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This is from Facebook COVID group for physicians. #1: The Chinese recognized promptly that this was not a “typical” pneumonia, and some physicians tried to warn us through their “censored channels” and early publications #2: It appears that these early publications handed down the wrong clinical playbook – and everyone is working under the assumption that this is a viral pneumonia/ARDS picture in the front-line setting #3: ICU physicians at the front-line telling us 2 things the last few weeks: - COVID-19 does not behave like typical ARDS - Clinical picture resembles high altitude pulmonary edema (HAPE) (video on this: https://www./watch?v=k9GYTc53r2o&fbclid=IwAR27lPrbVK3ti9q7zSil4-XwiVscvhJlmnAnY5ZtlIVPKU1LNf3T3JPnFW0). - High altitude pulmonary edema (HAPE): inspiration of air with a low oxygen tension (e.g. exposure to high altitude), which leads to acute constriction of pulmonary arterial blood vessels, thus elevating pulmonary artery pressure (PAP), and forcing the right ventricle to pump against increased vascular resistance. The resulting hydrostatic pressure on the pulmonary microvasculature leads to increased fluid extravasation into the lung parenchyma. Treatments typically aimed at lowering pulmonary pressures include vasodilators such as prostaglandin pathway agonists, phosphodiesterase inhibitors and other modulators of the nitric oxide (NO) signaling pathway, as well as, calcium channel blockers, glucocorticoids, and endothelin receptor antagonists – although they may have limited efficacy as rely on systemic circulation, which as limited in constricted pulmonary vessels. HAPE fits with the dry cough, dyspnea, myalgia, diarrhea, headaches as well. - If patients are ventilated based on recommendations for ARDS (low tidal volume/high PEEP strategies that are based on the ARDSnet data and other studies) but do not have a true ARDS, this could lead to many of the late decompensation due to ventilator induced lung injury. High PEEP could over distend alveoli and increasing pulmonary vascular resistance, leading to iatrogenic cor pulmonale, reduced cardiac output, etc. --> In a crisis mode, physicians, who don’t typically manage ventilators are just executing protocols and would not recognize the subtle differences in lung compliance/lung damage. Italian ICU recs: start with tidal volume of 8 cc/kg and relatively low PEEP, and titrate FiO2 to achieve target saturation 92-95%. #4: Physicians describe across the world what they pick up in their outpatient office: “silent” hypoxia in rest or minimal exertion in many asymptomatic patients. #5: New publications shed more light on COVID-19 structure and binding domains: The spike proteins (S) of SARS-CoV-2, ORF8 and ORF3a proteins, are significantly different from other known SARS-like corona viruses and only weakly binds to the ACE2 receptor compared to SARS corona virus (PMID: 32007145, 31996437, and the one quoted here https:///articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173). Structural studies suggest that E2 glycoprotein and envelope protein of the novel corona virus could bind well to porphyrins. Therefore, the coron avirus may also directly penetrate the human cell membrane through porphyrin binding and cause robust infection. S protein ORF8 and surface glycoprotein in modelling showed that the virus could combine with porphyrin to form a complex, while orf1ab, ORF10, ORF3a coordinately attack the heme on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin. This will result in decreased oxygen carrying capacity and could explain the clinically seen silent hypoxia. #6: Minor, otherwise clinically irrelevant variations of the Hgb B chains, could explain the difference in susceptibility and fatality, and why certain families have so many family members with severe outcome. Also, probably the initial viral load has lot to do with ability of heme to compensate and the immune system to mount an immune response. #7: Chloroquine is also a commonly used drug for treating porphyria and may help to correct abnormal heme metabolism. HAPE type of clinical picture initially could be result of low oxygen tension and we should consider using drugs that help to correct this and improve O2 delivery. Further lung injury may occur due to the secondary effect of intense inflammatory response due to the inability to exchange carbon dioxide and oxygen frequently, the accumulated free iron and ROS, plus the inadequate ventilation support geared toward treating “ARDS”. Patients may be able to initially compensate with elevated Hgb (which could decrease later with viral load), but with time they will have increased ferritin (trying to bind the iron), ESR, LDH and all the classic lab findings. #8: AI algorithm also showed that the 3 factors associated with the worse outcome were: mildly elevated LFT, increased Hgb and severe myalgia. Heme is also present in myoglobin, cytochrome, peroxidase, catalase, NOS, and one could suspect that SARS-CoV2 may also interacts with these systems, thus and could cause the liver and endothelial cell damage as well. How much of a role the ACE2 receptor has in this with the weak binding of the virus in this still unknown. Vitamin C and NAC are powerful antioxidants and could help binding ROS. #9: Clinically decompensating patients appear to have extensive microvascular thrombosis and end organ failure, which is a downstream effect of a dysregulated inflammatory response and robust activation of the innate immune system and complements, thus transient therapeutic anticoagulation helps to keep the balance, but just like the lung injury, it is probably not the primary underlying mechanism of how the virus destroys the susceptible human body. |
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