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Trying to understand all the manifestations of #COVID19 and #ACE2 receptor seems to be the key, Feel free to add info I miss. #SARS_COV_2 enters cells expressing this, abundant in 1) lungs, 2) heart, 3) endothelium and 4) GI #MedTwitter #cardiotwitter #pulmccm #pulmonary #gastro
1) Discordant pulse ox and relative clinical comfort indicates silent hypoxemia in these pts. Given normal SpO2-PaO2 gradient and improvement w supplemental O2, an impairment of normal hypoxic vasoconstriction is most likely explanation. Several studies have demonstrated...
...the role of ACE2 in hypoxic pulmonary vasoconstriction in vivo, such that viral mediated derangement would explain the mechanism of silent hypoxemia as being due to inefficient routing of blood to poorly oxygenated parts of the lung, in addition to predisposing to PE.
2) Evidence of #COVID19 directly and indirectly affecting the heart by affecting myocytes, vasc endothelium and plaque instability from elicited cytokines. Recent JAMA report summarized findings including worse outcomes w cardiac involvement https://jamanetwork.com/journals/jamacardiology/fullarticle/2763844
3) Increased incidence of thrombotic events including DVT/PE, PV, SVC thrombosis and microthrombi on path, w deranged coags. Agree that atleast part of morbidity/mortality is related to this. Review of ACE/AT1R role in endothelium PAI-1 and TPA https://www.ahajournals.org/doi/pdf/10.1161/01.HYP.0000153321.13792.b9
4) GI symptoms are now a recognized manifestation of #COVIDー19 with viral nucleic acids isolated from saliva and stool. ACE2 receptor expression is found in esophagus, ileum and colon and a target for viral entry along with host transmembrane serine protease (TMPRSS)...
...Along with elevated liver markers, viral nucelic acids have also been identified on liver biopsy, suggesting viral hepatitis possibly confounded by drug toxicity. https://www.gastrojournal.org/article/S0016-5085(20)30281-X/abstract#/article/S0016-5085(20)30281-X/abstract
Takeaways: 1) early therapeutic anticoagulation will likely be a mainstay of therapy 2) ARB (moreso then ACEI) should (and are) being studied as a poss defense to viral entry— tricky bc pts alrdy on this have coexisting conditions (perhaps dose can be...
...increased in pts who have been on long-standing ARBs w/ receptor upregulation) 3) utilizing non-affected side down positioning when ventilating patients to optimize V/Q match in absence of proper ACE mediated hypoxic vasoconstriction. 4) Troponins should be followed to assess
myocardial involvement and while they may have myocarditis, they are also at higher risk for ACS/MI. 4) ACE2 mediated viral entry is a multi step process (viral attachment, receptor recognition, protease cleaving, membrane fusion...
...and TMPRSS mediated viral spike protein priming/entry— all poss. viable targets for tx. Feel free to add anything I missed. @drsanjaygupta @CMichaelGibson @BrennanSpiegel @Doctor_V @jamesbeckerman @dlschermd @TravisStorkMD @nickmmark @medevidenceblog @kari_jerge @ssgirgis97
