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.
Bibliographical noteFunding Information:
MC is supported by the NIHR Newcastle Biomedical Research Centre. ECJ is supported by grants from the MS Society (grant number 076), Lupus UK, The Rosetrees Trust (M409), and The Dunhill Medical Trust (RPGF1902\117). MN is supported by the NIHR University College London Hospitals (UCLH) Biomedical Research Centre (grant number BRC525/III/CC). The Centre for Adolescent Rheumatology Versus Arthritis at University College London, UCLH, and Great Ormond Street Hospital (GOSH) is supported by grants from Versus Arthritis (grant numbers 21593, 20164, and 21226), Great Ormond Street Hospital Children's Charity (GOSCC), and the NIHR Biomedical Research Centres at GOSH and UCLH. JJM would like to acknowledge the helpful discussions with Prof David Moore, consultant in infectious diseases and tropical medicine at UCLH.
PM is a Medical Research Council–GlaxoSmithKline EMINENT clinical training fellow, which includes project funding outside the submitted work, and co-funding from the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre. CJAD reports grants from Wellcome Trust, during the conduct of the study. ADS reports grants and personal fees from AstraZeneca, Bayer, Chieisi, Teva, Forest Labs, Grifols, and Novartis, outside the submitted work. MS reports grants and advisory board fees from NewB, grants from the Defence Science and Technology Laboratory, Critical Pressure, Apollo Therapeutics, advisory board and speaker fees (paid to his institution) from Amormed, Biotest, GE, Baxter, Roche, and Bayer, and honorarium for chairing a data monitoring and safety committee from Shionogi. MC reports personal fees from Mallinkrodt, outside the submitted work. All other authors declare no competing interests.
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