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

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.

Citation

Manson, J. J., Crooks, C., Naja, M., Ledlie, A., Goulden, B., Liddle, T., Khan, E., Mehta, P., Martin- Gutierrez, L., Waddington, K. E., Robinson, G. A., Ribeiro Santos, L., McLoughlin, E., Snell, A., Adeney, C., Schim van der Loeff, I., Baker, K. F., Duncan, C. J. A., Hanrath, A. T., Lendrem, B. C., …Tattersall, R. (2020). COVID-19-associated hyperinflammation and escalation of patient care: a retrospective longitudinal cohort study. The Lancet Rheumatology, 2(10), e594-e602. https://doi.org/10.1016/S2665-9913%2820%2930275-7

• 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
• DOI: https://doi.org/10.1016/S2665-9913%2820%2930275-7
• Public URL: https://nottingham-repository.worktribe.com/output/4888585
• Publisher URL: https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30275-7/fulltext