Ok. Got it. That makes sense. Read "avidly" and thought it was referring to CO displacing O2.

Interesting, and thank you. I am having nightmare flashbacks to med school and Sleep boards.

Are you proposing a bit of a "double-hit" hypothesis? High ACE-2 concentration in lung alveolar cells leading to pulmonary parenchymal disease upon viral uptake, leading to impaired oxygenation. Plus or minus secondary ARDS, depending on immune response equals more hypoxemia. Second "hit" is O2 hemoglobin binding affecting the tissues peripherally by shifting the curve and "artificially" affecting PO2? Almost as if you took a person with methemoblobinemia to a high altitude? Then mixed in a cytokine storm.

Also, would the presence of high concentration of ACE-2 in vascular endothelium be a third "hit" to your hypothesis? That might also help to explain some of the thromboembolic phenomena that you and others have described, and the higher morbidity and mortality in hypertensive patients than you might otherwise expect (not just a pulmonary process, not your normal viral pneumonia). In that case, you would have underperfused and underoxygenated tissues throughout the body.

Tissue distribution of ACE2 protein, the functional receptor for SARS Coronavirus

Lastly, have you seen any patients on ECMO make a major improvement (or, to help prove your point, make much less of an improvement than you might expect)? Or am I thinking about this incorrectly?

Yes. Exactly my thoughts. We havent used ECMO at all.

My brain is full now. May I go home??

Marcus Aurelius said:

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So let's talk some basic pulmonary physiology here so we can communicate better on this forum. In arterial blood, 98.5% of O2 is bound to hemoglobin Hgb. It contains a porphyrin structure containing iron in its center which binds to O2. 1.5% of O2 dissolved in blood is not bound to Hgb. This is known as PO2. O2 sat % is the amount of hemoglobin with O2 bound to it. With a healthy person this is usually around 99%.

O2 binds to Hgb in the deoxygenated pulmonary arterioles as it is absorbed in the pulmonary alveoli. Hgb carries O2 peripherally thru the arterial blood supply to tissue were it is delivered/unloaded for oxidative phosphorylation or energy metabolism.

The relationship of PO2 to Hgb saturation has been thoroughly described. This is known as the O2/Hgb dissociation curve. Shown above. If one plots PO2 on X-axis and Hgb saturation on Y-axis, there is a sigmoidal shape to the curve. The critical level of PO2 is 60 mm Hg or 90% saturation. Below PO2 60mm Hg there is a precipitous decline in Hgb saturation %. Hence it is why it is so important in oxygen therapy to keep PO2> 60. Above PO2 60, the Hgb saturation curve is flat. Hence there is no need to drive PO2 > 80-90 mm Hg, as Hgb sat % peaks at 100%.

Certain disease states can shift the curve left and right. Shown above. Carboxy Hgb or carbon monoxide poisoning is a classic example of shifting the curve left. Hgb binds more avidly to O2 and less O2 is delivered peripherally to tissues, leading to peripheral ischemia. Sepsis is a classic example of the curve shifting to the right, unloading O2 easier peripherally during stress.

In COVID-19 patients PO2 is low due to pulmonary type 2 cell injury, inflammation and ARDS like physiology as we've discussed. I theorize that if COVID-19 is interfering with porphyrin O2 binding it is doing its damage peripherally in tissues and organs. Not in the lung primarily. Hence shifting the curve left, when it should be shifted right.

Hope that helps to understand.

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God bless you Marcus! I read that stupid article last week and I knew it wasn't right but, since I do not run blood gasses or manage vent patients daily, it was based off my medical school training 1995-99. Thank you for this refresher! I was talking about this with my non-medical wife and specifically said that ICU docs are not making decisions on pulse ox it is ABGs and the virus does not cause a shift in this curve like CO but intrinsic pulmonary injury is the problem.

Your theory would also help explain the disproportionate morbidity and mortality seen in diabetics. Obviously their IL response is delayed and blunted, but peripheral ischemia will be exacerbated where small and medium-sized vascular disease exists.

Didn't the Chinese use ECMO quite a bit for their severe cases? I remember WHO discussion that the amount of ECMO machines the Chinese had used greatly dwarfed most Western countries current capacity.