Plasma proteomic signature predicts who will get persistent symptoms following SARS-CoV-2 infection
Gabriella Captur,
James C. Moon,
Constantin-Cristian Topriceanu,
George Joy,
Leo Swadling,
Jenny Hallqvist,
Ivan Doykov,
Nina Patel,
Justyna Spiewak,
Tomas Baldwin,
Matt Hamblin,
Katia Menacho,
Marianna Fontana,
Thomas A. Treibel,
Charlotte Manisty,
Ben O'Brien,
Joseph M. Gibbons,
Corrina Pade,
Tim Brooks,
Daniel M. Altmann,
Rosemary J. Boyton,
Áine McKnight,
Mala K. Maini,
Mahdad Noursadeghi,
Kevin Mills,
Wendy E. Heywood
Affiliations
Gabriella Captur
UCL MRC Unit for Lifelong Health and Ageing, 33 Bedford Place, London WC1B 5JU, UK; Institute of Cardiovascular Science, University College London, Gower Street, London WC1E 6BT, UK; The Royal Free Hospital, Center for Inherited Heart Muscle Conditions, Cardiology Department, Pond Street, Hampstead, London NW3 2QG, UK
James C. Moon
Institute of Cardiovascular Science, University College London, Gower Street, London WC1E 6BT, UK; Barts Heart Center, The Cardiovascular Magnetic Resonance Imaging Unit and The Inherited Cardiovascular Diseases Unit, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK
Constantin-Cristian Topriceanu
UCL MRC Unit for Lifelong Health and Ageing, 33 Bedford Place, London WC1B 5JU, UK; Institute of Cardiovascular Science, University College London, Gower Street, London WC1E 6BT, UK
George Joy
Institute of Cardiovascular Science, University College London, Gower Street, London WC1E 6BT, UK; Barts Heart Center, The Cardiovascular Magnetic Resonance Imaging Unit and The Inherited Cardiovascular Diseases Unit, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK
Leo Swadling
Division of Infection and Immunity, University College London, London WC1E 6JF, UK
Jenny Hallqvist
Translational Mass Spectrometry Research Group, UCL Institute of Child Health and Great Ormond Street Hospital, 30 Guilford Street, London WC1N 1EH, UK
Ivan Doykov
Translational Mass Spectrometry Research Group, UCL Institute of Child Health and Great Ormond Street Hospital, 30 Guilford Street, London WC1N 1EH, UK
Nina Patel
Translational Mass Spectrometry Research Group, UCL Institute of Child Health and Great Ormond Street Hospital, 30 Guilford Street, London WC1N 1EH, UK
Justyna Spiewak
Translational Mass Spectrometry Research Group, UCL Institute of Child Health and Great Ormond Street Hospital, 30 Guilford Street, London WC1N 1EH, UK
Tomas Baldwin
Translational Mass Spectrometry Research Group, UCL Institute of Child Health and Great Ormond Street Hospital, 30 Guilford Street, London WC1N 1EH, UK
Matt Hamblin
Barts Heart Center, The Cardiovascular Magnetic Resonance Imaging Unit and The Inherited Cardiovascular Diseases Unit, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK
Katia Menacho
Institute of Cardiovascular Science, University College London, Gower Street, London WC1E 6BT, UK; Barts Heart Center, The Cardiovascular Magnetic Resonance Imaging Unit and The Inherited Cardiovascular Diseases Unit, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK
Marianna Fontana
Institute of Cardiovascular Science, University College London, Gower Street, London WC1E 6BT, UK; The Royal Free Hospital, Cardiac MRI Unit, Pond Street, Hampstead, London NW3 2QG, UK
Thomas A. Treibel
Institute of Cardiovascular Science, University College London, Gower Street, London WC1E 6BT, UK; Barts Heart Center, The Cardiovascular Magnetic Resonance Imaging Unit and The Inherited Cardiovascular Diseases Unit, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK
Charlotte Manisty
Institute of Cardiovascular Science, University College London, Gower Street, London WC1E 6BT, UK; Barts Heart Center, The Cardiovascular Magnetic Resonance Imaging Unit and The Inherited Cardiovascular Diseases Unit, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK
Ben O'Brien
Department of Perioperative Medicine, St. Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK; Department of Cardiac Anesthesiology and Intensive Care Medicine, German Heart Center, Augustenburger Platz 1, 13353 Berlin, Germany; Department of Cardiac Anesthesiology and Intensive Care Medicine, Charité Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Outcomes Research Consortium, Department of Outcomes Research, The Cleveland Clinic, 9500 Euclid Ave P77, Cleveland, OH 44195, USA
Joseph M. Gibbons
Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK
Corrina Pade
Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK
Tim Brooks
National Infection Service, Public Health England, Porton Down, UK
Daniel M. Altmann
Department of Immunology and Inflammation, Imperial College London, London W12 0NN, UK
Rosemary J. Boyton
Department of Infectious Disease, Imperial College London, London SW7 2AZ, UK; Lung Division, Royal Brompton Harefield Hospitals, Guy's and St Thomas’ NHS Foundation Trust, London SW3 6NP, UK
Áine McKnight
Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK
Mala K. Maini
Division of Infection and Immunity, University College London, London WC1E 6JF, UK
Mahdad Noursadeghi
Division of Infection and Immunity, University College London, London WC1E 6JF, UK
Kevin Mills
Translational Mass Spectrometry Research Group, UCL Institute of Child Health and Great Ormond Street Hospital, 30 Guilford Street, London WC1N 1EH, UK
Wendy E. Heywood
Translational Mass Spectrometry Research Group, UCL Institute of Child Health and Great Ormond Street Hospital, 30 Guilford Street, London WC1N 1EH, UK; Corresponding author at: UCL Translational Mass Spectrometry Research Group, Center for Translational Omics, Genetics & Genomic Medicine, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
Summary: Background: The majority of those infected by ancestral Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during the UK first wave (starting March 2020) did not require hospitalisation. Most had a short-lived mild or asymptomatic infection, while others had symptoms that persisted for weeks or months. We hypothesized that the plasma proteome at the time of first infection would reflect differences in the inflammatory response that linked to symptom severity and duration. Methods: We performed a nested longitudinal case-control study and targeted analysis of the plasma proteome of 156 healthcare workers (HCW) with and without lab confirmed SARS-CoV-2 infection. Targeted proteomic multiple-reaction monitoring analysis of 91 pre-selected proteins was undertaken in uninfected healthcare workers at baseline, and in infected healthcare workers serially, from 1 week prior to 6 weeks after their first confirmed SARS-CoV-2 infection. Symptom severity and antibody responses were also tracked. Questionnaires at 6 and 12 months collected data on persistent symptoms. Findings: Within this cohort (median age 39 years, interquartile range 30–47 years), 54 healthcare workers (44% male) had PCR or antibody confirmed infection, with the remaining 102 (38% male) serving as uninfected controls. Following the first confirmed SARS-CoV-2 infection, perturbation of the plasma proteome persisted for up to 6 weeks, tracking symptom severity and antibody responses. Differentially abundant proteins were mostly coordinated around lipid, atherosclerosis and cholesterol metabolism pathways, complement and coagulation cascades, autophagy, and lysosomal function. The proteomic profile at the time of seroconversion associated with persistent symptoms out to 12 months. Data are available via ProteomeXchange with identifier PXD036590. Interpretation: Our findings show that non-severe SARS-CoV-2 infection perturbs the plasma proteome for at least 6 weeks. The plasma proteomic signature at the time of seroconversion has the potential to identify which individuals are more likely to suffer from persistent symptoms related to SARS-CoV-2 infection. Funding information: The COVIDsortium is supported by funding donated by individuals, charitable Trusts, and corporations including Goldman Sachs, Citadel and Citadel Securities, The Guy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from University College London Hospitals (UCLH) Charity. This work was additionally supported by the Translational Mass Spectrometry Research Group and the Biomedical Research Center (BRC) at Great Ormond Street Hospital.
