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.
BackgroundThe number of proposed prognostic models for COVID-19 is growing rapidly, but it is unknown whether any are suitable for widespread clinical implementation.MethodsWe independently externally validated the performance candidate prognostic models, identified through a living systematic review, among consecutive adults admitted to hospital with a final diagnosis of COVID-19. We reconstructed candidate models as per original descriptions and evaluated performance for their original intended outcomes using predictors measured at admission. We assessed discrimination, calibration and net benefit, compared to the default strategies of treating all and no patients, and against the most discriminating predictor in univariable analyses.ResultsWe tested 22 candidate prognostic models among 411 participants with COVID-19, of whom 180 (43.8%) and 115 (28.0%) met the endpoints of clinical deterioration and mortality, respectively. Highest areas under receiver operating characteristic (AUROC) curves were achieved by the NEWS2 score for prediction of deterioration over 24 h (0.78; 95% CI 0.73–0.83), and a novel model for prediction of deterioration <14 days from admission (0.78; 0.74–0.82). The most discriminating univariable predictors were admission oxygen saturation on room air for in-hospital deterioration (AUROC 0.76; 0.71–0.81), and age for in-hospital mortality (AUROC 0.76; 0.71–0.81). No prognostic model demonstrated consistently higher net benefit than these univariable predictors, across a range of threshold probabilities.ConclusionsAdmission oxygen saturation on room air and patient age are strong predictors of deterioration and mortality among hospitalised adults with COVID-19, respectively. None of the prognostic models evaluated here offered incremental value for patient stratification to these univariable predictors.
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