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The impact of hypoxia on B cells in COVID-19
Prasanti Kotagiri; Federica Mescia; Aimee Hanson; Lorinda Turner; Laura Bergamaschi; Ana Penalver; Nathan Richoz; Stephen Moore; Brian Ortmann; Benjamin Dunmore; Helene Ruffieux; Michael Morgan; Zewen Kelvin Tuong; Rachael Bashford Rogers; Myra Hosmillo; Stephen Baker; Anne Elmer; Ian Goodfellow; Ravindra Gupta; Nathalie Kingston; Paul Lehner; Nicholas Matheson; Sylvia Richardson; Caroline Saunders; Michael Weekes; Berthold Gottgens; Mark Toshner; Christoph Hess; Patrick Maxwell; Menna Clatworthy; James A Nathan; John Bradley; Paul Lyons; Natalie Burrows; Kenneth G C Smith.
Afiliación
  • Prasanti Kotagiri; Cambridge University
  • Federica Mescia; Cambridge University
  • Aimee Hanson; Cambridge University
  • Lorinda Turner; Cambridge University
  • Laura Bergamaschi; Cambridge University
  • Ana Penalver; Cambridge University
  • Nathan Richoz; Cambridge University
  • Stephen Moore; Cambridge University
  • Brian Ortmann; Cambridge University
  • Benjamin Dunmore; Cambridge University
  • Helene Ruffieux; Cambridge University
  • Michael Morgan; Cambridge University
  • Zewen Kelvin Tuong; Cambridge University
  • Rachael Bashford Rogers; Oxford University
  • Myra Hosmillo; Cambridge University
  • Stephen Baker; Cambridge University
  • Anne Elmer; Cambridge University
  • Ian Goodfellow; Cambridge University
  • Ravindra Gupta; Cambridge University
  • Nathalie Kingston; Cambridge University
  • Paul Lehner; Cambridge University
  • Nicholas Matheson; Cambridge University
  • Sylvia Richardson; Cambridge University
  • Caroline Saunders; Cambridge University
  • Michael Weekes; Cambridge University
  • Berthold Gottgens; Cambridge University
  • Mark Toshner; Cambridge University
  • Christoph Hess; Cambridge University
  • Patrick Maxwell; Cambridge University
  • Menna Clatworthy; Cambridge University
  • James A Nathan; Cambridge University
  • John Bradley; Cambridge University
  • Paul Lyons; Cambridge University
  • Natalie Burrows; Cambridge University
  • Kenneth G C Smith; Cambridge University
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21260360
ABSTRACT
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 brought to mind 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. We demonstrated 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 we also observed in B cell VHL-deficient mice. This was corroborated by hypoxia-related transcriptional changes in COVID-19 patients, and by similar B cell abnormalities in mice kept in hypoxic conditions, including reduced marginal zone and germinal center B cells. Thus hypoxia might contribute to B cell pathology in COVID-19, and in other hypoxic states. Through this mechanism it may impact on COVID-19 outcome, and be remediable through early oxygen therapy.
Licencia
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Texto completo: Disponible Colección: Preprints Base de datos: medRxiv Tipo de estudio: Experimental_studies / Estudio pronóstico Idioma: Inglés Año: 2021 Tipo del documento: Preprint
Texto completo: Disponible Colección: Preprints Base de datos: medRxiv Tipo de estudio: Experimental_studies / Estudio pronóstico Idioma: Inglés Año: 2021 Tipo del documento: Preprint
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