Infection of Immature Red Blood Cells May Help Explain Low Oxygen Levels in COVID-19 Patients

Infection of Immature Red Blood Cells May Help Explain Low Oxygen Levels in COVID-19 Patients

College of Alberta researchers discover SARS-CoV-2 infects immature purple blood cells, decreasing oxygen in the blood and impairing immune response.

A brand new research revealed in the journal Stem Cell Experiences by College of Alberta researchers is shedding mild on why many COVID-19 sufferers, even these not in the hospital, are affected by hypoxia—a probably harmful situation in which there’s decreased oxygenation in the physique’s tissues. The research additionally exhibits why the anti-inflammatory drug dexamethasone has been an efficient remedy for these with the virus.

“Low blood-oxygen ranges have been a major downside in COVID-19 sufferers,” mentioned research lead Shokrollah Elahi, affiliate professor in the School of Drugs & Dentistry. “As a result of of that, we thought one potential mechanism is likely to be that COVID-19 impacts purple blood cell manufacturing.”

Within the research, Elahi and his group examined the blood of 128 sufferers with COVID-19. The sufferers included those that had been critically in poor health and admitted to the ICU, those that had reasonable signs and had been admitted to the hospital, and people who had a light model of the illness and solely spent a number of hours in the hospital. The researchers discovered that, because the illness grew to become extra extreme, extra immature purple blood cells flooded into blood circulation, typically making up as a lot as 60 p.c of the overall cells in the blood. By comparability, immature purple blood cells make up lower than one p.c, or none in any respect, in a wholesome particular person’s blood.

Shokrollah Elahi led new analysis that sheds mild on why many COVID-19 sufferers have low ranges of oxygen in their blood, and why the anti-inflammatory drug dexamethasone works to deal with the doubtless harmful situation. Credit score: College of Alberta

“Immature purple blood cells reside in the bone marrow and we don’t usually see them in blood circulation,” defined Elahi, who can be a member of the Ladies and Kids’s Well being Analysis Institute and the Most cancers Analysis Institute of Northern Alberta. “This means that the virus is impacting the supply of these cells. In consequence, and to compensate for the depletion of wholesome immature purple blood cells, the physique is producing considerably extra of them in order to supply sufficient oxygen for the physique.”

The issue is that immature purple blood cells don’t transport oxygen—solely mature purple blood cells do. The second problem is that immature purple blood cells are extremely vulnerable to COVID-19 an infection. As immature purple blood cells are attacked and destroyed by the virus, the physique is unable to switch mature purple blood cells—which solely dwell for about 120 days—and the power to move oxygen in the bloodstream is diminished.

The query was how the virus infects the immature purple blood cells. Elahi, recognized for his prior work , started by investigating whether or not the immature purple blood cells have receptors for SARS-CoV-2. After a sequence of research, Elahi’s group was the primary in the world to show that immature purple blood cells expressed the receptor ACE2 and a co-receptor, TMPRSS2, which allowed SARS-CoV-2 to contaminate them.

Working in conjunction with the lab of virologist Lorne Tyrrell on the U of A’s Li Ka Shing Institute of Virology, the group carried out investigative an infection testing with immature purple blood cells from COVID-19 sufferers and proved these cells obtained contaminated with the SARS-CoV-2 virus. 

“These findings are thrilling but additionally present two vital penalties,” Elahi mentioned. “First, immature purple blood cells are the cells being contaminated by the virus, and when the virus kills them, it forces the physique to attempt to meet the oxygen provide necessities by pumping extra immature purple blood cells out of the bone marrow. However that simply creates extra targets for the virus.

“Second, immature purple blood cells are literally potent immunosuppressive cells; they suppress antibody manufacturing and so they suppress T-cell immunity towards the virus, making your entire scenario worse. So in this research, we’ve demonstrated that extra immature purple blood cells imply a weaker immune response towards the virus.”

Following the invention that immature purple blood cells have receptors that enable them to develop into contaminated by the coronavirus, Elahi’s group then started testing varied medication to see whether or not they might cut back immature purple blood cells’ susceptibility to the virus.

“We tried the anti-inflammatory drug dexamethasone, which we knew helped to scale back mortality and the length of the illness in COVID-19 sufferers, and we discovered a major discount in the an infection of immature purple blood cells,” mentioned Elahi.

When the group started exploring why dexamethasone had such an impact, they discovered two potential mechanisms. First, dexamethasone suppresses the response of the ACE2 and TMPRSS2 receptors to SARS-CoV-2 in immature purple blood cells, decreasing the alternatives for an infection. Second, dexamethasone will increase the speed at which the immature purple blood cells mature, serving to the cells shed their nuclei quicker. With out the nuclei, the virus has nowhere to copy.

Fortunately, placing Elahi’s findings into observe doesn’t require vital modifications in the way in which COVID-19 sufferers are being handled now. 

“For the previous 12 months, dexamethasone has been broadly used in COVID-19 remedy, however there wasn’t understanding as to why or the way it labored,” Elahi mentioned. “So we’re not repurposing or introducing a brand new treatment; we’re offering a mechanism that explains why sufferers profit from the drug.”

Reference: “Erythroid precursors and progenitors suppress adaptive immunity and get invaded by SARS-CoV-2” by Shima Shahbaz, Lai Xu, Mohammed Osman, Wendy Sligl, Justin Shields, Michael Joyce, D. Lorne Tyrrell, Olaide Oyegbami and Shokrollah Elahi, 11 May 2021, Stem Cell Experiences.

Elahi famous that Wendy Sligl and Mohammed Osman had a vital function in recruiting COVID-19 sufferers for the research. The analysis was supported by Quick Grants, the Canadian Institutes of Well being Analysis and a grant from the Li Ka Shing Institute of Virology.

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