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Research Letter| Volume 22, ISSUE 3, P514-516, March 2021

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Letter to the Editor: Premorbid Frailty is a Better Prognostic Indicator Than Age in Oldest-Old Hospitalized With COVID-19

Published:January 18, 2021DOI:https://doi.org/10.1016/j.jamda.2021.01.059
      To the Editor:
      Older people have a higher susceptibility for coronavirus disease 2019 (COVID-19) and a higher risk of developing severe COVID-19 symptoms and mortality.
      • Bonanad C.
      • García-Blas S.
      • Tarazona-Santabalbina F.
      • et al.
      The effect of age on mortality in patients with COVID-19: A meta-analysis with 611,583 subjects.
      Current studies examining the relation between outcome and frailty in COVID-19 show contrasting results
      • Hewitt J.
      • Carter B.
      • Vilches-Moraga A.
      • et al.
      COPE Study Collaborators
      The effect of frailty on survival in patients with COVID-19 (COPE): A multicentre, European, observational cohort study.
      • Aw D.
      • Woodrow L.
      • Ogliari G.
      • Harwood R.
      Association of frailty with mortality in older inpatients with COVID-19: A cohort study.
      • Owen R.K.
      • Conroy S.P.
      • Taub N.
      • et al.
      Comparing associations between frailty and mortality in hospitalised older adults with or without COVID-19 infection: A retrospective observational study using electronic health records.
      • Miles A.
      • Webb T.E.
      • Mcloughlin B.C.
      • et al.
      Outcomes from COVID-19 across the range of frailty: Excess mortality in fitter older people.
      • Brill S.E.
      • Jarvis H.C.
      • Ozcan E.
      • et al.
      COVID-19: A retrospective cohort study with focus on the over-80s and hospital-onset disease.
      • De Smet R.
      • Mellaerts B.
      • Vandewinckele H.
      • et al.
      Frailty and mortality in hospitalized older adults with COVID-19: Retrospective observational study.
      ; however, these studies did not include illness severity as an effect. We conducted a multicenter cohort study in patients aged 80 years and older who were admitted with COVID-19 to 10 different acute hospitals in March and April 2020 in order to better understand the relation between frailty and in-hospital mortality combined with respiratory failure.
      In this cohort of 711 persons aged 80 and older hospitalized with COVID-19, one-third came from a nursing home. Median premorbid Clinical Frailty Score (CFS)
      • Rockwood K.
      • Song X.
      • MacKnight C.
      • et al.
      A global clinical measure of fitness and frailty in elderly people.
      was 7 (severely frail) on a scale that ranged from 1 (least frail) to 9 (greatest frailty). Comorbidities were frequent: more than 80% had cardiovascular disease and about 40% dementia, metabolic, and/or chronic kidney disease. Overall, observed all-cause in-hospital mortality was 34.6% (246/711) and did not differ between home-dwelling (150/447, 33.6%) vs patients admitted from a nursing home (96/264, 36.4%) (P = .757). Forty-seven percent of the cohort developed respiratory failure. In Table 1, the observed all-cause in-hospital mortality in relation to frailty, respiratory failure, and intensive care unit (ICU) treatment are shown.
      Table 1In-Hospital Mortality Related to Premorbid Clinical Frailty Scale Score, Respiratory Failure, and ICU Treatment in 710 Hospitalized Patients Aged 80 Years or Older
      Premorbid Clinical Frailty ScaleTotal Cohort:

      Total Mortality Overall,

      n/n (%)
      No Respiratory Failure

      (n=373)
      Respiratory Failure
      Criteria for respiratory failure were as follows: Pao2 ≤60 mmHg and/or low Spo2 (≤90% with supplemental oxygen or ≤88% without supplemental oxygen) and/or in need of more than 5 L/min oxygen supplementation.


      (n=337)
      Total Mortality

      No Respiratory Failure,

      n/n (%)
      ICU Admission,

      n/n (%)

      (n=7)
      No ICU Admission,

      n/n (%)

      (n=366)
      Total Mortality

      Respiratory Failure,

      n/n (%)
      ICU Admission,

      n/n (%)

      (n=45)
      No ICU Admission,

      n/n (%)

      (n=292)
      1: very fit0/8

      (0)
      0/4

      (0)
      0/1

      (0)
      0/3

      (0)
      0/4

      (0)
      0/4

      (0)
      2: fit9/28

      (32.1)
      0/13

      (0)
      0/13

      (0)
      9/15

      (60.0)
      6/9

      (66.7)
      3/6

      (50.0)
      3: managing well18/64

      (28.0)
      0/34

      (0)
      0/1

      (0)
      0/33

      (0)
      18/30

      (60.0)
      6/8

      (75.0)
      12/22

      (54.5)
      4: vulnerable32/86

      (37.2)
      2/36

      (5.6)
      0/1

      (0)
      2/35

      (5.7)
      30/50

      (60.0)
      9/12

      (75.0)
      21/38

      (55.3)
      5: mildly frail35/119

      (29.4)
      5/64

      (7.8)
      2/2

      (100)
      3/62

      (4.8)
      30/55

      (54.5)
      3/6

      (50.0)
      27/49

      (55.1)
      6: moderately frail62/191

      (32.5)
      16/112

      (14.3)
      1/1

      (100)
      15/111

      (13.5)
      46/79

      (58.2)
      4/5

      (80.0)
      42/74

      (56.8)
      7: severely frail74/195

      (37.9)
      14/99

      (14.1)
      0/1

      (0)
      14/98

      (14.1)
      60/96

      (62.5)
      1/1

      (100)
      59/95

      (62.1)
      8: very severely frail13/16

      (81.3)
      6/8

      (75.0)
      6/8

      (75.0)
      7/8

      (87.5)-
      7/8

      (87.5)
      9: terminally ill2/3

      (66.7)
      2/3

      (66.7)
      2/3

      (66.7)
      P value.005<.001.18
      1 missing on Clinical Frailty Score, P values: GEE model with random effect for hospital, unadjusted for other demographic and clinical characteristics.
      Criteria for respiratory failure were as follows: Pao2 ≤60 mmHg and/or low Spo2 (≤90% with supplemental oxygen or ≤88% without supplemental oxygen) and/or in need of more than 5 L/min oxygen supplementation.
      By means of a generalized estimating equation model, we compared the odds of mortality between older patients with different premorbid CFS and with and without respiratory failure during hospitalization. We found a significant interaction between CFS and respiratory failure (P = .027). For every increase in CFS, the odds ratio (OR) for mortality was 2.185 [95% confidence interval (CI) 1.469, 3.249] in the oldest old not developing respiratory failure vs 1.333 (95% CI 1.054, 1.687) in respiratory failure. Other variables significantly associated were variables reflecting the severity of respiratory failure (peripheral oxygen saturation (P < .001, OR 0.918, 95% CI 0.883, 0.954), amount of supplemental oxygen delivery (P < .001, OR 1.227, 95% CI 1.154, 1.304) and complications acute renal failure (P = .035, OR 1.715, 95% CI 1.038, 2.836) and septic shock (P < .001, OR 15.713, 95% CI 4.12, 59.927). Baseline patient characteristics age category (80-84, 85-89, 90+), gender, residence (nursing home vs home-dwelling), number of comorbidities, and ICU treatment (P = .33, OR 1.981, 95% CI 0.501, 7.834) were not significantly associated with in-hospital mortality.
      Importantly, neither age category nor residence but premorbid frailty was associated with in-hospital mortality. The association between frailty and in-hospital mortality was more pronounced in the oldest old without respiratory failure. Hospitalized patients with CFS 8-9 had high odds of dying, even when there was no respiratory failure. This may support that hospital referral of people with CFS 8-9 might only be appropriate if supportive or palliative care is insufficient in the (nursing) home or if requested by the individual.
      For older people living with CFS 1-7, hospital referral can be medically appropriate when supportive measures are insufficient in the (nursing) home; however clinicians should timely (preferably before hospital admission) think about whether or not to escalate care when respiratory failure develops. Octogenarians in this cohort who developed respiratory failure had an in-hospital mortality of about 60%. The results of this study point in the direction that the severity of the acute (pulmonary) reaction is predominant in determining the short-term outcome in the older person with COVID-19. We also found that ICU treatment was not associated with improved outcome either in the frail or in the fit oldest old in this study.
      In short, premorbid frailty is associated with in-hospital mortality in particular in moderate COVID-19 disease. No benefit from ICU treatment could be shown in frail older persons developing respiratory failure due to COVID-19. These study results help inform advance care planning in the nursing home.
      • Lapid M.I.
      • Koopmans R.
      • Sampson E.L.
      • et al.
      Providing quality end-of-life care to older people in the era of COVID-19: Perspectives from five countries.
      ,
      • Curtis J.R.
      • Kross E.K.
      • Stapleton R.D.
      The importance of addressing advance care planning and decisions about do-not-resuscitate orders during novel coronavirus 2019 (COVID-19).

      Acknowledgments

      The authors thank all certified geriatricians who also helped with the data collection: Celine Van de Vyver, Veerle Immegeers, Véronique Ghekiere, Ranjini D'Souza, Pieter Samaey, Charlotte De Clercq, Nele Schalck, Kyri Van Hecke, and Elke Steen.

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