Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19

Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) Covid BioResource Collaboration

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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.

Original languageEnglish
Pages (from-to)103971
Issue number3
Early online date8 Mar 2022
Publication statusPublished - 18 Mar 2022

Bibliographical note

This work was supported by the NIHR BioResource, the NIHR Cambridge Biomedical Research Centre and the NIHR Cambridge Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. We thank NIHR BioResource volunteers for their participation, and gratefully acknowledge NIHR BioResource centres, NHS Trusts and staff for their contribution. FV plasma assays were performed by the NIHR Cambridge Biochemical Assay Laboratory. The Cambridge University Hospitals Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre. FV constructs were prepared and expressed by Peak Proteins. Neutrophil proteins were characterized at the Mass Spectrometry Facility at the University of Dundee and the QMRI flow cytometry and cell sorting facility. Sequencing was supported by Paul Coupland from the CRUK Cambridge Institute Genomics Core. The graphical abstract was produced using Biorender ( The work was funded by awards from NIHR to the NIHR BioResource and the NIHR Cambridge Biomedical Research Centre, Evelyn Trust, Addenbrooke's Charitable Trust, UKRI/NIHR funding through the UK Coronavirus Immunology Consortium (UK-CIC) and a CSO award (COV/DUN/20/01). KGCS holds a Wellcome Trust Investigator award. BG holds an award from the Aging Biology Foundation Europe to BG. RKG holds a Wellcome Senior Fellowship (WT108082AIA). PK is supported by the Australian and New Zealand Society of Nephrology and the Royal Australasian College of Physicians. SRW holds a Wellcome Trust Senior Clinical Fellowship (209220). ERW holds a Wellcome Clinical Training Fellowship award (108717/Z/15/Z). NM was supported by a DFG Research Fellowship. PFC is a Wellcome Trust Principal Research Fellow (212219/Z/18/Z), and a NIHR Senior Investigator, and receives support from the Medical Research Council (MRC) Mitochondrial Biology Unit, the MRC International Centre for Genomic Medicine in Neuromuscular Disease, the Leverhulme Trust, an MRC research grant, and an Alzheimer's Society Project Grant. JAN holds a Wellcome Trust Senior Research Fellowship (215477/Z/19/Z).

Data Availability Statement

Data and code availability

scRNAseqdata is available through ArrayExpress. The DOI is listed in the key resources table. Whole blood RNAseq is available at the European Genome Archive. The DOI is listed in the key resources table.

De-identified human/patient data are publicly available as of the date of publication. DOI and accession numbers are listed in the key resources table.

This paper does not report original code.

Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.


  • Immunology
  • Microbiology
  • Omics
  • Transcriptomics


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