Risk factors for death in adult COVID-19 patients: Frailty predicts fatal outcome in older patients
Sara Tehrani, Anna Killander, Per Åstrand, Jan Jakobsson, Patrik Gille-Johnson
International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.071
This study investigated demographics, comorbidities, and death rate in hospitalized patients with confirmed COVID-19. In addition, we hypothesized that functional status, according to the Clinical Frailty Scale (CFS), in patients aged 65 years or older is a better predictor of poor outcome than age and comorbidities. Methods: A total of 255 randomly selected COVID-19 patients admitted to a university hospital were included and followed up for 60 days. Patient data were extracted manually from the electronic health records with use of a standardized protocol. Results: The age of the study population ranged between 20 and 103 years (mean age 66 years AE 17 years). Hypertension, diabetes mellitus, and obesity were the three most prevalent comorbidities. At the 60-day follow-up, 70 patients (27%) had died. In multivariate analyses, age, chronic kidney disease, and previous stroke were associated with death. Most fatal cases (90%) occurred in patients aged 65 years or older. Among such patients, CFS level was the only predictor of death in multivariate analyses. Conclusions: This study shows that increasing age, chronic kidney disease, and previous stroke significantly contribute to a fatal outcome in hospitalized patients with COVID-19. In patients aged 65 years or older, CFS level was the strongest prognostic factor for death.
Conflict of interest The authors have no conflict of interest to report for this study. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The protocol of this trial was approved by the Swedish Ethical Review Authority (record number 2020-0177).
References
Argenziano, Bruce, Slater, Tiao, Baldwin et al., Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series, BMJ
Cardona, Lewis, Kristensen, Skjot-Arkil, Ekmann et al., Predictive validity of the CriSTAL tool for short-term mortality in older people presenting at emergency departments: a prospective study, Eur Geriatr Med
Cheng, Luo, Wang, Zhang, Wang et al., Kidney disease is associated with in-hospital death of patients with COVID-19, Kidney Int
Chou, Wang, Liang, Chang, Liu et al., Risk of pneumonia among patients with chronic kidney disease in outpatient and inpatient settings, Medicine
Clegg, Young, Iliffe, Rikkert, Rockwood, Frailty in elderly people, Lancet
De Siqueira, Almeida, Zica, Brum, Barceló et al., Impact of obesity on hospitalizations and mortality, due to COVID-19: a systematic review, Obes Res Clin Pract
Docherty, Harrison, Green, Harwick, Pius et al., Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study, BMJ
Fortis, Garcia-Macedo, Maldonado-Bernal, Alarcon-Aguilar, Cruz, The role of innate immunity in obesity, Salud Publica Mex
Fried, Xue, Cappola, Ferrucci, Chaves et al., Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment, J Gerontol A Biol Sci Med Sci
Guan, Liang, Zhao, Liang, Chen et al., Comorbidity and its impact on 1590 patients with Covid-19 in China: a nationwide analysis, Eur Respir J
Henry, Lippi, Chronic kidney disease is associated with severe coronavirus disease 2019 (COVID-19) infection, Int Urol Nephrol
Hewitt, Carter, Vilches-Moraga, Quinn, Braude et al., The effect of frailty on survival in patients with COVID-19 (COPE): a multicentre, European, observational cohort study, Lancet Public Health
Hussain, Mahawar, Xia, Yang, El-Hasani, Obesity and mortality of COVID-19. Meta-analysis, Obes Res Clin Pract
Kassir, Petrilli, Jones, Yang, Rajagopalan et al., Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study, Obes Rev
Rockwood, Song, Macknight, Bergman, Hogan et al., A global clinical measure of fitness and frailty in elderly people, CMAJ
Sardu, Gambardella, Morelli, Wang, Marfella et al., Hypertension, thrombosis, kidney failure, and diabetes: Is COVID-19 an endothelial disease? A comprehensive evaluation of clinical and basic evidence, J Clin Med
Singer, Deutschman, Seymour, Shankar-Hari, Annane et al., The third international consensus definitions for sepsis and septic shock (Sepsis-3), JAMA
Smet, Mellaerts, Vandewinckele, Lybeert, Frans et al., Frailty and mortality in hospitalized older adults with COVID-19: retrospective observational study, J Am Med Dir Assoc
Wolf-Maier, Cooper, Banegas, Giampaoli, Hense et al., Hypertension prevalence and blood pressure levels in 6 European countries, Canada, and the United States, JAMA
Zhou, Yu, Du, Fan, Liu et al., Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, Lancet
{ 'indexed': {'date-parts': [[2024, 4, 2]], 'date-time': '2024-04-02T04:40:12Z', 'timestamp': 1712032812783},
'reference-count': 21,
'publisher': 'Elsevier BV',
'license': [ { 'start': { 'date-parts': [[2021, 1, 1]],
'date-time': '2021-01-01T00:00:00Z',
'timestamp': 1609459200000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'https://www.elsevier.com/tdm/userlicense/1.0/'},
{ 'start': { 'date-parts': [[2020, 10, 23]],
'date-time': '2020-10-23T00:00:00Z',
'timestamp': 1603411200000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'http://creativecommons.org/licenses/by/4.0/'}],
'content-domain': { 'domain': [ 'ijidonline.com', 'clinicalkey.jp', 'clinicalkey.com', 'clinicalkey.es',
'clinicalkey.fr', 'clinicalkey.com.au', 'elsevier.com',
'sciencedirect.com'],
'crossmark-restriction': True},
'published-print': {'date-parts': [[2021, 1]]},
'DOI': '10.1016/j.ijid.2020.10.071',
'type': 'journal-article',
'created': { 'date-parts': [[2020, 10, 31]],
'date-time': '2020-10-31T03:43:28Z',
'timestamp': 1604115808000},
'page': '415-421',
'update-policy': 'http://dx.doi.org/10.1016/elsevier_cm_policy',
'source': 'Crossref',
'is-referenced-by-count': 79,
'title': 'Risk factors for death in adult COVID-19 patients: Frailty predicts fatal outcome in older '
'patients',
'prefix': '10.1016',
'volume': '102',
'author': [ {'given': 'Sara', 'family': 'Tehrani', 'sequence': 'first', 'affiliation': []},
{'given': 'Anna', 'family': 'Killander', 'sequence': 'additional', 'affiliation': []},
{'given': 'Per', 'family': 'Åstrand', 'sequence': 'additional', 'affiliation': []},
{'given': 'Jan', 'family': 'Jakobsson', 'sequence': 'additional', 'affiliation': []},
{'given': 'Patrik', 'family': 'Gille-Johnson', 'sequence': 'additional', 'affiliation': []}],
'member': '78',
'reference': [ { 'key': '10.1016/j.ijid.2020.10.071_bib0005',
'doi-asserted-by': 'crossref',
'first-page': 'm1996',
'DOI': '10.1136/bmj.m1996',
'article-title': 'Characterization and clinical course of 1000 patients with coronavirus '
'disease 2019 in New York: retrospective case series',
'volume': '369',
'author': 'Argenziano',
'year': '2020',
'journal-title': 'BMJ'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0010',
'doi-asserted-by': 'crossref',
'first-page': '891',
'DOI': '10.1007/s41999-018-0123-6',
'article-title': 'Predictive validity of the CriSTAL tool for short-term mortality in '
'older people presenting at emergency departments: a prospective study',
'volume': '9',
'author': 'Cardona',
'year': '2018',
'journal-title': 'Eur Geriatr Med'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0015',
'doi-asserted-by': 'crossref',
'first-page': '829',
'DOI': '10.1016/j.kint.2020.03.005',
'article-title': 'Kidney disease is associated with in-hospital death of patients with '
'COVID-19',
'volume': '97',
'author': 'Cheng',
'year': '2020',
'journal-title': 'Kidney Int'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0020',
'doi-asserted-by': 'crossref',
'first-page': 'e174',
'DOI': '10.1097/MD.0000000000000174',
'article-title': 'Risk of pneumonia among patients with chronic kidney disease in '
'outpatient and inpatient settings',
'volume': '93',
'author': 'Chou',
'year': '2014',
'journal-title': 'Medicine (Baltimore)'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0025',
'doi-asserted-by': 'crossref',
'first-page': '752',
'DOI': '10.1016/S0140-6736(12)62167-9',
'article-title': 'Frailty in elderly people',
'volume': '381',
'author': 'Clegg',
'year': '2013',
'journal-title': 'Lancet'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0030',
'first-page': 'S1871',
'article-title': 'Impact of obesity on hospitalizations and mortality, due to COVID-19: a '
'systematic review',
'author': 'de Siqueira',
'year': '2020',
'journal-title': 'Obes Res Clin Pract'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0035',
'doi-asserted-by': 'crossref',
'first-page': '928',
'DOI': '10.1016/j.jamda.2020.06.008',
'article-title': 'Frailty and mortality in hospitalized older adults with COVID-19: '
'retrospective observational study',
'volume': '21',
'author': 'De Smet',
'year': '2020',
'journal-title': 'J Am Med Dir Assoc'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0040',
'doi-asserted-by': 'crossref',
'first-page': 'm1985',
'DOI': '10.1136/bmj.m1985',
'article-title': 'Features of 20 133 UK patients in hospital with covid-19 using the '
'ISARIC WHO Clinical Characterisation Protocol: prospective '
'observational cohort study',
'volume': '369',
'author': 'Docherty',
'year': '2020',
'journal-title': 'BMJ'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0045',
'doi-asserted-by': 'crossref',
'first-page': '171',
'DOI': '10.1590/S0036-36342012000200014',
'article-title': 'The role of innate immunity in obesity',
'volume': '54',
'author': 'Fortis',
'year': '2012',
'journal-title': 'Salud Publica Mex'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0050',
'doi-asserted-by': 'crossref',
'first-page': '1049',
'DOI': '10.1093/gerona/glp076',
'article-title': 'Nonlinear multisystem physiological dysregulation associated with '
'frailty in older women: implications for etiology and treatment',
'volume': '64',
'author': 'Fried',
'year': '2009',
'journal-title': 'J Gerontol A Biol Sci Med Sci'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0055',
'doi-asserted-by': 'crossref',
'first-page': '2000547',
'DOI': '10.1183/13993003.00547-2020',
'article-title': 'Comorbidity and its impact on 1590 patients with Covid-19 in China: a '
'nationwide analysis',
'volume': '55',
'author': 'Guan',
'year': '2020',
'journal-title': 'Eur Respir J'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0060',
'doi-asserted-by': 'crossref',
'first-page': '1193',
'DOI': '10.1007/s11255-020-02451-9',
'article-title': 'Chronic kidney disease is associated with severe coronavirus disease '
'2019 (COVID-19) infection',
'volume': '52',
'author': 'Henry',
'year': '2020',
'journal-title': 'Int Urol Nephrol'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0065',
'doi-asserted-by': 'crossref',
'first-page': 'e444',
'DOI': '10.1016/S2468-2667(20)30146-8',
'article-title': 'The effect of frailty on survival in patients with COVID-19 (COPE): a '
'multicentre, European, observational cohort study',
'volume': '5',
'author': 'Hewitt',
'year': '2020',
'journal-title': 'Lancet Public Health'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0070',
'first-page': 'S1871',
'article-title': 'Obesity and mortality of COVID-19. Meta-analysis',
'volume': '9',
'author': 'Hussain',
'year': '2020',
'journal-title': 'Obes Res Clin Pract'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0075',
'doi-asserted-by': 'crossref',
'first-page': 'e13034',
'DOI': '10.1111/obr.13034',
'article-title': 'Risk of COVID‐19 for patients with obesity',
'volume': '21',
'author': 'Kassir',
'year': '2020',
'journal-title': 'Obes Rev'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0080',
'doi-asserted-by': 'crossref',
'first-page': 'm1966',
'DOI': '10.1136/bmj.m1966',
'article-title': 'Factors associated with hospital admission and critical illness among '
'5279 people with coronavirus disease 2019 in New York City: prospective '
'cohort study',
'volume': '369',
'author': 'Petrilli',
'year': '2020',
'journal-title': 'BMJ'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0085',
'doi-asserted-by': 'crossref',
'first-page': '489',
'DOI': '10.1503/cmaj.050051',
'article-title': 'A global clinical measure of fitness and frailty in elderly people',
'volume': '173',
'author': 'Rockwood',
'year': '2005',
'journal-title': 'CMAJ'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0090',
'doi-asserted-by': 'crossref',
'first-page': '1417',
'DOI': '10.3390/jcm9051417',
'article-title': 'Hypertension, thrombosis, kidney failure, and diabetes: Is COVID-19 an '
'endothelial disease? A comprehensive evaluation of clinical and basic '
'evidence',
'volume': '9',
'author': 'Sardu',
'year': '2020',
'journal-title': 'J Clin Med'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0095',
'doi-asserted-by': 'crossref',
'first-page': '801',
'DOI': '10.1001/jama.2016.0287',
'article-title': 'The third international consensus definitions for sepsis and septic '
'shock (Sepsis-3)',
'volume': '315',
'author': 'Singer',
'year': '2016',
'journal-title': 'JAMA'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0100',
'doi-asserted-by': 'crossref',
'first-page': '2363',
'DOI': '10.1001/jama.289.18.2363',
'article-title': 'Hypertension prevalence and blood pressure levels in 6 European '
'countries, Canada, and the United States',
'volume': '289',
'author': 'Wolf-Maier',
'year': '2003',
'journal-title': 'JAMA'},
{ 'key': '10.1016/j.ijid.2020.10.071_bib0105',
'doi-asserted-by': 'crossref',
'first-page': '1054',
'DOI': '10.1016/S0140-6736(20)30566-3',
'article-title': 'Clinical course and risk factors for mortality of adult inpatients with '
'COVID-19 in Wuhan, China: a retrospective cohort study',
'volume': '395',
'author': 'Zhou',
'year': '2020',
'journal-title': 'Lancet'}],
'container-title': 'International Journal of Infectious Diseases',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://api.elsevier.com/content/article/PII:S1201971220322761?httpAccept=text/xml',
'content-type': 'text/xml',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://api.elsevier.com/content/article/PII:S1201971220322761?httpAccept=text/plain',
'content-type': 'text/plain',
'content-version': 'vor',
'intended-application': 'text-mining'}],
'deposited': { 'date-parts': [[2021, 4, 21]],
'date-time': '2021-04-21T21:29:58Z',
'timestamp': 1619040598000},
'score': 1,
'resource': {'primary': {'URL': 'https://linkinghub.elsevier.com/retrieve/pii/S1201971220322761'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2021, 1]]},
'references-count': 21,
'alternative-id': ['S1201971220322761'],
'URL': 'http://dx.doi.org/10.1016/j.ijid.2020.10.071',
'relation': {},
'ISSN': ['1201-9712'],
'subject': ['Infectious Diseases', 'Microbiology (medical)', 'General Medicine'],
'container-title-short': 'International Journal of Infectious Diseases',
'published': {'date-parts': [[2021, 1]]},
'assertion': [ {'value': 'Elsevier', 'name': 'publisher', 'label': 'This article is maintained by'},
{ 'value': 'Risk factors for death in adult COVID-19 patients: Frailty predicts fatal '
'outcome in older patients',
'name': 'articletitle',
'label': 'Article Title'},
{ 'value': 'International Journal of Infectious Diseases',
'name': 'journaltitle',
'label': 'Journal Title'},
{ 'value': 'https://doi.org/10.1016/j.ijid.2020.10.071',
'name': 'articlelink',
'label': 'CrossRef DOI link to publisher maintained version'},
{'value': 'article', 'name': 'content_type', 'label': 'Content Type'},
{ 'value': '© 2020 The Author(s). Published by Elsevier Ltd on behalf of International '
'Society for Infectious Diseases.',
'name': 'copyright',
'label': 'Copyright'}]}
