key: cord-1004897-qgqfwn2t authors: Ramos‐Rincon, Jose‐Manuel; Moreno‐Perez, Oscar; Pinargote‐Celorio, Hector; Leon‐Ramirez, Jose‐Manuel; Andres, Mariano; Reus, Sergio; Herrera‐García, Cristian; Martí‐Pastor, Ana; Boix, Vicente; Gil, Joan; Sanchez‐Martinez, Rosario; Merino, Esperanza title: Clinical Frailty Score vs Hospital Frailty Risk Score for predicting mortality and other adverse outcome in hospitalised patients with COVID‐19: Spanish case series date: 2021-07-16 journal: Int J Clin Pract DOI: 10.1111/ijcp.14599 sha: 35f3f2c41885cf8971d6a76acf6b71f8b0715428 doc_id: 1004897 cord_uid: qgqfwn2t OBJECTIVES: Frailty can be used as a predictor of adverse outcomes in people with coronavirus disease 2019 (COVID‐19). The aim of the study was to analyse the prognostic value of two different frailty scores in patients hospitalised for COVID‐19. MATERIAL AND METHODS: This retrospective cohort study included adult (≥18 years) inpatients with COVID‐19 and took place from 3 March to 2 May 2020. Patients were categorised by Clinical Frailty Score (CFS) and Hospital Frailty Risk Score (HFRS). The primary outcome was in‐hospital mortality, and secondary outcomes were tocilizumab treatment, length of hospital stay, admission in intensive care unit (ICU) and need for invasive mechanical ventilation. Results were analysed by multivariable logistic regression and expressed as odds ratios (ORs), adjusting for age, sex, kidney function and comorbidity. RESULTS: Of the 290 included patients, 54 were frail according to the CFS (≥5 points; prevalence 18.6%, 95% confidence interval [CI]: 14.4‐23.7) vs 65 by HFRS (≥5 points; prevalence: 22.4%, 95% CI 17.8‐27.7). Prevalence of frailty increased with age according to both measures: 50‐64 years, CFS 1.9% vs HFRS 12.3%; 65‐79 years, CFS 31.5% vs HFRS 40.0%; and ≥80 years, CFS 66.7% vs HFRS 40.0% (P < .001). CFS‐defined frailty was independently associated with risk of death (OR 3.67, 95% CI 1.49‐9.04) and less treatment with tocilizumab (OR 0.28, 95% CI 0.08‐0.93). HFRS‐defined frailty was independently associated with length of hospital stay over 10 days (OR 2.89, 95% CI 1.53‐5.44), ICU admission (OR 4.18, 95% CI 1.84‐9.52) and invasive mechanical ventilation (OR 5.93, 95% CI 2.33‐15.10). CONCLUSION: In the spring 2020 wave of the COVID‐19 pandemic in Spain, CFS‐defined frailty was an independent predictor for death, while frailty as measured by the HFRS was associated with length of hospital stay over 10 days, ICU admission and use of invasive mechanical ventilation. Frailty is defined as "a medical syndrome with multiple causes and contributors, characterized by diminished strength, endurance, and reduced physiologic function that increases an individual's vulnerability for developing increased dependency and/or death." 1 Fried et al 2 described a frailty phenotype based on five dimensions, including weight loss, exhaustion, physical activity, walking speed and grip strength. According to this phenotype, fulfilment of at least three criteria indicates frailty, while people with one or two are defined as prefrail and those who do not meet any criteria are considered robust. This measure also enables calculating a frailty index for each individual from 0 to 1 by dividing the total number of deficits present by the total number of deficits possible (higher values indicating more frailty). 3 Frailty is a reliable measure for predicting clinical and healthcarerelated outcomes in people with different conditions. [4] [5] [6] However, the notion of frailty as a predictor of adverse outcomes in older patients with coronavirus disease 2019 (COVID-19) remains unclear. 7, 8 Existing studies have been heterogeneous in terms of the frailty measures used, clinical context, design, definition of adverse outcomes and results. [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] The Clinical Frailty Score (CFS) 20 is the most common instrument for measuring frailty in COVID-19, but alternative scales may also be used, including the Hospital Frailty Risk Score (HFRS). 21 More evidence is still needed about the relevance of frailty for mortality, admission to the intensive care unit (ICU), use of invasive mechanical ventilation (IMV) and other adverse outcomes in people infected with COVID-19. The aim of this study was to analyse the prognostic value of two different frailty scores, the CFS 20 and the HFRS, 21 COVID-19 during the spring 2020 wave of the pandemic in Spain. We hypothesised that CFS-and HFRS-defined frailty would be strong predictors of adverse outcomes. This retrospective cohort study took place from 3 March to 2 May 2020 at the General University Hospital of Alicante (Spain). Eligible patients were adults (≥18 years) admitted to hospital and diagnosed with COVID-19 pneumonia using the reverse transcriptase polymerase chain reaction (RT-PCR) test for SARS-CoV-2. Frailty was assessed using two instruments: the CFS and HFRS. The CFS bases the frailty assessment on the patient's condition 2 weeks prior to hospital admission. 20 Patients are scored on an ordinal hierarchical scale from 1 to 9, with a score of 1 indicating the person is very fit; 2 well; 3 managing well; 4 vulnerable; 5 mildly frail; 6 moderately frail; 7 severely frail; 8 very severely frail; and 9 terminally ill. 15, 20 Frailty level was retrospectively decided for all patients by one junior physician, and all borderline cases were adjudicated by a specialist physician in line with previous studies. 18, 19 Data collected for taking the decision included reported physical activity levels, number of falls in the last year, visual and hearing deficits, history of cognitive impairment, fatigue, weight loss in the last year and functional status according to the Barthel Index. 22 We did not anticipate that there would be adequate number of events for each score, so we grouped them as 1-4 (no frailty), 5-6 (mild-to-moderate frailty: initial signs of frailty but with some degree of independence) and 7-9 (severe frailty) for the purposes of the analyses (Table S1) . We also analysed CFS as a continuous and dichotomous variable (no frailty [1] [2] [3] [4] vs frailty [5] [6] [7] [8] [9] ). The HFRS was previously developed and validated in a British cohort of older people. 21 To calculate this score, we reviewed clinical records from the Admission Service of our hospital for diagnostic codes from the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM), looking for 10 conditions recorded during any hospitalisation within the last 2 years. Each code registered was assigned a certain number of points (see Table S2 for itemised scoring criteria). Based on the calculated score, patients were classified into three frailty risk groups based on previously validated cut points for the HFRS: low (<5 points), intermediate (5-15 points) and high risk (>15 points). 21 Patients with scores of 5 or above were defined as frail in a dichotomous analysis (frailty vs no frailty), and we also used the HFRS as a continuous variable. The sample size was not calculated. All inpatients diagnosed with COVID-19 by PCR from 3 March to 2 May 2020 were included. Patients with missing clinical variables were not included in the analysis of these variables. More in-depth information about the data collection and definition of variables has been provided in papers by • Frailty is a reliable predictor of clinical and healthcarerelated outcomes in people with different conditions. • The Clinical Frailty Score (CFS) is the most common measure of frailty in COVID-19. • We assessed frailty using the CFS and the Hospital Frailty Risk Score in inpatients with COVID-19. • CFS-defined frailty was an independent predictor for death. the COVID-19 ALC research group. 23, 24 For patients diagnosed with COVID-19 during their hospital stay (nosocomial infection), the date of diagnosis was used in lieu of the date of admission. Preadmission comorbidities were collected from the patient's electronic medical record. Laboratory data were collected at admission, and renal function was evaluated by estimated glomerular filtration rate (eGFR) according to the CKD-EPI equation. The burden of comorbidities was assessed using the age-adjusted Charlson comorbidity Index (CCI), a method of estimating mortality risk from comorbid disease at 10 years. 25 The primary outcome was in-hospital mortality from any cause. Secondary outcomes were treatment with intravenous tocilizumab (TCZ) (reserved for severe cases at admission or those with progressive clinical, analytical and radiological deterioration), length of hospital stay (continuous variable), length of hospital stay ≥10 days (dichotomous), ICU admission and need for IMV. Categorical variables are expressed as frequencies (percentages) and continuous variables as medians (interquartile range) or mean (standard deviation, SD). Differences in CFS-and HFRS-defined frailty were examined using the χ 2 test for categorical variables and the Mann-Whitney U-test for continuous variables. Agreement between the two measures was assessed by Kappa score with 95% confidence intervals (CIs), while the Spearman's rho test was used to test correlation between the age, CFS, HFRS and CCI. Time-toevent analyses were reported with a Kaplan-Meier survival plot. We then analysed the outcomes using two logistic regression models: model A (adjusted for age, sex and eGFR) and model B (adjusted for age, sex, eGFR and CCI), calculating results for CFS and HFRS as continuous variables (score) and both dichotomous variables and categorical variables, as described above. Associations were expressed as adjusted odds ratios (OR) and 95% CIs. Two-tailed P values of less than .05 were considered significant. All analyses were performed using SPSS v25. The HFRS showed moderate concordance with the CFS (kappa = 0.38, 95% CI 0.24-0.52). Using the Spearman rank test, correlation between the CFS and HFSR was moderate (r s = 0.51, P < .001), between the CFS and CCI, high (r s = 0.79; P < .001), between the HFSR and CCI, moderate (r s = 0.50, P < .001), between age and CFS, high (r s = 0.748) and between age and HFRS, moderate (r s = 0.485). Demographics, comorbidities, laboratory findings and outcomes according to frailty (CFS or HFRS) are shown in Table 1 (all covariates are presented in Table S3 ). Prevalence of frailty increased with age according to both measures: 50-64 years, CFS 1.9% vs HFRS 12.3%; 65-79 years, CFS 31.5% vs HFRS 40.0%; and ≥80 years, CFS 66.7% vs HFRS 40.0% (P < .001). 25 .0% (P = .007). Both the CFS and the HFRS categories were significantly associated with survival ( Figure 1 ). Long hospital stays (≥10 days) were observed in 131 (45.2%) patients, treatment with TCZ in 80 (27.6%), ICU admission in 47 (16.2%) and IMV in 37 (12.8%). By CFS categories, long hospital stay was similar in people with no frailty and moderate-to-severe frailty. However, fewer moderately to severely frail patients were treated with TCZ (P < .001), admitted to the ICU (P = .019) or needed IMV (P = .027, Table 2 ). According to the three-category HFRS analysis, long hospital stay was associated with frailty risk (P = .002), as was ICU admission (P = .039) and use of IMV (P = .018), while treatment with TCZ was similar between groups ( Table 2 ). In the multivariable analysis, after adjusting for age, sex and renal function (model A), the CFS was significantly associated with higher odds of mortality, both as a continuous and categorical measure. However, after also adjusting for CCI (model B), only severe frailty was significantly associated with mortality. In both models, CFS-defined frailty (continuous and categorical) was significantly associated with lower odds of treatment with TCZ, but not with long hospital stay, ICU admission or requirement for IMV (Table 3) . According to both models A and B, the HFRS (continuous and categorical) was not associated with mortality or TCZ treatment. However, it was significantly associated with higher odds of long hospital stay, ICU admission and IMV (Table 4 ). This study compares two scales for measuring frailty in inpatients with COVID-19 and assesses their association with mortality and other severe adverse events. According to both scales, about one in every five adults admitted to our hospital with COVID-19 was frail. CFS-defined frailty was associated with in-hospital mortality, after adjusting for age, sex and eGFR, but not after adjusting for comorbidities (CCI), except in the "severe frailty" category. HFRS-defined frailty was not associated with in-hospital mortality. found that CFS level was a better predictor of outcomes than age or comorbidities. In our study, a CFS of 5 or higher was an independent prognostic factor for death, after adjusting for age, gender and kidney function. .039 .019 .013 Invasive mechanical ventilation .018 .027 . In this study of COVID-19 patients admitted to a university hospital in Spain, we found that CFS-defined frailty was a prognostic factor for death, after adjusting for age, gender and kidney function. Bold indicates statistically significant differences. The authors declare no conflict of interest. Abbreviations: aOR, adjusted odds ratio (OR); CI, confidence interval; HFRS, Hospital Frailty Risk Score. a Adjusted for age, gender and estimated glomerular filtration rate (eGFR). b Adjusted for age, gender, eGFR and Charlson comorbidity index. Bold indicates statistically significant differences. 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