Acknowledgements: We thank the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Disease (AASLD) for supporting the COVID-Hep and SECURE-Liver registries; S. Marciniak and P. J. Lehner for comments and feedback on the manuscript; I. Goodfellow for providing the viral isolate; M. Wills and S. Clare for all their work ensuring a safe CL-3 working environment; C. Cormie for general lab support; the NIHR Cambridge BRC Cell Phenotyping Hub for their help with flow cytometry and processing of samples; the building staff of the Jeffrey Cheah Biomedical Centre for maintaining the institute open and safe during the period of lockdown; K. Füssel for coordinating the volunteer study and sample collection at the University Medical Centre Hamburg-Eppendorf; J. Hails, K.-I. Nikitopoulou and A. Ford for collecting blood samples; M. Colzani for advising on flow cytometry; A. Wiblin for advising on antibodies; and the Cambridge Biorepository for Translational Medicine for the provision of human tissue used in the study. T.B. was supported by an EASL Juan Rodès PhD fellowship. F.S. was supported by a UKRI Future Leaders fellowship, the Evelyn trust, an NIHR Clinical Lectureship, the Academy of Medical Sciences Starter Grant for Clinical Lecturers, the Addenbrooke’s Charitable Trust and the Rosetrees Trust. In addition, the F.S. laboratory is supported by the Cambridge University Hospitals National Institute for Health Research Biomedical Research Centre and the core support grant from the Wellcome Trust and Medical Research Council (MRC) of the Wellcome–Medical Research Council Cambridge Stem Cell Institute. The L.V. laboratory is funded by the ERC advanced grant New-Chol, the Cambridge University Hospitals National Institute for Health Research Biomedical Research Centre and the core support grant from the Wellcome Trust and MRC of the Wellcome–Medical Research Council Cambridge Stem Cell Institute. M.M., S.F. and G.D. are funded by the NIHR Cambridge Biomedical Research Centre and NIHR AMR Research Capital Funding Scheme (NIHR200640). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. V.L.M. was funded by an MRC Clinical Research Training Fellowship. G.F.M. was funded by a post-doctoral fellowship from the National Institute for Health Research (NIHR) Rare Diseases–Translational Research Collaboration (RD-TRC) and by an MRC Clinical Academic Research Partnership (CARP) award. The UK-PBC Nested Cohort study was funded by an MRC Stratified Medicine award (MR/L001489/1). C.J.R.I. was supported by the Medical Research Council (MC_UU_12014). T.M. is funded by a Wellcome Trust Clinical Research Training Fellowship (102176/B/13/Z). The A.P.D. laboratory was supported by BHF TG/18/4/33770, Wellcome Trust 203814/Z/16/A and Addenbrooke’s Charitable Trust. The COVID-Hep.net registry was supported by the European Association for the Study of the Liver (EASL) and the SECURE-Liver registry was supported by the American Association for the Study of Liver Disease (AASLD). The lung perfusion experiment was supported by the National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation at Newcastle University and the University of Cambridge in partnership with NHS Blood and Transplant (NHSBT). The views expressed are those of the author(s) and not necessarily those of the NIHR, the Department of Health and Social Care or NHSBT. G.B. is funded by the European Reference Network for Hepatological Diseases (ERN RARE LIVER). A.O. acknowledges funding for preclinical research on treatment and prevention of COVID-19 from Unitaid (2020-38-LONGEVITY), the Engineering and Physical Sciences Research Council (EPSRC; EP/R024804/1), the Wellcome Trust (222489/Z/21/Z) and UK Research and Innovation (UKRI; BB/W010801/1). N.J.M. acknowledges funding from the MRC (CSF ref. MR/P008801/1 to N.J.M.), NHSBT (grant ref. WPA15-02 to N.J.M.) and Addenbrooke’s Charitable Trust (grant ref. to 900239 N.J.M.). This research was funded in whole, or in part, by the Wellcome Trust (203151/Z/16/Z, 203151/A/16/Z) and the UKRI Medical Research Council (MC_PC_17230). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.