Development and Validation of a Dynamic 48-Hour In-Hospital Mortality Risk Stratification for COVID-19 in a UK Teaching Hospital: A Retrospective Cohort Study (preprint)

Background: While numerous point-of-admission disease severity models for COVID-19 have been proposed, disease stratification that accounts for changes in a patient’s condition while in hospital is urgently needed to facilitate patient management and resource allocation.Methods: We developed a prognostic model for 48-hour in-hospital mortality using 473 consecutive patients with COVID-19 presenting to a UK hospital between March 1 and September 12, 2020; and temporally validated using data on 405 patients presenting between September 13, 2020 and January 3, 2021.The primary outcome was all-cause in-hospital mortality. We additionally considered the competing risks of discharge from hospital and transfer to a tertiary Intensive Care Unit for extracorporeal membrane oxygenation. We adopted a landmarking approach to dynamic prediction that accounts for competing risks and informative missingness, and selected predictors using penalised regression. The model estimates, at any point during a hospital visit, the probability of in-hospital mortality during the next 48 hours.Results: Our final model includes age, Clinical Frailty Scale score, heart rate, respiratory rate, SpO2/FiO2 ratio, white cell count, presence of acidosis (pH < 7.35) and Interleukin-6. Internal validation achieved an AUROC of 0.90 (95% CI 0.87–0.93) and temporal validation gave an AUROC of 0.91 (95% CI 0.88-0.95). Interpretation: Our model uniquely incorporates both static risk factors (e.g. age) and evolving clinical and laboratory data, to provide a dynamic risk prediction model that adapts to both sudden and gradual changes in an individual patient’s clinical condition. External validation outside the study hospital will be required before adoption.Funding: NIHR Cambridge Biomedical Research Centre, UKRI Medical Research CouncilDeclaration of Interest: None to declare. Ethical Approval: The study was approved by a UK Health Research Authority ethics committee (20/WM/0125). Patient consent was waived because the de-identified data presented here were collected during routine clinical practice; there was no requirement for informed consent.

Clinical features and inpatient trajectories of older inpatients with COVID-19: a retrospective observational study. (preprint)

Background: A comprehensive description of the clinical characteristics, inpatient trajectory and relationship with frailty of older inpatients admitted with COVID-19 is essential in the management of older adults during the COVID-19 pandemic. The aim of this study was to describe the clinical features and inpatient trajectory of older inpatients with confirmed COVID -19. Methods: This was a retrospective observational study of hospitalised older adults. Subjects include unscheduled medical admissions of older inpatients to a University Hospital with laboratory and clinically confirmed COVID-19. The primary outcome was death during the inpatient stay or within 14 days of discharge after a maximum follow up time of 45 days. The characteristics of the cohort were described in detail as a whole and by frailty status. Results: 214 patients were included in this study with a mean length of stay of 11 days (Range 6 to 18 days), of whom 140 (65.4%) patients were discharged and 74 (34.6%) patients died in hospital. 142 (66.4%) patients were frail with median Clinical Frailty Scale (CFS) score of 6. Frail patients were more likely to present with atypical symptoms including new or worsening confusion compared to non-frail patients (20.8% vs 45.1%, p<0.001) and were more likely to die in hospital or within 14 days of discharge (66% vs 16%, p=0.001). Older age, being male, presenting with high illness acuity and high frailty were all independently associated with higher risk of death and a dose response association between higher frailty and higher mortality was observed. Conclusions: Older adult inpatients with COVID-19 infection are likely to present with atypical symptoms, experience delirium and have a high mortality, especially if they are also living with frailty. Clinicians should have a low threshold for testing for COVID-19 in older and frail patients presenting to hospital as an emergency during periods when there is community transmission of COVID-19 and, when diagnosed, this should prompt early advanced care planning with the patient and family.