Update Dec. 29, 2020:

On Sept. 10, 2020 the journal Haematologica Vol. 105(12):2769-2773 reported in “No evidence of hemoglobin damage by SARS-CoV-2 infection” essentially refuting some of the theories outlined below. The report found:

…patients with COVID-19 do not exhibit any hemolytic anemia or a shift in the normal hemoglobin-oxygen dissociation curve. We therefore conclude that COVID-19 does not impact oxygen delivery through a mechanism involving red cell hemolysis and subsequent removal of iron from the heme prosthetic group in hemoglobin.

Haematologica Vol. 105(12):2769-2773 (Sept. 10, 2020) at 2769 (link).

However, other studies do support the proposition that SARS-CoV-2:

…interacts with hemoglobin molecules on the erythrocyte through ACE2, CD147, and CD26 receptors. This viral-hemoglobin interaction will cause the virus to attack the heme on the 1-beta chain of hemoglobin and causing hemolysis….

…SARS-CoV-2 may mimic the action of hepcidin which increases circulating and tissue ferritin (affecting liver, spleen, bone marrow, and muscles mainly), while inducing serum iron deficiency and lack of hemoglobin, by consequence. The resulting hyperferritinemia will give rise to ferroptosis, with high oxidative stress and lipoperoxidation that can precipitate the inflammatory/immune over-response (cytokine storm) and causing a severe outcome of the disease

Cavezzi A., Troiani E., Corrao S. COVID-19: hemoglobin, iron, and hypoxia beyond inflammation. A narrative review. Clinical Pract. 2020;10(2):1271. doi: 10.4081/cp.2020.1271. (link)

Accordingly, COVID-19 still remains a “moving target” for study and it is challenging at this time to find any one theory authoritative.

Respiratory distress is common in COVID-19 patients which may result from an attack on red blood cell hemoglobin. Researchers at Sichuan University in China published research April 27th 2020 relating to computer modeling of the way that COVID-19 proteins interact with red blood cells. Red blood cells carry oxygen to the body and they take carbon dioxide away. They are a necessary component in respiration.

How COVID-19 may cause respiratory distress by an attack on hemoglobin.

COVID-19 Disrupts Hemoglobin

COVID-19 proteins pull the iron molecule off the hemoglobin. This results in of the molecule becoming porphyrin. This takes that iron away. When the iron is gone, no oxygen can combine to it. The COVID-19 protein then bonds to the porphyrin (hemoglobin without iron). Thus, the body cannot access the hemoglobin. When this happens, the patient succumbs to respiratory distress. Effectively, the patient is suffocating from a lack of oxygen.

Hemoglobin molecule.
Hemoglobin and heme group

High Iron Creates Toxicity in Blood

Both the elevated iron in the blood stream and the elevated carbon dioxide create toxicity that that causes organ failure. This can result in death in some extreme cases. Researchers performing the computer modeling also looked at 99 COVID-19 patients who had severe pneumonia. They found the patients’ hemoglobin profiles had low hemoglobin. This is consistent with their computer modeling that COVID-19 attacks to hemoglobin to cause respiratory distress. They also found the patients had higher number of iron ions in the bloodstream. Furthermore, there were high levels of carbon dioxide and disassociated oxygen. Thus, the infection creates this toxic environment in the bloodstream.

There are higher rates of infection of COVID-19 with people with type A blood over type O blood. The topologies of the type A and type B modules are different. Type A blood may form an easier path way for these COVID-19 protein to interfere with the hemoglobin.

Why Anti-Malaria Drugs Might be Effective

Another observation is that malaria is caused by plasmodium which actually enters into the red blood cell and causes of the same type of respiratory distress as COVID-19. Therefore, if COVID-19 binds to hemoglobin, it is logical that certain antimalarial drugs show some therapeutic efficacy such as hydroxychloroquine. This research is preliminary. Its computer modeling and study-based evidence is at an early stage. However, it’s interesting to see that the COVID-19 pathway, if it is in working in this way, would explain why so many patients succumb to respiratory distress from the attack on hemoglobin. With this emerging knowledge, treatment and prevention might be possible.

Anton Hopen

U.S. Patent Attorney with smithhopen.com.