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Abstract
The recent SARS-CoV-2 pandemic manifests itself as a mild respiratory tract infection in most individuals, leading to COVID-19 disease. However, in some infected individuals, this can progress to severe pneumonia and acute respiratory distress syndrome (ARDS), leading to multi-organ failure and death. This study explores the proteomic differences between mild, severe, and critical COVID-19 positive patients to further understand the disease progression, identify proteins associated with disease severity, and identify potential therapeutic targets. Blood protein profiling was performed on 59 COVID-19 mild (n = 26), severe (n = 9) or critical (n = 24) cases and 28 controls using the OLINK inflammation, autoimmune, cardiovascular and neurology panels. Differential expression analysis was performed within and between disease groups to generate nine different analyses. From the 368 proteins measured per individual, more than 75% were observed to be significantly perturbed in COVID-19 cases. Six proteins (IL6, CKAP4, Gal-9, IL-1ra, LILRB4 and PD-L1) were identified to be associated with disease severity. The results have been made readily available through an interactive web-based application for instant data exploration and visualization, and can be accessed at https://phidatalab-shiny.rosalind.kcl.ac.uk/COVID19/. Our results demonstrate that dynamic changes in blood proteins associated with disease severity can potentially be used as early biomarkers to monitor disease severity in COVID-19 and serve as potential therapeutic targets.
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1 King’s College London, Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764); King’s College London, NIHR BioResource Centre Maudsley, NIHR Maudsley Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust (SLaM) & Institute of Psychiatry, Psychology and Neuroscience (IoPPN), London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764)
2 University of Gothenburg, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, Göteborg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582); the SAHLGRENSKA Academy at the University of Gothenburg, Sahlgrenska University Hospital, Department of Psychiatry and Neurochemistry, Wallenberg Centre for Molecular and Translational Medicine, Institute of Neuroscience and Physiology, Göteborg, Sweden (GRID:grid.8761.8); King’s College London, Department of Old Age Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764); NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK (GRID:grid.454378.9)
3 King’s College London, Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764); King’s College London, NIHR BioResource Centre Maudsley, NIHR Maudsley Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust (SLaM) & Institute of Psychiatry, Psychology and Neuroscience (IoPPN), London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764); UK Dementia Research Institute at UCL, London, UK (GRID:grid.13097.3c); Health Data Research UK London, University College London, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201); University College London, Institute of Health Informatics, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201); The National Institute for Health Research University College London Hospitals Biomedical Research Centre, University College London, London, UK (GRID:grid.485385.7) (ISNI:0000 0004 0495 5357)
4 Sahlgrenska Academy, University of Gothenburg, Department of Infectious Diseases, Institute of Biomedicine, Gothenburg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582); Region Västra Götaland, Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg, Sweden (GRID:grid.1649.a) (ISNI:000000009445082X)
5 University of Gothenburg, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, Göteborg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582); Sahlgrenska University Hospital, Clinical Neurochemistry Laboratory, Mölndal, Sweden (GRID:grid.1649.a) (ISNI:000000009445082X)
6 University of Gothenburg, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, Göteborg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582); Sahlgrenska University Hospital, Clinical Neurochemistry Laboratory, Mölndal, Sweden (GRID:grid.1649.a) (ISNI:000000009445082X); UCL Institute of Neurology, Department of Neurodegenerative Disease, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201); UK Dementia Research Institute at UCL, London, UK (GRID:grid.83440.3b)