Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19.
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Peer-reviewed
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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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Funder: Royal Australasian College of Physicians
Funder: NIHR
Funder: UKRI
Funder: Chief Scientist Office
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2589-0042
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Medical Research Council (G0900951)
Wellcome Trust (212219/Z/18/Z)
Medical Research Council (MR/S036113/1)
Wellcome Trust (215477/Z/19/Z)
Medical Research Council (MC_PC_17230)
Wellcome Trust (200871/Z/16/Z)
Medical Research Council (MR/W018861/1)
Medical Research Council (G0900951/1)