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Differential Impact of SARS-CoV-2 Isolates, Namely, the Wuhan Strain, Delta, and Omicron Variants on Erythropoiesis.
Saito, Suguru; Shahbaz, Shima; Sligl, Wendy; Osman, Mohammed; Tyrrell, D Lorne; Elahi, Shokrollah.
  • Saito S; School of Dentistry, Division of Foundational Sciences, University of Albertagrid.17089.37, Edmonton, Alberta, Canada.
  • Shahbaz S; School of Dentistry, Division of Foundational Sciences, University of Albertagrid.17089.37, Edmonton, Alberta, Canada.
  • Sligl W; Department of Critical Care Medicine, University of Albertagrid.17089.37, Edmonton, Alberta, Canada.
  • Osman M; Department of Medicine, Division of Infectious Diseases, University of Albertagrid.17089.37, Edmonton, Alberta, Canada.
  • Tyrrell DL; Department of Medicine, Division of Rheumatology, University of Albertagrid.17089.37, Edmonton, Alberta, Canada.
  • Elahi S; Department of Medical Microbiology and Immunology, University of Albertagrid.17089.37, Edmonton, Alberta, Canada.
Microbiol Spectr ; 10(4): e0173022, 2022 08 31.
Article in English | MEDLINE | ID: covidwho-1986341
ABSTRACT
SARS-CoV-2 variants exhibit different viral transmissibility and disease severity. However, their impact on erythropoiesis has not been investigated. Here, we show SARS-CoV-2 variants differentially affect erythropoiesis. This is illustrated by the abundance of CD71+ erythroid cells (CECs) in the blood circulation of COVID-19 patients infected with the original Wuhan strain followed by the Delta and Omicron variants. We observed the CD45+CECs are the dominant subpopulation of CECs expressing the receptor, ACE2, and coreceptor, TMPRSS2, and thus, can be targeted by SARS-CoV-2. Also, we found CECs exhibit immunosuppressive properties, specifically CD45+CECs are the dominant immunosuppressive cells and via reactive oxygen species (ROS) and arginase I expression can impair CD8+ T cell functions. In agreement, we observed CECs suppress CD8+ T cell effector (e.g., Granzyme B expression and degranulation capacity [CD107]), which was partially but significantly reversed with l-arginine supplementation. In light of the enriched frequency of CECs, in particular, CD45+CECs in patients infected with the original (Wuhan) strain, we believe this strain has a more prominent impact on hematopoiesis compared with the Delta and Omicron variants. Therefore, our study provides an important insight into the differential impact of SARS-CoV-2 variants on erythropoiesis in COVID-19 patients. IMPORTANCE Silent hypoxia has been the hallmark of SARS-CoV-2 infection. Red blood cells (RBCs) work as gas cargo delivering oxygen to different tissues. However, their immature counterparts reside in the bone marrow and normally absent in the blood circulation. We show SARS-CoV-2 infection is associated with the emergence of immature RBCs so called CD71+ erythroid cells (CECs) in the blood. In particular, we found these cells were more prevalent in the blood of those infected with the SARS-CoV-2 original strain (Wuhan) followed by the Delta and Omicron variants. This suggests SARS-CoV-2 directly or indirectly impacts RBC production. In agreement, we observed immature RBCs express the receptor (ACE2) and coreceptor (TMPRSS2) for SARS-CoV-2. CECs suppress T cells functions (e.g., Granzyme B and degranulation capacity) in vitro. Therefore, our study provides a novel insight into the differential impact of SARS-CoV-2 variants on erythropoiesis and subsequently the hypoxia commonly observed in COVID-19 patients.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study Topics: Variants Limits: Humans Language: English Journal: Microbiol Spectr Year: 2022 Document Type: Article Affiliation country: Spectrum.01730-22

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study Topics: Variants Limits: Humans Language: English Journal: Microbiol Spectr Year: 2022 Document Type: Article Affiliation country: Spectrum.01730-22