COVID-19 Is Not Over And Age Is Not Enough

Using Frailty for Prognostication in Hospitalized Patients

Márlon Juliano Romero Aliberti MD, PhD; Claudia Szlejf MD, PhD; Vivian I. Avelino-Silva MD, PhD; Claudia Kimie Suemoto MD, PhD, MSc; Daniel Apolinario MD, PhD; Murilo Bacchini Dias MD; Flavia Barreto Garcez MD, PhD; Carolina B. Trindade MD; José Renato das Graças Amaral MD; Leonardo Rabelo de Melo MD; Renata Cunha de Aguiar MD; Paulo Henrique Lazzaris Coelho MD; Naira Hossepian Salles de Lima Hojaij MD, PhD; Marcos Daniel Saraiva MD; Natalia Oliveira Trajano da Silva MD; Wilson Jacob-Filho MD, PhD; Thiago J. Avelino-Silva MD, PhD


J Am Geriatr Soc. 2021;69(5):1116-1127. 

In This Article

Abstract and Introduction


Background: Frailty screening using the Clinical Frailty Scale (CFS) has been proposed to guide resource allocation in acute care settings during the pandemic. However, the association between frailty and coronavirus disease 2019 (COVID-19) prognosis remains unclear.

Objectives: To investigate the association between frailty and mortality over 6 months in middle-aged and older patients hospitalized with COVID-19 and the association between acute morbidity severity and mortality across frailty strata.

Design: Observational cohort study.

Setting: Large academic medical center in Brazil.

Participants: A total of 1830 patients aged ≥50 years hospitalized with COVID-19 (March–July 2020).

Measurements: We screened baseline frailty using the CFS (1–9) and classified patients as fit to managing well (1–3), vulnerable (4), mildly (5), moderately (6), or severely frail to terminally ill (7–9). We also computed a frailty index (0–1; frail >0.25), a well-known frailty measure. We used Cox proportional hazards models to estimate the association between frailty and time to death within 30 days and 6 months of admission. We also examined whether frailty identified different mortality risk levels within strata of similar age and acute morbidity as measured by the Sequential Organ Failure Assessment (SOFA) score.

Results: Median age was 66 years, 58% were male, and 27% were frail to some degree. Compared with fit-to-managing-well patients, the adjusted hazard ratios (95% confidence interval [CI]) for 30-day and 6-month mortality were, respectively, 1.4 (1.1–1.7) and 1.4 (1.1–1.7) for vulnerable patients; 1.5 (1.1–1.9) and 1.5 (1.1–1.8) for mild frailty; 1.8 (1.4–2.3) and 1.9 (1.5–2.4) for moderate frailty; and 2.1 (1.6–2.7) and 2.3 (1.8–2.9) for severe frailty to terminally ill. The CFS achieved outstanding accuracy to identify frailty compared with the Frailty Index (area under the curve = 0.94; 95% CI = 0.93–0.95) and predicted different mortality risks within age and acute morbidity groups.

Conclusions: Our results encourage the use of frailty, alongside measures of acute morbidity, to guide clinicians in prognostication and resource allocation in hospitalized patients with COVID-19.


From the beginning of the coronavirus disease 2019 (COVID-19) pandemic, it was clear that age was associated with disease severity and prognosis. Early observational studies also pointed to an increased risk of hospitalization, need for mechanical ventilation, and mortality in older adults.[1,2] As the pandemic progressed, age, as an objective and easily obtained characteristic, started to be used as a primary factor to estimate prognosis and decide how to allocate patient care. However, age does not account for the enormous heterogeneity of the older population, and, applied alone, it is not a reliable, or even ethical, criterion to complete judicious medical decisions.[3–7] Therefore, a more comprehensive approach to prognostication is necessary and should include other factors such as comorbidities, extent of organ dysfunction, functional status, and frailty.[8,9]

Previous studies and guidelines have proposed frailty among the measures to guide resource allocation in geriatric care.[10,11] This syndrome reflects a state of vulnerability resulting from a lifetime accumulation of physiological deficits that leads to a limited capacity to respond to organic stressors. Frailty has been associated with several adverse outcomes (i.e., disability, hospitalization, and death) in older adults.[12] Although recent studies have suggested that frailty can predict short-term mortality and length of hospital stay in older adults admitted for COVID-19, some controversies remain.[13–15] Knopp et al. investigated clinical features associated with mortality in older adults admitted for COVID-19 and found that frailty was not independently associated with the outcome.[16] In another study on hospitalized older adults, frailty was only associated with increased mortality in participants without COVID-19.[17] Moreover, it is still unclear the prognostic value of frailty in middle-aged patients (50 to 64 years), a population also at higher risk of COVID-19-related adverse outcomes.[2,14]

Therefore, we aimed to investigate in middle-aged and older adults admitted to the hospital with COVID-19: (1) the association between frailty and 30-day and 6-month mortality; (2) the association between acute morbidity severity and 30-day and 6-month mortality, across frailty strata; and (3) the concurrent validity of the Clinical Frailty Scale (CFS)[18] with a well-validated frailty measurement (Frailty Index)[19] of the same population.