In the following thread I touch on the recent discussion on Covid19 hypoxia/hemoglobinopathy theory, its implications, problems with the proposal, how to test it, and alternative explanatory theories. (1/9)

A recent computational biology preprint publication proposed that non-structural proteins coded for by COVID-19 could bind to hemoglobin and “knock-out” iron atoms, disrupting the ability of red blood cells to carry oxygen. (2/9)

If correct, infected patients would not be able to deliver adequate oxygen to their organs even if able to breathe freely. In this paradigm, hypoxia precedes ARDS instead of the other way around. (3/9)

This proposed model supports the observation that in some ICU patients, the ARDS-like picture looks more like hypoxia-induced high-altitude pulmonary edema (HAPE). This has important treatment implications irrespective of the “hemoglobinopathy” mechanism. (4/9)

But problems with this paper: The iron-knockout theory is based on a series of calculated in-silico docking simulations between viral proteins and free heme molecules. No binding dynamics examined, nor theories put forward on how the viral proteins enter red blood cells. (5/9)

It is not clear if this iron-knockout mechanism might occur to a clinically relevant degree or if merely theoretical. We should be able to directly test this hypothesis using 4 options: (6/9)

1) hemoglobin electrophoresis - to detect if attach of viral particles severely deforming charge of hemoglobin proteins
2) spectrophotometry - to demonstrate the concentration of bound iron-porphyrin structures/show variations in local iron environment or oxidation state (7/9)

3) high-performance liquid chromatography - for more subtle measurements of protein subunit integrity
4) Arterial blood gas (PaO2) vs. Capillary pulse ox (SpO2): Normal PaO2 but desaturated hemoglobin in SpO2 would indicate some degree of hemoglobinopathy (8/9)

MY ASKS:

Have any hematologists performed electrophoresis/ spectrophotometry/ HPLC to look into this structural change of hemoglobin?

Are any ER/ICU docs seeing a notable mismatch between SpO2 and PaO2? What fraction on patients? (9/9)