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The effect of frailty on survival in patients with COVID-19 (COPE): a multicentre, European, observational cohort study

Our take —

In this multisite study in the UK and Italy, almost half of the 1,564 participants were considered frail (clinical frailty score >4). Frailty was associated with COVID-19 mortality after adjusting for other factors associated with death. The findings provide preliminary support that frailty assessment may help identify patients at high risk of death from COVID-19, but its clinical utility should be evaluated with additional studies, especially those among people aged <65 years (a population in whom the tool is not well validated).

Study design

Prospective Cohort

Study population and setting

This study included 1,564 patients from the COVID-19 in Older People (COPE) study, including 11 hospitals in the UK and Italy. Adult patients (18+ years old) with laboratory-confirmed SARS-CoV-2 who were admitted to the hospital were enrolled between February 27 and April 28, 2020, and only those with complete data were included. Data were collected through a combination of patient records, drug prescription charts, and prospective, standardized case report forms. Frailty was assessed with the 9-level clinical frailty score (CFS), and was categorized into the following groups: fit (1-2), vulnerable but not frail (3-4), initial signs of frailty (5-6), and severe frailty (7-9). A mixed effects multivariable model was used to estimate the impact of frailty on mortality, adjusting for factors associated with COVID-19 prognosis in previous studies (age, sex, smoking status, C-reactive protein, diabetes, coronary artery disease, hypertension, and impaired renal function).

Summary of Main Findings

Of the 1564 participants (median age: 74 [IQR: 61-83], 42% female), 18% were considered fit, 30% were vulnerable, 28% had initial signs of frailty, and 24% were severely frail. By study end, 425 (27%) participants died (median survival: 7 days [IQR: 4-11]) and 727 patients were discharged (median time to discharge: 9 days [IQR: 5-15]). Compared to participants who were considered fit (CFS 1-2), those who were vulnerable, had initial signs of frailty, or were severely frail had elevated risks of mortality with hazard ratios of 1.55 (95% CI: 1.00-2.41), 1.83 (95% CI: 1.15-2.91), and 2.39 (95% CI: 1.50-3.81). Increasing age, C-reactive protein (CRP) >40 mg/dL, and estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m2 were also associated with mortality. Higher frailty scores, increasing age, and increased CRP were also associated with longer duration of hospital stay. Results from subgroup analyses are relatively consistent with the main findings, though the association with frailty and mortality appears attenuated among participants >80 years.

Study Strengths

This was a multi-site study with standard data collection and the authors report the hospitals are representative of England, Scotland, and Wales. The clinical frailty score used in the study is validated for people >65 years old, and is easy to use in this setting. The study used an existing network of clinical centers that had experience collecting frailty data with the CFS.

Limitations

In adjusted analyses, age was categorized, and CRP and eGFR were dichotomized, which may result in residual confounding. No interactions were considered; for example, it is unclear why the association between frailty and death was weaker for older age groups, as observed in subgroup analyses presented in the appendix. 143 participants were excluded due to missing data or lack of access to patient records. Many participants remained hospitalized at the time of analysis, and their final outcomes are unknown. The study only includes hospitalized patients and only 10% of patients were from Italy, so the degree to which the results are generalizable to milder cases of COVID-19 beyond the UK is questionable.

Value added

This study had a focused objective of evaluating the role of frailty for COVID-19 outcomes, a concept which has not yet been explored in detail in the context of the pandemic.

This review was posted on: 11 September 2020