The COVID-19 hemoglobin hypothesis has other problems. In addition to Dr. Amdahl’s analysis, the hemoglobin preprint has a catastrophic error.
RBCs do not have ACE2 receptors on their surface normally so there is no obvious mechanism for entry. In addition, mature red blood cells lack ribosomes, so it would be impossible for the virus to reproduce inside them. This would mean that even if there was a way for the virus to enter RBCs, and extreme viremia granting entry, these proteins described (surface glycoprotein, ORF10, ORF8, ORF1ab, ORF3a) would not be present with the exception of the surface glycoprotein. They are synthesized inside infected cells, and don’t travel with the virus.
So that means only the surface glycoprotein would be a possible candidate. I’m not exactly sure what Liu and Li are talking about there because there is the spike, membrane, and envelope proteins that are all on the surface, stabilizing the bubble of cell membrane.
Hemoglobin is protected inside of the RBC. And the amounts of virus that would be able to enter an RBC would be pretty low. 1 in 100 by a purely geometric mechanism is high. The rule of thumb for large molecules passing the blood brain barrier is about 1 in 1000. (Yes, I know that’s not the same thing, but I’m trying to have some basis for an estimate, and large molecules like antibodies are seen interior to neurons and glial cells after passing the BBB. Best I can do, and doubtless way too generous.)
One RBC has about 300 million hemoglobin molecules [1] So if the virus could enter, to get a 50% reduction in ability to transport oxygen would require 150 million x 25 trillion RBCs in a body = 3.75×1⁰²¹. That’s a huge number. If we assume that each virus has a mass between 10E-18 and 10E–19 kg [2,3] that gives us between 375 and 3750 kilograms of virus, which is quite impossible. That would be between 8250 and 825 pounds of virus in a patient weighing maybe 70 kg.
Even if we presume that each virus entering an RBC (without a means to do so) can bind to 50 hemoglobin molecules, and thereby displace the iron ion, that would still be between 165 and 16.5 pounds of virus inside of RBCs in the blood stream to cut carrying capacity by half.
But we haven’t corrected for our lack of an entry mechanism. So if we assume that a wildly high estimated 1 in 100 viruses manages to get inside an RBC, that would mean the real mass of virus in blood would be 100 times higher. So at minimum 1650 pounds of virus would be needed to accomplish a 50% O2 reduction. If we use the BBB rule of thumb of 1 in 1000 viruses, then we are saying 16,500 pounds of virus would need to be present. This latter is virtually certain to be far too low a ratio.
Then we have the matter of where SARS-CoV-2 is found. It’s mostly rare in the bloodstream by PCR. It populates the respiratory tract, specifically the epithelial cells [4]. Damage those cells enough and that will seal off the O2 permeability quite well enough.
1. https://opentextbc.ca/anatomyandphysiology/chapter/18-3-erythrocytes/
2. https://pubmed.ncbi.nlm.nih.gov/20798312/
3. https://bionumbers.hms.harvard.edu/bionumber.aspx?&id=101667&ver=10
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081173/
