Some feedback on that article:
Jennifer L Kasten, MD, MSc, MSc
COVID-19 4/8: 1) Debunking the "COVID had us all fooled" hemoglobin theory; 2) British NHS cancels 3.5 million inferior-quality Chinese antibody tests.
Firstly, many have read an alternative physiologic mechanism of the coronavirus which has been circulating. The theory was originally published on Medium by a non-MD, non-physiologist; a self-titled "professional disrupter" called Andrew Gaiziunas (AKA "libertymavenstock"), who predominantly is on the internet as a cryptocurrency enthusiast but who happened to read a single non-peer reviewed journal article about SARS-CoV-2 inhibiting human heme synthesis, an education which he felt was sufficient to permit him to comment.
Let's start with the original paper. It involved computer analysis of the predicted structure of the virus' proteins, in three dimensions. (Computer simulation is a common technique in the field of proteomics). The authors noticed, wow, it looks like the structure of a couple of the surface proteins could "dock" with the heme synthesis mechanism human red blood cells employ. "Could" being the operative word- this has never been observed, as the virus is not found in human blood except rarely in ultra-highly-infected people. The authors quite inappropriately titled their paper "COVID-19 Attacks the 1-Beta Chain..." instead of "A couple of proteins in this virus could theoretically bind with the 1-beta chain.. based on our structural simulation."
So, the Gaiziunas piece started from the assumption that this was scientific fact instead of an extremely theoretical, unproven, unlikely assertion. He was then off to the races. His main premise is that basically COVID-19 isn't a primary respiratory disease, it's a blood disease. It causes organ failure of all organs, not just the lungs, at the same time, and that's what kills people. He asserts they don't have ARDS, but instead red blood cells release maverick, rogue radical oxygen species which causes unmitigated tissue damage.
There is no evidence for any of this, and if anyone took it seriously (treating COVID with blood transfusions instead of respiratory support) it would be extremely dangerous. Let's start: we pathologists can visualize the virus, with our eyes and our light & electron microscopes, infecting the Type 2 pneumocytes of the lungs, along with the cells lining the respiratory tree and associated mucinous glands. We know the virus enters these cells via its spike protein and the ACE receptor. And we also know the virus is generally never found in blood. Unlike the lung cells, we cannot see it in human red blood cells, though we've looked (out of interest in this theory a few people have tried hemoglobin electrophoresis and looked carefully at peripheral smears, and came up with nothing).
We can also see ARDS- there is a specific cascade of visible changes, including the filling of the airspaces with fluid which eventually coalesce into sticky coatings called hyaline membranes. I will attach a nice photo from Xiao et al of the lung pathology in COVID patients to this post, which include virus in the cells. The hyaline membranes coat the gas-exchange part of the lungs, making gas exchange difficult and sending the infected patient teetering off into respiratory failure. That being said- apart from him, there is some interest generated in alternative ventilatory strategies for COVID, because the patients do seem to tolerate hypoxemia (lower blood oxygen saturation) better than other respiratory failure patients, so some critical care doctors are letting them "go lower" to avoid intubation than they would usually be comfortable with.
I want to stress that anyone can come up with a good idea. The fact that Andrew Gaiziunas doesn't have a relevant background doesn't mean that his idea, if reasonable or interesting, shouldn't be considered. But it is rather fun to point out the howlers:
- he describes "high-pressure intubation" instead of mechanical ventilation
- he refers to the malaria parasite as "bacteria"
- he states confidently that ground-glass opacities on CT scan "are always bilateral" [no] in COVID and that this fact is somehow supportive of his theory
- he states the kidneys make erythropoietin which causes an acutely detectable rise in hemoglobin, in a matter of hours (takes weeks
- he states the acute liver damage in multi-system organ failure is due to iron scavenging (takes years)
2) I've written before about poor-quality tests with hasty/improper/skipped validation data and poor cross-reactivity. The damage to the public, if bad tests with lots of false positives due to reacting with "common cold" coronaviruses, is considerable. Britain had made widescale population-level antibody testing a cornerstone of its control & re-entry strategy, but returned the 3.5 million bad tests to China. Matt Hancock, Health Secretary and COVID patient, rightly said "no test is better than a bad test."
too bad, it had the truthiness to it
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