TACT...Nice photograph at the top. If that photograph doesn't scream 'FRESH AIR' , I don't know what does.
I enjoyed your quixotic hope in reference to the Center for Disease Circulation ("How many were vaccinated? Hopefully, they make this distinction clearer in updates.")
Don't hold your breath, TACT.
Regarding the JN.1 quasispecies swarm, see the last line in this reference.
There is something different about the JN.1 swarm, perhaps in the enzymes it is using to potentiate infection that have not yet been completely elucidated.
Fascinating. If not, slightly depressing update, but forewarned is forearmed. I’m particularly interested in the study on Paxlovid. As a lay person I’m making my way through it and having trouble understanding if they adequately accounted for all confounding variables. I see it mentioned BMI is a significant piece of missing data. age might be another. I thought I saw a vague reference to including that in the demographics, but wasn’t 100% clear. On a surface level, it seems hard to understand that a drug that dramatically and quickly reduces viral load in your body couldn’t be at least somewhat helpful for long-term downstream effects. The study didn’t look at what we now know are some of the most common long Covid symptoms as well, such as cognitive impairment/brain, fog, exercise, intolerance and PEM. Would love for people more experienced than I am in reading through study methodology to comment on how solid the conclusions of the study might be.
I am an N of 1. Paxlovid didn’t make me feel any better when I had covid in dec 22. I tested positive for 17 days! I assume i had a xbb variant. I was vaxxed and boosted. I have long covid. I had sepsis last summer. I have had shingles twice. The cytokine mcp-1 is very high. I have terrible “bone pain”. I take a cocktail so that I can have a semblance of a life. I am 60 and fluffy..fluffier since I got long covid. Also, the meds keep me bloated and keep weight on..
So devastating to read. This is a horrible virus. Sending you lots of wishes for physical and emotional health. Did the doctors have any explanation for why Paxlovid didn’t help you at all?
Don't know if the Center for Disease Circulation (CDC) has provided any information on measles breakthrough infections, but I did see one such case reported on Xitter from a parent of a fully vaccinated child in the Florida cohort. Fortunately, this case appears to have resolved quickly.
My spouse is one of 7 and he has 50 first cousins…the eldest cousin is 75. He has pulmonary fibrosis and in the hospital. His family doesn’t know why he has pulmonary fibrosis. 🤦🏾♀️
I could respond and say ..Duh…it’s called covid19 aka saracov2 - but they won’t believe me…
2020 -The burden of pulmonary fibrosis after COVID recovery could be substantial.
Progressive, fibrotic irreversible interstitial lung disease, which is characterised by declining lung function, increasing extent of fibrosis on CT, worsening symptoms and quality of life, and early mortality.
This appears to explain why people with the more severe symptoms or died often had very low levels of iron. Conversely, maintaining optimal iron level helps mitigate that risk. I hadn't seen a connection to how iron could influence severity of infection until now. This is a hypothesis but the findings suggest that maintaining optimal iron levels could be important for mitigating the severity of COVID-19, as low iron levels might enhance susceptibility to viral infection and worsen outcomes.
Increased TfR expression: The study indicates that SARS-CoV-2 infection up-regulates the expression of transferrin receptor protein 1 (TfR) in the lungs. Low iron levels may exacerbate this effect, leading to even higher levels of TfR expression. Elevated TfR expression could enhance the susceptibility of cells to SARS-CoV-2 infection, as TfR serves as a receptor for viral entry.
Enhanced viral entry: TfR mediates the endocytosis of SARS-CoV-2 by directly interacting with the virus spike protein. Low iron levels may lead to higher expression of TfR, providing more entry points for the virus into host cells. This increased viral entry could potentially result in more severe infection and tissue damage.
Iron metabolism disruption: Low iron levels may disrupt normal iron metabolism pathways, potentially leading to dysregulation of immune responses. Iron plays a crucial role in various immune functions, including the proliferation and function of immune cells. Disrupted iron metabolism could impair the ability of the immune system to mount an effective response against SARS-CoV-2, thereby exacerbating the severity of the infection.
How could low levels of iron lead to higher expression of TfR, thus provide more entry points for the virus into host cells?
Low levels of iron can lead to higher expression of transferrin receptor (TfR) through a mechanism known as iron-responsive element (IRE)-mediated regulation. This process involves the interaction between iron regulatory proteins (IRPs) and specific RNA sequences called iron-responsive elements.
When cellular iron levels are low, IRPs bind to iron-responsive elements located in the untranslated regions (UTRs) of mRNAs encoding proteins involved in iron metabolism, including TfR. Binding of IRPs to the iron-responsive elements stabilizes the mRNA transcripts encoding TfR, preventing their degradation and allowing for increased translation of TfR protein.
Conversely, when cellular iron levels are sufficient, IRPs undergo conformational changes that prevent their binding to iron-responsive elements, leading to decreased stability and translation of TfR mRNA.
Increasing iron levels above optimal levels might theoretically decrease SARS-CoV-2 infection by reducing TfR expression, it could also lead to other potential damage due to iron overload and disruption of immune function. In conclusion, maintaining optimal iron levels is the ideal path for the most effective immune response based on this information. However, further research is needed to fully understand the mechanisms underlying the relationship between iron metabolism and COVID-19 severity.
It is more likely to sustain if previously infected however there aren't studies that I have found, confirming the potential waning immunity timeline for vaccinated or previously infected. It might be wise to request an antibody test to ensure that you still have neutralizing levels.
TACT...Nice photograph at the top. If that photograph doesn't scream 'FRESH AIR' , I don't know what does.
I enjoyed your quixotic hope in reference to the Center for Disease Circulation ("How many were vaccinated? Hopefully, they make this distinction clearer in updates.")
Don't hold your breath, TACT.
Regarding the JN.1 quasispecies swarm, see the last line in this reference.
There is something different about the JN.1 swarm, perhaps in the enzymes it is using to potentiate infection that have not yet been completely elucidated.
https://www.biorxiv.org/content/10.1101/2024.02.14.579654v1
Lastly, while you mentioned measles (which is definitely a problem), don't sleep on DENGUE.
To the folks in Florida and Texas, all I can say is "SUMMER IS COMING"
Thanks for your tireless work.
Fascinating. If not, slightly depressing update, but forewarned is forearmed. I’m particularly interested in the study on Paxlovid. As a lay person I’m making my way through it and having trouble understanding if they adequately accounted for all confounding variables. I see it mentioned BMI is a significant piece of missing data. age might be another. I thought I saw a vague reference to including that in the demographics, but wasn’t 100% clear. On a surface level, it seems hard to understand that a drug that dramatically and quickly reduces viral load in your body couldn’t be at least somewhat helpful for long-term downstream effects. The study didn’t look at what we now know are some of the most common long Covid symptoms as well, such as cognitive impairment/brain, fog, exercise, intolerance and PEM. Would love for people more experienced than I am in reading through study methodology to comment on how solid the conclusions of the study might be.
I am an N of 1. Paxlovid didn’t make me feel any better when I had covid in dec 22. I tested positive for 17 days! I assume i had a xbb variant. I was vaxxed and boosted. I have long covid. I had sepsis last summer. I have had shingles twice. The cytokine mcp-1 is very high. I have terrible “bone pain”. I take a cocktail so that I can have a semblance of a life. I am 60 and fluffy..fluffier since I got long covid. Also, the meds keep me bloated and keep weight on..
After having sepsis- I am so glad to be alive.
I assume I won’t make it to 80…
So devastating to read. This is a horrible virus. Sending you lots of wishes for physical and emotional health. Did the doctors have any explanation for why Paxlovid didn’t help you at all?
Don't know if the Center for Disease Circulation (CDC) has provided any information on measles breakthrough infections, but I did see one such case reported on Xitter from a parent of a fully vaccinated child in the Florida cohort. Fortunately, this case appears to have resolved quickly.
A little light reading before bedtime...
https://pubmed.ncbi.nlm.nih.gov/36013985/
My spouse is one of 7 and he has 50 first cousins…the eldest cousin is 75. He has pulmonary fibrosis and in the hospital. His family doesn’t know why he has pulmonary fibrosis. 🤦🏾♀️
I could respond and say ..Duh…it’s called covid19 aka saracov2 - but they won’t believe me…
2020 -The burden of pulmonary fibrosis after COVID recovery could be substantial.
Progressive, fibrotic irreversible interstitial lung disease, which is characterised by declining lung function, increasing extent of fibrosis on CT, worsening symptoms and quality of life, and early mortality.
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30222-8/fulltext
2021- Lung fibrosis: an undervalued finding in COVID-19 pathological series
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30582-X/fulltext?amp=1
2022-A silent march-Post covid fibrosis in asymptomatics – A cause for concern?"
"On evaluation, after excluding other causes, the fibrosis was attributed to asymptomatic or mild COVID illness in the past."
"No definitive treatment for post-COVID fibrosis of the lungs."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131542/
2023-Increase of mast cells in COVID‐19 pneumonia may contribute to pulmonary fibrosis and thrombosis
"A significant increase of mast cells in SARS‐CoV‐2‐infected lung tissue compared to influenza."
https://onlinelibrary.wiley.com/doi/full/10.1111/his.14838
Well, well, well...it looks like it is NOT just ACE2.
We're not in Kansas, anymore...
https://www.pnas.org/doi/full/10.1073/pnas.2317026121
This appears to explain why people with the more severe symptoms or died often had very low levels of iron. Conversely, maintaining optimal iron level helps mitigate that risk. I hadn't seen a connection to how iron could influence severity of infection until now. This is a hypothesis but the findings suggest that maintaining optimal iron levels could be important for mitigating the severity of COVID-19, as low iron levels might enhance susceptibility to viral infection and worsen outcomes.
Increased TfR expression: The study indicates that SARS-CoV-2 infection up-regulates the expression of transferrin receptor protein 1 (TfR) in the lungs. Low iron levels may exacerbate this effect, leading to even higher levels of TfR expression. Elevated TfR expression could enhance the susceptibility of cells to SARS-CoV-2 infection, as TfR serves as a receptor for viral entry.
Enhanced viral entry: TfR mediates the endocytosis of SARS-CoV-2 by directly interacting with the virus spike protein. Low iron levels may lead to higher expression of TfR, providing more entry points for the virus into host cells. This increased viral entry could potentially result in more severe infection and tissue damage.
Iron metabolism disruption: Low iron levels may disrupt normal iron metabolism pathways, potentially leading to dysregulation of immune responses. Iron plays a crucial role in various immune functions, including the proliferation and function of immune cells. Disrupted iron metabolism could impair the ability of the immune system to mount an effective response against SARS-CoV-2, thereby exacerbating the severity of the infection.
How could low levels of iron lead to higher expression of TfR, thus provide more entry points for the virus into host cells?
Low levels of iron can lead to higher expression of transferrin receptor (TfR) through a mechanism known as iron-responsive element (IRE)-mediated regulation. This process involves the interaction between iron regulatory proteins (IRPs) and specific RNA sequences called iron-responsive elements.
When cellular iron levels are low, IRPs bind to iron-responsive elements located in the untranslated regions (UTRs) of mRNAs encoding proteins involved in iron metabolism, including TfR. Binding of IRPs to the iron-responsive elements stabilizes the mRNA transcripts encoding TfR, preventing their degradation and allowing for increased translation of TfR protein.
Conversely, when cellular iron levels are sufficient, IRPs undergo conformational changes that prevent their binding to iron-responsive elements, leading to decreased stability and translation of TfR mRNA.
Increasing iron levels above optimal levels might theoretically decrease SARS-CoV-2 infection by reducing TfR expression, it could also lead to other potential damage due to iron overload and disruption of immune function. In conclusion, maintaining optimal iron levels is the ideal path for the most effective immune response based on this information. However, further research is needed to fully understand the mechanisms underlying the relationship between iron metabolism and COVID-19 severity.
Controlling iron homeostasis may be a reason why lactoferrin could be beneficial in association with SARS-CoV-2.
https://www.mdpi.com/2072-6643/14/15/3090
So I’m hoping it’s still safe to consider myself immune after having had measles decades ago?
It is more likely to sustain if previously infected however there aren't studies that I have found, confirming the potential waning immunity timeline for vaccinated or previously infected. It might be wise to request an antibody test to ensure that you still have neutralizing levels.
Thank you. I was considering the test. Good to know.