An Edmonton research team has discovered why people who have contracted COVID-19 tend to have low oxygen levels.
The finding has helped uncover some of the mystery behind how the virus attacks the body and how relentless it can be.
The research suggests symptoms can start with a headache or confusion. There can also be a lack of symptoms until the person ends up in hospital.
Dr. Shok Rolla Elahi’s team studied the blood of 128 COVID-19 patients. Study participants included those who were critically ill and admitted to intensive care, those who had moderate symptoms and were admitted to hospital, and those who had mild symptoms and only spent a few hours in hospital.
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As the disease became more severe, the study found that more immature red blood cells flooded into blood circulation — sometimes making up as much as 60 per cent of total cells in the blood.
However, in a healthy individual’s blood, immature red blood cells made up none or less than one per cent.
“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 research team said there are two primary issues: immature red blood cells do not transport oxygen — only mature red blood cells have that capability — and immature red blood cells are highly susceptible to COVID-19 infection.
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As immature red blood cells are destroyed by the virus, the body is unable to replace mature red blood cells, which live for about 120 days, and the ability to transport oxygen in the bloodstream is hindered.
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Elahi and his team have discovered that immature red blood cells expressed the receptor ACE2 and co-receptor, TMPRSS2, which allows SARS-CoV-2 to infect them.
With the help of virologist Lorne Tyrell, the team conducted infection testing on immature red blood cells from COVID-19 patients, which showed the cells got infected with the SARS-CoV-2 virus.
“These findings are exciting but also show two significant consequences,” Elahi said. “First, immature red blood cells are the cells being infected by the virus, and when the virus kills them, it forces the body to try to meet the oxygen supply requirements by pumping more immature red blood cells out of the bone marrow. But that just creates more targets for the virus.
“Second, immature red blood cells are actually potent immunosuppressive cells; they suppress antibody production and they suppress T-cell immunity against the virus, making the entire situation worse, so in this study, we have demonstrated that more immature red blood cells mean a weaker immune response against the virus.”
Dexamethasone effects
The team also researched why the drug dexamethasone had an effect on the virus and discovered it suppresses the response of the ACE2 and TMPRSS2 receptors to SARS-CoV-2 in immature red blood cells, reducing the opportunity for infection.
The team found the drug also increases the rate at which immature red blood cells mature, helping the cells shed nuclei faster, and without the nuclei, the virus cannot replicate.
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“For the past year, dexamethasone has been widely used in COVID-19 treatment but there wasn’t a good understanding as to why or how it worked,” Elahi said.
“So we are not repurposing or introducing a new medication; we are providing a mechanism that explains why patients benefit from the drug.”
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