Longitudinal immune profiling reveals distinct features of COVID-19 pathogenesis

Elizabeth R. Mann, Madhvi Menon, Sean Blandin Knight, Joanne E. Konkel, Christopher Jagger, Tovah N. Shaw, Siddharth Krishnan, Magnus Rattray, Andrew Ustianowski, Nawar Diar Bakerly, Paul Dark, Graham Lord, Angela Simpson, Timothy Felton, Ling Pei Ho, Marc Feldmann, John R. Grainger, Tracy Hussell, Rohan Ahmed, Halima Ali ShuwaMiriam Avery, Katharine Birchall, Oliver Brand, Evelyn Charsley, Alistair Chenery, Christine Chew, Richard Clark, Emma Connolly, Karen Connolly, Simon Dawson, Laura Durrans, Hannah Durrington, Jasmine Egan, Claire Fox, Helen Francis, Miriam Franklin, Susannah Glasgow, Nicola Godfrey, Kathryn J. Gray, Seamus Grundy, Jacinta Guerin, Pamela Hackney, Mudassar Iqbal, Chantelle Hayes, Emma Hardy, Jade Harris, Anu John, Bethany Jolly, Verena Kästele, Saba Khan, Gabriella Lindergard, Sylvia Lui, Lesley Lowe, Alex G. Mathioudakis, Flora A. McClure, Joanne Mitchell, Clare Moizer, Katrina Moore, David Morgan, Stuart Moss, Syed Murtuza Baker, Rob Oliver, Grace Padden, Christina Parkinson, Laurence Pearmain, Mike Phuychareon, Ananya Saha, Barbora Salcman, Nicholas A. Scott, Seema Sharma, Jane Shaw, Joanne Shaw, Elizabeth Shepley, Lara Smith, Simon Stephan, Ruth Stephens, Gael Tavernier, Rhys Tudge, Louis Wareing, Roanna Warren, Thomas Williams, Lisa Willmore, Mehwish Younas, Alex Horsley, Tim Harrison, Joanna Porter, Ratko Djukanovic, Stefan Marciniak, Chris Brightling, Ling Pei Ho, Lorcan McGarvey, Jane Davies

Research output: Contribution to journalArticlepeer-review

Abstract

Background The pathogenesis of COVID-19, caused by a novel strain of coronavirus (SARS-CoV-2), involves a complex host-virus interaction and is characterised by an exaggerated immune response, the specific components of which are poorly understood. Here we report the outcome of a longitudinal immune profiling study in hospitalised patients during the peak of the COVID-19 pandemic in the UK and show the relationship between immune responses and severity of the clinical presentation.

Methods The Coronavirus Immune Response and Clinical Outcomes (CIRCO) study was conducted at four hospitals in Greater Manchester. Patients with SARS-CoV-2 infection, recruited as close to admission as possible, provided peripheral blood samples at enrolment and sequentially thereafter. Fresh samples were assessed for immune cells and proteins in whole blood and serum. Some samples were also stimulated for 3 hours with LPS and analysed for intracellular proteins. Results were stratified based on patient-level data including severity of symptoms and date of reported symptom onset.

Findings Longitudinal analysis showed a very high neutrophil to T cell ratio and abnormal activation of monocytes in the blood, which displayed high levels of the cell cycle marker, Ki67 and low COX-2. These properties all reverted in patient with good outcome. Unexpectedly, multiple aspects of inflammation were diminished as patients progressed in severity and time, even in ITU patients not recovering.

Interpretation This is the first detailed longitudinal analysis of COVID-19 patients of varying severity and outcome, revealing common features and aspects that track with severity. Patients destined for a severe outcome can be identified at admission when still displaying mild-moderate symptoms. We provide clues concerning pathogenesis that should influence clinical trials and therapeutics. Targeting pathways involved in neutrophil and monocyte release from the bone marrow should be tested in patients with COVID-19.

Funding The Kennedy Trust for Rheumatology Research, The Wellcome Trust, The Royal Society, The BBSRC, National Institute for Health Research (NIHR) Biomedical Research Centres (BRC).
Original languageEnglish
Number of pages30
JournalScience Immunology
Volume5
Issue number51
DOIs
Publication statusPublished - 1 Sept 2020

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