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This paper appears to yield a number of VERY USEFUL hypotheses and treatment for critical patients if true:
https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173
(1/n) https://twitter.com/friedberg/status/1244098769206923264
https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173
(1/n) https://twitter.com/friedberg/status/1244098769206923264
Using computational analysis (modeling the behavior of a molecule in a computer), they've worked out the probable mechanism by which SARS-nCov-2 wreaks havoc on patients, as well as why chloroquine and favipiravir seem to work.
Here's what I've figured out:
Here's what I've figured out:
Inside our red blood cells, there is a molecule called hemoglobin, which contains heme groups. Each heme group is a molecular "ring" (called a porphyrin) that can hold an iron (Fe) ion inside.
Having an iron ion inside is what allows this heme to carry O2 (and CO2) in our blood.
Having an iron ion inside is what allows this heme to carry O2 (and CO2) in our blood.
Red blood cells with hemoglobin inside pick up O2 on the heme groups as they pass through our lungs, and can also carry back CO2 to be exchanged again for O2. This is how our bodies move O2 to our tissues and remove CO2 waste products, i.e. "cardiovascular."
The virus's RNA also codes for a number of non-structural proteins. These are pieces that get made during viral replication but aren't part of the main virus particle.
Many viruses have these; they're like helper proteins that facilitate things that the virus does.
Many viruses have these; they're like helper proteins that facilitate things that the virus does.
The paper modeled these and found that the proteins "collaborate" to knock iron ions out of heme groups (HBB) and replace them with one of the proteins.
This makes the red blood cell unable to transport O2 and CO2.
This makes the red blood cell unable to transport O2 and CO2.
If the computer modeling is right, it shows that the virus hijacks our [red] blood [cells] and makes it unable to carry O2 to a patient's tissues/organs, and likewise unable to carry CO2 out of them.
This would lead to organ and tissue death, roughly in the same way as if a patient were being suffocated.
Even when a patient can breath (fill lungs with air), the oxygen isn't getting to the cells in their body.
Even when a patient can breath (fill lungs with air), the oxygen isn't getting to the cells in their body.
The inflammation in the lungs results from the lungs not being able to perform the oxygen/CO2 exchange, and would therefore appear to be a SECONDARY result of the hijacking of the blood.
The lungs not working is a result of lack of O2 in blood, not the cause of it.
The lungs not working is a result of lack of O2 in blood, not the cause of it.
The paper models the behavior of chloroquine and faviparavir as well, which appear to bind to the non-structural viral proteins that hijack the heme groups, thus inhibiting them from knocking out the iron and wrecking the O2-carrying ability of the red blood cells.
This also explains the observation made by various ER docs (incl this one in New Orleans) that patients tend to have elevated ferritin: ferritin is used to store excess iron. If a lot of iron is knocked out of heme groups and floating around, the body produces more ferritin:
If true, this may mean a few things:
1. Starting drug treatment while symptoms are mild keeps virus from hijacking too much blood, enabling a still-healthy body to mount an immune response.
Explains why early drug treatment (first week of symptoms) is often successful.
1. Starting drug treatment while symptoms are mild keeps virus from hijacking too much blood, enabling a still-healthy body to mount an immune response.
Explains why early drug treatment (first week of symptoms) is often successful.
2. Drug treatment and intubation once patient is critical will rarely work because tissues/organs are already damaged, blood can't carry O2, and the body is too weak to produce new red blood cells able to carry Fe (and thus oxygen/CO2) even if drugs inhibit more hijacking.
3. Thus: start severe patients on drug treatment upon hospital intake to suppress further hijacking of blood by the virus, then give them a blood transfusion of new red blood cells immediately that are unhijacked.
If all this is true, we would see rapid patient improvement.
If all this is true, we would see rapid patient improvement.
(i.e. this theory should be very testable)
Also, if it's true, we're gonna need a lot of blood donations.
So far as I know, there are no studies where we've tried transfusing blood from a patient who HASN'T had or recovered from COVID-19:
Also, if it's true, we're gonna need a lot of blood donations.
So far as I know, there are no studies where we've tried transfusing blood from a patient who HASN'T had or recovered from COVID-19:
https://jamanetwork.com/journals/jama/fullarticle/2763983
In this one, we transfused plasma (and antibodies) but not heme. But it was done 3rd week with no control group, it's of limited conclusiveness.
In this one, we transfused plasma (and antibodies) but not heme. But it was done 3rd week with no control group, it's of limited conclusiveness.
https://www.click2houston.com/news/local/2020/03/29/houston-methodist-first-in-nation-to-be-approved-by-fda-to-transfuse-donated-plasma-from-recovered-covid-19-patient/
Houston Methodist has been approved to do blood plasma transfusion therapy, but "the FDA must approve each patient using the donated convalescent serum" WHICH IS INSANE by the way.
Houston Methodist has been approved to do blood plasma transfusion therapy, but "the FDA must approve each patient using the donated convalescent serum" WHICH IS INSANE by the way.
We can verify/disprove this by comparing outcomes between plasma-only and full blood transfusion (and control), or just between blood transfusion vs control (both should be given hydroxy et al).
If anyone knows working ER docs handling incoming severe patients, please transmit.
If anyone knows working ER docs handling incoming severe patients, please transmit.
