Thread by @lumosbio

THREAD from the new #bradykinin research (pre-print) from 🇳🇱:

"We propose that the severity of the disease and many deaths are due to a local vascular problem due to activation of B1 receptors on #endothelial cells in the lungs."

#COVID19 #kinins

preprints.org/manuscript/202…

➡️"the B1 receptor on endothelial cells is upregulated by proinflammatory #cytokines

➡️ Without #ACE2 acting as a guardian to inactivate the ligands of B1, the lung environment is prone for local vascular leakage leading to #angioedema"

...

#bradykinin #COVID19

➡️"... and might explain the typical #CTscans and the feeling of people that they drown.

➡️In some pt., this is followed by a clinical worsening of disease around day 9 due to the formation antibodies directed against the spike (S)-antigen of #SARSCoV2 that binds to #ACE2"

➡️"inflammation induces more B1 expression, & possibly via antibody-dependent enhancement of viral infection leading to continued #ACE2 dysfunction in the lung."

➡️we propose that a #bradykinin -dependent local lung angioedema via B1/B2 receptors is an imp. feature of #COVID19."

/more from the full PDF/ #bradykinin #COVID19

"Importantly, we observed that #dyspnea and #tachypnea can differ from hour to hour and a feeling of drowning is described with sometimes sudden
recovery by patients."

#bradykinin #COVID19 🇳🇱

"Notably, plasma concentrations of D-dimers at this stage are increased without evidence of thromboembolic
events."

"This worsening seems to be accompanied specifically with further increases in #IL6, CRP, #ferritin,
without elevated procalcitonin."

#bradykinin #COVID19 🇳🇱

"Furthermore, PEEP shows poor recruitability in most patients. Hereby mechanical #ventilation may further
contribute to #lungdamage. Pulmonary hypertension is not an important clinical component."

"We propose it all starts with ACE2 & its role in the kallikrein-kinin system, which to date has not investigated in the pathogenesis of #SARS or #COVID19.

The clinical picture is in line with a single-organ failure of the #lung that is due to edema at the site of inflammation."

#bradykinin

"This most likely reflects the leakage of plasma substances involved in the coagulation cascade leading to fibrin & due to kallikrein activity is processed into D-dimer & leaks back into the circulation, reflecting subendothelial activation and kallikrein activity."

#bradykinin

"Pulmonary edema by ACE2 dysfunction was speculated to be due to increased hydrostatic pressure as a result of vasoconstriction of the pulmonary vasculature due to high angiotensin II (a vasoconstrictor).

However, further experiments showed no difference ..."

"Increased #bradykinin however could explain this observation without increased hydrostatic pressure. Notably, the RAS system controls vasoconstriction and vasodilatation, and the bradykinin system controls permeability and vasodilatation, whereas #ACE2 regulates both." #COVID19

END THREAD

👆is to the end of Page 5. There are 11 pages + 7 pages of references and figures.

Just seems like an intriguing observation, and many of the comments on preprint site reflect interest in delving deeper.

preprints.org/manuscript/202…

#COVID19 #bradykinin 🇳🇱 /theory/