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COVID-19-associated hyperinflammation and escalation of patient care: a retrospective longitudinal cohort study

Manson, Jessica J; Crooks, Colin; Naja, Meena; Ledlie, Amanda; Goulden, Bethan; Liddle, Trevor; Khan, Emon; Mehta, Puja; Martin- Gutierrez, Lucia; Waddington, Kirsty E; Robinson, George A; Ribeiro Santos, Liliana; McLoughlin, Eve; Snell, Antonia; Adeney, Christopher; Schim van der Loeff, Ina; Baker, Kenneth F; Duncan, Christopher J A ; Hanrath, Aidan T; Lendrem, B. Clare; De Soyza, Anthony; Peng, Junjie; J'Bari, Hajar; Greenwood, Mandy; Hawkins, Ellie; Peckham, Hannah; Marks, Michael; Rampling, Tommy; Luintel, Akish; Williams, Bryan; Brown, Michael; Singer, Mervyn; West, Joe; Jury, Elizabeth C; Collin, Matthew; Tattersall, Rachel


Jessica J Manson

Meena Naja

Amanda Ledlie

Bethan Goulden

Trevor Liddle

Emon Khan

Puja Mehta

Lucia Martin- Gutierrez

Kirsty E Waddington

George A Robinson

Liliana Ribeiro Santos

Eve McLoughlin

Antonia Snell

Christopher Adeney

Ina Schim van der Loeff

Kenneth F Baker

Christopher J A Duncan

Aidan T Hanrath

B. Clare Lendrem

Anthony De Soyza

Junjie Peng

Hajar J'Bari

Mandy Greenwood

Ellie Hawkins

Hannah Peckham

Michael Marks

Tommy Rampling

Akish Luintel

Bryan Williams

Michael Brown

Mervyn Singer

Professor of Epidemiology

Elizabeth C Jury

Matthew Collin

Rachel Tattersall


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.


Manson, J. J., Crooks, C., Naja, M., Ledlie, A., Goulden, B., Liddle, T., …Tattersall, R. (2020). COVID-19-associated hyperinflammation and escalation of patient care: a retrospective longitudinal cohort study. The Lancet Rheumatology, 2(10), e594-e602.

Journal Article Type Article
Acceptance Date Jul 20, 2020
Online Publication Date Aug 21, 2020
Publication Date Oct 1, 2020
Deposit Date Sep 8, 2020
Publicly Available Date Aug 22, 2021
Journal The Lancet Rheumatology
Electronic ISSN 2665-9913
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 2
Issue 10
Pages e594-e602
Public URL
Publisher URL


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