A tour de force review in @RPTHjournal of NETosis and its contribution to immunothrombosis. Neutrophils cast out NETs to catch bugs (including SARS-CoV-2) but they are highly proinflammatory and thrombogenic. #TeamClots
The original form of NETosis described by the Brinkmann & Zychlinsky labs was when neutrophils “dump their guts”, committing suicide by spilling out their nucleus, forming a fishnet-like structure. Read the @RPTHjournal review for updates on non-suicidal NETosis.… twitter.com/i/web/status/1…
A previous review from Denisa Wagner, with a strong emphasis on the role of NETosis, “Thromboinflammation: From Atherosclerosis to COVID-19”. ahajournals.org/doi/10.1161/AT…
Think about neutrophils as akin to Roman retiarius gladiators who, as a final suicidal act, eject their DNA guts in the form of a fishnet like Neutrophil Extracellular Trap to defeat their microbial adversaries. But NETs have the downside of attracting inflammation and clots.
It is hoped that by knocking out NETosis (eg with PAD4 inhibitors), we may be able to reduce the thromboinflammation that NETs attract. Slide from a talk @ISTH Berlin, 2017. Note that COVID microclots are always P-selectin positive. #TeamClots
Found a photo of myself at the conference centre of the 2017 Berlin @ISTH meeting. It seems like another world—back when arcane knowledge of immunothrombosis wasn't a matter of life and death. The past is a different country. #TeamClots 🥹
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And this week's Grand Rounds “just a cold” is another young patient with enterovirus-induced fulminant myocarditis needing intubation, ECMO, and an Impella LVAD. I've never seen so many severe post-infectious complications presented in my life.
Last week's Grand Round? Another “just a cold” with Mycoplasma in a paediatric patient who developed encephalopathy, needing IV pulse methylprednisolone and IVIg. It's like every week we see a new case of previously rare infectious complications in young patients.
Another Grand Rounds case. A pregnant woman with severe cardiomyopathy caused by a combined adenovirus and enterovirus infections. Required ECMO.
Subjecting trial subjects to wearing surgical mаsks against an airborne virus is like running a bike helmet RCT with subjects in Tupperware helmets that weren't designed for that purpose. “But we don't know it doesn't work until we run an RCT” isn't good enough.
“But there was a 30% reduction in head injuries in the Tupperware group vs. placebo.” Not good enough! In a high-risk scenario for major head injury, a Tupperware helmet won't do. The magnitude of risk test subjects were exposed to needs investigation and quantification.
Non-pharmaceutical physical protective devices are subject to engineering standards of proof of efficacy. In the case of helmets, that means crash testing in a lab to see how they fare in high-risk situations that live subjects can't be exposed to. helmet.beam.vt.edu/lab.html
A reminder that there was once a titanic struggle between contagionists vs miasmatists over the mechanism of transmission of cholera before the need to cleanse the water of waterborne pathogens was accepted. We are going through a similar struggle today, fighting for clean air. abc.net.au/news/2024-07-3…
If you want to read about how divisive the debates between the contagionists and miasmatists was, you should read “Death in Hamburg” by @RichardEvans36. They didn't need Twitter back then to be almost reduced to pistols at dawn.
This trial should have been reported as having an unacceptable 70% failure rate, showing that a surgical mаsk is grossly suboptimal in design and not fit for purpose as RPE. Engineered physical protective devices aren't drugs. bmj.com/content/386/bm…
You wouldn't consider a parachute that failed to deploy 70% of the time to be an acceptable design to test by RCT, and neither should droplet protection against an inhaled bioaerosol be considered ethically acceptable for a study design.
Physics permits greater predictability than pharmacology. This RIKEN supercomputer study already predicted the results of the BMJ study. For a loose surgical/non-woven mаsk, there is a 45% infection rate (55% reduction) to the wearer (76% effective as source control). This is a pre-Delta study.
Another factor is that children have been turned into let-it-rip vectors of forced mass infection who bring home diseases that debilitate the parents who are out of sick leave while killing the grandparents. sbs.com.au/news/article/a…
And yes, children have been demonstrated to be key vectors of disease.
Note to be forgotten is the adverse effect that infections with SARS-CoV-2 have on fertility. This article reviews the impacts on female reproductive health. frontiersin.org/journals/rehab…
Another fact that people often don't know is that the yolk of the “fried egg” shape of a monocyte is chock-a-block full of coagulation proteins, like tissue factor (TF), which moves to the cell surface on activation. This drives various disease processes.
As for monocytes collaborating with platelets to bring about immunothrombosis, this occurs via monocyte PSGL-1 binding to platelet P-selectin.
Another name for P-selectin is CD62P. Here is a #microclot from a #longCOVID patient, which has been stained with anti-CD62P antibody. P-selectin is a marker of platelet activation, indicating readiness to traffic with monocytes to drive #immunothrombosis.