Beyond Chronological Age: Frailty and Multimorbidity Predict In-Hospital Mortality in Patients With Coronavirus Disease 2019

Abstract Background We evaluated whether frailty and multimorbidity predict in-hospital mortality in patients with COVID-19 beyond chronological age. Method A total of 165 patients admitted from March 8th to April 17th, 2020, with COVID-19 in an acute geriatric ward in Italy were included. Predisease frailty was assessed with the Clinical Frailty Scale (CFS). Multimorbidity was defined as the co-occurrence of ≥2 diseases in the same patient. The hazard ratio (HR) of in-hospital mortality as a function of CFS score and number of chronic diseases in the whole population and in those aged 70+ years were calculated. Results Among the 165 patients, 112 were discharged, 11 were transferred to intensive care units, and 42 died. Patients who died were older (81.0 vs 65.2 years, p < .001), more frequently multimorbid (97.6 vs 52.8%; p < .001), and more likely frail (37.5 vs 4.1%; p < .001). Less than 2.0% of patients without multimorbidity and frailty, 28% of those with multimorbidity only, and 75% of those with both multimorbidity and frailty died. Each unitary increment in the CFS was associated with a higher risk of in-hospital death in the whole sample (HR = 1.3; 95% CI = 1.05–1.62) and in patients aged 70+ years (HR = 1.29; 95% CI = 1.04–1.62), whereas the number of chronic diseases was not significantly associated with higher risk of death. The CFS addition to age and sex increased mortality prediction by 9.4% in those aged 70+ years. Conclusions Frailty identifies patients with COVID-19 at risk of in-hospital death independently of age. Multimorbidity contributes to prognosis because of the very low probability of death in its absence.

[1]  Sharon J Peacock,et al.  Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. , 2020, JAMA.

[2]  F. Lattanzio,et al.  Frailty and COVID-19: A Systematic Scoping Review , 2020, Journal of clinical medicine.

[3]  J. Hewitt,et al.  The effect of frailty on survival in patients with COVID-19 (COPE): a multicentre, European, observational cohort study , 2020, The Lancet Public Health.

[4]  Coronaviruses pathogenesis, comorbidities and multi-organ damage – A review , 2020, Life Sciences.

[5]  A. Harky,et al.  COVID-19 and Multiorgan Response , 2020, Current Problems in Cardiology.

[6]  L. Aronson Age, Complexity, and Crisis - A Prescription for Progress in Pandemic. , 2020, The New England journal of medicine.

[7]  A. Laviano,et al.  Nutrition support in the time of SARS-CoV-2 (COVID-19) , 2020, Nutrition.

[8]  M. Cesari,et al.  COVID-19 in Italy: Ageism and Decision Making in a Pandemic , 2020, Journal of the American Medical Directors Association.

[9]  Ke Ma,et al.  Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study , 2020, BMJ.

[10]  A. Akbari,et al.  Prevalence of Underlying Diseases in Hospitalized Patients with COVID-19: a Systematic Review and Meta-Analysis , 2020, Archives of academic emergency medicine.

[11]  G. Onder,et al.  Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy. , 2020, JAMA.

[12]  P. Mehta,et al.  COVID-19: consider cytokine storm syndromes and immunosuppression , 2020, The Lancet.

[13]  Xin Zhou,et al.  Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China , 2020, The Journal of Emergency Medicine.

[14]  M. Loeb,et al.  Frailty Hinders Recovery From Influenza and Acute Respiratory Illness in Older Adults. , 2020, The Journal of infectious diseases.

[15]  Amjad D. Al-Nasser,et al.  SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far , 2020, Pathogens.

[16]  Jun Liu,et al.  Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing , 2020, Radiology.

[17]  Yan Zhao,et al.  Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. , 2020, JAMA.

[18]  Y. Hu,et al.  Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China , 2020, The Lancet.

[19]  -. Lombardy Section Italian Society Infectious And Tr Vademecum for the treatment of people with COVID-19. Edition 2.0, 13 March 2020. , 2020, Le infezioni in medicina.

[20]  M. Kivimaki,et al.  Social inequalities in multimorbidity, frailty, disability, and transitions to mortality: a 24-year follow-up of the Whitehall II cohort study , 2019, The Lancet. Public health.

[21]  Laura Fratiglioni,et al.  Comparing the prognostic value of geriatric health indicators: a population-based study , 2019, BMC Medicine.

[22]  L. Rodríguez-Mañas,et al.  Frailty and multimorbidity: a systematic review and meta-analysis. , 2019, The journals of gerontology. Series A, Biological sciences and medical sciences.

[23]  M. Bloch Frailty in people living with HIV , 2018, AIDS Research and Therapy.

[24]  L. Fratiglioni,et al.  Frailty predicts short-term survival even in older adults without multimorbidity. , 2018, European journal of internal medicine.

[25]  Farhad Dalal NICE , 2018, CBT: The Cognitive Behavioural Tsunami.

[26]  L. Ferrucci,et al.  Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty , 2018, Nature Reviews Cardiology.

[27]  Kate Walters,et al.  Frailty index as a predictor of mortality: a systematic review and meta-analysis , 2018, Age and ageing.

[28]  G. Kelley,et al.  Is sarcopenia associated with an increased risk of all-cause mortality and functional disability? , 2017, Experimental Gerontology.

[29]  Kenneth Rockwood,et al.  The impact of frailty on intensive care unit outcomes: a systematic review and meta-analysis , 2017, Intensive Care Medicine.

[30]  Thomas A. Jackson,et al.  Frailty and sarcopenia: The potential role of an aged immune system , 2017, Ageing Research Reviews.

[31]  Laura Fratiglioni,et al.  Assessing and Measuring Chronic Multimorbidity in the Older Population: A Proposal for Its Operationalization , 2016, The journals of gerontology. Series A, Biological sciences and medical sciences.

[32]  T. Flores,et al.  Multimorbidity and mortality in older adults: A systematic review and meta-analysis. , 2016, Archives of gerontology and geriatrics.

[33]  G. Sergi,et al.  Inflammation and frailty in the elderly: A systematic review and meta-analysis , 2016, Ageing Research Reviews.

[34]  E. Hoogendijk,et al.  Frailty measurement in research and clinical practice: A review. , 2016, European journal of internal medicine.

[35]  R. Biram,et al.  Association of the clinical frailty scale with hospital outcomes. , 2015, QJM : monthly journal of the Association of Physicians.

[36]  C. Sieber,et al.  Analysis of Rockwood et al’s Clinical Frailty Scale and Fried et al’s frailty phenotype as predictors of mortality and other clinical outcomes in older patients who were admitted to a geriatric ward , 2015, The journal of nutrition, health & aging.

[37]  Elizabeth Sapey,et al.  Impaired neutrophil extracellular trap formation: a novel defect in the innate immune system of aged individuals , 2014, Aging cell.

[38]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[39]  S. Iliffe,et al.  Frailty in elderly people , 2013, The Lancet.

[40]  A. Osterhaus,et al.  Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. , 2012, The New England journal of medicine.

[41]  B. Winblad,et al.  The impact of chronic multimorbidity and disability on functional decline and survival in elderly persons. A community‐based, longitudinal study , 2009, Journal of internal medicine.

[42]  I. McDowell,et al.  A global clinical measure of fitness and frailty in elderly people , 2005, Canadian Medical Association Journal.

[43]  Christian Drosten,et al.  Identification of a novel coronavirus in patients with severe acute respiratory syndrome. , 2003, The New England journal of medicine.

[44]  L. Fried,et al.  Frailty in older adults: evidence for a phenotype. , 2001, The journals of gerontology. Series A, Biological sciences and medical sciences.

[45]  R. Kronmal,et al.  Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. , 1999, The New England journal of medicine.