key: cord-0858253-1rd7sflv
authors: Di Bari, Mauro; Tonarelli, Francesco; Balzi, Daniela; Giordano, Antonella; Ungar, Andrea; Baldasseroni, Samuele; Onder, Graziano; Mechi, M. Teresa; Carreras, Giulia
title: COVID-19, Vulnerability and Long-Term Mortality in Hospitalized and Non-Hospitalized Older Persons
date: 2021-12-15
journal: J Am Med Dir Assoc
DOI: 10.1016/j.jamda.2021.12.009
sha: eb18445adf9490d3ed51b0962289ddaf1c53e1e3
doc_id: 858253
cord_uid: 1rd7sflv

Objective Studies suggesting that vulnerability increased short-term mortality in older patients with COVID-19 enrolled hospitalized patients and lacked COVID-negative comparators. Aim of this study was aim to examine the relationship between frailty and 1-year mortality in older patients with and without COVID-19, hospitalized and non-hospitalized. Design Cohort study Setting and Participants Patients 75+ accessing the Emergency Departments (ED) were identified from the ED archives in [location]. Methods Vulnerability status was estimated with the Dynamic Silver Code (DSC). COVID-19 hospital discharges (HC+) were compared to non-COVID-19 discharges (HC-). Linkage with a national COVID-19 registry identified non-hospitalized ED visitors with (NHC+) or without COVID-19 (NHC-). Results In 1 year, 48.4% and 33.9% of 1,745 HC+ and 15,846 HC- participants died (p<0.001). Mortality increased from 27.5% to 64.0% in HC+ and from 19.9% to 51.1% in HC- across DSC classes I to IV, with HC+ vs. HC- hazard ratios (HR) between 1.6 and 2.2. Out of 1,039 NHC+ and 18,722 NHC- participants, 18% and 8.7% died (p<0.001). Mortality increased from 14.2% to 46.7% in NHC+ and from 2.9% to 26% in NHC- across DSC; NHC+ vs. NHC- HR decreased from 5.3 in class I to 2.0 in class IV. Conclusions and Implications In hospitalized older subjects, mortality increases with vulnerability similarly in the presence and in the absence of COVID-19. In non-hospitalized patients, vulnerability-associated excess mortality is milder in subjects with than in those without COVID-19. The disease reduces survival even when background risk is low. Thus, apparently uncomplicated patients deserve closer clinical monitoring than commonly applied.

Since its beginning, the SARS-CoV-2 pandemic has severely hit older patients, in 37 whom COVID-19 mortality reaches stunning proportions. [1] [2] [3] An advanced age has been 38 identified as a major negative prognostic determinant in the course of COVID -19, 39 independent of disease-specific predictors. 4-6 Specifically, an exceeding COVID-19 mortality 40 has been reported in subsets of older patients at an increased background risk of death, 41 generically defined as frail. 7-14 Consequently, recommendations have been issued to 42 consider frailty in the decision-making process on whether or not to increase the level of 43 care in older patients with However, in the given context the use of the term 44 frailty may be questioned, because assessment of an increased risk status was based on 45 tools, such as the Clinical Frailty Scale (CFS), that rely on comorbidities and dependency 46 more than on the construct of frailty as a pre-disability condition, accepted in most current 47 literature. [16] [17] [18] [19] Therefore, the term vulnerability will be used hereinafter, even when frailty 48 had been used in the original reports. 49 Other studies showed that CFS-assessed vulnerability did not contribute to 50 predicting death in older persons hospitalized with COVID-19. 20 -21 Yet, the evidence 51 provided so far is unsatisfactory. Most of the studies considered only hospitalized subjects 52 and were limited to hospital mortality, 7-14 providing no information on the role of 53 vulnerability in subjects not requiring hospitalization nor on long term survival. Moreover, 54 they usually lacked non-COVID-19 comparators and, finally, assessed vulnerability a 55 posteriori on the basis of some operator-dependent tool, such as the CFS. Assessing the 56 excess risk associated with COVID-19 in vulnerable older subjects is, therefore, a 57 substantially unsolved issue.

J o u r n a l P r e -p r o o f ED in the area between March 1 and November 15, 2020. Additionally, we also consulted 82 the local demographics registry to obtain mortality data.

The ISS database 25 is the national registry of all the confirmed cases of COVID-19, 84 based on reverse transcriptase-polymerase chain reaction (RT-PCR) testing. It reports when, 85 but not where (i.e. hospital, community clinic, or patient's home), the diagnosis was made.

Assembly of study cohorts 87 Two different approaches were applied to select eligible subjects, depending on 88 whether ED access was followed or not by hospital admission.

Hospitalized subjects were identified by linking the ED database with the hospital 90 discharge database, using a unique identifier that does not allow personal identification.

Linkage was limited to cases accessing the ED not earlier than 2 months prior 92 hospitalization; in case of multiple ED access, the one closest to admission was kept. Elective Among subjects registered in the ED database but not admitted to the hospital, 102 those with COVID-19 (non-hospitalized COVID-19 cases, NHC+) were identified by linkage, using again the anonymous identifier, with the ISS database. When a participant had more 104 than one ED access, the closest to the date of COVID-19 diagnosis was considered. ED 105 records not linking with the ISS database were considered for comparison, as referring to 106 non-hospitalized, non-COVID-19 (NHC-) subjects. in class IV, with two-fold to three-fold greater hazards of death in class II-IV versus class I. In 179 HC-subjects, the absolute risk of death was always lower than in HC+ within each DSC class 180 and increased progressively across DSC classes, from 19.9% in class I through 51.1% in class 181 IV. HRs had a similar stepwise increase, from 1.9 to 2.9 ( Table 2) . Thus, in analyses stratified 182 by DSC class, the excess mortality associated with COVID-19, although always significant, 183 was comparable within each DSC stratum, with HRs ranging between 1.6 and 2.2 (Figure 2) . 184 Non-hospitalized participants 185 The characteristics of NHC+ and NHC-participants are presented in Table 1 . NHC+ 186 participants were older than NHC-, with a similar proportion of men. The distribution across 187 DSC classes was also different between the two groups. in class I to 26% in class IV among NHC-( Table 2) . Compared to class I, the hazard of death 194 across classes II-IV was 2.3, 3.5, and 3.7 greater in NHC+, and 3.6, 5.9, and 9.7 greater in 195 NHC-( Table 2 ). The excess mortality associated with COVID-19 decreased progressively with 196 advancing DCS class, from an HR of 5.3 in class I to an HR of 2.0 in class IV (Figure 3) . on the quality of the data collected, which may be suboptimal when taking history from an 269 older patient. Conversely, the DSC is objective, completely operator-independent, and can 270 also be obtained in non-collaborating patients.

The study has limitations. We had no other information, besides that conveyed by 

The authors had no conflict of interest to disclose. Table 1 . 

Our World in Data. Excess mortality during the Coronavirus Pandemic (COVID-19)

Excess deaths associated with covid-19 pandemic in 305 2020: age and sex disaggregated time series analysis in 29 high income countries

Factors associated with COVID-19-related death 308 using OpenSAFELY

Risk factors for mortality in patients with Coronavirus 311 disease 2019 (COVID-19) infection: a systematic review and meta-analysis of observational 312 studies

Italian National Institute of Health COVID-19

Clinical Characteristics of Hospitalized Individuals Dying With COVID-19 by

Age Group in Italy

Outcomes of hospitalized 318 patients with COVID-19 according to level of frailty

COPE Study Collaborators. The effect of frailty on 321 survival in patients with COVID-19 (COPE): a multicentre, European, observational cohort 322 study

Frailty and mortality in hospitalized older 331 adults with COVID-19: retrospective observational study

Older adults with SARS-CoV-2 infection: Utility of the 334 clinical frailty scale to predict mortality

Clinical frailty score as an independent predictor of 337 outcome in COVID-19 hospitalised patients

COMET research team. Association 340 between Clinical Frailty Scale score and hospital mortality in adult patients with

COMET): an international, multicentre, retrospective, observational cohort study

NICE guideline. COVID-19 rapid guideline: critical care in adults

Frailty: implications for 346 clinical practice and public health

The multidimensional prognostic index (MPI) for the prognostic stratification

Management of frailty: opportunities, challenges, and 355 future directions

Comparing associations between frailty and mortality in 358 hospitalised older adults with or without COVID-19 infection: a retrospective observational 359 study using electronic health records

Outcomes from COVID-19 across the range of frailty: 362 excess mortality in fitter older people

Real-time utilisation of administrative data in the ED to 365 identify older patients at risk: development and validation of the Dynamic Silver Code

Long-term Survival after Hospital Admission in Older 368 Italians: Comparison between Geriatrics and Internal Medicine across Different Discharge 369 Diagnoses and Risk Status

Estimating Prognosis and Frailty in Persons Aged 75+ 372 in the Emergency Department: Further Validation of Dynamic Silver Code

Association of frailty with outcomes in 381 individuals with COVID-19: A living review and meta-analysis

Clinical frailty scale as a point of care prognostic 384 indicator of mortality in COVID-19: a systematic review and meta-analysis

A Review of Persistent Post-COVID Syndrome 387 (PPCS)

Persistent Poor Health after COVID-19 Is Not 389

Associated with Respiratory Complications or Initial Disease Severity

Post-COVID syndrome in non-hospitalised 392 patients with COVID-19: a longitudinal prospective cohort study. Lancet Reg Health Eur

Age (years)

Data are mean±SEM, median [IQR], or n (%)

HC+: hospitalized COVID-positive; HC-: hospitalized COVID-negative; NHC+: non-hospitalized COVID-positive; NHC-: non-hospitalized COVIDnegative

 Table 1 . Comparison of the characteristics of participants who were or were not diagnosed with COVID-19, separately in those who were or were not hospitalized.