Hi Everyone!
Welcome to our 52nd (!) edition. It is crazy that is a whole year of newsletters (although I have intermittently taken breaks throughout the year).
Our featured topics include Northwestern Medicine's intensified research efforts, the identification of a gene linked to Long Covid, and the often-overlooked experiences of individuals in the global south. Additionally, we explore the lingering impact on taste and smell, chronic inflammation, autoreactivity, and more. We also delve into the realm of post-exertional malaise, oxidative biomarkers, gut microbiome assessment, and the immunology of Long Covid. Lastly, we bring you news on groundbreaking treatment studies, as AIM Immunotech enrolls and doses the first subject in a phase 2 trial.
Media
Article: Northwestern Medicine long COVID research ramping up | Crain's Chicago Business
SUMMARY:
The directors of Northwestern Medicine's Comprehensive COVID-19 Center have discovered that the predominant population of patients suffering from long COVID-19 syndrome are largely white women in their 40s who were not hospitalized with COVID and are suffering cognitive impairment and decreased quality of life.
Still, there's not a one-size-fits-all set of symptoms or treatments among long COVID patients, says Dr. Marc A. Sala, co-director of the center and one of the nation's first doctors to provide specific research into the new syndrome.
Article: Gene linked to long COVID found in analysis of thousands of patients
DEFINITIONS:
FOXP4: a gene that is active in the lungs and some immune cells and has been associated with both severe COVID-19 and lung cancer.
SUMMARY:
The first genome-wide search for long COVID risk factors has identified a DNA sequence near the FOXP4 gene as a potential genetic risk factor for the condition.
The study analyzed data from 6,450 people with long COVID across 16 countries and found that this DNA sequence is active in the lungs and in some immune cells.
Long COVID is a complex condition associated with more than 200 symptoms, and understanding its genetic risk factors is crucial for developing treatments and prevention strategies.
My Take:
The discovery of a potential genetic risk factor for long COVID is a significant breakthrough in understanding the condition.
Further research is needed to replicate and confirm these findings, as well as to identify additional genetic risk factors.
SUMMARY:
As almost all research on long Covid has focused on richer countries, there is little sense of the scale and nature of the health burden in low- and middle-income countries.
The WHO defines long Covid as the otherwise unexplained continuation of symptoms three months after the initial infection.
With 651 million documented Covid cases worldwide, it is estimated that around 65 million individuals have long Covid.
However, this could be an underestimate as many cases were never tested or went undocumented.
My Take:
It is critical to acknowledge the impact of long Covid in low- and middle-income countries, as research has primarily focused on richer countries.
The WHO's definition of long Covid helps to establish a standard for identifying and understanding the condition.
The estimated number of individuals with long Covid emphasizes the need for greater awareness and support for those affected, especially considering that many cases may have gone undocumented or untreated.
Article: About 25% of those with COVID-19 only partially recover taste or smell, or never do
DEFINITIONS:
Gustatory: relating to the sense of taste Intranasal corticosteroids: medications administered through the nose that reduce inflammation
SUMMARY:
Approximately one-quarter of adults who lost taste or smell following SARS-CoV-2 infection reported partial or no recovery of their senses, a study published in The Laryngoscope found.
Among patients who lost smell, 72.2% fully recovered, whereas 24.1% only saw a partial recovery and 3.7% never recovered at all.
Meanwhile, 76.8% of patients that lost taste fully recovered, 20.6% partially recovered, and 2.6% never fully recovered.
The risk of losing taste or smell was greater the more severe the case of COVID-19 was.
Mitchell and colleagues pointed out that although the findings may be useful for providers when consulting patients on sensory recovery, practitioners may still experience challenges "given lack of clear treatment guidelines."
My Take:
The study highlights the significant number of individuals who do not fully regain their sense of smell or taste after a COVID-19 infection.
It emphasizes the need for evidence-based treatment options for sensory recovery, especially in more severe cases.
The findings suggest a potential benefit from vaccines and treatments like Paxlovid in reducing the overall burden of the disease.
However, there is still a lack of clear treatment guidelines, posing challenges for healthcare providers.
Research
SUMMARY:
PASC should be subclassified into two distinct conditions: inflPASC and niPASC.
inflPASC is characterized by broad inflammatory signatures, neutrophil activity, and altered B-cell responses.
Proteomics screening and machine learning were used to identify signatures of ongoing B-cell development, immune-mediated fibrosis, and cell death in PASC patients.
inflPASC patients display active B-cell profiles, autoreactivity, and altered humoral targeting.
My Take:
I thought this was a super interesting read and highly recommend you check it out!
The findings have implications for diagnostic and therapeutic approaches in PASC and provide opportunities for further research to understand the underlying mechanisms of the condition.
DEFINITIONS:
Cardiopulmonary exercise testing (CPET): a test that evaluates the performance of the cardiovascular and respiratory systems during exercise.
Post-exertional malaise (PEM): a worsening of physical symptoms and reduction in function after physical exertion, typically seen in patients with chronic fatigue syndrome or other medical conditions.
SUMMARY:
The study analyzed cardiopulmonary exercise testing (CPET) in elite and recreational athletes with persistent exercise intolerance and post-exertional malaise (PEM) after COVID-19 infection.
The primary outcome was the point prevalence of the adequate cardiopulmonary response (ACPR), defined by specific criteria for exercise performance.
The study found that ACPR was not observed in all athletes with PEM, and certain parameters such as VE/VCO2 and the plateauing of O2 pulse were associated with exercise limitations.
These findings suggest that CPET can be beneficial in objectively assessing exercise limitations in athletes with PEM.
My Take:
The finding that not all athletes with PEM display an adequate cardiopulmonary response suggests the presence of underlying disease or incomplete recovery.
I could be wrong here, but I believe these findings have been replicated in ME/CFS.
DEFINITIONS:
Mitochondrial regulatory proteins: Proteins involved in the regulation of mitochondrial function and dynamics, such as PTEN-induced kinase 1 (PINK1), Dynamin-1-like protein (DNM1L), and Mitofusin-2 (MFN2).
Cytokines: Small proteins that play a role in cell signaling and the immune response, such as chemokine ligand 18 (CCL18), IL-6, and tumor necrosis factor-alpha (TNF-alpha).
SUMMARY:
This study aimed to investigate the association between post-COVID-19 pulmonary complications and mitochondrial regulatory proteins in the context of oxidative stress.
The serum concentrations of mitochondrial regulatory proteins were significantly higher in the group with long-term pulmonary complications compared to the control group.
Patients with long-term pulmonary complications also had higher levels of certain cytokines, such as chemokine ligand 18 (CCL18), IL-6, and tumor necrosis factor-alpha (TNF-alpha).
TNF-alpha could be a potential biomarker for predicting pulmonary complications and may be a target for therapeutic intervention in patients with post-COVID-19 complications.
DEFINITIONS:
Fusicatenibacter saccharivorans: A species of gut bacteria that has been linked to post-acute COVID syndrome or "long COVID."
Roseburia hominis: Another species of gut bacteria that has been associated with post-acute COVID syndrome.
SUMMARY:
In a study of hospitalized COVID-19 patients, researchers found significant differences in the gut microbial communities of patients with severe disease compared to those with moderate disease.
The study identified 48 species-level taxa associated with severe COVID-19, including depletions of Fusicatenibacter saccharivorans and Roseburia hominis, which have previously been linked to post-acute COVID syndrome or "long COVID."
A random forest machine learner accurately classified patients based on disease severity using gut microbial features, with an area under the receiver operating characteristic (AUROC) of 0.925.
Network analyses revealed significant disruptions to gut ecologic topology in severe COVID-19, characterized by fractured clustering and reduced negative selection.
Differential abundance testing of microbial pathways and predicted stool metabolites implicated altered bile acid metabolism and short-chain fatty acid levels in severe disease.
My Take:
The identification of specific taxa and microbial pathways associated with severe disease suggests that the gut microbiome may play a role in influencing disease outcomes.
The use of machine learning to accurately classify disease severity based on gut microbial features further highlights the potential for the gut microbiome as a diagnostic biomarker.
Another super interesting article!
DEFINITIONS:
microRNAs (miRNAs): short non-coding RNA sequences that regulate gene expression at the post-transcriptional level.
HHV-6A/6B: human herpesviruses that have been implicated as potential triggers of ME/CFS.
SUMMARY:
This study aimed to assess the diagnostic value of circulating miRNAs in distinguishing patients with ME/CFS from healthy controls.
miR-142-5p, miR-150-5p, and miR-448 were found to be upregulated in ME/CFS patients compared to controls, while miR-140-5p was significantly downregulated.
The upregulation of miRNAs was more prominent in patients with more severe symptoms.
Gene pathway analysis revealed potential target genes involved in immune response and tissue remodeling.
My Take:
The upregulation of specific miRNAs, such as miR-142-5p, miR-150-5p, and miR-448, and downregulation of miR-140-5p, may serve as biomarkers for ME/CFS.
Additionally, the severity of symptoms correlated with the abundance of these miRNAs, suggesting their role in disease progression.
Hope
DEFINITIONS:
Ampligen: is a first-in-class investigational drug called Ampligen (rintatolimod), a dsRNA and highly selective TLR3 agonist immuno-modulator with broad spectrum activity in clinical trials for globally important cancers, viral diseases, and disorders of the immune system.
SUMMARY:
AIM ImmunoTech has enrolled and dosed the first subject in its Phase 2 study evaluating Ampligen as a potential therapeutic for people with post-COVID conditions.
The study is expected to enroll approximately 80 subjects between the ages of 18 to 60 years across up to 10 centers in the United States.
The primary protocol planned outcome measure of the study is change from baseline to week 13 in PROMIS Fatigue Score.
I’m disappointed and disheartened that the Crain’s Chicago Business article was headlined and cited in your last newsletter. It was sloppy reporting by Crain’s and I’m disappointed there was no push back by you on their assertion that Long Covid is a 40 year old White Woman’s disease. A simple read of the actual report put out by Northwestern states the cohort are of patients they saw in their Long Covid Clinic. As someone who has attempted to get into all of the LC clinics in Chicago (and as anyone in any major city with LC can attest) these clinics are hard to get into. The demand is high. So the folks in the clinic are a small sliver of the LC population first off. Second, they are the patients that are either the most aggressive in getting care, have really good insurance (typically) and/or have some advocates helping them access that great care (another doctor, friend, influential person, nurse, social worker, etc) so they are not the typical person saddled with LC. Most don’t know about LC clinics. Many don’t even know or understand what LC is (I know this because I spend inordinate amounts of time explaining to people what LC is, what my symptoms are, what other diagnoses I have as a result of LC, what I can and cannot do, what medications I now need to take, and on and on). So the idea that this small number of folks in the LC clinic is some how representative of the entirety of the LC landscape is ludicrous. Finally, there’s this fact I can’t stop thinking about. During the pandemic African Americans and Latine people were overwhelmingly impacted by Covid. Their infections rates were above and beyond everyone else’s because they were overwhelmingly in jobs that put them face to face with the public. I’ve seen some estimates say 20% of people who get Covid develop LC and I’ve seen the number drop as low as 10% if that’s the case and Covid hit Black and Brown people so deeply how would it be possible this is a White Woman’s disease? I think it’s more likely the patients who sought out or were connected to care are the patients in the early cohort at Northwestern. Because folks of color are always the last to be seen, engaged, supported, treated, helped, believed, and healed. The Crain’s article now gives those providers already inclined and doing a half hearted job to further ignore the needs and health of Black and Brown Long Covid patients. I wish you had applied the critical analysis I’ve seen you utilize when reviewing other articles on the latest research instead of taking this one at face value. Black and Brown peoples lives are in the balance and I fear this puts them in further peril when it comes to those folks in the Long Covid community still being ignored and dismissed.
Kudos on the first-year milestone of these invaluable newsletters! Your dedication, commitment, and research play a key role in heightening awareness about long COVID. Many thanks!