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The impact of hypoxia on B cells in COVID-19 by Prasanti Kotagiri; Federica Mescia; Aimee L. Hanson; Lorinda Turner; Laura Bergamaschi; Ana Peñalver; Nathan Richoz; Stephen D. Moore; Brian M. Ortmann; Benjamin J. Dunmore; Michael D. Morgan; Zewen Kelvin Tuong; Berthold Göttgens; Mark Toshner; Christoph Hess; Patrick. H. Maxwell; Menna. R. Clatworthy; James A. Nathan; John R. Bradley; Paul A. Lyons; Natalie Burrows; Kenneth G.C. Smith is a Medicine article available to read on EtoBox.

What is The impact of hypoxia on B cells in COVID-19 about?

## Summary ## Background Prominent early features of COVID-19 include severe, often clinically silent, hypoxia and a pronounced reduction in B cells, the latter important in defence against SARS-CoV-2. This presentation resembles the phenotype of mice with VHL-deficient B cells, in which Hypoxia-Inducible Factors are constitutively active, suggesting hypoxia might drive B cell abnormalities in COVID-19. ## Methods Detailed B cell phenotyping was undertaken by flow-cytometry on longitudinal samples from patients with COVID-19 across a range of severities (NIHR Cambridge BioResource). The impact of hypoxia on the transcriptome was assessed by single-cell and whole blood RNA sequencing analysis. The direct effect of hypoxia on B cells was determined through immunisation studies in genetically modified and hypoxia-exposed mice. ## Findings We demonstrate the breadth of early and persistent defects in B cell subsets in moderate/severe COVID-19, including reduced marginal zone-like, memory and transitional B cells, changes also observed in B cell VHL-deficient mice. These findings were associated with hypoxia-related transcriptional changes in COVID-19 patient B cells, and similar B cell

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Author

Prasanti Kotagiri; Federica Mescia; Aimee L. Hanson; Lorinda Turner; Laura Bergamaschi; Ana Peñalver; Nathan Richoz; Stephen D. Moore; Brian M. Ortmann; Benjamin J. Dunmore; Michael D. Morgan; Zewen Kelvin Tuong; Berthold Göttgens; Mark Toshner; Christoph Hess; Patrick. H. Maxwell; Menna. R. Clatworthy; James A. Nathan; John R. Bradley; Paul A. Lyons; Natalie Burrows; Kenneth G.C. Smith

Publisher

Elsevier BV

Published

2022

Language

EN

Field

Medicine (Life Sciences)