https://www.facebook.com/1998386763777604/posts/2682318132051127/ Covid-19 is it really more of an endothelial disorder than a true viral pneumonia? Someone mentioned the other day that these strokes in young people are so rare that it is essentially meaningless. Well it is this type of rare occurrence that sometimes brings huge revelations to a disease. This is going to get complicated but we are going to put all the things we have been discussing together. It’s late and this is complicated so I will try to do this quickly. If I make a mistake, miss something or everyone is confused I can re-explain it later this week. So first let’s review the two types of pneumonia with Covid-19. There are some patients with a traditional wet pneumonia (phenotype H lungs look bad in picture) where the lungs are full of fluid or puss which leads to the traditional acute respiratory distress syndrome (ARDS). Remember this is a problem with not enough air getting into the lungs. When severe this is usually treated with a ventilator using more pressure to push air through the fluid to get oxygen. In response to the low oxygen level where the fluid is located, your lungs will start vasoconstricting (meaning squeezing down like stepping on a water hose) the arteries going to that portion of the lung full of fluid and diverting it to working areas. This hypoxic pulmonary vasoconstriction is normally a great protective mechanism to send blood to the areas that work and keep it away from the areas that don’t work. . However, we now know that more people (over 80%) are presenting with a dry pneumonia (Phenotype L lungs look normal in picture). These patients seem to respond to high flow oxygen rather than a ventilator. These patients are clinically still talking but having very low oxygen levels. As we said before clinically they look more like high altitude sickness than ARDS. So what’s happening in these patients? They are getting low oxygen levels everywhere. This is bad because there is now vasoconstriction throughout all of your lungs. You now have poor circulation to the entire lung. So you have a huge increase in the pulmonary artery pressure. . Their lungs are actually inflating fine but there is poor oxygenation going on. So some doctors are having success treating these patients with high flow nasal cannula oxygen rather than putting them on a ventilator. In fact some even believe using a ventilator may be doing more harm than good, since as much as 88% that go a ventilator never come off. So think about the discussion the other night on endothelial damage. Remember we discussed the virus using the ACE2 receptor in the endothelial cell to enter the cell damaging it. This damage can release Von Willebrands factor and Factor VIII which are procoagulants (means causes clots) into the circulation. The virus also binds to the ACE2 receptor making it ineffective and unable to oppose ACE now. This causes a release of reactive oxygen species (ROS, think free radicals) and angiotensin II to accumulate. ROS sometimes called oxidative stress causes more damage to the endothelial cells, possibly further increasing the risk of thrombosis. Oxidative stress is normally kept in check by angiotensin 1,7 which is now decreased because of the lack of angiotensin converting enzyme (ACE). (See the liver diagram for understanding) So now going back to the enzyme angiotensin II which we talked about last night. Angiotensin II increases the amount of it causing severe pulmonary vasoconstriction, increasing inflammatory cells, fibrosis and possibly pulmonary edema. This is not good!!! (See other diagram) Actually it is very bad, and this along with clots in the alveoli are likely the source of the severe disease in Covid-19. Leading to L type of pneumonia. So remember the other night the ARB’s block (AT1R on diagram) and push the cascade away from angiotensin II towards angiotensin 1,7 and AT2R which actually does the opposite vasodilation. This is good!!! (Also labeled on the diagram) Which is why we said last night they could have a role in treating this disease. This hypothesis actually explains a lot of what we are seeing. Why do some get diarrhea? Well we are knocking out the ACE2 receptors in the gut leading to endothelial damage in the lining of the stomach thus diarrhea. Next all strange rashes in legs like livedo reticularis, vasculitis, petechial rashes or one toe being blue. These are likely inflammation of the blood vessels endothelium and embolic features easily explained now. Why aren’t more people with COPD, asthma and other lung diseases getting severe disease? Well it is not really a lung disease it is endothelial disease instead. We have been asking why this disease is picking on obese, diabetics and people with heart disease? Well we know historically that diabetics and atherosclerosis have increased ROS (think free radicals which damage blood vessels) which causes them to have more heart attacks and strokes. We use ACE/ARB’s in these patients to help stabilize this plaque by increasing angiotensin 1,7 and decreasing these reactive oxygen species. If this is knocked out then an extremely high amount of reactive oxygen species could be causing significant damage in the body. Looks like it is time for me to freshen up on biochemistry so we can look into these pathways more. Or a biochemist like biochemAg97 can help me as it has been a long time since I studied all of these pathways in detail. So questions are will aspirin or anti platelet drugs potentially beneficial like we use post myocardial infarction? I think these are things to look at now that it appears this is more of an endothelial disease not a lung disease. Here is a repost of the supplements we have discussed. Zinc any amount is probably good but take what you can tolerate without making you feel bad up to 40mg. You do not want to be Zinc deficient as it is how many drugs like HCQ work. Quercetin from 250mg up to 1g twice per day Remember this is a Zinc ionophore. Green Tea either drink some or 1 pill per day alternate zinc ionophore N-acetylcysteine (NAC) - 600mg twice per day shown to decrease severity of influenza, improve lung functions and help with mental disorders. Melatonin 1mg to 10mg at night. Take what you can tolerate and what helps you sleep without making you feel drugged or tired in the morning. Vitamin C 250mg to 500mg twice per day. Effects debatable in oral form but IV did help in China. But is proven to strengthen immune system Vitamin D3 Take this for sure if you are deficient and I now recommend taking it as long as your values are not too high. Sleep greater than 8 hours per night As always the information and understanding of COVID-19 is changing rapidly. This information is for education purposes only and you should never make changes to your health without consulting your personal physician. Make a virtual appointment with your physician and discuss your health and the best possible treatment plan for you. It is also important to reiterate that there are no clinically evidence-based integrative prevention or treatment strategies for COVID-19 infection. Let’s all keep praying for all that are ill with this virus in the world. Gig’em!
