Hi everyone,
Thanks to everyone who participated in the vote for the Long Covid giveaway last week, here are the results:
It looks like Polybio and OMF are the clear winners. However, again, I would like to talk to a representative before donating so if anyone has one for either org that would be greatly appreciated.
Another thing I have been thinking about is that I feel like the ‘Research’ Category is too broad. There are way too many fields within LC to keep track of, so I am piloting a ‘Research’ section with ‘sub sections’. Let me know if this overcomplicates things but I think this may be a better solution to help further classify articles.
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In this edition, we explore a meta-analysis uncovering high rates of heart complications in long COVID patients and the challenges faced by Colorado's long COVID clinics due to overwhelming demand. This article, along with others on neuroimmune attack, mast cell populations, and the susceptibility of receptors to the SARS-CoV-2 spike protein, shed light on the multifaceted nature of long COVID and its potential treatments. Lastly, we highlight a case series and literature review on the improvements seen in patients with long COVID during long-term fasting, as well as explore blood-derived product therapies for both SARS-CoV-2 infection and long COVID.
Media
SUMMARY:
The prevalence of long-COVID is still uncertain, with estimates varying widely.
The World Health Organization (WHO) estimates that 10-20% of individuals continue to experience symptoms more than three months after SARS-CoV-2 infection, while the UK Office for National Statistics suggests a lower estimate of 2.7%.
However, a recent meta-analysis of 194 studies found that 45% of COVID-19 survivors had at least one unresolved symptom after an average follow-up of 126 days.
The findings revealed that the crude prevalence of at least one symptom attributable to SARS-CoV-2 infection was 13.8% at 6 months, 12.8% at 12 months, and 16.3% at 18 months.
However, after adjusting for potential confounders, the prevalence decreased to 6.6% at 6 months, 6.5% at 12 months, and 10.4% at 18 months.
DEFINITIONS:
Project Extension for Community Health Outcomes (ECHO): A program that connects primary care providers with specialists to learn how to manage certain conditions locally and to discuss complex patients.
SUMMARY:
Colorado doesn’t have enough capacity to treat everyone suffering with long COVID at the three specialized clinics in the state, so public health leaders are trying to figure out ways for more people to get the care they need closer to home.
Researchers estimated in November 2022 that between 228,000 and 651,000 Coloradans had symptoms that lingered after a COVID-19 infection, what has become known as long COVID.
One idea to bring care to more people with long COVID is building on Project Extension for Community Health Outcomes, or ECHO, which connects primary care providers with specialists to learn how to manage certain conditions locally and to discuss complex patients.
Dr. Kyle Leggott, primary care liaison for Project ECHO in Colorado, said the group put together seven online courses to cover the basics of long COVID care, which are free to providers who want them.
DEFINITIONS:
Endotype: a subtype of a disease or condition defined by distinct underlying biological mechanisms.
SUMMARY:
Leading long COVID researcher, Akiko Iwasaki, PhD, provides an update on the latest long COVID studies and clinical trials.
The knowledge about long COVID is converging to paint a more clear picture, although it is still a collection of multiple endotypes of diseases.
Drivers of long COVID include persistent virus infection, autoimmunity, latent herpes virus reactivation, and hypercoagulation and inflammation.
Recent research has identified distinguishing features of long COVID through immune profiling, including lower levels of cortisol, reactivation of latent herpes viruses, increased activation of B cells and T cells, and enhanced antibody responses to the spike protein.
My Take:
Dr. Iwasaki is one of the premiere researchers, glad to have her looking into Long Covid!
Research
Symptoms
Article: Vagus Nerve Dysfunction in the Post-COVID-19 Condition: a pilot cross sectional study
SUMMARY:
Study authors performed a cross-sectional pilot study in subjects with Post-Covid-19 Condition (PCC) with symptoms suggesting vagus nerve dysfunction (n=30) and compared to subjects fully recovered from acute COVID-19 (n=14) and individuals never infected (n=16). They evaluated the structure and function of the vagus nerve and evaluated the structure and function of respiratory muscles.
Of 341 patients identified as PCC, 67% had one or more vagus nerve-related symptom. Six out of 30 (20%) subjects with PCC as well as one SARS-CoV-2 uninfected individual (who complained of tachycardia, dyspnea, fatigue, arthralgia and myalgia) had vagus nerve alterations in the neck ultrasound
Fourteen out of 30 (47%) participants with PCC, but only 1/16 (6%) COVID 19-recovered and 2/14 (14%) SARS-CoV-2-uninfected subjects (p=0.049) had flattened diaphragmatic curves in the thoracic ultrasound exploration (p=0.007). Functional alterations were also documented in the study.
This study provides evidence of structural and functional alterations in various organs and body territories innervated by the vagus nerve in subjects with PCC, including the respiratory and digestive apparatus, and suggest the additional involvement of other respiratory nerves like the phrenic nerve. Our findings open a possible first avenue of interventions to ameliorate some of the most disabling symptoms of the PCC, such as dysphagia, dyspnea and dysautonomia.
Viral Persistence & Related
SUMMARY:
In the post COVID-19 era, new SARS-CoV-2 variant strains may continue emerging and long COVID is poised to be another public health challenge.
Here, we conduct multi-omic analysis of protein binding affinities, transcriptomic expressions, and single-cell atlases to characterize the molecular susceptibility of receptors to SARS-CoV-2 spike protein.
Initial affinity analysis explains the domination of delta and omicron variants and demonstrates the strongest affinities between BSG (CD147) receptor and most variants.
Our findings implicate important therapeutic targets for the development of receptor-specific vaccines and drugs for COVID-19.
Mast Cells
DEFINITIONS:
scRNAseq: single cell RNA-sequencing, a technique used to analyze gene expression at the single cell level.
SUMMARY:
Our recent study showed weight cycled mice have increased adipose mast cells compared to obese mice by single cell RNA-sequencing.
Further analysis of our dataset showed that our initial mast cell cluster could subcluster into two unique populations: one with very high expression of classical mast cell markers and another with elevated lipid handling and antigen presentation genes.
This new mast cell cluster accounted for most of the mast cells in the weight cycled group although it was not possible to detect the different populations by new studies with flow cytometry or Toluidine blue staining in mice, possibly due to a downregulation in classical mast cell genes.
Interestingly, a pilot study in humans did suggest the existence of two mast cell populations in subcutaneous adipose tissue from obese women that appear similar to the murine populations detected by sequencing; one of which was significantly correlated with weight variance.
My Take:
One hypothesis I think is quite viable for PEM is that it is mast cell induced.
DEFINITIONS
Mast cells: specialized immune cells that are strategically positioned in the skin and play a role in the defense against pathogens and the maintenance of barrier function.
Skin microbiome: the collection of microorganisms, including bacteria, fungi, and viruses, that reside on the skin and contribute to its health and function.
SUMMARY:
Recent research has focused on the interactions between mast cells and the skin microbiome, revealing the complex relationship between these two components and their impact on skin health and diseases.
Mast cells can recognize and tolerate commensal bacteria while remaining vigilant against potential pathogens, contributing to the balance between immune activation and immune tolerance in the skin.
My Take:
The interaction between mast cells and the skin microbiome is a fascinating area of research that has the potential to provide new insights into the maintenance of skin health and the development of skin diseases.
Understanding how mast cells recognize and respond to commensal bacteria while defending against potential pathogens can help us develop strategies to promote a healthy balance in the skin microbiome and prevent the development of inflammatory skin conditions.
Hope
DEFINITIONS:
Long-term fasting: a therapeutic approach that involves abstaining from food intake for a prolonged period of time.
Blood tests were performed before and after fasting to assess changes in metabolic health.
SUMMARY:
This case series reports beneficial changes in self-perceived symptoms in patients with long COVID after long-term fasting.
Benefits of long-term fasting included enhancements in overall health, improvements in common symptoms such as fatigue and breathlessness, and reductions in risk factors for cardiometabolic diseases.
Fasting triggers processes like autophagy, anti-inflammatory responses, and oxidative stress defense, which can contribute to a normalization of metabolism and improvements in cardiovascular risk factors in long COVID patients.
My Take:
Anecdotally, it works for me, but I think it is because eating tends to spike my heart rate.
DEFINITIONS:
Convalescent plasma (CP): Plasma obtained from patients who have recovered from a specific viral infection, which contains antibodies that can target the virus.
Hyperimmune globulin (HIG): A concentrated form of plasma that contains high levels of specific antibodies against a particular pathogen.
Intravenous immunoglobulin (IVIG): A blood product derived from the plasma of multiple donors, containing a range of antibodies that can help regulate the immune system.
SUMMARY:(I don’t think you need this either)
The effective application and development of blood-derived products are important strategies to combat the serious damage caused by COVID-19.
SARS-CoV-2-targeting blood-derived products, including COVID-19 convalescent plasma, COVID-19 hyperimmune globulin, and recombinant anti-SARS-CoV-2 neutralizing immunoglobulin G, are virus-targeting and can provide immediate control of viral infection in the short term.The development and appropriate use of these blood-derived products could serve as important strategies in combating the global impact of the pandemic.
SUMMARY:
In the Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 Acute (ACTIV-4a) trial, 727 non-critically ill patients hospitalised for COVID-19 were randomised to receive either therapeutic-dose or prophylactic heparin. The researchers sought to investigate whether therapeutic-dose heparin, compared with prophylactic heparin, was associated with fewer symptoms and better QoL (Quality of Life) at 90 days.
In multivariable analysis, no difference was observed in the presence of any symptoms at 90 days between patients treated with therapeutic-dose heparin and those treated with prophylactic heparin.
Additionally, therapeutic-dose heparin was associated with less moderate-to-severe impairment in the self-care domain of EQ-5D-5L, but not other domains, including mobility, usual activities, pain/discomfort, and anxiety/depression.
“To our knowledge, this is the first report of an acute intervention shown to be effective in a clinical trial for short-term outcomes to also reduce the possibility of post-acute sequelae of COVID-19 (PASC) in non-critically ill patients with acute COVID-19,” the authors remarked. “Our findings highlight the potential impact of acute interventions on PASC and might guide the design of future studies in this field.”
Ditto what Al said. I was diagnosed (not a self-diagnosis) in early April 2020 and was told to quarantine. Most of the early flu like symptoms either disappeared or perservered in a weakened form. Some of the symptoms were still with me a year later- March 2021, then 2 years- March 2022, then 3 years- March 2023. Now March 2024 is approaching and almost all minor symptoms are gone, but three major ones remain, two of which are seemingly undiminished in strength. Both of which I never experienced until ,2020. One of which is life-threatening- a cardiac condition. No one in my family for three generations on either side have had heart issues. I'm the first and I'm sure it was Covid caused. So, cardiac involvment in long Covid is for real, and in my case, incredibly tenacious. I hope it's a fairly rare sequelae, but if not, it is going to tax the hospital system cardiologists eventually.
Hi Brandon, thank you for all your work, which I really appreciate as a 2+ year long hauler. In the post you mention fasting, can I ask what pattern you use? Thanks!