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 S

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.