key: cord-0851628-zwrp4mn5
authors: Covino, Marcello; Russo, Andrea; Salini, Sara; De Matteis, Giuseppe; Simeoni, Benedetta; Della Polla, Davide; Sandroni, Claudio; Landi, Francesco; Gasbarrini, Antonio; Franceschi, Francesco
title: Frailty Assessment In The Emergency Department For Risk Stratification Of Covid-19 Patients ≥80 Years
date: 2021-07-20
journal: J Am Med Dir Assoc
DOI: 10.1016/j.jamda.2021.07.005
sha: 96cbd5f84da0c97b696a474b52dc83b6b94c87fd
doc_id: 851628
cord_uid: zwrp4mn5

Objectives To evaluate, in a cohort of adults ≥ 80 years old, the overlapping effect of clinical severity, comorbidities, cognitive impairment, and frailty, for the in-hospital death risk stratification of COVID-19 older patients since emergency department (ED) admission. Design Single-center prospective observational cohort study. Setting and participants The study was conducted in the ED of a teaching hospital which is a referral center for COVID-19 in central Italy. We enrolled all COVID-19 patients ≥ 80 years old consecutively admitted to the ED between April 2020 and March 2021. Methods Clinical variables assessed in the ED were evaluated for the association with all-cause in-hospital death. Evaluated parameters were: severity of disease, frailty, comorbidities, cognitive impairment, delirium, and dependency in daily life activities. Cox regression analysis was used to identify independent risk factors for poor outcomes. Results 729 patients aged ≥ 80 years were enrolled (median age 85 years [interquartile range 82-89]; 346 were males (47.3%)). According to clinical frailty scale 61 (8.4%) were classified as fit, 417 (57.2%) as vulnerable, and 251 (34.4%) as frail. Severe disease (Hazard Ratio 1.87 [1.31-2.59]), ≥ 3 comorbidities (HR 1.54 [1.11-2.13]), male sex (HR 1.46 [1.14-1.87]) and frailty (HR 6.93 [1.69-28.27]) for vulnerable, and HR 12.55 [2.96-53.21] for frail were independent risk factors for in-hospital death. Conclusions and Implications The ED approach to older COVID-19 patients should take into account the functional and clinical characteristics of patients being admitted. A sole evaluation based on the clinical severity and the presence of comorbidities does not reflect the complexity of this population. A comprehensive evaluation based on clinical severity, multi-morbidity, and frailty could effectively predict the clinical risk of in-hospital death for COVID-19 patients ≥ 80 years at the time of ED presentation.

Since December 2019, the novel coronavirus designated SARS-CoV-2 has determined the tragic 31 pandemic of the respiratory illness named COVID-19 1, 2 . Vaccination campaigns had started in most 32 countries of the world, however, the number of affected patients and the death toll is still 33 increasing 3 . Italy faces one of the worst clusters of COVID-19, and the mortality rate and death toll 34 are particularly high 4 . 35 The clinical course of COVID-19 is various, ranging from possible asymptomatic patients to severe 36 progressive pneumonia leading to death 5 . Overall, the prevalence of respiratory failure in patients 37 hospitalized with COVID-19 was estimated to be about 19%, with up to 12% of patients requiring 38 mechanical ventilation 1, 2, 6 . In this context of an overflow of critically ill patients, the Emergency 39 Department (ED) physician must establish clear and objective criteria to stratify COVID-19 death 40 risk. 41 Patients ≥ 80 years old are the most at risk of death for COVID-19 7-13 . Most of the current research 42 focuses on the presence of multiple comorbidities in these population to explain for the 43 disproportionate death rate which characterizes the clinical course of these patients 1-2, 5-13 . 44 However, it has been argued that these conditions cannot comprehensively predict the extremely 45 poor outcomes observed in older COVID-19 patients 13 . 46 Older adults have heterogeneous baseline clinical conditions. Often, chronological age and 47 comorbidities do not truly reflect the overall health status of older patients. To overcome these 48 issues, the frailty syndrome was introduced to include several dimensions of physical fitness and 49 autonomy. Frailty is defined as a condition characterized by a progressive declined physiologic 50 function and diminished strength leading to vulnerability and reduced resilience to stressors which 51 led to an increased risk of adverse outcomes 14 . Frailty was found to be an independent predictor for  Presence of cognitive impairment, based on an established dementia diagnosis before SARS- 78 CoV-2 infection. 79  Dependency in activities of daily life (ADL), based on the clinical status before SARS-CoV-2 80 infection. 81  Delirium occurrence was assessed based on the Richmond Agitation-Sedation Scale 28 Warning Score and the rate of presentation with severe disease were higher in frailer patients. The 157 rate of pulmonary involvement, reflected by consolidation at chest x-ray was similar among the 158 three groups. Interestingly, but not unexpectedly, delirium occurred only in vulnerable and frail 159 patients (Table 1) . 160 Most of the enrolled patients had comorbidities. Frail and Vulnerable patients had more 161 comorbidities as shown by a higher rate of patients having 3 or more major comorbidities. As largely 162 expected the frailer patients were more dependent in ADL and had a higher rate of cognitive 163 impairment (Table 1) .

Factors associated with in-hospital death 166 In line with several COVID-19 reports, the deceased patients in our cohort were significantly older 167 and were more frequently male (Table 2) . 168 Although main symptoms were similar for the deceased and survived group, physiological 169 parameters at admission were significantly deranged in the deceased group, particularly for lower 170 peripheral oxygen saturation ( Table 2) . As a result, the National Early Warning Score was higher in 171 J o u r n a l P r e -p r o o f the deceased, and the number of patients with severe disease was higher in the deceased group 172 ( When entered into a multivariate Cox regression analysis, several factors emerged as independent 181 predictors of poor outcomes in our cohort. 182 Among these, frailty was a significant risk factor for death, being the hazard ratio of vulnerable 183 patients 7 times higher than fit ones, with a further doubling of the risk for frail patients (Table 3) . 184 Interestingly but predictably, once adjusted for baseline covariates and frailty, both dementia and 185 dependency in ADL were not independent risk factors for death. Similarly, the occurrence of 186 delirium was not associated with an increased adjusted HR for death in this cohort (Table 3) . 187 As expected the clinical severity at admission, significantly increased the overall death risk, as well 188 as the presence of ≥ 3 comorbidities. The analysis also evidenced an increased risk for the male sex 189 (Table 3) . Overall the death risk progressively increased for severe disease, comorbidity, and frailty, An optimal screening tool for frailty in the ED setting should be practical, simple, and accurate. 219 Among the existing clinical score, we adopted the Clinical Frailty Scale which is already widely used 220 and is particularly efficient for the emergency setting because there are only five patient domains 221 that need to be assessed 31 . The CSF was already found to be linearly correlated with death in a meta-222 analysis on a pooled sample of 3,817 patients with COVID-19. However, the analysis included 223 patients of different age groups, and the pooled analysis was not fully adjusted for disease severity, 224 nor comorbidities 18 . 225 The concept of frailty is often confused in clinical practice with multi-morbidity. However, contrary 226 to general perception, multi-morbidity does not necessarily imply the onset of frailty 32,33 . In the present study, dementia was confirmed to be significantly associated with poor outcomes, however, when the analysis was adjusted for frailty status, it did not emerge as an independent 243 factor for death. This latter finding could help to clarify the role of cognitive impairment for COVID-244 19 prognosis. Based on a meta-analysis of available data, dementia seems to be associated with an is different from the simple assessment of multi-morbidity 50 . 298 As a final clue emerging from our investigation, we evaluated the changes in mortality rate between 299 the first phase of the pandemic, and the later "waves" of infection. Some authors reported a 300 decreased mortality over time in the geriatric population, particularly during the first wave 51 . 301 Although not completely explained, this observation could be ascribed to a general increase in the 302 awareness for the disease, associated with precocious diagnoses, and to a general improvement in 303 the hospital care for COVID-19. However, available data were not corrected for frailty, and thus it 304 could be also speculated that the high mortality rates at the very beginning of the pandemic could 305 be just due to a "harvest" effect on the frailer part of the geriatric population. This latter hypothesis 306 could be supported by the present study. Indeed, although the crude mortality rate was higher in 307 the early phase of the pandemic, the adjusted survival rates were similar when corrected for disease 308 severity, comorbidities, and frailty (Supplementary figure 1) . was defined as Fit for CFS 1-3, vulnerable for CFS 4-6, and frail for CFS 7-9. Green is for mortality 0-456 33%, yellow for mortality 33%-66%, and red for mortality > 66%. 

Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl 326

Clinical features of patients infected with 2019 novel coronavirus 328 in Wuhan

World Health Organization. WHO Coronavirus Disease (COVID-19) Dashboard

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With Mortality Among Patients With COVID-19 in Intensive Care Units in

Prognostic Factors of COVID-19 Infection in Elderly Patients: A 339 Multicenter Study

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ADL -Activities of daily living; CAD -Coronary artery disease

Chronic Obstructive Pulmonary Disease; NEWS -National Early Warning Score; CFS -Clinical Frailty Scale

Urea Nitrogen; LDH -Lactate dehydrogenase. *Severe COVID-19 was defined as: respiratory rate ≥ 30 times/min, PaO2 469 at rest ≤ 92%, PaO2/FiO2 ≤ 300 mm Hg

Crude death rate was 111/331 (34.4%) in the 80-84 year group, 97/231 (42.0%) in the 85-89 year group, 52/128 (40.6%) for the 90-94 year group, and 24/39 (61.5%) in the ≥ 95 year group

Overall, 203 patients were admitted in the first phase with 89 deaths (43.8%), and 526 patients were admitted in the second phase with 198 deaths (37.6%). The adjusted hazard risk for death was not significantly different