuals
Autoantigen profiling reveals a shared post-COVID signature in fully recovered and Long COVID patients
From Medrxiv:
Although much work has been done exploring the potential virologic and immunologic factors driving Long COVID, the evaluation of autoantibodies in this condition has been more limited.
While a distinct autoreactive signature was detected which separates individuals with prior COVID infection from those never exposed to COVID, we did not detect patterns of autoreactivity that separate individuals with Long COVID relative to individuals fully recovered from SARS-CoV-2 infection
None of the top 20 autoantibodies were enriched in severe Long COVID, and only 3 autoantibodies were statistically increased in any phenotype: TTF2 and KDM3B in those with cardiopulmonary symptoms and FUCA1 in those with upper respiratory symptoms
We were unable to identify a set of enriched proteins specific to any of these groups of patients which could effectively distinguish the cohort from controls
My Take: This research seemingly contradicts the research that has come out stating that autoantibodies are one of the distinct characteristics of Long Covid.
🩺 Hope & Potential Treatments
MetaboGen has reached a new crucial milestone in its development of novel probiotic products
From Biogaia:
After obtaining positive results in the initial clinical study with the strains Faecalibacterium prausnitzii (DSM 32379) and Desulfovibrio piger (DSM 32187), MetaboGen has now received approval from the Ethics Committee to proceed into its next clinical study, targeting a pre-diabetic population.
My Take: Speaking of the microbiome, this company is testing the effectiveness of two gut bacteria on a pre-diabetic population. Faecalibacterium prausnitzii is on the ‘super bugs’ in our gut, if interested in learning more please see this link.
MediciNova Announces Health Canada Grants Authorization to Commence Multi-arm Phase 2/3 Clinical Trial to Evaluate MN-166 (ibudilast) in Long COVID
From globenewswire:
today announced that Health Canada has completed its review of the clinical trial application and has granted authorization to commence a grant-funded, multi-center, randomized, clinical trial to evaluate MN-166 (ibudilast) and other therapies for the treatment of Long COVID, the lingering symptoms of COVID-19.
MN-166 (ibudilast) is a small molecule compound that inhibits phosphodiesterase type-4 (PDE4) and inflammatory cytokines, including macrophage migration inhibitory factor (MIF).
AIM ImmunoTech provides Phase III efficacy update on Ampligen for long Covid
From ClinicalTrialsArena:
AIM ImmunoTech has offered an update on its efforts underway for developing an effective treatment for long Covid with its investigational drug, Ampligen.
Rintatolimod (Ampligen) offered objective improvement in exercise tolerance in a prospective, randomised, double-blind, placebo-controlled Phase III AMP-516 clinical trial in ME/CFS.
“Although the time scale is much more condensed, the results from these four patients indicating improvement in fatigue in only 12 weeks is consistent with the hypothesis that a shorter duration of illness prior to treatment may improve responses to Ampligen.”
file:///Users/aimeeengebretson/Desktop/JAMA-long%20covid%20and%20vaccination.pdf
Not sure if you can see this, but here's one from JAMA Network Open, entitled "Persistent Covid-19 Symptoms at 6 Months after onset and the Role of Vaccination Before or After Sars-CoV2 Infection"