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Abstract
Infection with SARS-CoV-2 has highly variable clinical manifestations, ranging from asymptomatic infection through to life-threatening disease. Host whole blood transcriptomics can offer unique insights into the biological processes underpinning infection and disease, as well as severity. We performed whole blood RNA Sequencing of individuals with varying degrees of COVID-19 severity. We used differential expression analysis and pathway enrichment analysis to explore how the blood transcriptome differs between individuals with mild, moderate, and severe COVID-19, performing pairwise comparisons between groups. Increasing COVID-19 severity was characterised by an abundance of inflammatory immune response genes and pathways, including many related to neutrophils and macrophages, in addition to an upregulation of immunoglobulin genes. In this study, for the first time, we show how immunomodulatory treatments commonly administered to COVID-19 patients greatly alter the transcriptome. Our insights into COVID-19 severity reveal the role of immune dysregulation in the progression to severe disease and highlight the need for further research exploring the interplay between SARS-CoV-2 and the inflammatory immune response.
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1 Imperial College London, Section of Paediatric Infectious Disease, Faculty of Medicine, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Imperial College London, Centre for Paediatrics and Child Health, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)
2 Hospital Clínico Universitario de Santiago, Translational Pediatrics and Infectious Diseases, Pediatrics Department, Santiago de Compostela, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945); Universidad de Santiago de Compostela, Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP;), Instituto de Investigación Sanitaria de Santiago, Galicia, Spain (GRID:grid.11794.3a) (ISNI:0000000109410645)
3 Universidad de Santiago de Compostela, Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP;), Instituto de Investigación Sanitaria de Santiago, Galicia, Spain (GRID:grid.11794.3a) (ISNI:0000000109410645); Hospital Clìnico Universitario Santiago de Compostela, Servizo Galego de Saúde, Laboratorio de Inmunologìa, Servicio de Análisis Clìnicos, Galicia, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945)
4 Hospital Clìnico Universitario de Santiago de Compostela, Intensive Medicine Department, Galicia, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945)
5 Hospital Clìnico Universitario de Santiago de Compostela, Pneumology Department, Galicia, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945)
6 Hospital Clìnico Universitario de Santiago de Compostela, Microbiology Department, Galicia, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945)
7 Hospital Clínico Universitario de Santiago de Compostela, Preventive Medicine Department, Galicia, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945)
8 Hospital Clìnico Universitario de Santiago de Compostela, Digestive Department, Galicia, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945)
9 Universidad de Santiago de Compostela, Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP;), Instituto de Investigación Sanitaria de Santiago, Galicia, Spain (GRID:grid.11794.3a) (ISNI:0000000109410645); Hospital Clìnico Universitario de Santiago, Servizo Galego de Saúde, Unidade de Xenética, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, and GenPoB Research Group, Instituto de Investigación Sanitaria (IDIS), Galicia, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945)
10 Hospital Clínico Universitario de Santiago, Santiago de Compostela, Anesthesiology and Resuscitation Service, Galicia, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945)
11 Hospital Clínico Universitario de Santiago, Santiago de Compostela, Internal Medicine Service, Galicia, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945)
12 Universidad de Santiago de Compostela, Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP;), Instituto de Investigación Sanitaria de Santiago, Galicia, Spain (GRID:grid.11794.3a) (ISNI:0000000109410645)
13 Hospital Clínico Universitario de Santiago, Santiago de Compostela, Director of Nursing Processes, Galicia, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945)
14 Hospital Clínico Universitario de Santiago, Translational Pediatrics and Infectious Diseases, Pediatrics Department, Santiago de Compostela, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945)
15 Hospital Clínico Universitario de Santiago, Santiago de Compostela, Manager of the Health Care Area of Santiago de Compostela and Barbanza, Galicia, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945)
16 Hospital Clínico Universitario de Santiago, Santiago de Compostela, Clinical Chemistry Laboratory, Galicia, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945)
17 Hospital Clìnico Universitario de Santiago, Servizo Galego de Saúde, Unidade de Xenética, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, and GenPoB Research Group, Instituto de Investigación Sanitaria (IDIS), Galicia, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945)