The impact of hypoxia on B cells in COVID-19.
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Authors
Kotagiri, Prasanti
Mescia, Federica
Hanson, Aimee L
Turner, Lorinda
Bergamaschi, Laura
Peñalver, Ana
Richoz, Nathan
Moore, Stephen D
Ortmann, Brian M
Dunmore, Benjamin J
Morgan, Michael D
Tuong, Zewen Kelvin
Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration
Göttgens, Berthold
Hess, Christoph
Maxwell, Patrick H
Clatworthy, Menna R
Nathan, James A
Bradley, John R
Lyons, Paul A
Burrows, Natalie
Smith, Kenneth GC
Publication Date
2022-03Journal Title
EBioMedicine
ISSN
2352-3964
Publisher
Elsevier BV
Volume
77
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Kotagiri, P., Mescia, F., Hanson, A. L., Turner, L., Bergamaschi, L., Peñalver, A., Richoz, N., et al. (2022). The impact of hypoxia on B cells in COVID-19.. EBioMedicine, 77 https://doi.org/10.1016/j.ebiom.2022.103878
Description
Funder: Evelyn Trust
Funder: NHSBT
Funder: MRC
Funder: NIHR
Funder: Cambridge University Hospitals NHS Foundation Trust
Abstract
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 abnormalities were seen in mice kept in hypoxic conditions. INTERPRETATION: Hypoxia may contribute to the pronounced and persistent B cell pathology observed in acute COVID-19 pneumonia. Assessment of the impact of early oxygen therapy on these immune defects should be considered, as their correction could contribute to improved outcomes. FUNDING: Evelyn Trust, Addenbrooke's Charitable Trust, UKRI/NIHR, Wellcome Trust.
Keywords
Hypoxia, B cells, Lymphopenia, Covid-19
Sponsorship
Lister Institute of Preventive Medicine (unknown)
Wellcome Trust (215477/Z/19/Z)
Medical Research Council (MR/S036113/1)
Nadace Aging Biology Foundation Europe (7042020)
MRC (MRC--)
Evelyn Trust (20/75)
Wellcome Trust (200871/Z/16/Z)
Medical Research Council (MR/S035842/1)
Department of Health (via National Institute for Health Research (NIHR)) (RP-2017-08-ST2-002)
Medical Research Council (G0900951)
Medical Research Council (MC_PC_17230)
MRC (via University of Birmingham) (MR/V028448/1)
Wellcome Trust (096956/Z/11/Z)
Identifiers
35189575, PMC8856886
External DOI: https://doi.org/10.1016/j.ebiom.2022.103878
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335400
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/
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