Journal
ISCIENCE
Volume 25, Issue 3, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2022.103971
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Categories
Funding
- NIHR BioResource
- NIHR Cambridge Biomedical Research Centre
- NIHR Cambridge Clinical Research Facility
- CRUK Cambridge Institute Genomics Core
- NIHR
- Evelyn Trust
- Addenbrooke's Charitable Trust
- UKRI/NIHR through the UK Coronavirus Immunology Consortium (UK-CIC)
- CSO award [COV/DUN/20/01]
- Aging Biology Foundation Europe
- Wellcome Senior Fellowship [WT108082AIA]
- Australian and New Zealand Society of Nephrology
- Royal Australasian College of Physicians
- Wellcome Trust [209220]
- Wellcome Clinical Training Fellowship award [108717/Z/15/Z]
- DFG
- Medical Research Council (MRC) Mitochondrial Biology Unit
- MRC International Centre for Genomic Medicine in Neuromuscular Disease
- Leverhulme Trust
- MRC research grant
- Alzheimer's Society Project Grant
- Wellcome Trust Senior Research Fellowship [215477/Z/19/Z]
- Wellcome Trust [108717/Z/15/Z, 215477/Z/19/Z] Funding Source: Wellcome Trust
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The increased expression of Factor V in leukocytes correlates with severe COVID-19 and T-cell lymphopenia. Anticoagulants may suppress the adaptive immune system.
Clotting Factor V (FV) is primarily synthesized in the liver and when cleaved by thrombin forms pro-coagulant Factor Va (FVa). Using whole blood RNAseq and scRNAseq of peripheral blood mononuclear cells, we find that FV mRNA is expressed in leukocytes, and identify neutrophils, monocytes, and T regulatory cells as sources of increased FV in hospitalized patients with COVID-19. Proteomic analysis confirms increased FV in circulating neutrophils in severe COVID-19, and immunofluorescence microscopy identifies FV in lung-infiltrating leukocytes in COVID-19 lung disease. Increased leukocyte FV expression in severe disease correlates with T-cell lymphopenia. Both plasma-derived and a cleavage resistant recombinant FV, but not thrombin cleaved FVa, suppress T-cell proliferation in vitro. Anticoagulants that reduce FV conversion to FVa, including heparin, may have the unintended consequence of suppressing the adaptive immune system.
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