Jessica J Manson1,2, Colin Crooks3,4, Meena Naja1,5, Amanda Ledlie1,2, Bethan Goulden1, Trevor Liddle6, Emon Khan1, Puja Mehta1,7, Lucia Martin-Gutierrez1,2, Kirsty E Waddington1,2, George A Robinson1,2,5, Liliana Ribeiro Santos1,2, Eve McLoughlin1,2, Antonia Snell6, Christopher Adeney6, Ina Schim van der Loeff8,9, Kenneth F Baker8,9, Christopher J A Duncan6,9, Aidan T Hanrath6,8,9, B Clare Lendrem9, Anthony De Soyza6,9, Junjie Peng2,5, Hajar J'Bari1, Mandy Greenwood1, Ellie Hawkins1,2, Hannah Peckham1,2,5, Michael Marks10,11, Tommy Rampling12, Akish Luintel10, Bryan Williams13, Michael Brown10, Mervyn Singer14, Joe West3,4, Elizabeth C Jury2, Matthew Collin6,9, Rachel S Tattersall15. 1. Department of Rheumatology, University College London Hospitals National Health Service (NHS) Trust, London, UK. 2. Centre for Rheumatology Research, Division of Medicine, University College London, London, UK. 3. Nottingham Digestive Diseases Centre and NIHR Nottingham Digestive Diseases Biomedical Research Centre, Queens Medical Centre, Nottingham University Hospitals, University of Nottingham, Nottingham, UK. 4. Division of Epidemiology and Public Health, Nottingham City Hospital, University of Nottingham, Nottingham, UK. 5. Centre for Adolescent Rheumatology Versus Arthritis, Division of Medicine, University College London, London, UK. 6. Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. 7. Centre for Inflammation and Tissue Repair, UCL Respiratory, Division of Medicine, University College London, London, UK. 8. NIHR Newcastle Biomedical Research Centre at Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. 9. Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK. 10. Tropical Diseases, Division of Infection and Immunity, University College London Hospitals National Health Service (NHS) Trust, London, UK. 11. Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK. 12. Department of Virology, Division of Infection and Immunity, University College London Hospitals National Health Service (NHS) Trust, London, UK. 13. National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, University College London Hospitals National Health Service (NHS) Trust, London, UK. 14. Bloomsbury Institute for Intensive Care Medicine, University College London, London, UK. 15. Department of Rheumatology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
Abstract
BACKGROUND: A subset of patients with severe COVID-19 develop a hyperinflammatory syndrome, which might contribute to morbidity and mortality. This study explores a specific phenotype of COVID-19-associated hyperinflammation (COV-HI), and its associations with escalation of respiratory support and survival. METHODS: In this retrospective cohort study, we enrolled consecutive inpatients (aged ≥18 years) admitted to University College London Hospitals and Newcastle upon Tyne Hospitals in the UK with PCR-confirmed COVID-19 during the first wave of community-acquired infection. Demographic data, laboratory tests, and clinical status were recorded from the day of admission until death or discharge, with a minimum follow-up time of 28 days. We defined COV-HI as a C-reactive protein concentration greater than 150 mg/L or doubling within 24 h from greater than 50 mg/L, or a ferritin concentration greater than 1500 μg/L. Respiratory support was categorised as oxygen only, non-invasive ventilation, and intubation. Initial and repeated measures of hyperinflammation were evaluated in relation to the next-day risk of death or need for escalation of respiratory support (as a combined endpoint), using a multi-level logistic regression model. FINDINGS: We included 269 patients admitted to one of the study hospitals between March 1 and March 31, 2020, among whom 178 (66%) were eligible for escalation of respiratory support and 91 (34%) patients were not eligible. Of the whole cohort, 90 (33%) patients met the COV-HI criteria at admission. Despite having a younger median age and lower median Charlson Comorbidity Index scores, a higher proportion of patients with COV-HI on admission died during follow-up (36 [40%] of 90 patients) compared with the patients without COV-HI on admission (46 [26%] of 179). Among the 178 patients who were eligible for full respiratory support, 65 (37%) met the definition for COV-HI at admission, and 67 (74%) of the 90 patients whose respiratory care was escalated met the criteria by the day of escalation. Meeting the COV-HI criteria was significantly associated with the risk of next-day escalation of respiratory support or death (hazard ratio 2·24 [95% CI 1·62-2·87]) after adjustment for age, sex, and comorbidity. INTERPRETATION: Associations between elevated inflammatory markers, escalation of respiratory support, and survival in people with COVID-19 indicate the existence of a high-risk inflammatory phenotype. COV-HI might be useful to stratify patient groups in trial design. FUNDING: None.
BACKGROUND: A subset of patients with severe COVID-19 develop a hyperinflammatory syndrome, which might contribute to morbidity and mortality. This study explores a specific phenotype of COVID-19-associated hyperinflammation (COV-HI), and its associations with escalation of respiratory support and survival. METHODS: In this retrospective cohort study, we enrolled consecutive inpatients (aged ≥18 years) admitted to University College London Hospitals and Newcastle upon Tyne Hospitals in the UK with PCR-confirmed COVID-19 during the first wave of community-acquired infection. Demographic data, laboratory tests, and clinical status were recorded from the day of admission until death or discharge, with a minimum follow-up time of 28 days. We defined COV-HI as a C-reactive protein concentration greater than 150 mg/L or doubling within 24 h from greater than 50 mg/L, or a ferritin concentration greater than 1500 μg/L. Respiratory support was categorised as oxygen only, non-invasive ventilation, and intubation. Initial and repeated measures of hyperinflammation were evaluated in relation to the next-day risk of death or need for escalation of respiratory support (as a combined endpoint), using a multi-level logistic regression model. FINDINGS: We included 269 patients admitted to one of the study hospitals between March 1 and March 31, 2020, among whom 178 (66%) were eligible for escalation of respiratory support and 91 (34%) patients were not eligible. Of the whole cohort, 90 (33%) patients met the COV-HI criteria at admission. Despite having a younger median age and lower median Charlson Comorbidity Index scores, a higher proportion of patients with COV-HI on admission died during follow-up (36 [40%] of 90 patients) compared with the patients without COV-HI on admission (46 [26%] of 179). Among the 178 patients who were eligible for full respiratory support, 65 (37%) met the definition for COV-HI at admission, and 67 (74%) of the 90 patients whose respiratory care was escalated met the criteria by the day of escalation. Meeting the COV-HI criteria was significantly associated with the risk of next-day escalation of respiratory support or death (hazard ratio 2·24 [95% CI 1·62-2·87]) after adjustment for age, sex, and comorbidity. INTERPRETATION: Associations between elevated inflammatory markers, escalation of respiratory support, and survival in people with COVID-19 indicate the existence of a high-risk inflammatory phenotype. COV-HI might be useful to stratify patient groups in trial design. FUNDING: None.
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