Hi everyone,
Welcome back! The newsletter went on a short break last week but is back with a longer-than-average edition this week!
In this issue, we bring you a collection of insightful articles and studies that shed light on the perplexing nature of Long Covid and its lingering effects. From the discovery that one can experience Long Covid without testing positive for the virus, to the worrisome long-term innate immune system changes observed in severe Covid-19 cases, our newsletter aims to provide you with the latest findings and research in this evolving field. Additionally, we delve into the possible culprits behind chronic fatigue syndrome and the impact of hospitalization on Covid-19 patients' metabolome.
Media
Article: People can get long Covid without testing positive for virus: Study
SUMMARY:
A new study suggests that even more people may be suffering from the post-viral syndrome without having ever received an official diagnosis of Covid-19.
The study found that 41% of patients who reported long Covid symptoms but hadn't tested positive for Covid-19 had T cell or antibody responses to the virus, indicating exposure.
Patients who had long Covid without an official diagnosis faced treatment delays, receiving clinical evaluation at an average of 10.7 months after the onset of symptoms.
My Take:
This suggests that a positive Covid-19 test should not be a requirement for treating people with symptoms consistent with long Covid, as many individuals may have been exposed to the virus without ever testing positive.
SUMMARY:
For people who have contracted the COVID-19 virus, pain and suffering may continue two years after infection, according to a new study from Washington University School of Medicine in St. Louis and the Veterans Affairs St. Louis Health Care system.
The researchers found that people who had COVID-19 were still, up to two years after infection, at an elevated risk for diabetes, lung conditions, fatigue, blood clots and disorders affecting the gastrointestinal and musculoskeletal systems.
My Take:
Again it seems like information that is common knowledge within the Long Covid Community takes years to become common knowledge outside.
DEFINITIONS:
Innate immune system: The body's first line of defense against pathogens, including viruses and bacteria.
It is composed of cells and molecules that can quickly recognize and respond to foreign invaders.
Genes: Units of DNA that contain the instructions for making proteins, which carry out many functions in the body.
SUMMARY:
Severe COVID-19 may cause long-lasting alterations to the innate immune system, according to a small study funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.
These changes may help explain why the disease can damage so many different organs and why some people with long COVID have high levels of inflammation throughout the body.
The findings were published online this weekin the journal Cell.
In these rare stem cells—the parents of immune-system cells—taken from people recovering from COVID-19, the scientists identified changes in the instructions for which genes got turned on or off.
DEFINITIONS:
WASF3: A protein that plays a role in cell movement and has been found at high levels in the muscles of people with ME/CFS.
SUMMARY:
Researchers have identified a protein called WASF3 that is present at high levels in the muscles of people with chronic fatigue syndrome (ME/CFS).
The protein disrupts cells' ability to generate energy, which could explain the extreme exhaustion experienced by individuals with ME/CFS.
Elevated levels of WASF3 were found in muscle samples from people diagnosed with ME/CFS, indicating a potential link between the protein and the condition.
The findings suggest that targeting WASF3 or its effects on mitochondria could lead to new therapeutics for ME/CFS and related illnesses like Long Covid.
My Take:
Many researchers studying Long Covid have tried to "re-invent the wheel": many building blocks for research into ME/CFS have already been done, and Long Covid likely shares some of the same pathways.
Hopefully Long Covid researchers will incorporate these and other findings into their research!
Research
SUMMARY:
This study aimed to investigate the serum metabolomic changes due to hospitalization and COVID-19 disease progression in newly hospitalized moderate and severe patients.
The study analyzed untargeted serum metabolomics data from 71 patients in their first week after hospitalization at three different locations in Switzerland.
The researchers found drastic changes in serum metabolite concentrations for 448 out of 901 metabolites, including markers of hospitalization, physiological functioning, and COVID-19-induced metabolic reprogramming.
Potential markers of disease severity and progression were identified, such as glycerophosphorylcholine.
DEFINITIONS:
G-protein-coupled receptors (GPCRs): a large family of cell membrane receptors involved in signal transduction.
Autoantibodies: antibodies produced by the immune system that target and attack the body's own tissues or cells.
SUMMARY:
Antibodies against angiotensin II receptor type 1 (AT1R) and endothelin receptor type A (ETAR) are increased in COVID-19 patients compared to controls.
The increased titers of these antibodies are not associated with inflammatory markers or long-term symptoms in COVID-19 patients.
The formation of AT1R and ETAR antibodies may be related to vascular endothelial damage in COVID-19.
Article: COVID-19-induced gastrointestinal autonomic dysfunction: A systematic review
DEFINITIONS:
Autonomic dysfunction: A disruption of the autonomic nervous system that can cause gastrointestinal issues due to damage to the nerve supply in the digestive system.
Gastrointestinal autonomic dysfunction: The dysfunction of the autonomic nervous system that specifically affects the gastrointestinal tract, leading to gastrointestinal symptoms.
SUMMARY:
COVID-19 can damage the nerve supply to the digestive system, leading to gastrointestinal autonomic dysfunction.
Studies have shown that SARS-CoV-2 has a well-documented affinity for both neural and gastrointestinal tissues, and the virus can produce various gastrointestinal symptoms by reaching neural tissues through different pathways.
These symptoms include anorexia, dysgeusia, heartburn, belching, chest pain, regurgitation, vomiting, epigastric burn, diarrhea, abdominal pain, bloating, irregular bowel movements, and constipation.
Although COVID-19 vaccination may rarely induce autonomic dysfunction and gastrointestinal symptoms, COVID-19-induced autonomic effects significantly impact the patient's condition, general health, prognosis, and quality of life.
Early diagnosis and proper recognition are crucial for improving outcomes.
My Take:
The COVID-19 pandemic has highlighted the impact of the virus on various organ systems, including the gastrointestinal tract.
Gastrointestinal autonomic dysfunction can lead to a range of symptoms that significantly impact a patient's quality of life and prognosis.
When we think about Covid-induced autonomic issues we often think of POTs, but this offers a different lens.
SUMMARY:
Among the unknowns in decoding the pathogenesis of SARS-CoV-2 persistent symptoms in Long Covid is whether there is a contributory role of abnormal immunity during acute infection.
Here, SARS-CoV-2 humoral and cellular immunity was analyzed in 86 healthcare workers with laboratory confirmed mild or asymptomatic SARS-CoV-2 infection during the first wave.
During the period up to 18-weeks post-infection, no differences were observed in antibody responses to spike RBD or nucleoprotein, virus neutralization, or T cell responses.
Analysis at 1-year, after two vaccine doses, comparing those with persistent symptoms to those without, again shows similar SARS-CoV-2 immunity.
Thus, quantitative differences in these measured parameters of SARS-CoV-2 adaptive immunity following mild or asymptomatic acute infection are unlikely to have contributed to Long Covid causality.
My Take:
The results showed that there was no difference in antibody responses, virus neutralization, or T cell responses between those with persistent symptoms and those without.
This suggests that quantitative differences in immune responses following mild or asymptomatic infections are unlikely to be the cause of Long Covid.
DEFINITIONS:
Pigeon paramyxovirus 1 (PPMV-1) is an antigenic host variant of avian paramyxovirus 1.
SUMMARY:
This article reports a case of severe human pigeon paramyxovirus 1 (PPMV-1) infection in a patient with probable post-COVID-19 syndrome.
The patient, a 66-year-old man, had a rapidly progressing pulmonary infection and was admitted to the intensive care unit.
PPMV-1 was isolated from the patient's sputum and in samples from domesticated pigeons belonging to the patient's neighbor.
The PPMV-1 genome belonged to genotype VI.2.1.1.2.2 and had the 112RRQKRF117 motif, indicating high virulence.
SUMMARY:
This study aimed to investigate the chronic effects of COVID-19 on cerebral gray matter in young patients with mild COVID infection and no medical complaints at the time of examination.
Even without any subjective or objective neurological complaints at the time of the MR scan, subjects in the COVID group showed gray matter alterations in cortical thickness and subcortical gray matter volume.
My Take:
These findings suggest that COVID-19 may have long-lasting effects on the brain, even in patients with mild infections and no current symptoms.
Article: Frontiers | COVID-19 alters human microbiomes: a meta-analysis
SUMMARY:
The human microbiome plays an essential role in host health and well-being, and multiple studies targeting specific populations have reported altered microbiomes in patients infected with SARS-CoV-2.
Our reanalyses revealed communitywide alterations in the respiratory and gut microbiomes across human populations.
We found significant overall reductions in the gut microbial diversity of COVID-19-infected patients, but not in the respiratory microbiome.
In respiratory microbiomes, COVID-19 infection resulted in an increase in the relative abundance of potentially pathogenic bacteria, including Mycoplasma.
My Take:
The decrease in gut microbial diversity in COVID-19-infected patients may have important implications for disease severity and opportunistic infections.
DEFINITIONS:
Alzheimer's disease (AD): A neurodegenerative disorder characterized by progressive memory loss, cognitive decline, and behavioral changes.
Spike protein: A viral protein on the surface of SARS-CoV-2 that enables the virus to enter human cells.
SUMMARY:
Alzheimer's disease (AD) is a major cause of dementia and cognitive decline among the aging population.
While the aggregation of amyloid peptide Aβ has been implicated in AD, the role of viral infection in the disease is less understood.
In this study, researchers identified a short fragment of the spike protein of the SARS-CoV-2 coronavirus that displayed toxic and amyloidogenic properties.
The fragment promoted the aggregation and toxicity of Aβ, suggesting a potential link between SARS-CoV-2 infection and AD pathogenesis.
Article: Associations Among Menstrual Cycle Length, Coronavirus Disea... : Obstetrics & Gynecology
SUMMARY:
A retrospective cohort analysis analyzed prospectively tracked cycle-length data from users of a period tracker application who also responded to a survey regarding COVID-19 symptoms and vaccination.
The study included 6,514 users from 110 countries representing 32,570 cycles (COVID-19 symptoms: 1,450; COVID-19 vaccination: 4,643; control: 421). The COVID-19 cohort experienced a 1.45-day adjusted increase in cycle length during cycle 4 (COVID-19) compared with their three preevent cycles (95% CI 0.86–2.04)
Experiencing COVID-19 is associated with a small change in cycle length similar to COVID-19 vaccination. These changes resolve quickly within the next cycle.
Hope
DEFINITIONS:
Traditional Chinese medicine (TCM): a system of healing that dates back thousands of years and includes practices such as acupuncture, herbal medicine, and mind-body exercises.
SUMMARY:
The study aims to evaluate the efficacy and safety of three traditional Chinese medicine drugs and three herbal formulas (3-drugs-3-formulas) in patients with COVID-19.
The 3-drugs-3-formulas can play an active role in treating all stages of COVID-19.
No severe adverse events related to 3-drugs-3-formulas were observed.
The results indicate that 3-drugs-3-formulas combined with conventional therapies have effective therapeutic value for COVID-19 patients.
Further long-term high-quality studies are essential to demonstrate the clinical benefits of each formula.
Great work as always! That ME/CFS study looks so compelling. Delighted to see that the NIH is talking about following it up with some treatment trials too
It’s interesting, in some previous studies, antibodies against angiotensin II receptor type 1 (AT1R) have been associated with Long Covid. In this study about these antibodies, it’s saying they are NOT associated with long-term symptoms. I think the sample size here was fairly small.