A new study has shed light on why many COVID-19 patients, even those who are not in hospital, suffer from hypoxia.
The study, published in the journal Stem Cell Reports, and conducted by researchers from the University of Alberta, also shows why the anti-inflammatory drug dexamethasone is an effective treatment for those infected with the virus.
The study’s lead author, Shukrullah Elahi, associate professor in the College of Medicine and Dentistry, said: “Low blood oxygen levels have been a major problem in COVID-19 patients. The reason for this, we believe, is that one possible mechanism may be that COVID-19 is affecting red blood cell production.
In the new study, Elahi and his team examined the blood of 128 patients with “Covid-19”. The patients included those who were in a critical condition and admitted to the intensive care unit, those who developed moderate symptoms and were hospitalized, and those who had a mild version of the disease and spent only a few hours in the hospital.
The researchers found that as the disease worsens, immature red blood cells flow into the circulation, sometimes making up as much as 60% of the total cells in the blood. By comparison, immature red blood cells make up less than 1%, or not at all, in a healthy individual’s blood.
“Immature red blood cells are found in the bone marrow and we don’t usually see them in the circulation. This indicates that the virus is affecting the source of these cells. As a result, to compensate for the depletion of healthy, immature red blood cells, the body produces significantly more of them,” Elahi explained. In order to provide enough oxygen to the body.
The problem is that immature red blood cells do not carry oxygen (only mature red blood cells do). The second issue is that immature red blood cells are highly susceptible to COVID-19 infection. When the virus attacks and destroys immature red blood cells, the body is unable to replace mature red blood cells, which only live for 120 days, and the ability to transport oxygen in the bloodstream is diminished.
The question was how the virus infects immature red blood cells.
Elahi, known for his previous work showing that immature red blood cells make certain cells more susceptible to HIV infection, began investigating whether immature red blood cells contained receptors for SARS-CoV-2.
After a series of studies, his team was the first in the world to show that immature red blood cells express the ACE2 receptor and the co-receptor, TMPRSS2, which allowed SARS-CoV-2 to infect them.
Working alongside the laboratory of virologist Lorne Terrell at the University of Albertas Li Ka-Shing Institute of Virology, the team conducted a screening test for infection using immature red blood cells of COVID-19 patients and confirmed that these cells were infected with SARS-CoV-2. .
“These findings are exciting but show two important findings. First, immature red blood cells are the cells infected with the virus, and when the virus kills them, it forces the body to try to meet its oxygen supply requirements by pumping out more immature red blood cells from the bone marrow,” Elahi said. “But that only creates more targets for the virus. And secondly, immature red blood cells are actually active immunosuppressive cells, they suppress antibody production and T-cell immunity to the virus, making the situation worse. So in this study, we showed that more of immature red blood cells means a weak immune response against the virus.”
After discovering that immature red blood cells have receptors that allow them to infect the coronavirus, the research team began testing several drugs to see if they could reduce the exposure of immature red blood cells to the virus.
“We tried the anti-inflammatory drug dexamethasone, which we knew helped reduce mortality and duration of illness in Covid-19 patients, and we found a significant reduction in the infection of immature red blood cells,” Elahi explained.
And when the team set out to explore why dexamethasone might affect dexamethasone, they found two possible mechanisms: First, dexamethasone suppresses the response of ACE2 and TMPRSS2 receptors to SARS-CoV-2 in immature red blood cells, reducing the chances of infection. Second, dexamethasone increases the rate at which immature red blood cells mature, which helps the cells eliminate their nuclei faster. Without the nuclei, the virus has nowhere to multiply.
Source: Medical Express