Effects of Ancestral SARS-CoV-2 versus Variants of Concern Delta and Omicron on Megakaryocyte Activation and Transcriptome

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a hyperreactive platelet phenotype, which is thought to contribute to the high incidence of thrombosis in COVID-19 patients. Mutations of SARS-CoV-2 resulted in several virus variants with differences in transmissibility, infectivity and mortality. This study was designed to investigate how SARS-CoV-2 variants of concern, delta and omicron, affect the transcriptome and function of megakaryocytes (MKs) relative to the ancestral WA1 strain. Human CD34+-derived megakaryocytes from 4 unvaccinated COVID-19 donors were infected with WA1, Delta or Omicron SARS-CoV-2 variants or vehicle control for 24 hours.