Megakaryocyte phenotyping in response to SARS-CoV-2 variants

Area of Science:

• Hematology
• Virology
• Immunology

Background:

• SARS-CoV-2 infection is linked to platelet hyperreactivity and thrombosis.
• Different SARS-CoV-2 variants exhibit varying transmissibility, infectivity, and clinical outcomes.

Purpose of the Study:

• To investigate the impact of ancestral SARS-CoV-2 (WA1) and its Delta and Omicron variants on human megakaryocyte (MK) phenotype and transcriptome.
• To assess the correlation between SARS-CoV-2 variants, MK activation, and cytokine profiles in COVID-19 patients.

Main Methods:

• Human CD34+-derived MKs were exposed to WA1, Delta, or Omicron SARS-CoV-2 variants for 24 hours.
• MK activation markers, RNA sequencing, and cytokine release were analyzed.
• Plasma cytokines were measured in hospitalized COVID-19 patients.

Main Results:

• All SARS-CoV-2 variants induced similar increases in classical MK activation markers.
• Distinct transcriptomic changes were observed among the variants, with 60 overlapping genes including CXCL8.
• SARS-CoV-2-exposed MKs showed elevated IL-8 secretion, and higher plasma IL-8 levels were found in COVID-19 patients with thrombotic events or death.

Conclusions:

• Ancestral SARS-CoV-2, Delta, and Omicron variants similarly activate classical MK responses but induce unique transcriptomic alterations.
• Elevated IL-8 levels in COVID-19 patients may serve as a biomarker for platelet hyperreactivity and thrombotic events.