The deadly coronavirus infects immature red blood cells (RBCs), reducing oxygen in the blood and impairing the immune response, say researchers. It adversely impacts the process of replacement of oxygen carrying mature red blood cells in many Covid-19 patients.
The study, published in the journal Stem Cell Reports, sheds light on why many Covid-19 patients, even those not in hospital, are suffering from hypoxia — a potentially dangerous condition in which there is decreased oxygenation in the body’s tissues. The study also shows why anti-inflammatory drug dexamethasone has been an effective treatment for those with the virus.
“Low blood-oxygen levels have been a significant problem in Covid-19 patients,” said study lead Shokrollah Elahi, associate professor in the Faculty of Medicine & Dentistry. “Because of that, we thought one potential mechanism might be that Covid-19 impacts red blood cells production.”
In the study, Elahi and his team examined the blood of 128 patients with Covid-19. The patients included those who were critically ill and admitted to the ICU, those who had moderate symptoms and were admitted to hospital, and those who had a mild version of the disease and only spent a few hours in hospital.
The researchers found that as the disease progresess, more immature RBCs flood into blood circulation, making up as much as 60 per cent of the cells in the blood. Generally, immature RBCs make up less than one per cent, or none at all, in a healthy individual’s blood.
“Immature red blood cells reside in the bone marrow and we do not normally see them in blood circulation,” Elahi explained. “This indicates that the virus is impacting the source of these cells. As a result, and to compensate for the depletion of healthy immature red blood cells, the body is producing significantly more of them in order to provide enough oxygen for the body.”
The problem is that immature red blood cells do not transport oxygen--only mature red blood cells do. The second issue is that immature red blood cells are highly susceptible to Covid-19 infection. As immature red blood cells are attacked and destroyed by the virus, the body is unable to replace mature red blood cells--which only live for about 120 days--and the ability to transport oxygen in the bloodstream is diminished.
The question was how the virus infects the immature red blood cells. Elahi, known for his prior work demonstrating that immature red blood cells made certain cells more susceptible to HIV, began by investigating whether the immature red blood cells have receptors for SARS-CoV-2. After a series of studies, Elahi’s team was the first in the world to demonstrate that immature red blood cells expressed the receptor ACE2 and a co-receptor, TMPRSS2, which allowed SARS-CoV-2 to infect them.
Working in conjunction with the the lab of virologist Lorne Tyrrell at the U of A’s Li Ka Shing Institute of Virology, the team performed investigative infection testing with immature red blood cells from Covid-19 patients and proved these cells got infected with the SARS-CoV-2 virus.