TYPE: Abstract
TOPIC: Chest Infections
PURPOSE: The COVID Cytokine Storm appears to be through activation and self-propagation of the AT1 pathway via Angiotensin II. Antibodies or antigen-antibody complexes causing inhibition of ACE2 would eliminate the regulation of the AT1 pathway. Without ACE2 to generate Angiotensin (1,7), the anti-inflammatory mediator, the Angiotensin II will cause continued inflammation and stimulate IL1, IL6, and TNFa. All of which also self-propagate the AT1 pathway.
METHODS: were a literature review and unfortunately extensive clinical experience.
RESULTS: The results of this pathophysiology / pathway would explain every aspect of COVID-19. Including the “higher risk” populations, the disproportionate inflammatory cascade, the tissues most affected, and the background for the more effective treatments.
CONCLUSIONS: Inhibition of ACE2 via any mechanism would present with excessive inflammation and tissue injury in any part of the body, but it would most impact the heart, lungs, and kidneys. Additionally, any repeat stimulation of the RAAS or AT1 pathway could cause excessive impact. Without ACE2, Angiotensin II would cause ongoing inflammation/damage, the AT1 pathway also involves stimulation of IL1, IL6, and TNFa. All of which have positive feedback, and the AT1 pathway is based on JAK-STAT signaling. Tocilizumab and baricitinib appear to be the best treatments so far. Further inhibiting RAAS/Angio II with Hypertonic Saline may also help.
CLINICAL IMPLICATIONS: This could suggest further avenues of research but most specifically it offers insight into further COVID-19 treatments. Further inhibition of any aspect of the AT1 pathway may yield similar results. Additionally, full RAAS inhibition using ARBs or Hypertonic Saline may be even better.
DISCLOSURE: Nothing to declare.
KEYWORD: covid