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Predictors of Poor Outcomes in Older Inpatients With COVID

William H. Hung, MD, MPH


March 16, 2021

William H. Hung, MD, MPH

Older adults with COVID-19 are at increased risk for poor outcomes, including hospitalization, respiratory failure, and in-hospital death. Because this is a novel illness, we are still discerning whether factors known to predict poor outcomes in older adults, such as preexisting conditions, delirium, and frailty, may confer similar risks for older adults with COVID-19. In particular, prior studies of the effect of delirium and frailty on short- and long-term outcomes in older adults with COVID-19 have produced conflicting results. The findings from the studies highlighted here help to clarify the relationship between delirium and frailty and outcomes in older adults with COVID-19.

Specifically, these studies showed that delirium and frailty are associated with increased risk for in-hospital mortality and a higher likelihood that patients will need increased care after discharge. These findings further our understanding of the risk factors beyond older age that can affect both short-and long-term outcomes for older adults hospitalized with COVID-19. In addition, they can help inform decisions around in-hospital care of these patients as well as transitions of care and ongoing care for those who have survived hospitalization.

Delirium and In-hospital Mortality

The first study was conducted at four hospitals in Italy and involved 516 patients aged 65 and older who were admitted with COVID-19. The study objectives were to report the prevalence of delirium in these patients, identify factors associated with delirium, and evaluate the association between delirium and in‐hospital mortality. Older adults with a positive nasopharyngeal swab test for SARS-CoV-2 consecutively admitted to two geriatric units, one acute medical unit, and one rehabilitation unit were included. The methods used to assess for delirium varied across sites and included the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria; the modified Richmond Agitation-Sedation Scale (RASS); the 4AT tool; and clinical impression. All patients underwent a comprehensive medical assessment in which data on demographics, smoking status, functional and cognitive status, clinical history including comorbidities, and laboratory and radiographic findings were gathered. The clinical outcome studied was all-cause in-hospital mortality. The estimated incidence of delirium in this cohort was 14%; among the factors associated with presenting with delirium were a history of dementia (odds ratio [OR], 4.66; 95% CI, 2.03-10.69), higher number of chronic diseases (OR, 1.20; 95% CI, 1.03-1.40), and radiographic findings of chest infiltrates (OR, 3.29; 95% CI, 1.12-9.64). Patients with delirium were nearly twice as likely to die in the hospital (OR, 1.88; 95% CI, 1.25-2.83).

This study clarifies the factors associated with delirium and also demonstrates the negative consequences associated with delirium. Its strengths are the size of the cohort and the multicenter design. A notable limitation is that the centers that participated in this study used different methods to identify delirium, although, as the authors point out, this limitation is understandable given the time constraints and stress that clinicians experienced during the height of the pandemic. However, the varying methods used to assess for delirium may have led to an underestimation of the prevalence of delirium in this group of older patients with COVID-19. Given this study's findings, clinicians must be alert to factors associated with delirium so that delirium can be reliably identified; also, clinicians must consider the prognostic significance of delirium when caring for these older adults.

Frailty and In-hospital Mortality

The second study, conducted in 15 hospitals in the Netherlands, evaluated the association between frailty and in-hospital mortality in 1376 older patients (≥ 70 years) consecutively admitted for COVID-19. This study was undertaken because prior studies examining whether frailty is associated with poor outcomes in older adults COVID-19 produced inconclusive results. Frailty was assessed using the Clinical Frailty Scale (CFS), a 9-point scale ranging from very fit (score of 1) to terminally ill (score of 9). Approximately 12.9% of patients were assessed using the CFS at the time of admission (prospectively), and the remainder were assessed retrospectively by a geriatrics clinician specialist using clinical data collected at the time of admission, including those gathered via the Dutch National Safety Management System, a tool that assesses physical impairment, delirium, falls, and malnutrition in the weeks or months prior to admission.

Patients were assigned to one of three groups based on CFS scores: fit (score of 1-3), pre-frail (4 or 5), and frail (6-9). The authors used a multivariable logistic regression model to examine the association between frailty and in-hospital mortality, accounting for variables including age, sex, comorbidity, and disease severity. Patients who were more frail (CFS score of 6-9) were more likely to present with a shorter duration of COVID-19 symptoms and to have a lower level of disease severity on presentation, as indicated by a lower amount of oxygen needed and a lower C-reactive protein concentration, compared with those categorized as less frail. However, frailty was associated with a higher rate of in-hospital mortality: those with a CFS score of 6-9 were nearly three times more likely to die while in hospital (OR, 2.8; 95% CI, 1.8-4.3), and those with a score of 4 or 5 were two times more likely to die while in hospital (OR, 2.0; 95% CI, 1.3-3.0), compared with fit patients (CFS score of 1-3).

Strengths of this study are its large cohort size and its use of routinely collected data that allowed for CFS to be determined retrospectively. A limitation is that care pathways can differ for those who are more frail (eg, less use of intensive care unit), which may have biased the study results. Nonetheless, the takeaway from this study is that because frailty is associated with poor in-hospital outcomes for older patients admitted with COVID-19, all patients should be assessed for frailty, as the results will inform discussions of appropriate care and advance care planning, especially for frail older adults admitted to the hospital with COVID-19.

Dementia and Frailty

The third study, which involved 5711 older patients (median age, 74 years) with COVID-19 who were admitted to 55 hospitals in 12 countries (in Europe, Asia, and United States), found that age and frailty were associated with increased mortality as well as increased care needs in those who survived initial hospitalization. Led by the Geriatric Medicine Research Collaborative, where routinely collected clinical information is shared through a secure REDCAP webpage, this study included all adults aged 18 and older admitted with COVID-19.

Frailty was determined using the 9-point CSF through prospective clinical assessment or retrospective assessment based on medical records of function 2 weeks prior to admission. Delirium was assessed using the 4AT tool. The study's primary outcome was mortality during the index hospitalization; secondary outcomes were critical care admission, incident delirium, and increased care requirements on discharge, defined as transition across three care levels: living in home without formal care, living in home with formal care, and living in a 24-hour long-term care facility. In this study, frailty was independently associated with increased in-hospital mortality. Adults with a CFS score of 8 were three times more likely to die in hospital compared with those with a score of 1-3 (OR, 3.03; 95% CI, 2.29-4.00). Those with a CFS score of 7 were seven times more likely to have increased care needs after discharge compared with those with a score of 1-3 (OR, 7.00; 95% CI, 5.27-9.32). This finding was consistent across different levels of frailty. Other factors independently associated with increased care needs were dementia (OR, 1.73; 95% CI, 1.39-2.16), delirium (OR, 1.83; 95% CI, 1.59-2.19), and history of mental health issues (OR, 1.57; 95% CI, 1.22-2.01). Of note, delirium was not associated with in-hospital mortality in this study but was associated with increased rates of intensive care unit admission, in addition to increased care needs upon discharge.

A limitation of this study is that the data were collected retrospectively, which could introduce issues with accuracy and reliability. Also, the study did not find an association between delirium and mortality, which is not consistent with some prior reports and could be related to differences in data collection methods and cohort design. Nonetheless, the findings highlight frailty as a factor linked to increased care needs after discharge and contributes to our understanding of the sequelae of COVID-19 in older frail patients.


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