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Stage II of Virus and Bacteria Synergistic Infection of Covid-19: A physical model
0. Recap:
Virus breaks cell and ECM adhesion, letting the endogenous bacteria in:
https://twitter.com/joshux321/status/1264387117200756736?s=20
The virus is largely non-cytopathic:
https://twitter.com/joshux321/status/1277489815735300096?s=20
This causes a delay in the immune response: https://twitter.com/joshux321/status/1284516291110293506?s=20
Virus breaks cell and ECM adhesion, letting the endogenous bacteria in:
https://twitter.com/joshux321/status/1264387117200756736?s=20
The virus is largely non-cytopathic:
https://twitter.com/joshux321/status/1277489815735300096?s=20
This causes a delay in the immune response: https://twitter.com/joshux321/status/1284516291110293506?s=20
Which allows the bacteria to produce biofilm and use up oxygen:
https://twitter.com/joshux321/status/1271281209331478528?s=20
In the process, the bacteria community become anaerobic dominant, as @sanchak74 has discovered:
https://osf.io/usztn/
https://twitter.com/joshux321/status/1271281209331478528?s=20
In the process, the bacteria community become anaerobic dominant, as @sanchak74 has discovered:
https://osf.io/usztn/
1. Affecting the blood vessels
Initially, the bacterial biofilm silently grows in the interstitium.
But the bacteria would eventually approach the blood vessel, where it would have preference towards since the vessel is a source of nutrients: https://twitter.com/joshux321/status/1279364997382934528?s=20
Initially, the bacterial biofilm silently grows in the interstitium.
But the bacteria would eventually approach the blood vessel, where it would have preference towards since the vessel is a source of nutrients: https://twitter.com/joshux321/status/1279364997382934528?s=20
The virus would also take advantage of the broken barrier and and eventually access the blood vessels.
The virus then infects the endothelium. Similar to the epithelium, it causes Endothelial-to-Mesenchymal transition (EndMT).
Some evidence for EndMT: https://twitter.com/joshux321/status/1284063825445048321?s=20
The virus then infects the endothelium. Similar to the epithelium, it causes Endothelial-to-Mesenchymal transition (EndMT).
Some evidence for EndMT: https://twitter.com/joshux321/status/1284063825445048321?s=20
EndMT combined with biofilm-induced hypoxia, cause hightened angiogenesis:
https://twitter.com/joshux321/status/1283366041641381888?s=20
Note: mesenchymal cells are a kind of stem cells, hence enhance proliferation, this case angiogenesis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2579683/
Hypoxia and angiogenesis: https://twitter.com/joshux321/status/1281544623609896960?s=20
https://twitter.com/joshux321/status/1283366041641381888?s=20
Note: mesenchymal cells are a kind of stem cells, hence enhance proliferation, this case angiogenesis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2579683/
Hypoxia and angiogenesis: https://twitter.com/joshux321/status/1281544623609896960?s=20
EndMT means the endothelial cell adhesion or tight junction is broken.
This allows the bacteria/biofilm fragments/endotoxins to get into the blood.
At this point, the immune response would finally be activated (remember they were delayed).
This allows the bacteria/biofilm fragments/endotoxins to get into the blood.
At this point, the immune response would finally be activated (remember they were delayed).
Final note for section 1:
Similar to the epithelial cells, the virus is also non-cytopathic to the endothelial cells. They just break the junction.
The damage is mild, easier to repair.
It's the reason that there's not much bleeding or hemorrhage. https://twitter.com/Leo_ReapDO/status/1254620444164046850?s=20
Similar to the epithelial cells, the virus is also non-cytopathic to the endothelial cells. They just break the junction.
The damage is mild, easier to repair.
It's the reason that there's not much bleeding or hemorrhage. https://twitter.com/Leo_ReapDO/status/1254620444164046850?s=20
2. NETs, autoimmunity, and coagulation
The immune system is alerted. Neutrophils are recruited responding to bacteria/biofilm/endotoxins.
They're overwhelmed, since the bacteria and biofilm have been brewing for some time. https://twitter.com/joshux321/status/1293699567263735809?s=20
The immune system is alerted. Neutrophils are recruited responding to bacteria/biofilm/endotoxins.
They're overwhelmed, since the bacteria and biofilm have been brewing for some time. https://twitter.com/joshux321/status/1293699567263735809?s=20
Also, biofilm is too large for neutrophils to engulf:
https://twitter.com/joshux321/status/1293491926608404480?s=20
The natural response would be NETosis.
However, this potentiates pathological conditions.
https://twitter.com/joshux321/status/1293491926608404480?s=20
The natural response would be NETosis.
However, this potentiates pathological conditions.
Note: evidence of NETs in covid:
https://twitter.com/Aiims1742/status/1290413007789527041?s=19 https://twitter.com/jasonsknight/status/1271811378626596864?s=20
https://twitter.com/Aiims1742/status/1290413007789527041?s=19 https://twitter.com/jasonsknight/status/1271811378626596864?s=20
NETs' function is to block pathogens and prevent host material leakage: https://twitter.com/joshux321/status/1293485582321033217?s=20
NETs' DNA provide scaffolding for platelets aggregation. This is one mechanism for the clotting.
NETs' DNA provide scaffolding for platelets aggregation. This is one mechanism for the clotting.
NETosis would also induce other parts of the immune system, in particular complements, which would further influence coagulation.
NETosis, complement, coagulation, influence each other:
https://twitter.com/pathdoc3/status/1290319156378771458?s=20
NETosis, complement, coagulation, influence each other:
https://twitter.com/pathdoc3/status/1290319156378771458?s=20
The complement system also respond to the bacteria themselves: https://twitter.com/sanchak74/status/1268507268829437953?s=20
These are part of the reasons for clotting in covid-19.
However, the pattern of coagulation is a bit different than regular sepsis induced disseminated intravascular coagulation (DIC).
However, the pattern of coagulation is a bit different than regular sepsis induced disseminated intravascular coagulation (DIC).
In autopsy findings, the distinct vascular pattern is:
1. Thrombotic microangiopathy
2. Microthrombi
3. Hightened angiogenesis (we've covered this one: caused by hypoxia and EndMT) https://twitter.com/joshux321/status/1283365939472248833?s=20
1. Thrombotic microangiopathy
2. Microthrombi
3. Hightened angiogenesis (we've covered this one: caused by hypoxia and EndMT) https://twitter.com/joshux321/status/1283365939472248833?s=20
In addition, the condition resembles APS (antiphospholipid syndrome). https://twitter.com/joshux321/status/1285558066373513216?s=20
And indeed, there's antiphospholipid antibodies in covid-19 patients: https://twitter.com/joshux321/status/1287308425152487425?s=20
Which may explain the B cell dysfunction: https://twitter.com/joshux321/status/1287362958780059648?s=20
Which may explain the B cell dysfunction: https://twitter.com/joshux321/status/1287362958780059648?s=20
The pattern matches Antiphospholipid:
1) "Thrombotic microangiopathy" linked to Antiphospholipid syndrome:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3193674/
2) "Microthrombi" in patients with .. anti-phospholipid antibodies
https://academic.oup.com/rheumatology/article/48/8/1003/1787301
Now the question is: how does covid trigger autoimmune?
1) "Thrombotic microangiopathy" linked to Antiphospholipid syndrome:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3193674/
2) "Microthrombi" in patients with .. anti-phospholipid antibodies
https://academic.oup.com/rheumatology/article/48/8/1003/1787301
Now the question is: how does covid trigger autoimmune?
2.5 Battle of Biofilm, NETs -> induce autoimmunity, APS
Biofilm as we argued, naturally induce NETs, and they enhance each other: https://twitter.com/joshux321/status/1293505347794006018?s=20
Biofilm as we argued, naturally induce NETs, and they enhance each other: https://twitter.com/joshux321/status/1293505347794006018?s=20
Incomplete clearance of the host DNA or other intracellular materials would potentiate autoimmunity:
https://twitter.com/joshux321/status/1286577763130851328?s=20
Adding to that, biofilm also extrude DNA, tangled with NETs' DNA would cross-react and more likely trigger autoimmunity.
https://twitter.com/joshux321/status/1286577763130851328?s=20
Adding to that, biofilm also extrude DNA, tangled with NETs' DNA would cross-react and more likely trigger autoimmunity.
Evidence for anti-NET antibodies in APS, with impaired clearance of NETs.
https://twitter.com/ACR_Journals/status/1293232963287764992?s=20
In covid, the body is overwhelmed by the bacteria/biofilm, so less resources for the clearance.
Biofilm is also difficult for the immune system to clear.
https://twitter.com/ACR_Journals/status/1293232963287764992?s=20
In covid, the body is overwhelmed by the bacteria/biofilm, so less resources for the clearance.
Biofilm is also difficult for the immune system to clear.
